pH-controlled silicone microspheres for controlled drug delivery

• Published in: Journal of controlled release Vol. 33; no. 1; pp. 163 - 171
• Main Authors: Sutinen, R., Laasanen, V., Paronen, P., Urtti, A.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 1995; Elsevier
• Subjects: Biological and medical sciences; Controlled release; General pharmacology; Medical sciences; Microspheres; pH-adjusting agents; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Silicone; Timolol; Microspheres; Timolol; Controlled release; pH-adjusting agents; Silicone; Microsphere; Controlled release form; Control release polymer; Dosage form; pH; Active ingredient; Siloxane polymer; Release
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/0168-3659(94)00080-E

Several types of controlled drug release microspheres has been developed. In this study, we describe a new type of microspheres that control drug release with changing inner core pH. In the microspheres, micronized model drug, timolol maleate and pH-adjusting agents (mono, di, and trisodium phosphate or Tris buffer) were either dry blended by mixing or coprecipitated by spray drying, and encapsulated in X7-3012 silicone microspheres using emulsion vulcanization technique. Upon water influx into microspheres, buffer dissolves and adjusts the inner pH. Thus, the fraction of unionized drug is increased by higher pH and, consequently, partition-driven release of basic drug from the microspheres is accelerated. Scanning electron micrographs showed that spray dried materials were completely encapsulated by the elastomer, and the drug was homogenously distributed in silicone micromatrices. An amine resistant silicone elastomer could be used to make microspheres incorporating up to 30 wt% of solid particles. Typical size range of the pH-controlled microspheres was 150–200 μm. Timolol release from the microspheres followed square root of time kinetics, and it was proportional to wt% loading level of drug in the micromatrices. In vitro release of timolol from microspheres can be controlled over a wide range of rates by selecting a suitable pH adjusting agent and by varying its amount in the microspheres. Spray drying of the drug and buffer together was the most effective in controlling the drug release since, in this case, buffer was in the same microcompartment inside silicone and thus buffering effect was maximal. Drug release from pH-controlled microspheres was independent of pH of dissolution medium.