Enhancement of bioavailability of a hydrophobic amine antimalarial by formulation with oleic acid in a soft gelatin capsule.
The relative availability of the orally administered hydrophobic antimalarial alpha-(dibutylaminomethyl)-6,8-dichloro-2-(3',4'-dichlorophenyl)-4-quinolinemethanol (I) from two dosage forms was determined in beagle dogs. Compound I was soluble in oleic acid to the extent of 23.5% (w/w), and oleic acid was suitable for encapsulation in soft gelatin capsules. The availability of I formulated as its hydrochloride salt in a standard hard gelatin capsule formulation was significantly lower than that of I formulated in a soft gelatin capsule with oleic acid as the solvent. A 20% solution of I in oleic acid (soft gelatin capsules) maintained at 23 degrees provided 4% of the oleic acid ester of I iwithin 1 month. Further reaction, however, was not seen over 2 years.
D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000378:metabolism*; D001682:Biological Availability; D002214:Capsules; D002626:Chemistry, Pharmaceutical; D004285:Dogs; D004355:Drug Stability; D005260:Female; D007408:Intestinal Absorption; D008297:Male; D009829:Oleic Acids; D011804:Quinolines / Q000008:administration & dosage / Q000378:metabolism*; D012995:Solubility
D000962:Antimalarials; D002214:Capsules; D009829:Oleic Acids; D011804:Quinolines; C006292:WR 30090