Study of nifedipine solubility in physical mixtures and solid dispersions

Introduction. Poor aqueous solubility significantly hinders the bioavailability of numerous orally administered drugs. Nifedipine, a widely-used cardiovascular agent, is categorized as practically insoluble according to pharmacopoeias, thus presenting a significant challenge in formulation development. This study investigates the potential of solid dispersion (SD) technology and physical mixtures to improve the dissolution profile of nifedipine. Aim. Development of a technological method for increasing the solubility of nifedipine by developing physical mixtures and SD with the aim of creating a dosage form with improved properties. Materials and methods. Nifedipine, methanol, nifedipine standard samples, potassium dihydrogen phosphate, sodium heptanesulfonate, phosphoric acid (85 %), purified water, and pvp K-30. Solubility studies were performed by HPLC using three objects: nifedipine, a physical mixture (PM), and SD of nifedipine with PVP K-30. The study assessed the effect of different ratios (nifedipine : PVP K-30) in the physical mixture and SD on nifedipine solubility. Fourier transform infrared spectroscopy (IR spectroscopy) and powder X-ray diffractometry were used to characterize the samples. Results and discussion. A notable increase in nifedipine solubility was observed in both PM3 (1 : 3 nifedipine : PVP K-30) and SD3 (1 : 3 nifedipine : PVP K-30). PM3 exhibited a solubility of 9.70 %, while SD3 demonstrated a remarkable enhancement to 32.07 % compared to the pure nifedipine (0.24 %). FTIR analysis did not reveal significant interactions between nifedipine and PVP K-30. PXRD results confirmed the transition of nifedipine from a crystalline to amorphous form within the hydrophilic PVP K-30 matrix, contributing to the observed solubility enhancement. Conclusion. The study highlights the effectiveness of SD technology in significantly improving nifedipine solubility and potential bioavailability. The 134-fold increase in solubility achieved with SD3 at a 1 : 3 ratio demonstrates the significant potential of this approach for enhancing the pharmacokinetic properties of poorly soluble drugs. This research opens up new avenues for developing innovative formulations with improved dissolution characteristics and potentially enhanced therapeutic efficacy.