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Volume 1 Issue 3 www.ijrpb.com May-June 2013
Indian Journal of Research in Pharmacy and Biotechnology
ISSN: 2320-3471 (Online)
ISSN: 2321-5674 (Print)
Editor
B.Pragati Kumar, M.Pharm, Assistant Professor,
Nimra College of Pharmacy
Consulting editor
Dr. S Duraivel, M.Pharm, Ph.D., Principal,
Nimra College of Pharmacy
Associate Editors
Mr. Debjit Bowmick, M.Pharm., (Ph.D)
Assistant Professor, Nimra College of Pharmacy
Mr. Harish Gopinath, M.Pharm., (Ph.D)
Assistant Professor, Nimra College of Pharmacy
Dr. M. Janardhan, M.Pharm., Ph.D.
Professor, Nimra College of Pharmacy
Dr. A. Ravi Kumar, M.Pharm., Ph D.
Professor, Bapatla College of Pharmacy
Editorial Advisory Board
Dr.Y.Narasimaha Reddy, M. Pharm., Ph D.
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Sciences, Kakatiya University, Warangal.
Dr. Biresh Kumar Sarkar,
Asstt.Director (Pharmacy),
Kerala
Dr.V.Gopal, M. Pharm., Ph D.
Principal, Mother Theresa Post Graduate & Research
Institute of Health Sciences,Pondicherry-6
Dr. M.Umadevi, M.Sc. (Agri), Phd
Research Associate, Tamil Nadu Agricultural
University, Coimbatore
Dr. J.Balasubramanium, M. Pharm., Ph D.
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R A Chem Pharma Ltd., Hyderabad
Dr. V.Prabhakar Reddy, M. Pharm., Ph D.
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Research, Warangal
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Dr. S.D.Rajendran, M. Pharm., Ph D.
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ISSN: 2321-5674 (Print)
S.No. Contents Page No.
1. Development and evaluation of drotoverine taste masked tablets with improved
dissolution efficiency using solid dispersion technique
Anusha P, Nirajana V.A, Syed Mohammed, Shaik Jilani, Ch. Murali Krishna, Harish.G
275-280
2. Effect of different disintegrants on Ciprofloxacin conventional tablets
Harish.G, Ch.Bhargavi, A.Riyajune, Md.Yasmeen, Syed Mohammed, Ch.Murali Krishna,
Sk.Jilani, Nirajana.V.A
281-287
3. Chronotherapy for nocturnal asthama
Papola Vibhooti , Rajan G, Bisht Seema , Dr. Kothiyal Preeti
288-298
4. Recent trends in scope and opportunity of clinical research in India
Hemant Singh, Abhinav Srivastva
299-304
5. Sustained release drug delivery system
Navin Dixit, Sheo Dutt Maurya, Bhanu P.S.Sagar
305-310
6. Antibacterial activity of ethanolic extracts of Nyctanthes arbortristis and Nerium
oleander
A.Ravi Kumar, Ch.S.D.Phani Deepthi Yadav
311-313
7. Food poisoning and its safety precaution
M. Umadevi, K.P.Sampath Kumar, Sai Pavan, Sd.Gosia Sultana, D. Bhowmik
314-323
8. Microencapsulation technology
K.P.Sampath Kumar,Tejbe.Sk, Shameem Banu, P.Naga Lakshmi , D.Bhowmik
324-328
9. An overview about pharmacy education in India
Praneta Desale
329-332
10. Phytochemical evaluation of Nyctanthes arbortristis, Nerium oleander and Catharathnus
roseus
Ch.S.D. Phani Deepthi Yadav, N.S.P. Bharadwaj, M. Yedukondalu, Ch. Methushala, A. Ravi
Kumar
333-338
11. Angina pectoris epidemic in India: a comprehensive review of clinical features,
differential diagnosis, and remedies
Shravan Paswan, Ranjan Kumar Sharma, Alok Ranjan Gaur, Avinash Sachan,
Mahendra Singh Yadav, Preeti Sharma, Mrinmoy Gautam
339-345
12. Stability Indicating HPLC method for the estimation of Cinacalcet hydrochloride API
Manikandan Krishnan, Santhana Lakshmi Karunanidhi, Gayathri Sola, Akshitha .Y
346-350
13. Bioavailability: criteria for approving a drug product for marketing
Sandhya Singh, Faheem Ajmal Ansari, Shravan Paswan, Rnjan Kumar Sharma, Alok Ranjan
Gaur
351-359
14. The effect of superdisintegrants on the dissolution of calcium carbonate fast dissolving
tablets
Mohammed Farhana, J.Preeti, Md Faizulla, Budda Chellibabu, Harish.G, Rajnesh Kumar
Singh
360-364
15. Phytochemical and pharmacological studies on whole plant of Asystasia gangetica
T.K.Gopal, Megha.G, D.Chamundeeswari, C.Umamaheswara Reddy
365-370
16. Investigation of in-vitro anti-oxidant, anti-inflammatory and anti-arthritic activity of
aerial parts of Securinega leucopyrus (willd.) Muell
T.K.Gopal, T.Sheela, D.Chamundeeswari, C.Umamaheswara Reddy
371-378

ISSN: 2321-5674 (Print)
17. Transdermal sonophoresis technique- an approach for controlled drug delivery
K.P.Sampath Kumar, Debjit Bhowmik, M.Komala
379-381
18. A comprehensive review of Eladi Vati
Navin Dixit, Sheo Dutt Maurya , Bhanu P.S.Sagar
382-384
19. Preparation and characterization of some herbal ointment formulations with evaluation of
antimicrobial property
Pulak Majumder and Susmita Majumder
385-390
20. The effects of air pollution on the environment and human health
Shyam Bihari Sharma, Suman Jain, Praveen Khirwadkar, Sunisha Kulkarni
391-396
21. Formulation and evaluation of orodispersible tablets of Cinnarizine by super
disintegrants addition method
Praveen Khirwadkar, Kamlesh Dashora, Shyam Bihari Sharma
397-400
22. Effective hypoglycemic action of metformin combinations against Dexamethasone
induced diabetes mellitus in rats
Mohanraghupathy.S, Jayabharath N, Bhuvana Tejay, Hameera Khanam B, Lavanya Lahari B
401-403
23. A review on medicinal plants having antioxidant potential
Prof.S.K Sharma, Mr. Lalit Singh, Suruchi Singh
404-409
24. Invitro anti-inflammatory activity of Strychnos potatorum linn seed by HRBC membrane
stabilization
V.Vijayakumar, Dr C.K.Hindumathy
410-412
25. Synthesis and characterization of 1, 3, 4-oxadiazole and 1,3,4- thiadiazole
Ramanji Naik
413-419
26. Preparation, characterization and evaluation of Olmesartan medoxomil β- cyclodextrin
complexes
V. Prudhvi Raj, Subhashis Debnath, Maleswari, M. Niranjan Babu
420-427
27. Wafers technology – a newer approacah to smart drug dilevery system
Papola Vibhooti*, Kothiyal Preeti
428-439
28. Evaluation of anti-ulcer effects of ethanolic extract of Delonix regia flower
Samaresh Pal Roy, Kamlesh Prajapati, Ramji Gupta, Dipanwita Bhadra, Nikunj Patel,
Archana Batiwala, Gautam Sonara, Neerav Gheewala, T. Kannadasan
440-445
29. A study on medication non-adherence in ambulatory diabetic patients and need for
pharmacist intervention for improving patient adherence
Dr. Praveen Kumar G
446-447
30. Recent trends in positive and negative aspects of food on bioavalabilty of drugs
Gowthami B, Sk Nahida Fazilath, Sanaulla Md, K Prudhvi Raj, Dastagiriah G, Tabassum Sk
448-460
31. A review on collagen based drug delivery systems
Sahithi B, Ansari Sk, Hameeda Sk, Sahithya G, Durga Prasad M, Yogitha Lakshmi
461-468

