INTRODUCTION:

Recent advances in novel drug delivery systems (NDDS) aim to enhance safety and efficacy of drug molecule by formulating a convenient dosage form for administration and to achieve better patient compliance i.e., one, which will rapidly disintegrate in the mouth without need of water (fast dissolving tablet). Advantages of this drug delivery system include administration without water, accuracy of dosage, easy portability, alternative to liquid dosage forms, ideal for pediatric and geriatric patients and rapid onset of action. The concept of formulating orodispersible tablets containing pioglitazone offers a suitable and practical approach in serving desired objective of rapid disintegration and dissolution characteristics with increased bioavailability.¹

The orally disintegrating tablets are also called as orodispersible tablets, quick disintegrating tablets, fast disintegrating tablets, porous tablets and rapimelts. However the United States Pharmacopoeia (USP) approved these dosage forms as orodispersible tablets. Recently, European Pharmacopoeia has used the term “orodispersible tablet” for tablets that disperse readily and within three minutes before swallowing. Upon ingestion, the saliva serves to disperse/dissolve the dosage form; the saliva containing the dissolved/dispersed medicament is then swallowed in the normal way. Some drugs are absorbed from the mouth, pharynx and esophagus as the saliva passes down into the stomach. In these cases, the bioavailabilities of drugs are significantly greater than those observed from conventional solid forms such as tablets and capsules.²

Diabetes mellitus is often simply considered as diabetes, a syndrome of disordered metabolism with abnormally high blood glucose levels (hyperglycaemia). The two most common forms of diabetes are type 1diabetes (diminished production of insulin) and type 2 diabetes (impaired response to insulin and b-cell dysfunction). Both lead to hyperglycaemia, excessive urine production, compensatory thirst, increased fluid intake, blurred vision, unexplained weight loss, lethargy, and changes in energy metabolism.³

Pioglitazone is a prescription drug of the class thiazolidinedione with hypoglycemic (anti hyperglycemic, anti diabetic) 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 glaciated hemoglobin in the bloodstream.

MATERIALS:

The drug pioglitazone was a generous gift sample from Aarti Drug Ltd. Mumbai, Maharashtra. Other reagents and organic solvents used were of analytical grade.

METHOD:

Fast dissolving tablets of pioglitazone was prepared by direct compression method by using superdisintegrant sodium starch glycolate, crosprovidone together with binding agent like MCC, Magnesium stearate and talc were used as lubricants.

PREPARATION OF FAST DISSOLVING PIOGLITAZONE TABLET:

Tablets containing 30 mg of Pioglitazone were prepared by direct compression method and the formula used in this study are shown in (table 1). The drug and diluents were passed through sieve on 40. All the materials were transferred to a mortar and triturated till it was uniform. Talc and magnesium stearate were passed through mesh number 80, mixed well and blended with initial mixture. The resulting powder blend was evaluated for angle of repose, bulk density, tap density and compressibility index & compressed into tablets using single punch tablet machine. ⁴

Table 1: Composition of fast dissolving tablets

Ingredients	F1 (mg)	F2 (mg)	F3 (mg)	F4 (mg)	F5 (mg)
Pioglitazone	30	30	30	30	30
Crosprovidone	-	6	8	7	10
Sodium starch glycolate	8	-	7	12	10
Microcrystalline cellulose	120	120	120	120	120
Mannitol	86	88	79	75	74
Magnesium strearate	4	4	4	4	4
Talc	2	2	2	2	2

EVALUATION OF BLENDS:

Angle of Repose⁵:

It was calculated by using Funnel method. Powder blend was poured on vertically placed funnel until cone of maximum height was formed.

Tan Ɵ = h/r

Ɵ = Angle Of repose,

h = Height of cone,

r = Radius of the cone base.

Bulk density⁴:

Bulk density was calculated by pouring the powder blend in the graduated cylinder. Then bulk volume (V) was noted and after that mass (M) was noted by weighing on electric balance. Bulk density was noted by using following formula,

Bulk Density=weight of the podwer / bulk volume of the podwer

Tapped density:

Specified quantity of powder from each formulation, previously lightly shaken to break any agglomerates formed was introduced into 25 ml measuring cylinder. After the initial volume was observed, the cylinder was allowed to tap by using the Tap density tester (USP) for the 100 taps and then final tapped volume was observed.

Tapped density-weight of the podwer / tapped volume of the podwer

Carr’s Index:

The Carr’s index of the powder blend was determined by using formula:

Carr’s index % =Tapped density –bulk density*100

Tapped density

Hausner’s Ratio:

Hausner’s ratio is an indirect index of ease of powder flow. It is calculated by the following,

Hausner ratio = Tapped density / Bulk density

EVALUATION OF PREPARED TABLETS:

Hardness⁶:

For each formulation, the hardness of 5 tablets was determined using the Monsanto hardness tester.

