HYDROPHILIC VEHICLE-BASED DUAL CONTROLLED RELEASE MATRIX SYSTEM

摘要

A hydrophilic vehicle-based dual controlled-release matrix system, suitable for encapsulation in hard or soft capsules, has been developed. The matrix is in the form of a solution or a suspension, which allows for easier formulation of low dose compounds. The matrix includes two rate controlling barriers for the controlled release of one or more pharmaceutically active agents. The primary rate controlling barrier includes a hydrophilic vehicle, such as a combination of high molecular weight and low molecular weight polyethylene glycols. The primary rate controlling barrier can further comprise one or more solvents which are miscible with the hydrophilic vehicle. The secondary rate controlling barrier includes a hydrogel-forming polymeric material dissolved or dispersed in the hydrophilic vehicle. Formation of the hydrogel can occur during drying when water migrates from the shell into the fill or upon dissolution of the capsule shell as the surrounding aqueous media comes into contact with the matrix. Polymer hydration and the subsequent swelling of the polymeric material controls release of the drug by diffusion through, and/or erosion of, the hydrogel. This system allows for the formation of a clear controlled release liquigel for drugs that are soluble in hydrophilic media. Judicious selection of the qualitative and quantitative composition of the polymer matrix allows one to modulate the release profile of the drug, including a biphasic drug release profile, for up to 24 hours. The presence of the hydrogel-forming polymeric material, which forms a hydrogel upon contact with an aqueous solution, thus trapping the drug, makes extraction of the drug from the dosage form more difficult. This feature could be beneficial in preventing or minimizing the misuse of dosage forms which contain drugs which are prone to abuse.