Combined dosage form of pioglitazone and felodipine as mucoadhesive pellets via hot melt extrusion for improved buccal delivery with application of quality by design approach

The content of investigation was to develop and optimize buccal hot melt extruded (HME) pellets for Pioglitazone (PIO) and Felodipine (FDP) in combined dosage form for the management of diabetes and hypertension using Box–Behnken design. In this study, three factors evaluated at three levels. Amount of PEON80 (A1), amount of HPMCK4M (A2) and amount of plasticizer (A3) as independent variables and bioadhesion strength (BS) (B1), erosion (B2) and percent drug release in 1 h Q1 (B3) as responses. Pellets were prepared by hot melt extrusion technique. HME pellets were evaluated for compatibility, physicochemical properties, ex vivo permeation, in vivo bioavailability in pigs and stability studies. Pellets demonstrated no drug excipient interaction and excellent content uniformity. Statistically optimized HME pellet showed BS of 2.92 ± 0.04 N, erosion of 10.5 ± 2.05% and percent drug release of 31.9 ± 2.1% and 29.2 ± 1.9% for PIO and FDP respectively. Statistically optimized pellet prolonged in vitro drug release of 96.6% PIO and 94.5% FDP release in 6 h and permeated 68.6 and 66.4% with flux of 0.372 and 0.361 mg h−1 cm−2 of PIO and FDP respectively through porcine buccal membrane. Statistically significant (p < 0.01) improvement in bioavailability was observed for PIO (1.9-folds) and FDP (2.1-folds). No significant changes were observed in 6 months during stability studies.

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