Preparation And Quality Control Of Clindamycin Phosphate For Injection

Clindamycin phosphate is one of derivatives of clidamycin and has no antibacterial activity in vitro. Clindamycin phosphate could be hydrolyzed to clindamycin in vivo immediately and play antibacterial activity, thus, clindamycin phosphate could act as one of the prodrugs of clindamycin. It is generally applied for various infectious diseases caused by Gram-positive bacteria.On the basis of literature review, such as the research status of the same drug and the formulations of same dosage forms, the formulation and the process parameters of clindamycin phosphate for injection were studied and optimized. HPLC methods were established for determation of the drug contents and were selected as the main analysis technique to control the quality of clindamycin phosphate for injection. The preliminary stability of clindamycin phosphate for injection were studied. Therefore, the experimental basis for future research and large-scale production of the new drug mentioned were founded.Three different specifications of clindamycin phosphate for injection were designed and prepared according to the standard proparation process. The different adjuvants were compared and the formulation were optimized. The pH value of the preparations obtained according to the optimized formulation were between 5.5 and 6.3, which meet the medical standard appropriately. To avoid contamination of pyrogen (bacterial endotoxin) is one of the important quality control indexes of the injection preparations, the amount of the activated carbon was investigated because that adsorptive process for removing pyrogen by activated carbon was accepted as the most important method to removing pyrogen. To decrease the adsorption of drugs causing by the activated carbon, the amount of the activated carbon was set at the minimum level. Nine batches of the clindamycin phosphate for injection prepared according to the optimized formulation and the optimized process parameters were used to studied the quality characterization.The identification, acidity, clarity,color, moisture content, related substances, bacterial endotoxins, visible foreign matter, insoluble particles, load difference, drug contents and the compatibility were investigated. According to the results of these investigations, as well as the results of the preliminary stability studies, the standards of the quality control of clindamycin phosphate for injection were established.The results of the preliminary stability tests were as follows:the preparations were stable enough after standing for 10 days under light (45001x) and high humidity (RH 90%), respectively. While, the color of the preparations were darken gradually, the related substances increased significantly, and the drug content decreased under high temperature (60℃) for 10 days. These results indicated that the clindamycin phosphate for injection was stable to humidity and light, was unstable to high temperature. The related substances increased and the drug content decreased significantly under accelerated testing (40℃, RH 75%) for 3 months, though other indexes were still fiting the requirements. Thus, the accelerated testing under 30℃and RH 65% were carried out for 3 months to evalute the stablity of the clindamycin phosphate for injection. The results showed that the preparations were stable enough under this accelerated testing condition. For long-term testing, the samples were investigated under room temperature (25℃, RH 60%) for 12 months, the results showed that the preparations were stable enough under this long-term testing condition.Conclusion:The formulation and the preparation process were feasible, the quality was controlled and the product quality standard was qualified.