Gelatin-acacia microcapsules for trapping micro oil droplets containing lipophilic drugs and ready disintegration in the gastrointestinal tract.
Nonhardened gelatin-acacia microcapsules were studied for encapsulation of microdroplets of oil solution containing a lipophilic drug as core material and ready disintegration with release of micro oil droplets in the gastrointestinal tract. Probucol and S-312-d, a Ca-channel blocker, were employed as model lipophilic drugs. Glyceryl tricaprylate and tricaprate mixture solutions containing these drugs were encapsulated according to the complex coacervation method and were recovered as free-flowing powders without any hardening (cross-linking) step. The microcapsules obtained were disintegrated, and the emulsion was reproduced within 3 min at 37 degrees C in the first or second test solution defined in the Japanese Pharmacopeia XII. When the microcapsules were stored as a powder at room temperature in a closed bottle, no significant change in their appearance or disintegration time upon rehydration was observed even after 1 year. Oral bioavailabilities of model drugs from the microcapsules were tested in rats and dogs and compared with those from other conventional formulations. Gastrointestinal absorption of both probucol and S-312-d from the microcapsules was remarkably more efficient than that from other formulations such as powders, granules, or oil solution. The proposed method for microencapsulation could be useful for powdering drug-containing oil solutions or O/W emulsions while maintaining excellent bioavailability.
Jizomoto
H
H
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Kanaoka
E
E
Sugita
K
K
Hirano
K
K
D000045:Acacia / Q000737:chemistry*; D000818:Animals; D001682:Biological Availability; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000097:blood; D002214:Capsules; D002851:Chromatography, High Pressure Liquid; D004064:Digestive System / Q000378:metabolism*; D004095:Dihydropyridines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D004285:Dogs; D004355:Drug Stability; D004655:Emulsions; D005780:Gelatin / Q000737:chemistry*; D008297:Male; D009821:Oils / Q000737:chemistry*; D011208:Powders; D011341:Probucol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet
D002121:Calcium Channel Blockers; D002214:Capsules; D004095:Dihydropyridines; D004655:Emulsions; D009821:Oils; D011208:Powders; C059447:S 312; D005780:Gelatin; D011341:Probucol