ISSN: 2321-5674(Print)
ISSN: 2320 – 3471(Online)
Anusha P et.al Indian Journal of Research in Pharmacy and Biotechnology
Volume 1(3) May-June 2013 Page 275
DEVELOPMENT AND EVALUATION OF DROTOVERINE TASTE
MASKED TABLETS WITH IMPROVED DISSOLUTION EFFICIENCY USING
SOLID DISPERSION TECHNIQUE
Anusha P*1
, Nirajana V.A2
, Syed Mohammed1
, Shaik Jilani1
, Ch. Murali Krishna, Harish.G1
1. Nimra college of Pharmacy, Jupudi, Vijayawada, Andhra Pradesh, India
2. Faculty of Pharmacy, Sri Ramachandra University, Porur, Chennai.
*Corresponding author: E.Mail:anupharma88@gmail.com
ABSTRACT
The purpose of this research is to mask the bitter taste of the drug, Drotoverine using solid dispersion
technique. The taste-masked drug is formulated in to a conventional tablet by direct compression method for ease
of administration. Taste masking was done by solid dispersion using polymer such as urea and mannitol by
melting/fusion method Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM)
were performed to identify the physicochemical interaction between drug and carrier, hence its effect on
dissolution. Conventional taste masked tablets were evaluated for weight variation, disintegration time, hardness
and friability. In vitro drug release studies were performed for conventional tablets of drotoverine. Bitterness
score was evaluated on volunteers. FTIR spectroscopy and SEM showed no interaction between drug and carriers.
Conventional tablets prepared using solid dispersion, showed faster disintegration and complete bitter taste
masking of drotoverine. In addition the prepared tablets exhibited better dissolution profile. Taste evaluation of
taste masked tablets in human volunteers rated tasteless with a score of 0. Thus, results conclusively demonstrated
successful masking of taste and oral disintegration of the formulated tablets in the oral cavity with improved
dissolution.
Key words: Drotoverine, conventional tablet, solid dispersion, taste masking
INTRODUCTION
The oral route is the most convenient, appropriate and acceptable way to administer medications. Several
oral active pharmaceuticals ingredients and bulking agents have Unpleasant bitter taste; hence this often times
results to non compliance to medications by Patients. Taste masking is a means of masking the bitter taste of drug
in order to improve the Palatability of the drug, which in turn improves patience compliance. Drotoverine is a
novel non-Anticholinergic smooth muscle antispasmodic drug. Its Chemical name is 1- [(3, 4-diethoxy phenyl)
methylene]-6, 7-diethoxy-1, 2, 3, 4-tetrahydroisoquinoline with a molecular formula of C24 H31NO4. HCl. It
decreases the influx of active calcium into smooth muscles due to inhibiting of phosphodiesterase and
intracellular increase of cAMP level. Its oral bioavailability is about 100% with a biologic half- life of about 7 to
12 h. It adult dose is about 40 to 80mg one to three times a day.
Drotoverine has poor aqueous solubility, and thus resulting in incomplete absorption after oral
administration. This is due to a large fraction of the dose remaining undissolved for absorption. Under such
conditions, the bioavailability can be increased by using, a more water soluble formulation. Solid dispersion is an
efficient means of improving the dissolution rate and hence the bioavailability of a range of poorly soluble drug.
Further drotoverine has an extremely unpleasant bitter taste. The exact mechanism of bitterness is unknown.
Masking of bitter taste of the drotoverine is an extremely important factor in the formulation of tablets to ensure
patient compliance. Taster masked tablets were useful in patients, such as pediatric, geriatric, who may face
difficulty in swallowing conventional tablets or capsules and liquid orals or syrup.
Many reported techniques such as polymer coating, microencapsulation, use of lecithins and related
substances, liposomes and various polymeric materials mask the bitterness by controlling drug release at salivary
pH. However it is a major challenge to develop taste masked conventional tablets with improved drug release.
Thus in the present study an attempt has been made to formulate taste masked conventional tablets of drotoverine
with improved dissolution so as to prepare a “patient-friendly dosage form”. Furthermore, the study undertakes to
investigate solid-state characterization, and attempts to see the possible mechanism of taste masking and
improved dissolution rate.
2. MATERIALS AND METHODS
2.1. Materials: Drotoverine was obtained as a gift sample from Apex laboratory ltd, Chennai; sodium starch
glycolate, aspartame, magnesium stearate and micro crystalline cellulose was obtained as a gift sample from Intex
chemicals, Chennai.

2.2. Methods
2.2.1. Preparation of Drotoverine Solid Dispersion Using Mannitol and Urea as Carriers: The solid
dispersion of drotoverine with urea and mannitol in 1:1, 1:2 and 1:3 ratios were carried out using melting or
fusion method. The preparation of physical mixture of a drug and a water-soluble carrier and heating it directly
until it melted. The melted mixture is then solidified orally in an ice-bath under vigorous stirring. The final solid
mass is crushed, pulverized and sieved.
2.2.2. Characterization of solid dispersion: The prepared drotoverine and mannitol, drotoverine and urea solid
dispersions were characterized for solubility studies, FTIR studies and SEM studies.
2.2.3. Tablet Formulation: Oral conventional tablets containing equivalent of 80 mg of drotoverine were
compressed on an eight-station single rotary tabletting press (GMC, using a flat punch with break line by direct
compression technique.
3. Characterization of Prepared Tablets: The prepared tablets were evaluated for its physical characteristics
like hardness thickness, weight variation, friability, disintegration test.
3.1. In vitro dissolution study: One tablet of F1 or F2 or MKT formulation were placed in a cylindrical basket
(aperture size 425μm: diameter 20mm; height 25mm), and immersed in 900ml of leaching fluid (Stimulated
gastric fluid maintained at 37 ± 2oC). The fluid was stirred at 100rpm (Model Disso 2000, Lab India). Samples of
the leaching fluid (5ml) were withdrawn at selected time intervals with a syringe fitted with a cotton wool plug
and replaced with an equal volume of drug-free dissolution fluid. The samples were suitably diluted with blank
dissolution fluid and were analyzed for content of drotaverine hydrochloride spectrophotometrically at λmax,
302.8 nm by using an ElicoSL 210 UV-Visible double beam spectrophotometer (Elico, India). The amounts
released were expressed as a percentage of the drug content in each dissolution medium. The dissolution test was
carried out in quadruplicate and the mean results reported.
3.2. Taste evaluation: Taste evaluation was done on 6 volunteers by using time intensity method. One tablet was
held in mouth for 10 seconds bitterness levels were recorded instantly and after 10 seconds,
30seconds, 1 minute and 2 minutes, bitterness levels were recorded.
4. RESULTS
Table.1. Formulation table for solid dispersion Table.2. Formulation Table for Tablets
Formulation code Polymer Ratio
F1 Mannitol 1:1
F2 Mannitol 1:2
F3 Mannitol 1:3
F4 Urea 1:1
F5 Urea 1:2
F6 Urea 1:3
*for all the formulations
Name of the ingredient Quantity per single tablet*
Drug polymer SD 80mg
Sodium starch glycolate 6.6mg
Aspartame 1.1mg
Microcrystalline cellulose 16.8mg
Magnesium stearate 5.5mg
Total 110mg
Table.3. Pre-compression parameters for drug polymer solid dispersion
Formulation code F1 F2 F3 F4 F5 F6
Angle of repose 25°71’ 26°42’ 28°93’ 24°32’ 25°43’ 29°47’
Bulk Density(gm/ml) 0.74 0.72 0.69 0.64 0.75 0.78
Tapped Density(gm/ml) 0.86 0.82 0.87 0.85 0.89 0.89
Compressibility Index (%) 13.95 12.19 20.68 24.70 15.73 12.35
Hausners ratio 1.18 1.14 1.25 1.30 1.16 1.14
Table.4. Post compression studies
Formulation
code
Weight
variation (mg)
Thickness
(mm)
Hardness
(Kg/cm2)
Friability
(%)
Assay
(%)
F1 Complies 1.9 4 0.05 99.56
F2 Complies 1.9 4 0.06 98.45
F3 Complies 2.0 5 0.03 99.12
F4 Complies 1.9 4 0.05 98.22
F5 Complies 2.1 5 0.06 97.44
F6 Complies 2.0 4 0.01 99.61

Table.5. In-vitro dissolution study for Drotoverine solid dispersion
Time in
min
Percent drug release formulation code
F1 F2 F3 F4 F5 F6
0 0 0 0 0 0 0
5 14.11 14.75 15.39 16.56 22.25 26.03
10 25.03 26.14 30.01 32.78 39.56 45.35
15 34.22 36.78 40.56 43.06 54.09 69.46
20 41.86 45.67 52.88 55.12 67.03 78.75
25 52.45 55.76 61.75 67.95 73.25 86.95
30 58.56 65.20 67.25 72.15 84.02 92.10
Table.6. In-vitro dissolution study for
marketed drotoverine tablets
Table.7.Comparison of dissolution profile for formulated
and marketed products
Time in min Percent drug release
0 0
5 24.36
10 35.12
15 54.32
20 67.75
25 75.55
30 82.36
Time in
min
%Drug Release
Marketed drotoverine
tablets
Formulated
drotoverine tablets
0 0 0
5 24.36 26.03
10 35.12 45.35
15 54.32 69.46
20 67.75 78.75
25 75.55 86.95
30 82.36 92.10
Table.8. Bitterness evaluations of prepared drotoverine tablets:
volunteers Formulation code and bitterness
F1 F2 F3 F4 F5 F6
1 0 0 0 0 0 0
2 0 0 X 0 0 0
3 0 0 0 X 0 0
4 x 0 0 0 x 0
5 0 0 0 0 0 0
0=No bitterness; x=Threshold bitterness
Figure.1. IR spectro of the pure drug, Drotaverine Hcl Figure.2.IR spectro of the formulation F1
Figure.3.IR spectro of the formulation F2 Figure.4. IR spectro of the formulation F3

Figure.5.IR spectro of the formulation F4 Figure.6.IR spectro of the formulation F5
Figure.6. IR spectro of the formulation F6
Figure.7.SEM image of the pure drug,
Drotaverine Hcl
Figure.8.SEM image of the formulation F1
Figure.9.SEM image of the formulation F2 Figure.10.SEM image of the formulation F3
Figure.11. SEM image of the formulation F4 Figure.12.SEM image of the formulation F5
Figure.13. SEM image of the formulation F6

