Application of the Solid Dispersion Method to the Controlled Release of Medicine. VII. Release Mechanism of a Highly Water-Soluble Medicine from Solid Dispersion with Different Molecular Weights of Polymer

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Solid dispersion films were prepared with a highly water-soluble medicine (oxprenolol hydrochloride (OXP)), four grades of water-insoluble ethylcellulose (EC) having different molecular weights and water-soluble hydroxypropyl cellulose (HPC). The internal structure of the solid dispersion films and the penetration of the dissolution medium into the films were studied to clarify the mechanism of OXP release from the OXP-EC and OXP-EC-HPC solid dispersion systems having various molecular weights of EC.In the OXP-EC system, the release rate of OXP slightly decreased with increasing molecular weight of EC and the mechanism of OXP release was hardly affected by the molecular weight of EC. In the OXP-EC-HPC system, the release rate of OXP markedly decreased with increasing molecular weight of EC. When EC with the lowest molecular weight of the four grades was used, the same mechanism of OXP release was observed as in the OXP-EC system, but it was clear that OXP was released from the films with the two higher-molecular-weight grades of EC through a diffusion-controlled release mechanism. This result can be explained in terms of diffusion of OXP through the quasi-equilibrium swollen gel region formed by rapid hydration of HPC with water penetrating into the solid dispersion film.
公益社団法人日本薬学会の論文
1995-04-15