Crystallization and polymorphic transition behavior of chloramphenicol palmitate in 2-hydroxypropyl-beta-cyclodextrin matrix

Chloramphenicol palmitate (CPP) formed inclusion complexes with 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) in a molar ratio of 1:2 (guest/host) and the low solubility of CPP in water was significantly improved by the complexation. CPP was converted to an amorphous complex when spray-dried with HP-beta-CyD, and no crystallization of CPP was observed for at least 2 months under the storage condition of 50 degrees C and 50% relative humidity. On the other hand, a metastable form of CPP, Form subB, was predominantly formed by spray-drying in the absence of additives, and Form subB was easily converted to Form B with a half-life of 0.5 h under the above storage conditions. The dissolution rate of CPP/HP-beta-CyD complex in aqueous polyoxyethylene hydrogenated castor oil 60 (HCO-60) solution was much faster than CPP polymorphs, which was reflected in the in vivo absorption behavior of CPP following oral administration in dogs.