FORMULATION DEVELOPMENT AND IN VITRO EVALUATION OF MOUTH DISSOLVING TABLETS OF PIOGLITAZONE HYDROCHLORIDE

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ABOUT AUTHORS
Kambham Venkateswarlu*, Jami Komala Preethi
1Department of Pharmaceutics, JNTUA-Oil Technological and Pharmaceutical Research Institute, Jawaharlal Nehru Technological University Anantapur, Ananthapuramu, Andhra Pradesh, India.
k.v.reddy9441701016@gmail.com

ABSTRACT
The present investigation was focussed on formulation and in vitro evaluation of mouth dissolving tablets (MDTs) of Pioglitazone Hydrochloride (PGTZN) thereby enhancing the dissolution rate. MDTs were prepared by wet granulation and direct compression methods using Croscarmellose sodium, Crospovidone and Sodium starch glycolate as superdisintegrants. Powder blends were evaluated for flowability and all the powder blends showed acceptable flowability. The prepared tablets were evaluated for post compression parameters like hardness, friability, wetting time and showed acceptable results. Formulations F8 and F15 showed disintegration time of 23 and 22 sec respectively. Dissolution was performed in pH 1.2 HCl buffer and formulations F15 showed maximum drug release within 30 min. drug release from F15 was more than that of the marketed drug. Hence, it could be concluded that formulation F15 showed good drug release than marketed drug and there is a lot of scope for future in vivo studies.

REFERENCE ID: PHARMATUTOR-ART-2453

INTRODUCTION
Drug Delivery Systems (DDS) area is the strategic tool for expanding markets/indications, extending product life cycles and generating opportunities. DDS make a significant contribution to global pharmaceutical sales through market segmentation, and are moving rapidly. Despite of tremendous advancements in drug delivery, the oral route remains the perfect route for the administration of therapeutic agents because of low cost of therapy, ease of administration, accurate dosage, self‐medication, pain avoidance, versatility, leading to high levels of patient compliance.^[1] Improved patient compliance has achieved enormous demand. Consequently demand for their technologies is also increasing manifolds. To develop a chemical entity, a lot of money, hard work and time are required. Hence, focus is rather being laid on the development of new drug delivery systems for already existing drugs, with enhanced efficacy and bioavailability, thus reducing the dose and dosing frequency to minimize the side effects.^[2] It is always the aim of a scientist or a dosage form designer to enhance the safety of a drug molecule while maintaining its therapeutic efficacy. Recent advances in Novel Drug Delivery Systems (NDDS) aim for the same by formulating a dosage form, convenient to be administered so as to achieve better patient compliance.^[3] Pharmaceutical technologists have put in their best-efforts to develop a Fast Dissolving Drug Delivery System i.e. Mouth Dissolving Tablet (It is a tablet that disintegrates and dissolves rapidly in the saliva, within a few seconds without the need of drinking water or chewing). A mouth dissolving tablet usually dissolves in the oral cavity within 15 sec to 3 min. Most of the MDTs include certain super disintegrants and taste masking agents.^[4]

Diabetes  Mellitus  (DM)  is  a  group  of  syndromes  and  chronic  metabolic  disorder characterized  by  hyperglycemia,  altered  metabolism  of  lipids,  carbohydrates  and proteins  because of a lack of or ineffective use of the  hormone insulin and associated with  reduced  life  expectancy,  significant  morbidity  due  to  specific  diabetes  related micro vascular complications and diminished quality of life. A fasting blood glucose level of 126 mg/dl and 200 mg/dl post prandial (oral Glucose load) is considered as indication of DM.^[5] In present work, an investigation was made to use crospovidone and sodium starch glycolate, Croscarmellose sodium as superdisintegrants in the design of mouth dissolving tablets.

MATERIALS AND METHODS

FTIR studies
It was performed to know the compatibility between pure drug and excipients used in the formulation development. The physicochemical compatibility between the PGTZN and excipients was carried out by using Perkin Elmer Fourier Transform Infra Red spectrophotometer, Shelton USA. KBr disc method was employed and the samples were scanned from 4000 cm^-1 to 400 cm^-1. An obtained IR spectrum of pure drug was compared with the IR spectra of its physical mixtures to know the chemical interactions between drug and excipients used in the formulation.^[6]

Preparation of PGTZN MDTs by direct compression method
Tablets containing 15 mg of PGTZN were prepared by direct compression method and the various formulae used in this study are shown in table 1. The drug and diluents were passed through sieve on 40. All the above ingredients were properly mixed together (in a poly-bag). Talc and magnesium stearate were passed through mesh number 80, mixed well and blended with initial mixture in a poly-bag followed by compression of the blend using Rotary tablet punching machine, station 10, Elite scientific and equipment, India.

