Track: Manufacturing and Analytical Characterization - Chemical - Analytical - Physical Characterization Techniques
Category: Poster Abstract
Determination of Saturation Solubility of Clotrimazole in Different Fatty Alcohols Using Differential Scanning Calorimetry (DSC)
Purpose: Differential scanning calorimetry (DSC) is a thermoanalytical technique used to measure enthalpy changes due to changes in the physical and chemical properties of a material as a function of temperature or time. To develop a lipid-based formulation it is important to determine the drug solubility in the lipid excipients. However, it is challenging to measure the solubility of drugs in the solid and semisolid lipids. In the current work DSC was used as a tool to measure the saturation solubility of clotrimazole in different fatty alcohols. Methods: Sample preparation: Different percentage (0, 10, 25, 50 and 75% W/W) of clotrimazole was added to 5 different fatty alcohols (Kolliwax CSA 50, CSA 70, MA, CA and SA) containing in glass vials. The drug-excipient mixture in glass vials was heated on a hot plate at a temperature slightly above the melting point of the excipient to prepare molten state mixture and stirred with a magnetic stir for 30 min. After 30 minutes of mixing drug-excipient molten mixture was transferred into the DSC pans.
Differential scanning calorimetry (DSC) analysis: DSC was performed using the TA instruments discovery series DSC 25, New Castle, DE, USA. The drug-excipient mixture in the molten state was weighed inside the aluminum pan/ DSC pan and the pan was sealed with the aluminum lid/ hermetic lid tightly. DSC pans were allowed to equilibrate for 1 hour. After 1hr, DSC analysis was performed over the temperature range of 20 ℃ to 200 ℃ at 20 ℃/min increments. TRIOS software was used to analyze the enthalpy of melting. Results: Differential scanning calorimetry (DSC) results demonstrated that there was a decrease in the enthalpy of fusion of the excipient observed with an increase in the percentage of clotrimazole in all fatty alcohols. The phenomenon will continue until the excipient is saturated with the drug, beyond which the endothermic peak of the drug could be observed. In clotrimazole and fatty alcohol mixtures (Kolliwax CSA 50, CSA 70, MA, and CA), the endothermic peak of the API occurred at concentration over 75% w/w drug load in the excipient indicating that the solubility of clotrimazole was in the range of 50-75%. Only in case kolliwax SA the solubility was found to be between 25-50% w/w. Conclusion: The study demonstrates that DSC can be used as an excellent tool to determine the saturation solubility of lipophilic drugs in solid lipid excipients. The method also could be used to screen the potential excipients for a lipid-based drug delivery system or a topical product.