1. DEVELOPMENT & EVALUATION OF MUCOADHESIVE
MICROSPHERES OF PIOGLITAZONE MALEATE
By
2Ram Chand Dhakar, 2Sheo Datta Maurya
*1Sanwarmal, 1Manisha Gupta,
1HIMTCollege of Pharmacy, Gr Noida
2 Department of Pharmacy, IEC Group of Institution, Gr Noida
For Correspondence
Sanwarmal
Lecturer, HIMT College of Pharmacy, Gr Noida, INDIA-201308
E-mail: snas_kir@yahoo.co.in

2. AIM, SCOPE & OBJECTIVES OF THE STUDY
AIM: The present work was aim to formulate & evaluate
mucoadhesive microspheres of Pioglitazone maleate.
Microspheres were prepared by emulsification solvent
evaporation method using SCMC, CP & SA as
mucoadhesive polymers.
SCOPE: Prepared microspheres are expected to adhere in
the gastrointestinal mucosa and can be utilized for
controlled release of Pioglitazone maleate for an
extended period in the management of Diabetes type-II.
Objectives: Reduce the Dosing frequency
Fluctuations in therapeutic blood level is avoid
Increase patient compliance
Decrease in dose-related side effects

3. INTRODUCTION
What is microspheres?
Microspheres are solid spherical particles
consisting of protein or synthetic polymers
ranging in size from 1-1000μm.
A Microsphere has its drug dispersed throughout the particle i.e. the
internal structure is a matrix of drug and polymeric excipients.
However, the success of these microspheres is limited owing to their
short residence time at the site of absorption. This problem can be
avoid by coupling mucoadhesion characteristics to the microspheres
and developing mucoadhesive microspheres.2-6
What is mucoadhesive microspheres?
These microspheres are made by polymers that bind or Adhere
to the mucosal tissue and offer local as well as systemic
controlled release of drug for longer duration.

4. Selection of drug and Polymers:
Pioglitazone maleate is an antidiabetic drug belongs to
thiazolidinediones class. It requires control release due to
its short t1/2 of 3-4 hours11. To reduce the dosing
frequency of drug, it’s necessary to develop a newer
formulation which release drug in sustained release
manner. Thus mucoadhesive microspheres of
pioglitazone would become promising candidate in
management of diabetes type-II.
Literature survey revealed that SCMC, SA & CP shows
good mucoadhesive property & efficiently controlled the
drug release. Thus these are the suitable candidate for
mucoadhesive microspheres of pioglitazone maleate.

5. Preparation of microspheres12, 15
W/O Emulsification solvent evaporation method
Aq. Sol. of SCMC, SA & CP Drug dissolved in DMSO
D-P Solution
Syringe containing
D-P solution
liquid paraffin containing
0.5 % span 20 D+P droplets
Stirring at 500 RPM
·
·
·
Microspheres 500 RPM, 800C Evaporation of solvent
for 4 Hours Solidification of D-P droplets
Drying Washing
Filtration

6. Table-1 Composition of drug loaded microspheres
Formulation Drug SCMC CP-934 P Na-alginate
code
F1 100 mg 900 mg -- --
F2 100 mg -- 900 mg --
F3 100 mg -- -- 900 mg
F4 100 mg 450 mg 450 mg --
F5 100 mg 450 mg -- 450 mg
F6 100 mg -- 450 mg 450 mg
All formulation were prepared at 2% polymer conc. and 500 rpm stirring speed

7. Surface morphology:
visualize by SEM at BSIP, Lucknow.
Drug entrapment efficacy17:
50 mg of microsphere were taken and drug was extracted
from microspheres by digesting for 24 hours with 10 ml
of simulated gastric fluid(pH 1.2). During this period the
suspension was agitated. After 24 hours, the solution was
filtered & the filtrate was analyzed for the drug content.
The drug entrapment efficiency was calculated using the
following formula:
Entrapment efficiency = (Actual drug content/theoretical
drug content) 100

8. Particle Size17, 18: by optical microscopy
A small amount of dry microspheres was suspended in n-
hexane (10 mL).
A small drop of suspension thus obtained was placed on a
clean glass slide. The slide containing microspheres was
mounted on the stage of the microscope and particles
were measured using a calibrated ocular micrometer. The
average particle size was determined by using the
Edmondson's equation
D mean = ∑nd/∑n,
where n= number of microspheres
and d= mean size range.

