Hidetoshi Horibe

Novel oral controlled-release microspheres using polyglycerol esters of fatty acids

Abstract A novel oral controlled-release drug delivery system which consists of microspheres of 75–500 μm in diameter has been designed and developed. A drug is dispersed in a spherical micromatrix of poly-glycerol esters of fatty acids (PGEFs). The microspheres were prepared by a spray-chilling method using a rotating disc and had a narrow particle size distribution. A required size could easily be obtained by altering the spray conditions. In the in vitro dissolution tests, drug release was found to be affected by the size of the microspheres and the drug content in the microspheres. However, release of the drug could be regulated by selecting an appropriate hydrophile-lipophile balance value of PGEF. PGEF-based micromatrix system could provide stable controlled release, i.e., the surface morphology and the release profiles did not change during a long storage period at 40°C while the surface morphology and the release profiles changed after only one-day storage at 40°C when hydrogenated cotton seed oil (HSCS) was used as the matrix base.

Anti-hypertensive effect of oral controlled-release microspheres containing an ACE inhibitor (Delapril hydrochloride) in rats

Abstract— An oral controlled‐release drug delivery system based on microspheres of polyglycerol esters of fatty acids (PGEFs), was applied to an anti‐hypertensive, delapril hydrochloride. The in‐vitro release profile was controlled by selecting a PGEF with an appropriate hydrophilic‐lipophilic balance value for the matrix. The microspheres from which 80% of the drug was released in 6 h were orally administered to rats. The plasma concentration of the active metabolite was sustained after administration of the microspheres in comparison with administration of a solution. The in‐vivo release profile was in good agreement with the in‐vitro release profile. When the microspheres were administered, the pharmacological effect of delapril hydrochloride on the angiotensin I‐induced pressor response was also sustained showing consistency with the plasma concentration‐time curve.