Carmustine belongs to the category of alkylating agent meant for chemotherapy to treat certain types of brain tumors. The main objective of this work is to develop a novel stable lyophilized dosage form for carmustine with respect to that of the available brand product. The stabilization of the drug product is critical due to the storage condition of the drug substance (-20°C) and the storage condition of drug product (2-8°C). Carmustine for injection was prepared by using lyophilization technique with suitable solvent system. As per the literature review, none of the functional excipient present in the finished product as the drug substance is directly lyophilized with the help of suitable solvent system. The selection of solvent system depends upon the solubility and stability of drug substance and also feasibility during manufacturing. Dehydrated alcohol, acetone and dimethyl sulfoxide were evaluated for the solublization and stabilization of the drug substance. During the formulation design, the formulated bulk solution was evaluated for the impact of process temperature, process time and compatibility with the contact parts. Due to the usage of organic solvents, the formulated bulk solution was freezed at -50°C and the primary drying was done at -15°C (less than critical product temperature) followed by secondary drying at 15°C. The lyophilization process was optimized with respect to the critical quality attributes of assay, related substances, pH of the reconstituted solution, reconstitution time and residual solvents. There was no significant change in description, pH, assay and related substances of bulk solution up to 24 hrs at refrigerated condition (2-8°C). The bulk solution was found to be compatible with SS 316 vessel, glass, silicon tubing, PVDF filters and nylon filters. The total time for optimized lyophilization process was about 61 hours. The optimized freeze dried product meets the predefined specifications. Based on the observations and conclusions, it can be concluded that the carmustine for injection can be stabilized by lyophilization process with the proposed organic solvents i.e dehydrated alcohol, acetone and dimethyl sulfoxide.
