Correlation between the bioavailability of microencapsulated bacampicillin hydrochloride in suspension and in vitro microcapsule dissolution.
The relative bioavailability of microencapsulated bacampicillin hydrochloride in suspension was correlated with the in vitro dissolution half-lives of the microcapsules. Simultaneously, a sensory evaluation was performed to evaluate the taste acceptability of the suspension. The in vitro dissolution half-life is directly related to the coating thickness of the microcapsules. The four suspensions of bacampicillin hydrochloride, containing microcapsules with different coating thickness, were given as single 400-mg oral doses to 12 healthy volunteers after overnight fasting using a crossover design with balanced sequences. Bacampicillin is a prodrug of ampicillin, the concentration of which was determined in plasma and urine by bioassay. There were significant inverse linear relationships between the dissolution half-life and plasma peak concentration, area under the curve, and urinary recovery. The terminal exponential disposition phases of the curves were similar for all four suspensions. There was a significant direct linear relationship between the dissolution half-life and overall taste and bitterness. The results show that the mean bioavailability of bacampicillin hydrochloride from a microcapsule suspension can be predicted from an in vitro dissolution half-life. The results also suggest that bacampicillin hydrochloride can be given in a suspension with sufficient microcapsule film thickness to reduce the bitter taste of the drug and still retain adequate bioavailability.
D000328:Adult; D000667:Ampicillin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D001682:Biological Availability; D002214:Capsules; D005260:Female; D006207:Half-Life; D006801:Humans; D007408:Intestinal Absorption; D007700:Kinetics; D008297:Male; D012995:Solubility; D013535:Suspensions
D002214:Capsules; D013535:Suspensions; D000667:Ampicillin; C011674:bacampicillin