Microencapsulation of the renin inhibitor FK906 by phase separation of ethylcellulose in cyclohexane

Abstract

Microencapsulation of the renin inhibitor FK906 (tripeptide) by phase separation of ethylcellulose in cyclohexane was performed to obtain sustained release of the drug for a once-a-day application. Owing to the binding characteristics and to the very low solubility of FK906 in cyclohexane, microencapsulation can be performed after granulation of the drug with an inert filler, and no additional binder is required. Microcapsules with a particle size of 180–590 μm are obtained in a yield of 70%). Drug content determinations and SEM-micrographs reveal the almost complete incorporation of the polymer for the coating and the high quality of the microcapsule wall. Despite the strongly pH-dependent solubility of FK906 (HCl) in water, the microcapsules show almost identical sustained-release curves at pH 1.2 and 6.0 (0.05M phosphate buffer). This is explained by an acidic microenvironment inside the microcapsules at both pHs investigated and was attributed to the intrinsic physico-chemical properties of FK906 which help to overcome the buffer capacity of the phosphate buffer, pH 6.0, inside the microcapsules. This theory was confirmed by solubility experiments at pH 6.0 using excess amounts of FK906 as well as by dissolution tests as a function of the buffer capacity and the osmolality of the dissolution medium. The buffer capacity was found to be the parameter with greater influence on the release rate.

Key Words:

• Renin inhibitor
• phase separation
• sustained release
• microencapsulation
• ethylcellulose