9. In-vitro mucoadhesivity19:
By in-vitro wash-off test.
A 1 1 cm piece of rat stomach mucosa was
tied onto a glass slide using thread.
Microspheres were spread on the wet, rinsed,
tissue specimen & prepared slide was hung onto one of the
groves of a USP tablet disintegrating test apparatus.
The apparatus was operated such that the tissue specimen was
given regular up and down movements in a beaker
containing the simulated gastric fluid (pH 1.2).
At hourly intervals up to 10 hours, the number of
microspheres still adhering onto the tissue was counted.
% mucoadhesion = (no. of microspheres remains / no. of
applied microspheres) 100

10. In-vitro drug release13
 USP XXI paddle type dissolution test apparatus
 Dissolution medium: simulated gastric fluid (pH 1.2), 900
ml
 100 mg Microspheres are spread on wet double layer muslin
cloth and hanged with the paddle of disso apparatus.
Temperature of bath=37 1 C.
Paddle speed = 50 rpm.
Sample volume= 10 ml,
Sampling interval= 1 hour
 Sample analyzed for drug content by UV-Visible
spectrophotometer at 268.9 nm.

11. RESULTS AND DISCUSSION
Surface morphology: Examined by SEM.
The SEM showed that the mixture of SCMC and CP
produced spherical with smooth surface microspheres due
to their high solubility in water6.
While SA microspheres were of irregular shape with a rough
morphology due to less water solubility & non uniform
evaporation of water from the surface of microspheres.
Figure : SEM of formulation F1 showing population of microspheres

12. Particle size analysis:
Average p. size was found to be in the range of 31.20 to 47.54 μm.
Increase in stirring speed Increase in polymer conc
produce high energy for breaking high viscosity of polymer sol
of droplets
Particle size increases
Particle size decreased
Drug entrapment efficiency:
 It was found in the range of 54.00 to 80.00 % .
 Formulation F2 containing CP showed max drug loading about 80 %
 Formulation F6 containing CP/SA shows min drug loading about 53%
 Microspheres of SA are irregular in shape therefore more drug loss
from surface during washing leads to less drug entrapment efficiency.
 Rank order of % drug loading of various formulations:
F2 > F4 > F1 > F5 > F3 > F6

13. Table –2 Comparative % yield, Particle size, % drug
entrapment and % mucoadhesion of microspheres
Formulation % yield Particle size % Mucoadhesion % Drug
code (µm) after 1 hr entrapment
F1 73.45 3.20 34.54 2.43 94.33 2.33 69 2.45
F2 71.56 2.80 31.20 1.88 89.22 2.43 80 3.23
F3 79.10 2.95 47.54 3.24 87.23 2.83 57 2.86
F4 75.52 2.84 38.62 2.78 72.20 1.90 78 2.75
F5 72.12 3.10 43.12 2.84 95.33 2.95 63 2.84
F6 74.44 2.60 41.85 3.15 76.44 2.32 54 3.68
Values are represented as mean standard deviation (n=3).
All formulation were prepared at 2% polymer conc. and 500 rpm stirring speed

14. In-vitro mucoadhesivity test:
 Formulation F1 containing SCMC showed the highest mucoadhesivity
due to anionic nature of the polymer.
 Formulation F6 containing SA/CP-934 showed the lowest
mucoadhesivity due to the irregular surface of microspheres.
 Rank order of % mucoadhesivity, after 8 hours was found to be as
follows: F1 > F2 > F3 > F5> F4 > F6

15. DRUG RELEASE STUDY:
Dissolution medium: SGF(pH 1.2), Temp: 370C 1.
 Drug release form these microspheres were found to be
slow, extended and dependent on the type and conc. of
polymer used.
 Formulation F1 containing SCMC showed the max. release
91.45 % after 10 hrs, due to rapid swelling property and high
dissolution of SCMC in SGF.
High swelling of SCMC Faster drug release
Dissolution medium permeation is facilitated
 While SA microspheres showed the slow drug release due to
less swelling action as compared to SCMC.

16. Figure : Comparative % drug release of microspheres formulations

17. CONCLUSION
 The SEM reveals smooth surface microspheres.
 The particle size of microspheres ranged from 31-47 μ.
 The entrapment efficiency ranged between 54-80%.
 All the formulation show significant mucoadhesion
property and it depends on the type of polymer used.
 The in-vitro release & the mucoadhesion studies shows
SCMC formulation was the best which released 98.60%
drug at the end of 12th hour.

18. ACKNOWLEDGEMENT:
Authors is highly thankful to HIMT College of Pharmacy,
& Dept of Pharmacy, IEC Group of Institution, Greater
Noida for providing us best lab facilities and Indswift Labs
Pvt ltd, for providing drug sample.

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20. Thank You