Figure.14. In-Vitro Dissolution studies of the
formulated batches
Figure.15. In-Vitro Dissolution studies Optimized
and marketed
5. DISCUSSION
Fourier Transform Infrared Spectroscopy: Infrared spectra matching approach was used for thedetection of
any possible chemical reaction between the drug and the polymer. The IR spectrum of the physical mixture was
done to detect any appearance or disappearance of peaks. The compatibility between the drug and the polymer
were evaluated using FTIR matching method. The IR spectra of pure drug and polymer are shown in (figure 1).
Pre-Formulation Studies: The angle of repose of prepared drotaverine tablet mixture was in the range 20°-30°.
Normally if the value falls between 20°-30°, it shows good flow property. The bulk density and tapped density
were found to be in the range of 0.7 to 0.8 g/cm3. A Hausner’s ratio was within the range of 1.13 to 1.32, lesser
than 1.25 is considered to be an indication of
good flow property. The compressibility index was within the range of 10-25 hence falls within the good range.
Post-Compressional studies: The post compressional characteristic for all the formulated batches was found to
be within the limits as per Indian pharmacopeia. The hardness was found to be within 4-5 Kg/cm2 in all the
formulations. In all the formulations, the friability value is less than 1% giving an indication that tablets
formulated are mechanically stable. All the tablet formulations compile the weight variation test. The weight of
all the formulations was found to be within the limits. The assay of all the formulations was found to be within the
pharmacopoeial (Table 4).
In-vitro dissolution study: All the formulation was subjected to dissolution studies and it was absorbed that the
batch F6 showed about 92.10% of release and was found to be maximum when compared to other batches.
Formulated batch F1 and F2 showed a slow release pattern with about only 58.56% and 65.20% of drug release at
the end of 30mins. (table 5), and the batches F3, F4, F5 showed a release of about 67.25% to 84.02% of drug
release. For the formulation f7 the percentage amount of drug release was found to be with the pharmacopeial
limits.the comparission of dissolution profiles for formulated drotaverine and marketed drotaverine tablets were
shown in the table no 8 and it was concluded that percent drug release for formulated drotaverine tablets was
more when comparared to marketed drotaverine tablets.
Taste evaluation of all formulations: The time intensity study for taste in human volunteers of the formulated
drotaverine hydrochloride with the polymer SD revealed considerable masking of the bitter taste of drotaverine
HCl with degree of bitterness below the threshold value within 120seconds (See Table 8). Sensory evaluation of
the tablets with both polymers proved good palatability.
6. CONCLUSION
This study has established effective taste masking of drotaverine HCl with the use of the solid dispersion
techniques using urea and mannitol as carriers. Taste masking and rapid dissolution of drotaverine HCl tablets
formulated in this investigation may possibly help in the administration of drotaverine HCl in a more palatable
form in the absence of water and more importantly since drotaverine HCl solid dispersion tablet formulations are
not presently in the market. Hence, “patient-friendly dosage form” of bitter drugs, especially for pediatric and
geriatric patients, can be developed using this technique.
7. REFERENCES
A. Rajpoot, Formulation and In-vitro Evaluation of Immediate release tablets of Drotaverine HCl, J. Chem.
Pharm. Res, 3(4), 2011, 333-341

Srikanth MV, Uhumwangho MU, Sunil SA, Design and evaluation of taste masked Drotaverine HCl
orodispersible tablets using polymethacrylate polymers, Der Pharmacia Lettre, 2(6), 2010, 223-231.
Vijayanand P, Formulation, Development and Evaluation of Novel Dosage Form Containing Silk Fibroin for
Elderly Patients, RJPBCS, 3(1), 2010, 524,

Harish G et.al Indian Journal of Research in Pharmacy and Biotechnology
EFFECT OF DIFFERENT DISINTEGRANTS ON CIPROFLOXACIN
CONVENTIONAL TABLETS
Harish.G1
*, Ch.Bhargavi1
, A.Riyajune1
, Md.Yasmeen1
, Syed Mohammed1
, Ch.Murali Krishna1
, Sk.Jilani1
,
Nirajana.V.A2
1.Nimra College of Pharmacy, Jupudi, Vijayawada.
2. Faculty of pharmacy, Sri Ramachandra University, Chennai.
*Corresponding author: E.Mail: harishgopinath4u@gmail.com
ABSTRACT
The objective of the present study is to design and evaluate the effect of disintegrating agents such as
Starch, Cross Caramellose Sodium and Sodium starch glycolate on ciprofloxacin tablet. The nature of the
Ciprofloxacin which is slightly soluble in water which affects the drug disintegration process there by inhibits the
drug release from the Conventional Tablet. Hence in the present study the effect of disintegrating agents at
different concentrations is carried out on the ciprofloxacin hcl to find out the optimized concentration followed by
stability studies for a period of 3 months.
INTRODUCTION
Despite increasing interest in controlled-release drug delivery systems, the most common tablets are those
intended to be swallowed whole and to disintegrate and release their medicaments rapidly in the gastrointestinal
tract (GIT). The proper choice of disintegrant and super-disintegrant to improve its consistency of performance is
of critical importance to the formulation development of such tablets. Drug release from a solid dosage form can
be enhanced by addition of suitable disintegrants. In more recent years, increasing attention has been paid to
formulating fast dissolving and/or disintegrating tablets that are swallowed, but also orally disintegrating tablets
that are intended to dissolve and/or disintegrate rapidly in the mouth. The present study is an attempt to select best
possible combination of drug and disintegrating agent to formulate rapidly disintegrating tablet of ciprofloxacin
conventional tablets which disintegrates faster thereby reducing the time of onset of action. Lactose is selected as
diluents, Starch, Sodium starch glycolate, CCS and Crospovidone were selected as disintegrants. PVP K 30M
paste was used as a binder in all formulations, Magnesium stearate and Talc as a Lubricant, Aerosil as a Glidant.
The percentage Drug content of all tablets was found to be between 95% - 105%, which was within the limit.
From the data obtained, it is observed that the formulation containing crosprovidone disintegrant disintegrate
rapidly when compared to other disintegrating agents such as Starch, SSG, and CCS with ciprofloxacin.
MATERIALS AND METHODS
Ciprofloxacin obtained as a gift sample from Intex chemicals Pvt ltd, Chennai. Starch, Cross Caramellose
Sodium and Sodium Starch Glycolate was obtained from Fischer Ltd, Chennai. All other excipients which are
used are of high standard analytical grade.
Pre-Formulation Studies:
Drug-excipients compatibility studies: Compatibility of drug with excipients was determined by FTIR using
kBr pellet technique, in the wavelength region of 4000-400cm-1
.
Table 1: Formulation Table of Ciprofloxacin Hcl conventional tablet
Formulation FA1 FA2 FA3 FB1 FB2 FB3 FC1 FC2 FC3 FD1 FD2 FE1 FE2
Ciprofloxacin
(mg)
500 500 500 500 500 500 500 500 500 500 500 500 500
Starch (%) 50 10 15 - - - - - - - - - -
SSG (%) - - - 4 5 6 - - - - - - -
CCS (%) - - - - - - 10 20 30 - - - -
BCD (%) - - - - - - - - - 40 80 40 80
Aerosil (%) 200 200 200 200 200 200 200 200 200 200 200 200 200
Lactose 220 260 255 246 265 264 260 250 240 230 90 230 90
PVP (%) 50 50 50 50 50 50 50 50 50 50 50 50 50
Talc (%) 50 50 50 50 50 50 50 50 50 50 50 50 50
Magnesium
Sterate (%)
30 30 30 30 30 30 30 30 30 30 30 30 30
Total Weight
(mg)
1000 1000 1000 1000 1000 1000 1000 1000 1000 1000 1000 1000 1000

Quantity sufficient of Ciprofloxacin for a batch of 50 tablets was separately mixed to ensure complete
mixing. A tablet containing 500 mg equivalents of ciprofloxacin was compressed. All ingredients were weighed
and passed through 40# sieve, blended in a Poly Bag except Magnesium Stearate for 10 minutes. Mix half the part
of the disintegrated with the above mixture after passing through the sieve. The resultant mixture was wet massed
using suitable binder (qs) for granulation. This wet mass was passed through 20# sieve in order to form granules.
These granules were dried and the dried granules were passed through 30# sieve. These dried granules were
lubricated with Magnesium stearate, which was previous, passed through 60# Sieve. The lubricated granules were
punched to tablets using single punching machine.
Drug content: The estimation of drug content for ciprofloxacin tablets was performed by crushing three tablets
and quantity equivalent to 45mg was taken and determined using 0.1M Hcl using UV spectrophotometer at about
276nm
Weight Variation: The USP weight variation test was run by weighing 20 tablets individually, calculating the
average weight, and comparing the individual tablet weights to the average. The tablets met the USP tests that
were not more than 2 tablets were outside the percentage limit and no tablets differed by more than 2 times the
percentage limit.
Hardness: Hardness of the tablets was determined by breaking it between the second and third fingers with
thumb being as a fulcrum. There was a sharp snap the tablet was deemed to have acceptable strength. Hardness of
the tablets was determined by Stokes Monsanto Hardness Tester and the hardness should be found within the
range of 3.5-5.5 kg/cm².
Friability: The friability of tablets was determined by Roche Friablator. 20 tablets were taken and weighed. After
weighing the tablets were placed in the Roche Friablator and subjected to the combined effects of abrasion and
shock by utilizing a plastic chamber that revolves at 25RPM for minutes dropping the from a distance of six
inches with each revolution. After operation the tablets were de-dusted and reweighed.
Content Uniformity: In this test, 30 tablets were randomly selected contained for sample, Ciprofloxacin
Hydrochloride should contain not less than 98.0 per cent and not more than 102.0 percent.
Thickness: The thickness of a tablet was the only dimensional variable related to the process. 10 tablets were
measured for their thickness and diameter with a Caliper, Thickness Gauge. Average thickness and diameter were
calculated.
Disintegration Test: Disintegration time is considered to be one of the important criteria in selecting the best
formulation. For most tablets the first important step toward solution is break down of tablet into smaller particles
or granules, a process known as disintegration. Place one tablet into each tube and suspend the assembly in to the
1000ml beaker containing water maintained at 37 ± 2o
C and operate the apparatus for 30 seconds. Remove the
assembly form the liquid. Observe the tablets, if one or two tablets fail to disintegrate completely; repeat the test
on 12 additional tablets. The requirement is met if not less than 16 of the total of 18 tablets tested are
disintegrated.
In-Vitro Drug Release Studies: In our case to study the release kinetics of drug we used USP II apparatus
(Paddle type, 2) with 900 ml, pH 6.8 phosphate buffer as the dissolution medium. The paddle was rotated 50 rpm
and 5ml of aliquots were withdrawn at pre-determined time intervals and an equal amount of thee medium was
replaced to maintain sink conditions. The aliquots were diluted suitably and the amount of drug(s) released was
determined spectrophotometrically using U.V. at wavelength 271 nm.
Evaluation of Formulated Ciprofloxacin Tablet:
Evaluation of blend characteristics: Ciprofloxacin Tablet was prepared by using wet granulation method.
Various formulations were made as shown in table: 6. The Formulated Ciprofloxacin tablet were evaluated for
Pre-formulation parameters like angle of repose, bulk density, tapped density, Compressibility index and
Hausner’s Ratio.
The results of disintegration time of all the tablets prepared by wet granulation found to be varied with
change in concentration of disintegrating agents from few seconds to several minutes. Formulations FD 1 and FE1
disintegrated within 3min and found to be more effective. The disintegration time of the tablets using different
disintegrants decreases in the following order BC > croscarmellose sodium > SSG > Starch. It is observed that,
when BC is used as disintegrant, tablets disintegrate rapidly with in less time compared to other tablets prepared
using croscarmellose sodium, starch and sodium starch glycolate disintegrants. Though tablets prepared by intra
and extra granulation method found to be more effective in comparison with formulation prepared by only extra

