FORMULATION AND EVALUATION OF FAST DISSOLVING
TABLETS OF PIOGLITAZONE
C.Sadak Vali*1, Department of Pharmaceutics, Fathima Institute of Pharmacy, Kadapa. A. P.
Mohammad Rayees Ahmad1, Department of Pharmaceutics, Fathima Institute of Pharmacy, Kadapa.
A. P.
Mitta Raghavendra2, Department of Pharmacology, Fathima Institute of Pharmacy, Kadapa. A. P.
Correspondence:
C.Sadak Vali,
Department of Pharmaceutics,
Fathima Institute of Pharmacy,
Kadapa- 516 002. A.P. INDIA.
Mobile: +91 9052520483
E-mail: sadak_chettukrindi@hotmail.com
ABSTRACT
The purpose of this research was to develop fast dissolving tablets of pioglitazone.
Tablets containing pioglitazone, croscarmellose & crospovidone were prepared by direct
compression technique. The tablets were evaluated for weight variation, hardness, percentage
friability, wetting time, and disintegration time. Nine formulation having superdisintegrants in
different concentrations levels were prepared to access their efficiency and critical concentration
level. Tablets containing croscarmellose sodium along with crospovidone is showing excellent
results as compare to other formulations.
KEYWORDS: Fast dissolving tablet, pioglitazone, croscarmellose, crospovidone.
INTRODUCTION
Tablets are the most widely used dosage form because of its convenience in terms of self
administration, compactness, and ease in manufacturing. Geriatric and paediatric patients
experience difficulty in swallowing conventional tablets, which leads to poor patient compliance.
Traditional tablets and capsules administered with 250 ml of water may be inconvenient or
impractical for such patients. To overcome this, scientists have developed innovative drug
delivery systems known as "melt in mouth" or "mouth dissolve (MD)" tablets. Fast Dissolving
tablets disintegrate/dissolve/disperse quickly in saliva. Fast dissolving tablets can be
administrated without water, anywhere, anytime to geriatric and paediatric patients. They are
also suitable for the mentally ill, the bedridden, and patients who do not have easy access to
water. The benefits, in terms of patient compliance, rapid onset of action, increased
bioavailability, and good stability make these tablets popular as a dosage form of choice in the
current market1, 2 .The disintegrated mass can slide down smoothly along the oesophagus with
the help of saliva, so even people who have swallowing or chewing difficulties can take it with
ease. The sublingual route usually produces a faster onset of action than orally ingested tablets
and the portion absorbed through the sublingual blood vessels bypasses the hepatic first-pass
metabolic processes3-5.
The basic approach used in the development of the fast-dissolving tablet is the use of
superdisintegrants. Croscarmellose sodium and crospovidone were screened in the present study,
and the best one was used for further studies. Another approach used in developing fast
dissolving tablets is maximizing pore structure of the tablets. Freeze-drying6, direct compression
and vacuum-drying techniques are commonly used to maximize the pore structure of tablet
matrix. Freeze drying is cumbersome and it yields a fragile and hygroscopic product. Therefore,
it was decided to adopt the direct compression technique in the present investigation. It is likely
that a porous hydrophilic matrix will easily pick up the disintegrating medium and break
quickly.MDT can be formulated using various methods. Some of them involve increasing the
porosity of the tablet and decreasing the disintegration time (DT) 7. Superdisintegrants are used
that swell or absorb water rapidly to disintegrate the tablet8. Technologies like Zydis based on
lyophilization yield tablets that dissolve in a few seconds. Most of the techniques aim at lowering
the DT, but doing this always compromises the mechanical strength. Zydis tablets need special
packaging and patient counseling for removing the tablets from the strip9. Hence, the objective of
this work was to formulate and optimize mouth-dissolving tablets of pioglitazone HCl that
disintegrate in a few seconds and still have good mechanical strength.
Pioglitazone is a prescription drug of the class thiazolidinedione with hypoglycemic
(antihyperglycemic, antidiabetic) action. Pioglitazone reduces insulin resistance in the liver and
peripheral tissues; increases the expense of insulin-dependent glucose; decreases withdrawal of
glucose from the liver; reduces quantity of glucose, insulin and glycated haemoglobin in the
bloodstream. Following oral administration, in the fasting state, pioglitazone is first measurable
in serum within 30 minutes, with peak concentrations observed within 2 hours. Food slightly
delays the time to peak serum concentration to 3 to 4 hours, but does not alter the extent of
absorption.
MATERIALS AND METHODS:
The drug pioglitazone Hydrochloride was a generous gift sample from Suzikem
Pharmaceuticals, Hyderabad. Croscarmellose sodium, crospovidone were supplied from Signet
Pharmaceuticals (Mumbai). Magnesium stearate, talc was supplied from S.D. Fine Chemicals
(Mumbai). Mannitol was purchased from Merck India Ltd, Mumbai, India. Other reagents and
organic solvents used were of analytical grade.
