Examination of drug solubility, polymer types, hydrodynamics and loading dose on drug release behavior from a triple-layer asymmetric configuration delivery system

Abstract

The significance of factors such as drug solubility, polymer molecular weight, drug loading and hydrodynamic conditions on drug release from a swellable triple layer asymmetric configuration delivery system is investigated. Poly(ethylene oxide) (PEO) of various molecular weights and hydroxypropylmethyl cellulose (HPMC) were major polymeric constituents of the delivery system. Theophylline, propranolol hydrochloride and diltiazem hydrochloride with water solubilities of <1, 5 and >50%, respectively, were used as drug models. The triple-layer delivery system was produced by compressing particulate systems on a laboratory Carver press with a 10-mm diameter punch and die. Results show that due to the geometry, system design and maintenance of constant surface area linear release kinetics are achievable. Increase in drug solubility expedites drug release rate and shortens duration of release; while increase in polymer molecular weight results in reduction of release rate and prolongation of release period. Drug loading does not seem to affect the release behavior significantly even though a freely water-soluble drug such as diltiazem hydrochloride was employed. In addition, with an increase in stirring rate there was a corresponding increase in release rate, while linearity of release profile remained unaltered. Results further indicate that, as long as surface area is controlled, front synchronization is not a prerequisite for achieving zero-order release kinetics. Moreover, from a pharmaceutical perspective, the complex behavior of release mechanisms for different drugs in relation to matrix erosion, polymer swelling capacity and system design is explained.