granulation. When concentration of Starch, SSG, CCS and BC is increased, the disintegration time was reduced
The angle of repose of prepared Ciprofloxacin tablet was in the range of 20°-30°. Normally if the value falls
between 20°-30°, it shows good flow property. The bulk density and tapped density were found to be in the range
of 0.37 to 0.38 g/cm3
and 0.44 to 0.45g/cm3
respectively. A Hausner ratio was within the range of 1.16 to 1.17,
lesser than 1.25 is considered to be an indication of good flow property. The compressibility index was within the
range of 5-15 hence falls within the excellent range.
The results were tabulated in table 15. The pre-formulation characteristics results for all the
formulation of ciprofloxacin tablets using FB as disintegrating agent found to be within the range, compressibility
index for FB1 and FB3 was found to be with in good range of 12-16 were as FB2 was in excellent range. The
angle of repose of prepared tablet was in the range of 20°-30°. Normally if the value falls between 20°-30°, it
shows good flow property. The bulk density and tapped density were found to be in the range of 0.34 to
0.36g/cm3
and 0.39 to 0.40 g/cm3
respectively. A Hausner ratio was within the range of 1.07 to 1.18, lesser than
1.25 is considered to be an indication of good flow property. The compressibility index was within the range of 5-
15 hence falls within the excellent range. The results were tabulated in table 16.
The pre-formulation characteristics results for all the formulation of ciprofloxacin tablets using FC as
disintegrating agent found to be within the range, angle of repose and compressibility index was found to be
within good range. The angle of repose of prepared ciprofloxacin tablet was in the range of 20°-30°. Normally if
the value falls between 20°-30°, it shows good flow property. The bulk density and tapped density were found to
be in the range of 0.35 to 0.36 g/cm3
and 0.39 to 0.41 g/cm3
respectively. A Hausner ratio was within the range of
1.08 to 1.18, lesser than 1.25 is considered to be an indication of good flow property. The compressibility index
was within the range of 5-15 hence falls within the excellent range. The results were tabulated in table 17. The
formulation of ciprofloxacin using 4% B.C disintegrant found to be within the limits for both FD1 and FD2 and
falls in good range. The angle of repose of prepared ciprofloxacin tablet was in the range of 20°-30°. Normally if
the value falls between 20°-30°, it shows good flow property. The bulk density and tapped density were found to
be in the range of 0.36 to 0.38g/cm3
and 0.40 to 0.41 g/cm3
respectively. A Hausner ratio was within the range of
1.07 to 1.16, lesser than 1.25 is considered to be an indication of good flow property. The compressibility index
was within the range of 5-15 hence falls within the excellent range.
The angle of repose of prepared ciprofloxacin using FE as disintegrant was in the range of 20°-30°.
Normally if the value falls between 20°-30°, it shows good flow property. The bulk density and tapped density
were found to be in the range of 0.36 to 7 g/cm3
and 0.340 to 0.41g/cm3
respectively. A Hausner ratio was within
the range of 1.10 to 1.11, lesser than 1.25 is considered to be an indication of good flow property. The
compressibility index was within the range of 5-15 hence falls within the excellent range.
The post compressional characteristic for all the formulated batches was found to be within the limits as
per Indian pharmacopeia 2007. The hardness was found to be within the range of 3.5 to 5.5 Kg/cm2
in all the
formulations indicating good mechanical strength with an ability indicating physical and mechanical strength with
an ability to withstand physical and mechanical stress conditions while handling. In all the formulations, the
friability value is less than 1% giving an indication that tablets formulated are mechanically stable. All the tablet
formulations passed the weight variation test. The weight of all the formulations was found to be within the limits.
The assay of all the formulations was found to be with in the 90% to 110% acceptable limits.
The disintegration time of the entire Formulated batch varies with change in concentration of
disintegrating agents from few seconds to several minutes. Formulations FD2 and FE2 disintegrated within 3min
and found to be more effective. The disintegration time of the tablets using different disintegrants decreases in the
following order Starch > CCS > SSG >CP. It is observed that, when BC is used as disintegrant, tablets
disintegrate rapidly with in less time compared to other tablets prepared using croscarmellose sodium, starch and
sodium starch glycolate disintegrants. Though tablets prepared by intra and extra granulation method found to be
more effective in comparison with formulation prepared by only extra granulation. When concentration of Starch,
SSG, CCS and BC is increased, the disintegration time was reduced significantly show in table 2..
In vitro drug release studies were conducted for the formulation using USP dissolution apparatus type-II
(paddle), at 50 rpm. The percentage drug release at the end of 30 min was found in the range 48 – 73% using FA
as disintegrant and 67-77% using FB as disintegrant. Invitro drug release studies were conducted for the
formulation using USP dissolution apparatus type-II (paddle), at 50 rpm. The percentage of drug release was
determined at a time interval of 0, 5, 10, 15, 20, 25, 30 min and at the end of 30 min it was found in the range 80-

95% using FC as disintegrant. Invitro drug release studies were conducted for the formulation using USP
dissolution apparatus type-II (paddle), at 50 rpm. The percentage of drug release was determined at an time
interval of 0, 5, 10, 15, 20, 25, 30 min and at the end of 30 min it was found in the range 81-95% using 4% BC as
disintegrant and 78-98% using 8% BC as disintegrant shown in figure 9, 10 and 11.
Stability Studies: Drug molecules are of reactive naturally, the additives are considered to be inert substance but
this may not be true for all additives in a formulations. Hence, in developing any formulation, when additive are
selected the same must be super imposed on to drugs and with other additives present in the formulation, to see
how compatible they are with the other formulation ingredients. A lot of literature has got piled up on drug-
excipients incompatibilities, which is a handy tool in the hand of a formulation man, to avoid possible drug-
excipient interactions. But even with this literature at the back, formulation may be highly individualistic and each
formulation may have problems of its own. There are methods called FTIR, differential scanning calorimetric,
thin layer chromatography for investigating these interactions in short period of time.
On many occasions, even with the sum total of knowledge available, it is not possible to envisage, all the
interactions and a formulation while remaining good for a certain period of time, may go bad in the long run.
There is not ready made answer for such situation and all that is possible is to “wait and watch”, the method
called “Real time study”. As per ICH guide line for stability study, which advice the formulation to store their
products at 30 ° c and 65 % RH to find out actual shelf life period or to assure the product quality free from
unwanted interactions. Real time study of ICH guidelines involves storage of products at 40° C& 65 % RH for the
complete proposed shelf life period, and analyzing the product sample every month in the first 3 months, every 3
months from 4th
month onwards up to one year, every 6 month in the second year of storage, afterwards once in a
year till shelf life is completed. ICH guidelines also demands for storing samples at 40 ° c and 75 % RH (stress
condition or accelerated stability study) for relatively short period of time (3-6 months) which depends on claimed
shelf life period as well as the zone (zone 1/2/3/4 of the world) to which the product is meant to be exported. This
later study (with stress conditions) is to mine the alternating climates condition during the shelf life of the product.
The stability parameters for all the formulation were evaluated after 15, 30, 45, 60, and 90 days for 40 °C at 75%
RH.
Tab 2: Disintegration Time of the Ciprofloxacin Fast disintegrating tablet
Formulation With Disk Without Disk
I II III I II III
FA1 11min 43 sec 10 min 30 sec 10min 52sec 14min 32 sec 15min 11sec 15min 48 sec
FA2 8min 2sec 9min 33 sec 8min 18 sec 11min 14sec 12min 31 sec 11min 56 sec
FA3 4min 41 sec 5min 8 sec 4min 55sec 9min 23sec 9min 51 sec 8min 50sec
FB1 11min 41 sec 10min 21 sec 10min 54 sec 14min 11sec 14min 56sec 13min 34sec
FB2 8min 43sec 9min 21sec 9min 5sec 12min 37sec 14min 12sec 12min 44sec
FB3 4min 21sec 5min 32 sec 4min 13sec 7min 23sec 7min 47 sec 6min 43sec
FC1 9min 21sec 8min 55 sec 10min 12 sec 11min 15 sec 11min 24 sec 10min 55min
FC2 7min 43sec 8min 11 sec 8 min 5sec 9min 22 sec 9min 17 sec 10 min 31 sec
FC3 5min 22 sec 5min 42sec 6min 31sec 6 min 4 sec 7min 41sec 7min 18sec
FD1 4min 45 sec 4min 52 sec 3min 21sec 7min 19 sec 7min 47 sec 6min 14 sec
FD2 2 min 51 sec 2min 11 sec 1min 33sec 3min 46sec 4min 23 sec 4min 11sec
FE1 4min 31sec 5min 55sec 4min 14sec 9min 50sec 8min 14sec 8min 19sec
FE2 3min 11 sec 2 min 47 sec 3min 17sec 5min 11sec 6min 42sec 5min 4 sec