Preparation Of Pioglitazone Tablets
Various techniques can be used to formulate rapidly-disintegrating or dissolving
tablets10,11. Direct compression, one of these techniques, requires the incorporation of a
superdisintegrants into the formulation, or the use of highly water-soluble excipients to achieve
fast disintegration of tablets. Watanabe et al12and Bi et al
13
were the first to evaluate the ideal
excipients proportions and other related parameters using a superdisintegrant in order to
formulate durable fast disintegrating tablets for oral administration.
Pioglitazone mouth dissolve tablets were prepared according to the formulae given in
Table 1. The raw materials were passed through a screen (40 mesh) prior to mixing.
Pioglitazone (30 mg) was mixed with the other excipients and compressed on a single-punch
tablet machine (REMIK, mini press, B-tooling machine, India) equipped with round 6-mm
punches.
EVALUATION OF BLENDS
The quality of tablet, once formulated by rule, is generally dictated by the quality of
physiochemical properties of the blend. There are many formulation variables and process
variables involved in the mixing step which will affect the characteristics of blends produced.
The blends were characterised by mass-volume relationship (bulk density, tapped density,
Hauser’s ratio, compressibility index) and flow properties (static angle of repose) 14.
EVALUATION OF THE PREPARED TABLETS
The crushing strength of the tablets was measured using a Monsanto hardness tester
(Sheetal Scientific Industries Mumbai, India). The friability of tablets was measured using a
Roche Friabilator (Electrolab). Five tablets were selected randomly from each formulation batch
and tested for hardness, disintegration time and wetting time15-19.The wetting time of the tablets
was measured using a simple procedure. Five circular tissue papers of 10-cm diameter were
placed in a Petri dish with a 10-cm diameter. Ten millilitres of water containing eosin, a watersoluble dye was taken in the Petri dish. A tablet was carefully placed on the surface of tissue
paper. The time required for water to reach the upper surface of the tablets was noted as the
wetting time. The disintegration time was measured using a modified disintegration method.
RESULTS AND DISCUSSION
The use of superdisintegrants for preparations of fast dissolving tablets is highly effective
and commercially feasible. These superdisintegrants accelerate disintegration of tablets by virtue
of their ability to absorb a large amount of water when exposed to aqueous environment. The
absorption of water results in breaking of tablets and therefore faster disintegration is reported to
have an effect on dissolution characteristics as well. A prepared fast-dissolving tablet gets
dispersed in the mouth quickly and released the drug as early as compared to its formulated
conventional tablets. Two different superdisintegrants namely Croscarmellose sodium and
crospovidone were tried to achieve fast dispersion of tablets. Blends evaluated for angle of
repose shown excellent flowability.
CONCLUSION
Tablets containing Croscarmellose sodium along with crospovidone formulation F-6
shown fastest disintegration, as shown in (figure-3). Characteristics of tablets are further
tabulated in Table-2. The study shows that the dissolution rate of pioglitazone can be enhanced
to a great extent by direct compression technique with the addition of mixture of
superdisintegrants.
ACKNOWLEDGEMENT
The authors are thankful to BAL PHARMA, Banglore for providing the gift sample of
Pioglitazone and also thankful to management of Fathima Institute of Pharmacy for providing
the all facilities to carry out this research work.
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Table No 1: Formulae Of Pioglitazone Fast Dissolving Tablet
Formulation
F1
F2
F3
F4
F5
F6
F7
F8
F9
Ingredients
(mg)
(mg)
(mg)
(mg)
(mg)
(mg)
(mg)
(mg)
(mg)
Pioglitazone
30
30
30
30
30
30
30
30
30
4
8
12
4
8
12
4
8
12
-
-
-
5
5
5
10
10
10
120
120
120
120
120
120
120
120
120
80
76
72
75
71
67
70
66
62
2
2
2
2
2
2
2
2
2
4
4
4
4
4
4
4
4
4
Croscarmellose
sodium
Crospovidone
Microcrystalline
Cellulose
D-Mannitol
Magnesium
stearate
Talc
Table No 2: Evaluation Of Fast Dissolving Tablets OfPioglitazone Hydrochloride
Parameter
F1
F2
F3
F4
F5
F6
F7
F8
F9
0.375
0.416
0.357
0.394
0.416
0.340
0.441
0.375
0.312
0.441
0.576
0.468
0.625
0.535
0.468
0.535
0.500
0.394
1.1176
1.384
1.310
1.750
1.286
1.206
1.213
1.333
1.055
14.96
27.70
23.71
36.96
22.24
16.35
17.57
25.00
5.28
25.35
23.44
25.42
26.43
23.33
20.19
26.53
23.43
26.31
4.1
4.1
4.3
4.2
4.3
4.9
4.6
4.7
4.9
71
69
68
66
62
51
61
60
59
Friability (%)
0.190
0.199
0.227
0.249
0.282
0.129
0.321
0.324
0.327
Weight
220
240
250
230
220
240
230
250
230
variation
±20
±10
±10
±10
±10
±10
±10
±10
±10
48
47
46
43
40
31
36
38
34
Bulk density
(g/cm3)
Tapped density
(g/cm3)
Hausner’s
Ratio
Compressibility
Index
Angle of
Repose
Hardness
(kg/cm2)
Disintegration
time (sec)
Wetting time
(sec)