ABSTRACT
Low-order high-energy nifedipine (NIF) solid dispersions (SDs) were generated by melt solvent amorphization with polyethylene glycol (PEG) 1450 and hypromellose acetate succinate (HPMCAS-HF) to increase NIF solubility while achieving acceptable physical stability. HPMCAS-HF was used as a crystallization inhibitor. Individual formulation components, their physical mixtures (PMs), and SDs were characterized by differential scanning calorimetry, powder X-ray diffraction, and Fourier transform infrared spectroscopy (FTIR). NIF solubility and percent crystallinity (PC) were determined at the initial time and after 5 days stored at 25 °C and 60% RH. FTIR indicated that hydrogen bonding was involved with the amorphization process. FTIR showed that NIF:HPMCAS-HF intermolecular interactions were weaker than NIF:PEG 1450 interactions. NIF:PEG 1450 SD solubilities were significantly higher than their PM counterparts (p < 0.0001). The solubilities of NIF:PEG 1450:HPMCAS-HF SDs were significantly higher than their corresponding NIF:PEG 1450 SDs (p < 0.0001-0.043). All the SD solubilities showed a statistically significant decrease (p < 0.0001) after storage for 5 days. SDs PC were statistically lower than their comparable PMs (p < 0.0001). The PCs of SDs with HPMCAS-HF were significantly lower than SDs not containing only PEG 1450. All SDs exhibited a significant increase in PC (p < 0.0001-0.0089) on storage. Thermogravimetric analysis results showed that HPMCAS-HF bound water at higher temperatures than PEG 1450 (p < 0.0001-0.0039). HPMCAS-HF slowed the crystallization process of SDs, although it did not completely inhibit NIF crystal growth.
