Effect of gel strength on drug release from swellable matrices through polymer erosion.

摘要

Swellable matrix tablets have been used extensively in oral controlled drug delivery systems. Upon contact with aqueous medium, water diffuses into the matrix and the glassy polymer begins to undergo a glassy-to-gel transition to form a viscous mucilaginous gel layer; a diffusional barrier that retards further ingress of water and acts as a rate-controlling barrier to drug release. Gel strength has been argued as a key attribute that influences the resultant drug dissolution. Yet, no systemic work has been done to correlate the gel strength and drug release and no tool is available for routine tests of gel strength. Therefore, the focus of this thesis is to study how gel strength affects drug release from swellable hydrophilic matrices through influencing polymer erosion. Hydroxypropyl methylcellulose (HPMC) was the model polymer used in this study.; We first developed a method of using Texture Analyzer to characterize polymer gel strength. Using the above method, the effects of some formulation related variables, such as polymer viscosity/molecular weight and concentration, and excipient types (lactose and Starch 1500) on the strength of both homogeneous HPMC gels and HPMC swelling tablets were studied. Gel strength increased with both polymer molecular weight and concentration; and Starch 1500 was found to be a gel-strength enhancing agent, while lactose had no effect. Texture Analyzer was also used to delineate the structure of swollen HPMC tablets. Profiles of gel strength, gel layer thickness and polymer concentration in the gel layer were obtained and the latter two results were found to be in agreement with previous ones obtained using more sophisticated techniques in the literature.; A mathematical model was constructed and validated to correlate gel strength and polymer erosion, and was used to study the effect of polymer molecular weight, excipient type and/or content on polymer erosion. HPMC erosion rate decreased with molecular weight, quantitatively in agreement with the model prediction. Addition of Starch 1500 decreased the erosion of HPMC matrix, while lactose had no effect. A case study of drug release from Depakote ER RTM tablets in different medium demonstrated the direct correlation of gel strength and drug release through polymer erosion.