Analysis of the Release Process of Phenylpropanolamine Hydrochloride from Ethylcellulose Matrix Granules III. Effects of the Dissolution Condition on the Release Process

Abstract

Controlled drug release is a topic of much interest and it is important to understand the properties of drug release and the entire release process.2) The release properties of the matrix system were mathematically treated by Higuchi,3) and matrix systems have often been used as a method of controlled drug release. However, it was thought that the mathematical analysis of the release process was insufficient, and the entire release process could not be explained. 1,4) In previous papers, the release process was divided into two stages to understand the entire release process and these were analyzed by the square-root time law and cube-root law equations. 1,4) The validity of the analysis was confirmed by simulating the release process.In vitro drug dissolution studies are most useful for monitoring drug product stability, manufacturing process control and also predicting the release process in the human body. 5)One method for identifying formulation factors that affect drug bioavailability is the dissolution test, 6) which is very important and necessary to predict the controlled release process. There are many individual practices that differ from person to person. In particular, the status of the human stomach is thought to decide the properties of drug release in the body. Thus, considering the motion and volume of the stomach, the dissolution test was applied, changing some conditions such as volume, rotation speed, pH, and the drug amount.In this paper, following the Japanese Drug Approval and Licensing Procedures for the dissolution test, release measurements were carried out under various conditions to examine their effects on release properties. 7) Usually, the results are analyzed at any 3 time points with release ratios of 0.2-0.4, 0.4-0.6, and over 0.7, following the guidelines.7) This method is very simple and useful but it is not able to confirm detailed drug release properties. Accordingly, the results of the dissolution test were analyzed using both methods, i.e., the method following the guidelines and the previously reported analysis method using a combination of the squareroot time law and cube-root law equations to examine their practical use. Their validity and utility were subsequently compared and confirmed. Experimental MaterialsThe materials described in the previous paper were used. 1,4)Phenylpropanolamine hydrochloride (Powder, Alps Pharmaceutical Ind. Co., Ltd., Gifu, Japan: (PPA)), ethylcellulose 10 cps (ETHOCEL STD 10 cps, DOW Chemical, Tokyo, Japan: (EC)), and ethanol (Wako Pure Chemical Industries, Ltd., Osaka, Japan: (EtOH)) were used. Equipment The equipment described in the previous paper was used. 1,4)A high shear granulator (High Speed Mixer, LFS-GS-5, volume 5.0 l, Fukae Ind. Co., Ltd., Hyogo, Japan), extrusion granulator (Granulator machine type of LAB, KAR-130, Tsutsui Physics and Chemistry Apparatus Co., Ltd., Tokyo, Japan) were used for granulation. The granules were ground using a speed mill (D-30-4560, Showa Engineering Co., Ltd., Tokyo, Japan). Preparation of Matrix Gr...

Analysis of the Release Process of Phenylpropanolamine Hydrochloride from Ethylcellulose Matrix Granules V. Release Properties of Ethylcellulose Layered Matrix Granules

“…[1][2][3][4][5] It was confirmed in previous papers that ethylcellulose (EC) matrix granules and EC layered granules showed similar release properties. 1) There are many methods for the preparation of layered granules.…”

“…[1][2][3][4] Following the previously reported methods, 1-4) the release process could be divided into two stages. In the initial stage, PPA was released from the gel layer of swollen EC.…”

“…[1][2][3][4] Phenylpropanolamine hydrochloride (PPA) (Powder, Alps Pharmaceutical Ind. Co., Ltd., Gifu), ethylcellulose 10 cps (EC) (ETHOCEL STD 10 cps, DOW Chemical, Tokyo), Nonpalel 103 (NP) (Sugar cubes, Freund Industrial…”

“…Equipment The equipment described in the previous paper was used. [1][2][3][4] Preparation by a high shear granulator (High Speed Mixer, LFS-GS-5, volume 5.0 l, Fukae Ind. Co., Ltd., Hyogo) was abbreviated as method B, and preparation by a fluidized bed with rotor disk granulator (SPIR-A-FLOW, SFC-MINI, Freund Industrial Co., Ltd., Tokyo) was abbreviated as method C, and were used for granulation.…”

“…Because the equation can not explain the entire release process. [1][2][3][4] In previous papers, the release process could be divided into two stages to understand the entire release process and these were analyzed using a combination of the square-root time law and cuberoot law equations. [1][2][3][4] Then, it was concluded that predicting drug release properties using this analysis method was useful.…”