Preparation of PGTZN MDTs by wet granulation method
Tablets containing 15 mg of PGTZN were prepared by wet granulation method and the various formulae used in the study are shown in the table 1. The drug and diluent were passed through sieve no 12 and all the above ingredients were properly mixed together (in a poly-bag). Talc and magnesium stearate were passed through mesh number 80, mixed well and blended with intial mixture in a poly-bag followed by compression of the blend using Rotary tablet punching machine, station 10, Elite scientific and equipment, India.

Table 1. Preparation of PGTZN MDTs

Evalution of tablets

Determination of precompression characteristics
The precompression parameters like Angle of repose,^[7] Carr’s Index, Hausner’s ratio, Dispersibility^[8] and Porosity (Ø)^[9] were performed to know the powder characteristics.

Determination of post compression characteristics
The post compression parameters like thickness, friability,^[10] hardness, weight variation,^[11] disintegration time,^[12] wetting time^[2] and drug content ^[13] were evaluated for the formulated tablets.

Dissolution studies
The release rate of PGTZN was determined by using USP dissolution apparatus type-II (Paddle) (Electro Lab TDT-06N USP dissolution apparatus, India). 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. Sample solution was filtered, drug content of the filtrate was determined spectrophotometrically.

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RESULTS AND DISCUSSION
MDTs of PGTZN were formulated by wet granulation and direct compression methods using Croscarmellose, Crospovidone and Sodium starch glycolate as disintegrating agents, microcrystalline cellulose and lactose as diluents. The PGTZN and sulfonylurea are given in combination for treatment of type-2 Diabetes mellitus for long term therapy. During this therapy, it is observed that there is uncontrolled increase of blood glucose level due to the hepatic metabolism of drugs. Therefore, MDTs of PGTZN were prepared to overcome this unusual problem i.e, to protect the drug from gastric secretion and enhance the absorption.^[5]

FTIR studies
The IR spectrum of pure drug and its physical mixture were studied. The characteristic absorption peaks of PGTZN like N-H str, C-H str, C-O Str and C-H ben were obtained at wave numbers 3474.20 cm^-1, 3085.05 cm^-1, 1149.01 cm^-1, 849.66 cm^-1 respectively and also those peaks were observed in IR spectra of physical mixtures (Figure 1). Hence, it indicates there were no chemical interactions between the pure drug and its physical mixture.

Figure 1. FTIR studies. A) IR spectra of pure drug, B) IR spectra of physical mixture

Precompression studies
The powder blends have the bulk density ranged from 0.290 to 0.456 and tapped density from 0.330 to 0.569. The compressibility index values less than 10, 11-15, 16-20, 21-25, 26-31, 32-37 and greater than 38 indicates excellent, good, fair, possible, poor, very poor and very very poor flow respectively and powder blends of all the formulations were found to be possessing the excellent to fair flowability i.e. 5.1 to 18.18 %. The ideal Hausner’s ratio values of 1.0-1.11, 1.12-1.18, 1.19-1.25, 1.26-1.34, 1.35-1.45, 1.46-1.59 and greater 1.60 indicates excellent, good, fair, possible, poor, very poor and very very poor flow respectively and powder blends of all the formulations were found to be possessing the excellent to fair flowability i.e. 1.05 to 1.22. The ideal angle of repose values of less than 25, 25-30, 30-40 and greater than 40 indicates excellent, good, passable and very poor respectively and the experimental values of all the formulations were ranged from 27.92º to 37.59º indicates good to passable flowability. Powder blend also showed acceptable dispersibility and porosity results (Table 2).

Table 2. Precompression Parameters

Disintegration time
The most important parameter that is need to be optimized during the development of  MDTs is disintegrating time of tablets (Table 3). The disintegration test of the tablets was conducted in pH 6.8 phosphate buffer and showed disintegration time from 22 to 32 sec. However, disintegration time of the tablets prepared with of superdisintegrants (1:1) is in the acceptable range with no much deviation due to the combinational effect of super disintegrant mixture. Comparatively, the disintegration time of the prepared tablets are in the order as F15<F8<F11<F9<F10<F13=F5 <F14<F7<F12<F6=F4=F2<F1.

Wetting time
Wetting time of tablets containing the mixture of superdisintegrants (1:1) with various concentrations are in the range of 11-24 sec (Table 3). Usually the crospovidone having the low swelling rate has also showed the fast wetting effect due to the combinational effect of superdisintegrants. This is also due to the synergistic effect of crospovidone along with other superdisintegrants will modify the wetting property of crospovidone and formulations prepared with the mixture of it. It was observed that there was no significant change in the wetting time with increase in the concentration of superdisintegrants mixture and however, the formulations with mixture of superdisintegrants like Croscarmellose sodium and Sodium starch glycolate showed least disintegration time. The wetting of tablets are in the following order F15<F8<F10=F11<F9<F13 <F14<F7<F5<F12<F6<F4<F3<F1<F2.

Table 3. Evaluation of post compression parameters

Table 4.  In-vitro dissolution profiles of PGTZN MDTs

REFERENCES
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