Formulation development and characterization of highly water-soluble drug-loaded extended-release pellets prepared by extrusion–spheronization technique

Abstract

The objectives of current study were (a) to prepare extended-release plain (without polymers) and matrix pellets of itopride hydrochloride (ITP) by extrusion and spheronization technique, (b) to control the initial fast release of drug from the matrix pellets by coating using ethylcellulose, Eudragit® RL/RS100 (2:1), and Kollicoat® SR 30D, and (c) to investigate the influence of different types and concentration of coating polymers on release of highly water-soluble drug. The plain pellet contained microcrystalline cellulose and lactose without polymer, whereas matrix pellet formulations were composed of hydroxypropyl methylcellulose (HPMC K4M, K15M, and K100M) and ethylcellulose (EC 7 cps). Matrix pellet formulations failed to control the drug release, up to targeted period of 12 h. Five pellet formulations—one without polymer (F1) and one from each polymer category (F4, F7, F10, and F13)—were screened out for coating using different types and levels of polymers. The DDSolver (an add-in software for MS Excel) was used to analyze the dissolution profile data for drug release kinetics. However, drug release from pellet formulation (F7) containing HPMC as a matrix former and coated with EC followed zero-order kinetics (R2 = 0.897–0.998). The release mechanism of EC-coated formulations F7, F10, and F13 was non-Fickian diffusion (anomalous transport), whereas F1 and F4 were Fickian diffusion mechanism. The stability studies of all 5% EC-coated ITP pellet formulations were conducted at room and accelerated temperature as per ICH guidelines, and results were found satisfactory. It is concluded that ethylcellulose other than Eudragit® RL/RS100 (2:1) and Kollicoat® SR 30D was found to be an excellent release controlling agent for ITP which showed good controlled-release characteristics.