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Use of rabbits for absorption studies on polymorphs of chloramphenicol palmitate.

The α and β forms of chloramphenicol palmitate (CPP) crystals were successfully obtained in similar particle sizes by utilizing wet micronization. Comparisons of the absorbability of CPP suspensions of the above crystals using conventionally fasted rabbits were unsuccessful because of the low plasma level after dosing the β form (less than 1 μg/ml). Plasma levels were then compared by dosing CPP suspensions of the α and β forms to stomach-emptying-controlled (SE-controlled) rabbits in a crossover manner. Compartive absorption studies were also performed in the SE-controlled rabbits with a capsule form of CP and suspensions of CPP in the α and β forms. It was demonstrated that absorption occurred in the order CP>CPP (α form)>CPP (β form). The correlation between in vitro extent of hydrolysis and in vivo absorbability in terms of AUC is discussed. These results suggest that the SE-controlled rabbit is a very useful animal model for preliminary bioavailability studies on oral dosage forms for human clinical use.