Noncross-linked and cross-linked ampholytic polymers for controlled release carriers.

摘要

Modern design of controlled release delivery systems deviates from the use of standard polymeric materials available and concentrates on development of novel biopolymers. In this study, new synthetic linear and cross-linked ampholytic polyelectrolytes consisting of tertiary amine and carboxylic acids were synthesized. The noncross-linked (linear) polymers endowed with swellable/erodible characteristics were evaluated as matrix controlled carriers by compressing tablets weighing (600 ± 3%) mg containing different drugs and loading levels. The drug dissolution studies were carried out at pH 1.5 and 7 buffer solutions separately using USP apparatus 1 (basket) method at 100-rpm. The drugs, representing a wide range of solubility and chemical types showed a unique pH dependent and buffer strength independent linear release. Besides the swelling and erosion processes, interactions between the drug and the polymer functionalities play a major role in prolonging release kinetics of drugs. The linearity of release profiles and the diffusional exponent n, an important indicator of release mechanism, were determined mathematically. The initial or early time release showed a burst effect or lag time depending on the drug solubility and loading level. A highly desirable range of values was obtained for exponent n. Several other contributing factors affecting the drug release such as copolymer composition, buffer composition, nature of drug, loading, and hydrodynamic condition were investigated. The copolymers were identified using elemental analysis, differential scanning calorimetry (DSC), FTIR, and aqueous gel permeation chromatography. FTIR and DSC studies performed on copolymer and copolymer-drug combinations supported the interactions between drug-polymer functionalities that lead to linear release kinetics.; The cross-linked copolymers were investigated based on the theory of ion exchange. The equilibrium swelling behavior of these copolymers were evaluated at different pHs and ionic strengths. A number of anionic drugs were loaded on to the polymer disks and then the in-vitro release studies were carried out at pH 1.5 and 7 buffer solutions by using USP apparatus 2 (paddle) method at 100-rpm. The release profiles exhibited a composition dependent initial burst. There is a limiting compositional dependence of pH independent drug release from the copolymer disks. DSC studies confirmed the complexation of drug and the polymer during drug loading process.