Fig 1: IR spectra of the pure drug, Ciprofloxacin
Hcl.
Fig 2: IR spectra of FA
Fig 3: IR spectra of FB Fig 4: IR spectra of FC
Fig 5: IR spectra of the FD&FE Disintegrant Fig 6: IR spectra of the mixture of the
Ciprofloxacin and FA
Fig 7: IR spectra of the mixture of the Ciprofloxacin
and FB
Fig 7: IR spectra of the mixture of the
Ciprofloxacin and FC

0
20
40
60
80
100
0 10 20 30 40
%Cumulativeamountofdrug
release
Time in Minutes
FA1
FA2
FA3
FB1
FB2
FB3
0
20
40
60
80
100
0 20 40
release Time in minutes
FC1
FC2
FC3
0
20
40
60
80
100
120
0 20 40
release
Time in minutes
FD1
FD2
FE1
FE2
Fig 8: IR spectra of the mixture of the Ciprofloxacin and FD &FE
Fig 9: Dissolution profile of Ciprofloxacin tablets
Using FA and FB as disintegrant
Fig 10: Dissolution profile of Ciprofloxacin tablets
Using FC disintegrants
Fig 11: Dissolution profile of Ciprofloxacin tablets Using FD disintegrants
CONCLUSION
Selecting appropriate formulation excipients and manufacturing technology can obtain the design
feature of fast disintegrating tablet. The disintegrants have the major function to oppose the efficiency of the tablet
binder and the physical forces that act under compression to form the tablet. The stronger the binder, the more
effective must be the disintegrating agents in order for the tablet to release its medication. Ideally, it should cause
the tablet to disrupt, not only into the granules from which it was compressed, but also into powder particles from
which the granulation was prepared. From this study, it is concluded that the disintegrants such as Starch, SSG,
CCS was compared with combination of disintegrants and in this study optimized combination of disintegrant
prepared by intra and extra granulation method was found to be the most effective as they disintegrate rapidly
when compared to other disintegrants, and the percentage drug release also shows a higher dissolution profile.
REFERENCES
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Chaudhary K P R, Sujata Rao, Formulation and Evaluation of Dispersible tablets of poorly soluble drugs, Indian
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Cohen Y, Lach JL, Factors affecting the Effect of Disintegrating Agent, J. Pharm. Sci, 52, 1963, 122.
Cousin, Rapidly Disintegrable multiparticular Tablets, U S Patent, 5, 464, 632 (1995).
E Sallam, Ibrahim H, R Abu Dahab, M Shubair, Enam Khalil, Drug.Dev and Industrial Pharmacy, Vol. 24(6),
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Garnpimol C, Ritthidej, Parichat Chomto, Sunibhond Pummangura, Piamsak Menasveta, Chitin and Chitosan as
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Papola Vibhooti Indian Journal of Research in Pharmacy and Biotechnology
CHRONOTHERAPY FOR NOCTURNAL ASTHAMA
Papola Vibhooti*
Rajan G, Bisht Seema, Dr.Kothiyal Preeti
Shri Guru Ram Rai Institute of Technology & Sciences Dehradun, Uttarakhand, India
*Corresponding author:papola.vibhooti47@gmail.com
ABSTRACT
Chronotherapeutic drug delivery system is useful in the treatment of disease, in which drug
availability is timed to match rhythm of disease, in order to optimize therapeutic effect and minimize side
effect. Nocturnal asthma is defined as any sleep related worsening of reversible airway disease.
Approximately 80 percent of severe asthmatic attacks occur between midnight and 8 a.m. Nocturnal
asthma is associated with critical symptoms and urgent need for proper medications. The onset of
nocturnal asthmatic attacks is rare in the first part of night, 80% of asthmatic attacks occur between
midnight and 8 a.m., and deaths from asthma are more common during these hours. In a study of asthma
mortality, 79% of the patients who died had a disturbed sleep before the death. In a survey of almost 8000
patients with varying degrees of asthma found that approximately - 75% of asthmatics attacks happened
once a week with symptoms, 64 % three times a week, and 39 % every night. Nocturnal asthma is
currently controlled by taking either a long-acting β2 agonists like salmetrol inhalers, sustained release
theophylline. All the current sustained release formulation has a shortcoming of inability to maintain high
blood levels for that long period. This may lead to leaving the patient unprotected against the worse
events of nocturnal asthma. Thus, a smart drug delivery that is administrated before sleep and maintains
high blood levels for longer period (from midnight to 8 am in the morning) could be very much beneficial
for proper management of nocturnal asthma.
Key words: Chronotherapy, cardian rhythm, nocturnal, morbidity, diurnal
INTRODUCTION
In order to increase the effectiveness of drug there are many approaches which have been applied. The
pharmaceutical formulations which are for direct ingestion for oral administration and orally administrated drugs
are generally absorbed from the gastrointestinal tract. Many functions of the human body show considerable
change in a day. These variations cause changes both in disease state and in plasma drug concentrations (Lin,
2011). Coordination of biological rhythms with medical treatment is called chronotherapy. Chronotherapy
considers a person’s biological rhythms in determining the timing and amount of medication to optimize a drug’s
desired effects and minimize the undesired ones. Study of influence of biological rhythm on the effects of
medication is known as chronopharmacology while the science of study of biological rhythms is known as
chronobiology. With the understanding of biological time keeping the idea came that these rhythms must affect
how the body responds to drugs administered over the course of the day (Hizli, 2009) (Ohdo, 2006).
Appropriate timing of administration can improve efficacy and diminish toxicity. Chronotherapy is
relevant when the risk or intensity of the symptoms of disease vary with time as in the case of allergic rhinitis,
arthritis, asthma, myocardial infarction, congestive heart failure, stroke and peptic ulcer disease (Haus, 2007).
The human circadian rhythm is based on sleep activity cycle, is influenced by our genetic makeup and hence,
affects the body’s functions day and night (24-hour period) (Devdhawala, 2010).
Coordination of biological rhythms with medical treatment is called Chronotherapy. Chronotherapy
considers a person’s biological rhythms in determining the timing and amount of medication to optimize a drug’s
desired effects and minimize the undesired ones. Study of influence of biological rhythm on the effects of
medication is known as chronopharmacology while the science of study of biological rhythms is known as
chronobiology. To understanding the biological time keeping the idea came that these rhythms must affect how
the body responds to drugs administered over the course of the day (Awasthi, 2010) (Hizli, 2009).
raditionally, drug delivery systems have focused on constant/sustained drug output with the objective of
minimizing peaks and valleys of drug concentrations in the body to optimize drug efficacy and to reduce adverse
effects. A reduced dosing frequency and improved patient compliance can also be expected for the
controlled/sustained release drug delivery systems, compared to immediate release preparations (Saigal N, 2009).
Some of the rhythms that affect our body are ultradian (cycles shorter than a day like firing of neurons take
milliseconds), circadian (cycles lasting 24 h such as sleeping and waking pattern), infradian (cycles longer than a
day like menstrual cycles) and seasonal rhythms (such as seasonal affective disorders causing more depression in

susceptible individuals in winter). Circadian rhythm governs every process of our body. The term circadian
rhythm was first given by Halberg and Stephens in 1959.
Chronotherapy: The term "chrono" basically refers to the observation that every metabolic event undergoes
rhythmic changes in time. Perhaps the best known and studied chronobiology frequency is the circadian rhythm
which approximates the earth's 24-hour rotation around the sun. Researchers have recently concluded that both
disease states and drug therapy are affected by a multitude of rhythmic changes that occur within the human body.
Chronotherapeutic refers to a treatment method in which in vivo drug availability is timed to match rhythms of
disease in order to optimize therapeutic outcomes and minimize side effects. It is based on the observation that
there is an interdependent relationship between the peak-thorough rhythmic activity in disease symptoms and risk
factors, pharmacologic sensitivity and pharmacokinetics of many drugs. Biological rhythms concern to the control
of biological functions including those of the autonomic nerve system, endocrine system, and immune system, are
fundamental in homeostasis and in protection against various diseases.
Chronotherapeutics: The first chronotherapy to be widely applied in clinical practice was introduced in the
1960s the alternate-day morning schedule of conventional tablet corticosteroid medication. Other chronotherapies
have since been widely used in clinical medicine in the U S, Europe, and Asia; These include special evening
theophylline systems for chronic obstructive pulmonary disease, conventional evening H2 -receptor ant agonists
for peptic ulcer disease, and conventional evening cholesterol medications for hyperlipidemia.
Chronotherapeutics refers to a treatment method in which in vivo drug availability is timed tomatch
rhythms of disease in order to optimize therapeutic outcomes and minimize side effects. It is based on the
observation that there is an interdependent relationship between the peak-to trough rhythmic activity in disease
symptoms and risk factors, pharmacologic sensitivity, and pharmacokinetics of many drugs .
Figure.1.Human biological lock
Circadian Time Structure: Circadian rhythms are the rhythm in the chronotherapeutic and the dysfunction of
circadian rhythms can affect the brain functioning and it can be improved by the chronotherapeutic approach.
Circadian rhythms are self-sustaining, endogenous oscillations that occur with a periodicity of about 24
hours.Circadian rhythm regulates several body functions such as metabolism, physiology, behavior, sleep
patterns, hormone production, and so on. The circadian rhythm not only affects most physiological functions but
also influences the absorption, distribution, metabolism, and elimination (ADME) of drugs, leading to changes in
drug availability and target cell responsiveness.

