Release of highly water-soluble medicinal compounds from inert, heterogeneous matrixes. I: Physical mixture

✍ Scribed by Todd P. Foster; Eugene L. Parrott

• Book ID: 102918453
• Publisher: John Wiley and Sons
• Year: 1990
• Tongue: English
• Weight: 501 KB
• Volume: 79
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.2600790913

✦ Synopsis

The release from a matrix compressed from a physical mixture of hydrogenated castor oil and ephedrine hydrochloride or procaine hydrochloride has been investigated. The effects on release of the concentration of medicinal compound, particle size of medicinal compound, agitation of dissolution medium, and porosity and tortuosity of the matrix are presented. An attempt is made to fit the experimental data to an acceptable diffusion model.

A method of obtaining a sustained-release product is to embed or disperse the solid medicinal compound in a n insoluble matrix. Insoluble matrixes may be prepared by compression of (1) a congealed mixture of the medicinal compound and waxy or polymeric material which had been melted, cooled, and milled, or (2) a physical mixture of the medicinal compound and waxy or polymeric material. Release of the medicinal compound occurs as the water penetrates the matrix and dissolves the medicinal compound, and the dissolved medicinal compound diffuses out into the bulk solution.

The release of the medicinal compound from a planar surface of an insoluble, heterogeneous matrix by diffusion through the intergranular openings created by the porosity of the matrix was described by the Higuchi square root equation:l where Q is the quantity of medicinal compound released per unit area at time t, D is the diffusivity of the medicinal compound in the dissolution medium, E is the porosity of the matrix, C, is the solubility of the medicinal compound in the dissolution medium, T i s the tortuosity of the matrix, and A is the concentration of the medicinal compound in the tablet, expressed as g/mL. It has been shown experimentally that eq