Purpose: Solid Dispersion is one of the methods to improve solubility of poorly-soluble drug. Hypromellose acetate succinate (HPMCAS) is widely used as a carrier of solid dispersion. In this study, we evaluated the Nifedipine/HPMCAS solid dispersion by several methods, XRD, DSC and their hyphenated analysis DSC-XRD.
Methods: Solid dispersion was prepared by film casting method (FCM), which is simple and easy to prepare. HPMCAS and Nifedipine were dissolved in dichloromethane/ethanol (1/1 w/w) and heated at approx. 120ºC for 7 min. to completely vaporize the solvent and form a solid film with several drug loading levels (25%, 33%, 40% and 50%). Several grades of HPMCAS: AS-LG, MG and HG were used for comparison. Obtained film was pulverized into powder by force mill (Wander Blender, Osaka Chemical Co.). The FCM samples were analyzed by DSC (DSC2300SA, Bruker), XRD (MiniFlex, Rigaku) and DSC-XRD (SmartLab SE, Rigaku). Dissolution test was performed according to USP40 (paddle method; 100 rpm, 37ºC, 900 mL of pH6.8 USP phosphate buffer).
Results: XRD analysis showed an amorphous profile when the drug load was less than 40%, whereas DSC analysis showed melting peak when the drug load was 33% or more. DSC-XRD profile showed emerged peaks around 130ºC which is close to crystallization temperature of Nifedipine. The result indicated that Nifedipine was crystallized during the DSC procedure by heat and enthalpy of melting means instability of each samples. Enthalpy of melting with 33% drug-loaded FCM powder by DSC was AS-LG > AS-MG > AS-HG which is estimated as instability order of FCM samples.
Conclusion: DSC-XRD was a good tool to visualize what occurs during the DSC procedure and to know its phase transition.