Figure.2. Human circadian time structure
Circadian rhythms can change the sleep-wake cycles, hormone release, body temperature, and other important
bodily functions driving the alteration of various physiological, biochemical, and behavioral processes.
Circadian Rhythms of Diseases: The biological rhythm studies help in defining the temporal organization of
human beings. One means of illustrating the human circadian time structure is to depict the peak time of 24-h
rhythms on a clock--like diagram. The 24 h clock pattern of diseases showing prominent day-night patterns when
symptoms of disease are most frequent .Variation in the severity of many diseases over a 24-hour period is well
known diseases such as bronchial asthma, myocardial infarction, angina pectoris, rheumatic disease, ulcers 43,
diabetes, and attention deficit syndrome, hypercholesterolemia and hypertension show symptomatic changes due
to circadian rhythm city. Aggravation of asthmatic attacks occur after midnight or in the early morning due to
limited lung function promoted by circadian changes at that time. Many common diseases also display a marked
circadian variation during onset or exacerbation of symptoms,
Figure.3.The circadian pattern of diseases
Asthma: Asthma may be the most common disease with the largest circadian variation. It is considered as a
chronic condition where airways are hyperreactive to certain irritants which can constrict them, and so making
difficulty in breathing. Such a constriction is often called as bronchospasm and is followed by excess production
of mucus and inflammation in the membranes lining the walls of the airways. “Breathing through a straw” is a
commonly description that can explain the situation. Allergens, fumes, smoke, and/or dry and cold air are
common irritants. Laughing or exercise can also cause the constriction of airways. Asthmatics vary considerably
in the impact of illness on their life, response to treatment and severity of symptoms. Because asthma has such a
striking circadian variation, several types of chronotherapy have been tried. In one study, use of a timed-release
formulation of theophylline (Theo- 24) achieved therapeutic drug concentrations during the night and avoided
toxic levels during the day. Asthma is well suited for chronotherapy, with beta 2- agonists and oral
corticosteroids.

Nocturnal asthma: Some biological rhythms come about monthly or even annually, asthma changes fairly
predictably on a circadian cycle or 24 hour. Even in normal, lung function differs between day and night. The
activity of the lung exhibits a circadian rhythm with a maximum around 4 p.m. and a minimum around 4 a.m. In
asthmatic patients, the intensity of variation in lung function is as much as 50% in a day. Bronchial reactivity
generally follows the same circadian cycle in Asthmatic patients. It can be defined as any sleep-related Worsening
of reversible airway disease. Shortness of breath or wheezing at night is symptoms generally shown. Nocturnal
asthma is associated with critical symptoms and urgent need for proper medications. The onset of nocturnal
asthmatic attacks is rare in the first part of night 80% of asthmatic attacks occur between midnight and 8 a.m., and
deaths from asthma are more common during these 9 hours. In a study of asthma mortality, 79% of the patients
who died had a disturbed sleep before the death. In a survey of almost 8000 patients with varying degrees of
asthma found that approximately 75% of asthmatics attacks happened once a week with symptoms, 64 % three
times a week, and 39 % every night.
Causes of Nocturnal Asthma: Nocturnal asthma is probably because of multiple factors than to a single cause.
Asthma attacks are aggravated mainly by irritants. Exposure to allergens daytime can be as important as exposure
to allergens in the bedroom during sleep. A series of physiological events from three to eight hours are poorest
about 4 a.m after the initial exposure called late-asthma response (LAR); it may match to the night time for some
people and it can persist over nights. An increase in a susceptible patient's risk of LAR from 40 to 90 % by
allergen exposure in the evening. In some people, the inflammation worsens correspondingly with circadian
changes in peak expiratory flow rates in night. Another contributing factor to nocturnal asthma may be airway
secretions. About 70 % of asthmatics experience postnasal drip and/or chronic sinusitis. Asthma often improves
when the sinuses are cleared in daytime. Influence of airway temperature on onset of symptoms was studied.
Bronchospasm is produced after a brief exposure to cold and dry air. Breathing warm humidified air can reverse
this.
Diagnosis of Nocturnal Asthma: If asthma symptoms worsen at night it is important to inform clinician.
Monitoring lung function using a peak flow meter is necessary. Peak flow meter is a portable device that
measures the lung volume and how time by which air can be expelled from the lungs. Low peak flow meter
values indicates that there is a tightening of the airways, and can be an early warning of impending respiratory
symptoms, such as shortness of breath and wheezing. Recording peak flow rates at bedtime serves as a document
for nocturnal asthma. During any awakening at night and in the morning also serves as a record .
Chronotharapy of asthma:Asthma and Sleep: In asthma, the relative role of circadian and sleep systems has
been a subject of controversy, and this issue remains unresolved.Initially, it was suspected that sleep systems
played the major role. In a study of shift-workers, there appeared to be an immediate phase shift in the circadian
rhythm of peak expiratory flow (PEF) when subjects rotated shifts, such that the decline in airway function
remained coupled to the sleep period. In asthma, the resistance increases progressively across the night, whether
subjects sleep or not, although the increase is much greater during sleep. These results are supported by the
observations that the onset of asthmatic attacks is less common in the first part of the night. These data allow us to
reach certain conclusions. First, it seems likely that both circadian and sleep factors play a role in asthma. Also,
the progressive decline in airway function across the night does not suggest a typical change in a neuronal control
process coupled to sleep. Notably, airway function is maximal at the time of increased sleepiness during the
afternoon, and declines as sleep pressure dissipates during sleep.
Effect of nocturnal asthma on daytime performance, morbidity, and mortality: With the decreased sleep
efficiency in asthma, and reports of daytime tiredness/sleepiness, the possibility exists that performance at work
or school will be affected. A study of nocturnal asthmatic and control subjects demonstrated that the asthmatic
subjects had increased scores for subjective sleepiness. This reflected decreased objective sleep quality.
Interestingly, daytime cognitive performance was worse in the nocturnal-asthma group. This area of research
needs further investigation. The morbidity of ventilatory failure, and also the mortality in asthma, are linked to the
nocturnal worsening of lung function, which may be related to a blunted arousal mechanism caused by
fragmented sleep. Interestingly, in one study of asthma mortality, 79% of the 168 patients who died had a sleep
disturbance reported prior to the terminal event This contrasts with the usually accepted mortality risk factors of a
previous ICU admission (5% in the study cited ), more than two hospitalizations/emergency- room (ER) visits in
the preceding year (28%), or psychologic disturbance (13%).

Circadian/sleep physiologic and challenge response:
Lung function and thoracic blood volume: It has been shown that sleep enhances the nocturnal increases in
airway resistance and also leads to marked reduction in the volume of hyperinflated lungs in patients with
nocturnal asthma. Such volume changes do not account directly for all of the nocturnal change in airway
resistance. However, artificially reducing lung volumes in awake asthmatic individuals to their typical levels
during sleep did trigger worsening of airway obstruction, suggesting that the effects of sleep on lung volume
could contribute to the nocturnal worsening of asthma. The effects of sleep on lung volume could be mediated by
several different mechanisms including:a sleep associated reduction in inspiratory muscle tone, a decrease in
pulmonary compliance; and an increase in intrapulmonary blood pooling. In particular, the effects of sleep on
intrapulmonary blood volume (IPBV) are intriguing, since there is evidence that such pooling of blood can
promote airway narrowing. Using capillary volume (Vc) as a surrogate marker of IPBV, it has been shown that
Vc increased overnight in asthmatic individuals with nocturnal worsening of lung function .
Gastrointestinal Function and the Lung: There is significant variation in gastrointestinal (GI) function during
sleep. The circadian rhythm of human basal gastric-acid secretion is characterized by a peak in the early evening
and a nadir between 5:00 and 11:00 in the morning. There are conflicting data as to whether esophageal acid
causes a decrease in airway function. In one study of sleeping individuals with nocturnal asthma, no significant
acute or sustained change was observed in airflow resistance relative to periods of increased esophageal acid
content, suggesting that gastroesophageal reflux (GER) contributed little to the nocturnal worsening of asthma.
Although it appears that asthma is more responsive to the ets of GER during the diurnal cycle than during the
nocturnal cycle, the exact role of circadian/sleep effects in esophageal acid-induced bronchoconstriction remains
unclear.
Nasal-Sinus–Lung Interaction: There is evidence that upper-airway disease (i.e., allergic rhinitis, sinusitis, and
nasal polyps) influences and may contribute to the intensity of lower-airway disease. Allergic rhinitis, for
example, can intensify airway responsiveness and even provoke asthma symptoms. Data indicate that treatment of
allergic rhinitis diminishes bronchial responsiveness and asthma. Active sinusitis can also cause an increase in the
asthma process as shown in animal models, which appears to involve drainage of nasal mediators into the lower
airway. Other processes that link the nasal sinus to the lung have been identified in studies of viral infections of
the nose that produce an increase in lower-airway reactivity. Also, there is a day– night cycle in nasal patency and
perhaps in inflammation. All of these data suggest an important interaction between the nasal sinus and lower-
airway function.
Chronotherapy
General Principles: Bodily functions have been incorrectly assumed to be relatively constant throughout the 24 h
of the day and other periods of time. Numerous studies have shown that the kinetics and dynamics of
pharmacotherapies vary significantly according to the biologic time of administration during the 24 h-cycle,
menstrual cycle, or annually, owing to the cumulative effect of endogenous rhythms in crucial physiologic and
biochemical functions. Chronotherapeutics is the synchronization of medication levels in time with reference to
need, taking into account biologic rhythms in the pathophysiology of medical conditions, and/or rhythm-
dependencies in patient tolerance for given chemical interventions. Chronotherapeutics can sometimes be
achieved by the judicious timing of conventional sustained- release (SR) formulations, although reliance on
special drug-delivery systems seems to constitute a more dependable means of matching drug level to biologic
need and tolerance.
β2-Agonists, Theophylline, and Anticholinergic Therapy: Certain SR formulations of theophylline can be
administered so that a rising blood level of the drug occurs when airway obstruction is increasing, while adverse
effects are reduced. For this purpose, SR theophylline is administered once daily, in the evening, for the
management of nocturnal asthma. Various tablet formulations for the sustained-release of b-agonists have been
used in a chronotherapeutic fashion for the management of asthma. As with theophylline, very little information
exists about comparing the effects of or adding a long-acting b2-agonist oral preparation to an inhaled
corticosteroid using chronotherapeutic techniques. Salmeterol has been shown to control symptoms of nocturnal
asthma to a substantial degree, and to improve sleep quality and daytime cognitive performance in patients with
chronic asthma. Drugs that antagonize the vagal nervous system should be useful in the management of nocturnal
asthma as a means of counteracting the enhanced nocturnal parasympathetic tone that occurs in the disease.

