EFFECT OF ANNEALING, PRESSURE VALUE, AND RAMPING METHOD ON QUALITY AND CYCLE TIME OF LYOPHILIZED CYCLOPHOSPHAMIDE POWDER FOR INJECTION

• Main Author: Alexander, Frederick
• Format: Theses
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/66140
• Institution: Institut Teknologi Bandung

With the increasing prevalence of cancer and the need for anticancer drugs, the pharmaceutical industry must be able to be present in meeting the needs of the community. Cyclophosphamide is known as one of the effective anticancer drugs and has been used for a long time. Cylophosphamide is available in the form of injection powder dosage form due to its unstable nature in solution form. However, in producing injection powder, it takes a lot of time and energy so the industry must be able to improve process efficiency while still prioritizing product quality. In this study, the optimization of the lyophilization cycle was carried out by optimizing the freezing and drying processes using the one factor at a time (OFAT) method. Furthermore, the variables optimized include annealing technique, pressure value, and continuous ramping techniques. At each stage of the optimization of the lyophilization cycle, physical and chemical evaluations were carried out with a stress test at a temperature of 30 o C and 40 o C for 2 weeks. The data shows that annealing optimization has an impact on increasing the physical stability of the product. The pressure value of ?150 µbar is able to change the crystal form of cyclophosphamide from monohydrate to anhydrous which affects the stability of the product. The continuous ramping technique is able to speed up the lyophilization cycle and improve the physico-chemical stability of the finished product. Based on the optimization results, the new lyophilization cycle was able to reduce the COGM value up to 32.5% and increase the production capacity by 48% in 1 year to the installed capacity.