METHOD OF EVALUATION OF SUSTAINED-RELEASE MICROSPHERE FORMULATIONS USING THE OPEN CHEMOSTAT SYSTEM

The sustained release of cephalexin (CPX) as the monohydrate and cipro floxacin (CFX) as the hydrochloride from separate 100 000 Mel. Wt poly (L-lactic acid) microspheres (250-425 mu m sieve size range) was evalu ated in an open chemostat system. Drug concentrations in pH 7.4 phosph ate buffer solution (PBS) reached peak levels which were sustained for different periods of time, depending on the flow rate of PBS at a con stant volume of 120 mi in the chemostat. At 0.46 ml/min flow rate CPX microspheres (33% w/w loading) sustained CPX concentrations for approx . 90 min (solubility = 40 mg/ml at pH 7.4, 37 degrees C) whereas CFX ( solubility = 5 mg/ml) was sustained for at least 6 h. Increasing drug loading increased peak levels of either antibiotic but decreased the s ustained period of CPX only. Decreasing microsphere size to 125-250 mu m increased CPX or CFX concentration levels and decreased the sustain ed period to about 45 min and 2 h, respectively. At higher doses, CFX was sustained at higher concentrations over the 6 h period. Decreasing the flow rate in the chemostat increased sustained levels of CFX whil e increasing the flow rate decreased sustained levels. Thus, the chemo stat system is convenient for testing the sustained release of drugs a s a function of formulation parameters and to obtain information about the optimum doses of sustained release medication for in vivo adminis tration.