Corticosteroids and Leukotriene-active Drugs: Corticosteroids have been used in a chronotherapeutic manner,
with the finding that their long-term oral administration at 8:00 A.M. and 3:00 P.M. was more effective in
controlling nocturnal asthma than the same doses given at 3:00 P.M. and 8:00 P.M. Other studies have shown that
a single 3:00 P.M. dose of prednisone improved lung function and reduced airway inflammation more effectively
than the same single dose given at 8:00 A.M. and 8:00 P.M (Beam, 1992). Not only can oral steroids be dosed
chronotherapeutically, but inhaled corticosteroids can also be efficacious when used in this manner (Pincus,
1995). Although the leukotriene-active drugs, including zileuton, zafirlukast and montelukast, are new in the
treatment of asthma, they have been shown to alleviate the symptoms and the decrement in lung function seen in
nocturnal asthma. It has been shown that zileuton in particular decreased nighttime increases in leukotriene B4
(LTB4) and (LTE4) while improving lung function (Wenzel, 1995). Zafirlukast has also been shown to decrease
nighttime awakenings and improve morning PEF rates . Although these agents have only been studied at set doses
and times regardless of the presence or absence of nocturnalasthma, the improvements observed were significant,
and it is likely that these agents will prove very useful in the treatment of nocturnal asthma when used
chronotherapeutically.
Ideal Characteristics of Chronotherapeutic Drug Delivery System should:
 be non-toxic within approved limits of use,
 have a real-time and specific triggering biomarker for a given disease state,
 have a feed- back control system (e.g. self-regulated and adaptative capability to
 circadian rhythm and individual patient to differentiate between awake – sleep status),
 be biocompatible and biodegradable, especially for parenteral administration,
 be easy to manufacture at economic cost,
 be easy to administer in to patients in order to enhance compliance to dosage regimen.
Chronotherapeutic drug delivery systems: Controlled release formulations can be divided into subgroups of
rate-controlled release,delayed-release and pulsed-release formulations. Delayed-release formulations include
time controlled release and site specific dosage forms. When constant drug plasma levels need to be avoided, as in
chronotherapy, time-controlled or pulsed-release formulations are preferable, especially in the treatment of early
morning symptoms. By timing drug administration, plasma peak is obtained at an optimal time and the number of
doses per day can be reduced. Saturable first-pass metabolism and tolerance development can also be avoided.
Various technologies to develop timecontrolled peroral drug delivery systems have been extensively studied in
recent decades. Some of these systems are discussed in the following subsections.
Enteric-coated systems: Enteric coatings have traditionally been used to prevent the release of a drug in the
stomach Enteric coatings are pHsensitive and drug is released when pH is raised above 5 in the intestinal fluid.
These formulations can be utilised in time-controlled drug administration when a lag time is needed. Because of
the unpredictability of gastric residence, such systems cannot be the first choice when a time-controlled release is
required. In the treatment of nocturnal asthma, a salbutamol formulation containing a barrier coating which is
dissolved in intestinal pH level above about 6, has been successfully used. The system contains a core which is
film coated with two polymers, first with HPMC and then with a gastro-resistant polymer (Eudragit® L30D). In
this system the duration of the lag phase in absorption can be controlled by the thickness of the HPMC layer.
Figure.4.Schematic representation of Enteric coated system
Layered systems: These are one or two impermeable or semipermeable polymeric coatings (films or compressed)
applied on both sides of the core. To allow biphasic drug release, a three-layer tablet system was developed . The
two layers both contain a drug dose. The outer drug layer contains the immediately available dose of drug. An
intermediate layer, made of swellable polymers,separates the drug layers. A film of an impermeable polymer

coats the layer containing the otherdose of drug. The first layer may also incorporate a drug-free hydrophilic
polymer barrier providing delayed (5 h) drug absorption. Conte et al has also studied a multi-layer tablet system
(Geomatrix®).It consists of a hydrophilic matrix core containing the drug dose. This kind of three layer device
has been used in the treatment of Parkinsonian patients using L-- dopa/benserazide. Nighttime problems and
early-morning symptoms of Parkinsonism can be avoided by using a dualrelease Geomatrix@ formulation, which
allows daily doses of drug to be reduced and leads to extent of bioavailability 40 % greater than when a traditional
controlled release formulation is employed.
Figure.5. Geminex TIMERx technology based bilayered dual release tablet
Time-controlled explosion systems (TES): These have been developed for both single and multiple unit dosage
forms [80],[81]
. In Both cases, the core contains the drug, an inert osmotic agent and suitable disintegrants.
Individual units can be coated with a protective layer and then with a semipermeable layer, which is the rate
controlling membrane for the influx of water into the osmotic core. As water reaches the core, osmotic pressure is
built up. The core ultimately explodes, with immediate release of the drug. The explosion of the formulation can
also be achieved through the use of swelling agents. Lag time is controllable by varying the thickness of the outer
polymer coating.
Sigmoidal release systems (SRS): For the pellet-type multiple unit preparations, SRS containing an osmotically
active organic acid have been coated with insoluble polymer to achieve different lag-times. By applying different
coating thicknesses, lag times in vivo of up to 5 hours can be achieved. Release rates from SRS, beyond the lag
time, has been found to be independent of coating thickness.
Press-coated systems: Delayed-release and intermittent-release formulations can be achieved by press-- coating.
Presscoating, also known as compression coating, is relatively simple and cheap, and may involve direct
compression of both the core and the coat, obviating the need for a separate coating process and the use of coating
solutions. Materials such as hydrophilic cellulose derivatives can be used and compression is easy on a laboratory
scale. On the other hand, for large-scale manufacture, special equipment is needed. The major drawbacks of the
technique are that relatively large amounts of coating materials are needed and it is difficult to position the cores
correctly for the coating process. Conte et al have developed a press coated device in which the inner core
contains the drug and the outer coat is made of different types of polymers. The outer barrier, which controls drug
release, can be either swellable or erodible. Lag times can be varied by changing the barrier formulation or the
coating thickness (Halsas M, 1998). Hydrophilic polymers such as hydroxypropyl methylcellulose and sodium
alginate have been used in the coat to control drug release.
In recent years, various controlled release, especially time-controlled release; drug delivery systems based
on compression coating technology have been studied. Most such Formulations release drug after a lag phase,
followed by a rapid dissolution of a core. Tablets formulated with Penwest's TIMERx ®
oral controlled release
technology comprise an inner core containing drug and an outer layer compression-coated with TIMERx, a
hydrophilic matrix of the heteropolysaccharides xanthan and locust bean gum (Baichwal A, 2002).
Figure.6. TIMERx based drug delivery system
Examples of chronopharmaceutical technologies: Currently key technologies in chronopharmaceutics includes:
CONTINR, physico-chemical modification of the active pharmaceutical ingredient (API), OROSR, CODASR,

