PH-CONTROLLED SILICONE MICROSPHERES FOR CONTROLLED DRUG-DELIVERY

Several types of controlled drug release microspheres has been develop ed. In this study, we describe a new type of microspheres that control drug release with changing inner core pH. In the microspheres, micron ized model drug, timolol maleate and pH adjusting agents (mono, di, an d trisodium phosphate or Tris buffer) were either dry blended by mixin g or coprecipitated by spray drying, and encapsulated in X7-3012 silic one microspheres using emulsion vulcanization technique. Upon water in flux into microspheres, buffer dissolves and adjusts the inner pH. Thu s, the fraction of unionized drug is increased by higher pH and, conse quently, 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 resis tant silicone elastomer could be used to make microspheres incorporati ng up to 30 wt% of solid particles. Typical size range of the pH-contr olled microspheres was 150-200 mu m Timolol release from the microsphe res followed square root of time kinetics, and it was proportional to wt% loading level of drug in the micromatrices. In vitro release of ti molol from microspheres can be controlled over a wide range of rates b y selecting a suitable pH adjusting agent and by varying its amount in the microspheres. Spray drying of the drug and buffer together was th e most effective in controlling the drug release since, in this case, buffer was in the same microcompartment inside silicone and thus buffe ring effect was maximal. Drug release from pH-controlled microspheres was independent of pH of dissolution medium.