FORMULATION AND EVALUATION OF DICLOFENAC SODIUM SUSTAINED RELEASE TABLETS
1. FORMULATION AND EVALUATION OF DICLOFENAC
SODIUM SUSTAINED RELEASE TABLETS
A seminar to submitted to the
Jawaharlal Nehru Technological University, Hyderabad
In partial fulfillment of the requirements for the degree of
BACHELOR OF PHARMACY
AUN BIN AMAR BAZAHER 15S61R0084
RUQSAR FATIMA 15S61R0016
MUBEEN FATIMA 15S61R0046
SABA SIDDIQUA 15S61R0055
Under the guidance of
Dr. Niranjan Panda, M. Pharm.,Ph.D., FICCP
Department of Pharmaceutics
Anwarul Uloom College of Pharmacy
New Mallepally, Hyderabad -500001
Affiliated to JNTUH , Approved by AICTE and PCI
3. Diclofenac, sold under the trade name Volteran among others is a
non-steroidal anti-inflammatory drug (NSAID) used to treat pain
and inflammatory diseases such as gout.
Common side effects include abdominal pain, G.I.bleeding,
nausea, dizziness, headache and swelling. Serious side effects
include heart diseases, stroke, kidney problems and stomach
Diclofenac was patented in 1965 by Ciba-Geigy and came into
medical use in the United States in 1988.
DEPARTMENT OF PHARMACEUTICS, AUCOP 3
4. Sustained release dosage forms are dosage forms designed to release a
drug at a predetermined rate.
These agents are formulated to produce maximum stability, activity and
Some drugs possess solubility problems. In such cases, a method of
continuous administration of therapeutic agent is desirable to maintain
fixed plasma levels.
Ideally two main objectives exist for these systems: Spatial delivery,
which is releated to the control over the location of drug release.
Temporal drug delivery, in which drug is delivered over an extended
period of time during treatment.
DEPARTMENT OF PHARMACEUTICS, AUCOP 4
Diclofenac Sodium is the sodium salt form of diclofenac, a benzene acetic
acid derivative and NSAID with analgesic, antipyretic and
Emperical formula: C14H10Cl12NNaO2
Chemical name: sodium; 2-[2-(2, 6-dichloroanilino) phenyl] acetate
Molecular Weight: 318.129 g/mol
Category: Non-steroidal ant-inflammatory drug (NSAID)
Dose: Diclofenac sodium 50 mg is used for pain relief.
DEPARTMENT OF PHARMACEUTICS, AUCOP 5
6. DEPARTMENT OF PHARMACEUTICS, AUCOP 6
Absorption: Diclofenac sodium is 100% absorbed after oral administration compared to I.V.
Administration as measured by urine recovery. However, due to first pass metabolism only
about 50% of the absorbed dose is systematically available. The extent of absorption of
diclofenac is not significantly affected by food intake.
7. • Distribution : The apparent volume of distribution (Vf) of diclofenac sodium is 1.4 L/kg.
Diclofenac is more than 99% bound to human serum proteins, primarily to albumins. Serum
protein binding is constant over the concentration range of 0.15-105 mcg/mL acheived with
• Metabolism : Five diclofenac metabolites have been identified in human plasma and urine. The
major diclofenac metabolite 4’-hydroxy-diclofenac, has very weak pharmacological activity. The
formation of this diclofenac metabolite is mediated by CYP2C8. Both diclofenac and its oxidative
metabolites undergo glucoronidation or sulfation followed by biliary excretion. In patients with
renal dysfunction, peak concentration of metabolites 4’-hydroxy and 5’-hydroxy diclofenac were
approximately 50% and 4 % of the parent compound after single oral dosing compared to 27%
and 1% in normal healthy subjects.
• Excretion : Diclofenac is eliminated through metabolism and subsequent urinary and biliary
excretion of the glucoronide and the sulfate conjugates of the metabolites. Approximately 65 % of
the dose is excreted in the urine and 35% in the bile as conjugates of unchanged diclofenac plus
metabolites. The terminal half-life of unchanged diclofenac is approximately 2-hours.
DEPARTMENT OF PHARMACEUTICS, AUCOP 7
8. Mechanism of action:
The primary mechanism responsible for its ant-inflammatory, antipyretic and analgesic action is
thought to be inhibition of prostaglandin synthesis by inhibition of the transiently expressed
prostaglandin- endoperoxidase synthase-2 (PGES-2) also known as cycloxygenase-2 (COX-2).
It also appears to exhibit bacteriostatic activity by inhibiting bacterial DNA synthesis.
Diclofenac sodium tablet is used to relief all grades of pain and inflammation in a wide range of
conditions including :
Arthritic conditions: rheumatoid arthritis, osteoarthritis, acute gout, ankylosing spondylitis.
Acute musculoskeletal disorders such as periarthritis (eg: frozen shoulders), tendinitis,
Other painful conditions resulting from trauma, including fracture, lower back pain, sprains,
strains, dislocations, orthopedic,dental and other minor surgery.
DEPARTMENT OF PHARMACEUTICS, AUCOP 8
•Enteric coated tablet: a total of 75-150 mg daily given in two or three divided doses.
•Sustained release tablets: one tablet daily, taken whole with liquid, preferably during meal.
•Enteric coated tablet: 1-3 mg/kg per day in divided doses.
•Sustained release tablets: not recommended.