CEFORMR, DIFFUCAPSR, chronomodulating infusion pumps, TIMERxR, threedimensional printing,
controlled-release (CR) erodible polymer and CR microchip strategies. Readers may find advantages and
disadvantages of each technology depending on their specific needs on the website of each developer/marketer
website before selection. Informations on FDA approval status and dosage formed were compiled from the FDA
electronic orange book.
For asthma (CONTINR technology): In this technology, molecular coordination complexes are formed between
a cellulose polymer and a non-polar solid aliphatic alcohol optionally substituted with an aliphatic group by
solvating the polymer with a volatile polar solvent and reacting the solvated cellulose polymer directly with the
aliphatic alcohol, preferably as a melt. This constitutes the complex having utility as a matrix in controlled release
formulations since it has a uniform porosity (semipermeable matrixes) which may be varied. This technology has
concretely enabled the development of tablet forms of sustained-release aminophylline, theophylline, morphine,
and other drugs. Research suggested that evening administration of UniphylR (anhydrous theophylline) tablets
represented a rational dosing schedule for patients with asthma who often exhibit increased bronchoconstriction in
the morning. Patients demonstrated improved pulmonary function in the morning compared with use of twice-
daily theophylline when once-daily UniphylR was administered in the evening. Thus, evening administration of
once-daily theophylline may block the morning dip in lung function commonly seen. CONTINR technology
provides for closer control over the amount of drug released to the bloodstream, and benefits patients in terms of
reducing the number of doses they need to take every day, providing more effective control of their disease
(particularly at night), and reducing unwanted side effects.
Marketed preparation for asthma till now
 FDA approval date – Sept.01.1982
 API- Theopylline
 Proprietary name dosage form - Uniphyl
 Chronopharmaceutical technology- CONTIN
CONCLUSION
Chronopharmaceutics will certainly improve patient outcome and optimize disease management in the
future. Research in chronopharmacology has demonstrated the importance of biological rhythms in drug therapy
and this has led to a new approach to the development of drug delivery systems. Optimal clinical outcome cannot
be achieved if drug plasma concentrations are constant. If symptoms of a disease display circadian variation, drug
release should also vary over time. Different technologies have been applied to develop time-controlled, pulsed,
triggered and programmed drug delivery devices in recent years. Since it is seems that timing of drug
administration in disease therapy has significant impact upon treatment success, chronotherapeutics remains an
important area for continuing research. It is concluded that the treatment of asthma with the Chrono-optimized
preparation over night is more effective than treatment with a conventional preparation in twice-daily dosage. In
addition, lung function showed greater stability, throughout the day, with once-daily evening therapy than with
traditional 12 hr dosing. It is well known that human body temperature, blood pressure, and pulse rate reach high
values during the day and fall at night. Similarly, all other physiological functions and activities are subject to a
daily cyclical variation known as their circadian rhythm. The respiratory function is no exception and is known to
experience a trough in activity from late night until early morning. In other words, in application once daily at
bedtime could be expected to prevent asthma attacks for practically the entire 24-hour period and, as maximum
blood concentration is reached in the early morning, would be particularly effective against attacks caused by
morning dip.
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Hemant Singh Indian Journal of Research in Pharmacy and Biotechnology
RECENT TRENDS IN SCOPE AND OPPORTUNITY OF CLINICAL
RESEARCH IN INDIA
Hemant Singh*
, Abhinav Srivastva
I.E.C. College of Eng & Technology, Greater Noida.
*Corresponding author:hemanthsingh198611@gmail.com
ABSTRACT
Clinical Research is one of the most knowledge-intensive industry. It is complete biography of drug
from its inception in the lab to its introduction to the consumer market and beyond. Any molecule is
identified is subjected to pre-clinical and clinical trials before entering in to market. Though post
marketing surveillance is also part of the same. Pre-clinical studies are associated with effect of drug on
animals. All the toxicological studies, tests for teratogenicity, carcinogenicity are carried out.After this,
the data obtained from the studies are submitted as an IND (Investigational Drug Application) to take
permission for human studies. Then, it is enter in to clinical trials. There are 4 phases in it. It is very clear
that India has become a very preferred destination for clinical research. The industry is growing
exponentially and is expected to reach Rs. 7000 Cr by 2010. Statics shows that if India's clinical trial
business grows to 10% of that in US by 2015, the industry will need approximately 50,000 clinical
research professionals.
Key Words: Clinical Research, healthy volunteers, Clinical Trial Phases.
INTRODUCTION
Clinical Research is a systematic study to evaluate the effectiveness and safety of medications or medical
devices by monitoring their effects on large groups of people. Clinical research has become a multi-billion and
multidisciplinary industry. A number of factors favor India as a clinical research hub. There are numerous
government-funded medical and pharmaceutical institutions with state-of-the-art facilities, which can serve as
ideal centers for multi-centered clinical trials.India boasts of well-trained and qualified manpower, well versed in
English. The research and the development process in India can be done at a more affordable price. More
importantly, there is vast clinical material, which can be utilised, due to the prevalence of a large variety of
diseases, including widespread cases of cancer and diabetes, India is viewed the world over as the ideal location
for clinical research trials for the pharmaceutical industry.India is becoming a hub for clinical research; the
demand for professionals in this field is growing rapidly. Clinical research business in India will be worth $1
billion by 2010. Thus, there will soon be a massive demand for clinical research professionals, making it an
interesting career option with massive growth potential. According to a survey, there are 2,50,000 vacancies
available worldwide 50,000 job openings in India by 2010. Highest remuneration packages owing to the shortage
of skilled professionals.There are high demand for trained professionals in this field; the pay package is
impressive at the entry level. Freshers can expect a pay packet of around three lakhs or more per anum. If you
have a master’s degree backing your qualifications, then the amount is almost doubles. Clinical research is an
industry where experience counts, thus the longer you are in this field; higher the salary you can expect.So there is
really a very good scope for clinical research in India.
HUMAN CLINICAL TRIAL PHASES
Phase I: Studies assess the safety of a drug or device. This initial phase of testing, which can take several months
to complete, usually includes a small number of healthy volunteers (20 to 100), who are generally paid for
participating in the study. The study is designed to determine the effects of the drug or device on humans
including how it is absorbed, metabolized, and excreted. This phase also investigates the side effects that occur as
dosage levels are increased. About 70% of experimental drugs pass this phase of testing.
Phase II: Studies test the efficacy of a drug or device. This second phase of testing can last from several months
to two years, and involves up to several hundred patients. Most phase II studies are randomized trials where one
group of patients receives the experimental drug, while a second "control" group receives a standard treatment or
placebo. Often these studies are "blinded" which means that neither the patients nor the researchers know who has
received the experimental drug. This allows investigators to provide the pharmaceutical company and the FDA
with comparative information about the relative safety and effectiveness of the new drug. About one-third of
experimental drugs successfully complete both Phase I and Phase II studies.

Hemant Singh Indian Journal of Research in Pharmacy and Biotechnology
Phase III: Studies involve randomized and blind testing in several hundred to several thousand patients. This
large-scale testing, which can last several years, provides the pharmaceutical company and the FDA with a more
thorough understanding of the effectiveness of the drug or device, the benefits and the range of possible adverse
reactions. 70% to 90% of drugs that enter Phase III studies successfully complete this phase of testing. Once
Phase III is complete, a pharmaceutical company can request FDA approval for marketing the drug.
Phase IV: Studies, often called Post Marketing Surveillance Trials, are conducted after a drug or device has been
approved for consumer sale. Pharmaceutical companies have several objectives at this stage to compare a drug
with other drugs already in the market; to monitor a drug's long-term effectiveness and impact on a patient's
quality of life; and to determine the cost-effectiveness of a drug therapy relative to other traditional and new
therapies. Phase IV studies can result in a drug or device being taken off the market or restrictions of use could be
placed on the product depending on the findings in the study.
SCOPE FOR CLINICAL RESEARCH IN SOUTH ASIAN NATIONS
With a very large number of drugs, worth more than $50 billion in annual revenues, coming off patent in
the next few years, many western pharma companies are now increasingly relinquishing business activities that
are not considered core, such as clinical research, and are moving towards contract research. Since in the western
countries, clinical research is characterized by extremely high costs and long gestation periods and the same work
can be performed in developing countries at a fraction of the cost and much faster, many global pharma
companies are increasingly turning their attention to Asia to benefit from low R&D costs in the region and also to
gain access to Asia's drug markets. Clinical trials have thus gone ‘global,’ because CROs find it easier to conduct
them in underdeveloped countries, as this is cheaper or has less ethical encumbrances or legal risks. Naïve patient
populations, English speaking doctors, low costs and other advantages offered by developing countries have
opened up new avenues for the clinical trials market. Hence there is lot of scope for clinical research activities for
the South Asian nations if they make use of the upcoming opportunities in this field.
India: The future of clinical research in India continues to be hazy. While on the one hand there are predictions
that India will be the next hotspot for clinical trials, on the other , industry forums speak of ongoing challenges
and stagnant growth for a variety of reasons, such as regulatory delays in approval, escalating costs, inconsistent
quality, ethical irregularities etc. While several CROs have started operations in India basing their future on the
rosy predictions, it is equally true that existing players are struggling to grow or even sustain their current
business.
Since registration of clinical trials in Clinical Trial Registry of India (CTRI) was made mandatory from
mid-2009 onwards, close to 1800 trials have been registered in this database. Of these, about 69 per cent are
sponsored by the pharmaceutical industry (both multinational and Indian companies), the rest being funded by
grants from various government and not-for-profit institutions (e.g. DBT, CSIR, AIIMS, ICMR, Ministry of
Defence,).
Indian CROs can now look forward for more opportunities to conduct clinical studies within the generic
space. For drugs that are not absorbed in the GI tract, plasma concentrations are not useful to determine delivery
of the drug to the site of activity, and hence bioequivalence of the generic product to the innovator cannot be
established by BA/BE studies. In such cases, one needs to demonstrate therapeutic equivalence with clinical or
pharmaco-dynamic studies.
Assocham had predicted that India would garner about 15 per cent of the global clinical trials opportunity.
However, out of over 1,00,000 human trials being conducted in 178 countries, less than 2,000 (two per cent) are
being done in India compared to over 9,000 (nine per cent) in China.
Some of the advantages that India offers as a clinical trial destination are : availability of diverse patient
population across major therapeutic segments such as oncology, metabolics, neurology etc; high degree of
compliance to international guidelines such as the ICH GCP and the regulations laid down by the US FDA;
availability of well qualified, English speaking research professionals including physicians; lower costs compared
to the west; increasing prevalence of illnesses common to both developed and developing countries; availability
of good infrastructure and changes in Patent Laws since January 2005.
Bangladesh: According to an article in The Pharma World, leading health Journal in Bangladesh,
notwithstanding its potential, clinical research is still underdeveloped in Bangladesh. There is a lack of capacity
for bioequivalence studies, no analytical capacity (samples have to be shipped to foreign countries such as
Singapore for any analytical treatment) and limited bio-banking and documentation of clinical specimens. There

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