Thickness¹⁰:

Tablet was selected at random from individual formulations and thickness was measured by using Vernier caliper scale, which permits accurate measurement.

Weight variation test¹⁰:

Weigh tablets individually, calculate the average weight, and comparing the individual tablet weight to average weight. The % deviation was calculated and checked for weight variation as per Indian Pharmacopoeia.

Friability⁵:

Friability test is performed to assess the effect of friction and shocks, which may often cause tablet to chip cap or break. Preweighed sample of five tablets were placed in the friabilator, which was then operated for 100 revolutions. After 100 revolutions the tablets were dedusted and reweighed. Calculate the percentage loss in weight as follows,

Wetting Time³:

A piece of tissue paper folded twice was placed in a small Petri-dish (internal diameter of 5 cm.) containing 6 ml of water. A tablet was placed on the paper and the time required for water to reach the upper surface of the tablets was noted as the wetting time. It is measured in the unit of second.

Disintegration Time³:

The test was carried out on six tablets using water at 370C±20C as disintegration media and the time in second taken for complete disintegration of the tablet with no palable mass remaining in the apparatus were measured in seconds.

In Vitro Dissolution studies⁸:

The release rate of Pioglitazone was determined by using USP dissolution apparatus type-II (Paddle). The dissolution test was performed using 900 ml of pH 6.8 phosphate buffer solution for 30 min which was maintained at 37 ± 0.2°C and rate of stirring at 50 rpm. At each time point of analysis, 5 ml sample was withdrawn and replaced with freshly prepared dissolution media maintained at same conditions.

RESULTS AND DISCUSSION:

In the present study, fast dissolving tablets of pioglitazone prepared by using different concentrations of superdisintegrants like crosprovidone and sodium starch glycolate. These superdisintegrants play major role in 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. F1 to F5 formulations prepared by direct compression method. Precompression evaluation were carried out and the results found to be within the prescribed limits (Table No. 2) having good flow properties. The compressed tablets were evaluated for weight variation, thickness, friability, hardness, drug content, wetting time, disintegration time and dissolution studies as per official Pharmacopoeia. The most important parameter that needs to be optimized in the development of mouth dissolving tablets is the disintegration time. In the present study disintegration time was found in the range of 53to70 sec (Table2). Formulation batch F4 shows lowest disintegration time. Wetting time was found in the range of 38 to 48sec. Hardness was found between 3.3 to 3.7kg/cm2 which indicate good mechanical strength. Friability was found below 1% indicating good resistance against mechanical shear. Formulation batch F4 shows better drug release than other formulatios.

Table No 2: Evaluation of Fast Dissolving Tablets of Pioglitazone

Parameter	F1	F2	F3	F4	F5
Bulk density (g/cm3)	0.345	0.354	0.362	0.378	0.357
Tapped density (g/cm3)	0.402	0.413	0.410	0.418	0.415
Hausner’s Ratio	1.165	1.166	1.132	1.105	1.162
Compressibility Index	14.17	14.28	11.70	9.56	13.97
Angle of Repose	24	23	24	23	24
Hardness (kg/cm2)	3.7	3.5	3.7	3.4	3.3
Thickness(mm)	3.3	3.2	3.1	3.3	3.3
Disintegration time (sec)	70	65	68	53	58
Friability (%)	0.157	0.140	0.214	0.102	0.163
Wetting time (sec)	48	44	39	38	46

Table No. 3: Cumulative % drug release of prepared formulation batches

Formulation batch	2min	4min	6min	8min
F1	46.12	71.34	85	97.41
F2	39.86	67.14	78.12	89.38
F3	41.25	62.56	88	96.79
F4	47.16	70.12	90.12	98.22
F5	35.41	64.98	83.54	91.63

CONCLUSION:

Fast dissolving tablets of Pioglitazone is type 2 anti-diabetic agent can be efficiently and successfully formulated using novel co processed super disintegration by direct compression. Tablets containing sodium starch glycolate along with crospovidone formulation F-4 shows fastest disintegration, as shown in (Table-2). Formulations F4 showed minimum disintegration time of 53 sec and maximum drug release. Characteristics of tablets are further tabulated in Table-2. The study shows that the disintegration rate of pioglitazone can be enhanced to a great extent by direct compression technique with the addition of mixture of superdisintegrants. Tablets containing sodium starch glycolate along with crospovidone is showing excellent results as compare to other formulations.

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Received on 23.11.2018 Accepted on 31.12.2018

Asian J. Pharm. Tech. 2019; 9(1):23-26.

DOI: 10.5958/2231-5713.2019.00005.9