Nonisothermal stability assessment of stable pharmaceuticals: testing of a clindamycin phosphate formulation.
The stability of an antibiotic formulation (clindamycin phosphate in dextrose), which is stable at room temperature, was assessed by nonisothermal kinetic analysis at elevated temperatures. A preliminary study, conducted to establish apparent rate order, verified the appropriateness of a first-order kinetic model. The test formulation was then heated linearly from 70 to 90 degrees C over 12 hr. Data (drug concentration, temperature, and time) were fitted to the first-order model using nonlinear least-squares regression. Arrhenius parameter estimates obtained from three nonisothermal trials, and rate constants at 25 degrees C derived by extrapolation, demonstrated acceptable reproducibility and were in agreement with values derived from isothermal experiments at 30, 45, 55, 65, and 75 degrees C. First-order rate constants obtained from studies conducted for 20 months at 25 degrees C were in accord with isothermal and nonisothermal results.
Kipp
J E
JE
Baxter Healthcare Corporation, Pharmaceutical R&D, Round Lake, Illinois 60073.
Hlavaty
J J
JJ
D002981:Clindamycin / Q000031:analogs & derivatives*; D004355:Drug Stability; D007700:Kinetics; D013816:Thermodynamics
D002981:Clindamycin; C007084:clindamycin phosphate