Modifying the Diffusion Layer of Soluble Salts of Poorly Soluble Basic Drugs To Improve Dissolution Performance

被引：44

作者：

Hawley, Michael ^{[1
]}

Morozowich, Walter ^{[1
]}

机构：

[1] Pfizer Inc, Groton, CT 06340 USA

来源：

MOLECULAR PHARMACEUTICS | 2010年 / 7卷 / 05期

关键词：

Dissolution; precipitation; supersaturation; salts; diffusion layer; UNBUFFERED CONDITIONS; DELAVIRDINE MESYLATE; FORMS; MODEL; PH; FORMULATION; INHIBITION; HYDROLYSIS; SOLUBILITY; ABSORPTION;

D O I：

10.1021/mp100117k

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

The dissolution mechanism of soluble salts of poorly soluble bases can be complex because both the dissolution of the salt and precipitation of the free base can occur depending on the experimental conditions and properties of the molecule. The dissolution of three soluble salts of poorly soluble bases is described in this paper. Two of these compounds precipitate as free base under normal stomach pH conditions (pH from 2-4) during dissolution. This free base precipitation is a result of formation of free base on the surface of the dissolving salt. Diffusion Layer modulated (DLM) solids are defined and presented that can effectively counteract this precipitation mechanism. These DLM materials employ excipients in order to modify the pH or solubility conditions at the surface of the dissolving salt to minimize precipitation of the free base that can occur. Rotating disk dissolution data is presented which shows how these formulated solids can act to improve the dissolution profile for these materials.

引用

页码：1441 / 1449

页数：9

共 27 条

[1]

Adams W J, 1998, Pharm Biotechnol, V11, P285

[2]

AGUIRREODE F, 1987, J CHEM EDUC, V64, P957

[3] AN APPROACH FOR THE PREDICTION OF THE INTRINSIC DISSOLUTION RATES OF DRUGS UNDER UNBUFFERED CONDITIONS [J].