•Hypersensitivity against diclofenac
•History of allergic reactions (bronchospasm, shock, rhinitis, urticaria)
following the use of other NSAIDs such as aspirin
•Severe insufficiency of the heart (NYHA III/IV)
DEPARTMENT OF PHARMACEUTICS, AUCOP 9
10. Gastrointestinal experiences including: abdominal pain, constipation, diarrhea,
dyspepsia, flatulence, gross bleeding/perforation, heartburn, nausea, GI ulcers
(gastric/duodenal) and vomiting.
Abnormal renal function, anemia, dizziness, edema, elevated liver enzymes,
headaches, increased bleeding time, pruritus, rashes and tinnitus.
DEPARTMENT OF PHARMACEUTICS, AUCOP 10
12. Table 2: List of instruments used.
DEPARTMENT OF PHARMACEUTICS, AUCOP 12
13. METHODS USED:
DEPARTMENT OF PHARMACEUTICS, AUCOP 13
Preformulation testing is the first step in the rationale development of dosage forms of a
•To establish the necessary physicochemical characteristics of a new drug substance.
•To determine its kinetic release rate profile.
•To establish its compatibility with different excipients.
Preformulation studies on the obtained sample of drug include colour, taste, solubility
analysis, melting point determination, compatibility study.
(a) Identification of pure drug Solubility Analysis
Preformulation solubility analysis was done, which included the selection of suitable
solvent system to dissolve the drug as well as various excipients.
(b) Melting Point Determination
Melting point determination of the obtained drug sample was done; as it is a
first indication of purity of the sample.
14. DEPARTMENT OF PHARMACEUTICS, AUCOP 14
Sustained release tablets of Diclofenac sodium were prepared by wet granulation
technique using different proportions of polymers and excipients. All the powders were passed
though #60 sieve. This is accomplished by adding a liquid binder or an adhesive to the powder
mixture, passing the wetted mass through a screen of the desired mesh size, drying the
granulation and then passing through a second screen of smaller mesh to reduce further the size
of the granules. Diclofenac sodium sustained release tablets were prepared with excipients and
other additives. Diclofenac sodium and microcrystalline cellulose were mixed together, and
granulate it with excipients solution until a wet mass was obtained. Then the coherent mass was
passed through #10 and the granules were dried at 40 +2°C for 2 hours. Dried granules were
passed through #16 and lubricated it with magnesium stearate and talc was added to the
granules. Then the lubricated granules were compressed into tablets using tablet punching
machine. The compressed tablets were dedusted and evaluated for various tablet properties.
Different formulations were shown in following table.
16. DEPARTMENT OF PHARMACEUTICS, AUCOP 16
•Angle of repose
•Weight variation test.
•In vitro dissolution studies.
•Kinetics of drug release.
26. DEPARTMENT OF PHARMACEUTICS, AUCOP 26
1. Diclofenac sodium is used for the treatment of pain and inflammation. The plasma
half-life of Diclofenac sodium for about 1.2-2 hrs and the dose is administered twice
daily as orally.
2. To decrease the quantity of administration and to enhance patient compliance, a single
daily dose of sustained release drug (diclofenac sodium) was sufficient.
3. The goal of the current study was to optimize and depict sustained release diclofenac
sodium matrix tablet using polymers like hydroxyl propyl methyl cellulose (HPMC
K4M, HPMC K15M) and microcrystalline cellulose.
4. The tablet were prepared by wet granulation method.
5. The in-vitro drug release characteristics were studied in phosphate buffer ph 6.8 for a
period of 10-12 hrs using USP type-II (paddle type) dissolution apparatus.
6. In-vitro drug release kinetic studies were carried out for the optimized formulation (F6)
with zero order, first order , Higuchi and Korse Meyer Peppass kinetic model.
27. DEPARTMENT OF PHARMACEUTICS, AUCOP 27
1. Diclofenac sodium sustained release matrix tablets formulations were successfully
developed with various ratios of HPMC K4M and HPMC K15M as polymers .
2. Fourier transform infrared spectroscopy (FTIR) studies released that the drug and
excipients were compatible with each other and formulation is thermally stable.
3. It was confirmed that a continous release rate for prolong period of time.
4. From the research work it was concluded that the Diclofenac sodium sustained
release matrix tablet is a appropriate formulation as it can be used as once daily dosage
form and overall daily dose can be decreased.
5. The release form of that formulation is similar with marketed formulations and can
achieve patient requirement.
28. DEPARTMENT OF PHARMACEUTICS, AUCOP 28
1. http://www.aapspharscitech.org/excipient/tabling ingredient
2. Brahmankar DM, Jaiswal SB. Biopharmaceutics and Pharmacokinetics a treatise (page no. 397-422)
3. Jain NK et al. Controlled and Noval drug delivery. I ed. New Delhi: CBS Publishers and Distributors 1997.
4. Vyas SP, Kar R.K., Text Book of controlled Drug Delivery. I ed. New Delhi Vallabh Prakashan; 2002.
5. Robinson Jr, Lee VHL. Controlled drug Delivery, Fundamentals and applications II ed New York: Marcel Dekker: 1978.
7. CVS Subramanyam Text Book of physical pharmaceutics
10. Remington’s the science and practice of pharmacy 20th ed, Lippan cott. 1995:721-52
11. In vitro dissolution kinetic study of theophylline from mixed controlled release matrix tablets, containing hydroxy propyl
methylcellulose and glycerylbehenate. (LJPS may-june-2006, page 308)
12. Formulation and release behavior of sustained release Ambroxol hydrochloride HPMC matrix tablet (sept-oct-2006,
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