Use of Buffers in Matrix Capsule Formulations

Abstract

Relatively few reports have appeared in the literature on the formulation of the hydrophilic matrix capsule as compared to the matrix tablet. This study was concerned with the development of a matrix capsule formulation to control the release rate of the drug specifically through the incorporation of buffers. One of the characteristics of hydrophylic matrix drug delivery systems is that the initial rate of release is high. The release rate is gradually brought under control as the diffusional barrier of hydrating polymers is established. Many weak bases are more soluble at a gastric pH than at neutrality. Such drugs are generally unsuitable for matrix systems since constant rates of drug release under the dynamic conditions of increasing pH make release rate control difficult. However, by using an appropriate buffer system it was possible to suppress the initial release in acid by decreasing the solubility of the drug within the environment of the capsule matrix thereby controlling the rate of drug release. A buffered matrix capsule of an investigational drug was administered to normal healthy subjects in order to examine if a sustained plasma profile could be achieved. The absorption rate of the drug was calculated according to the Wagner-Nelson method. A dissolution test method was developed which correlated well with the in vivo data by selecting appropriate buffers and agitation rates. Capsule formulations exhibiting several different release rates between 6 and 24 hours were then prepared. The dissolution test conditions used for the drug release study were based upon the in vivo - in vitro correlation.