Aqueous ethyl cellulose dispersions containing plasticizers of different water solubility and hydroxypropyl methylcellulose as coating material for diffusion pellets: I. Drug release rates from coated pellets

• Published in: International journal of pharmaceutics 1999-01, Vol.177 (1), p.69-82
• Main Authors: Frohoff-Hülsmann, Maria A., Schmitz, Annemarie, Lippold, Bernhard C.
• Format: Article
• Language: English
• Subjects: Aqueous ethyl cellulose dispersion; Biological and medical sciences; Cellulose - analogs & derivatives; Cellulose - chemistry; Curing; Drug Implants; General pharmacology; Hydroxypropyl methylcellulose; Lactose - analogs & derivatives; Medical sciences; Methylcellulose - analogs & derivatives; Osmolar Concentration; Oxazines; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Plasticizers - chemistry; Plasticizers - pharmacokinetics; Plasticizers of different water solubility; Release mechanism; Release stability; Solubility; Tablets, Enteric-Coated - pharmacokinetics; Temperature; Theophylline - pharmacokinetics; Water
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/S0378-5173(98)00327-5

The present work investigates release mechanisms of theophylline pellets coated with an aqueous ethyl cellulose (EC) dispersion containing plasticizers and hydroxypropyl methylcellulose (HPMC) as a water soluble pore former. Three different drug release mechanisms from coated pellets can be determined as a function of the water solubility of the plasticizers and the ionic strength of the release medium. Coated pellets with the addition of more hydrophilic plasticizers such as triethyl citrate (TEC) or diethyl phthalate (DEP) show an approximate zero-order-release rate. In contrast, two-phase release profiles can be observed from pellets coated with dispersions containing hardly soluble plasticizers such as dibutyl phthalate (DBP) or dibutyl sebacate (DBS). Only in a release medium of high ionic strength the water soluble pore former will remain in the coating. Thus the drug diffuses through a hydrated swollen membrane containing EC, HPMC and insoluble plasticizer. The release mechanisms depend on the glass transition temperature of the ethyl cellulose and therefore on the migration of the plasticizers and the pore former. This was shown by investigation of the migration of the additives and the influence of the temperature of the release medium on the release. Additionally, the study investigates the effect of curing and storage conditions of coated pellets on the drug release rate.