Development of Nifedipine Amorphous Solid Dispersion Composed of Surface-Active Agents

The amorphous solid dispersions (ASDs) containing amino methacrylate copolymer and surface-active agents were prepared to improve the nifedipine (NDP) dissolution. The different types of surface-active agent i.e., polysorbates 80, sodium lauryl sulfate (SLS) and polyethylene glycol (PEG) 400 were used. In order to evaluate the ASDs formulation,powder X-ray diffractometry and thermal analysis to characterize NDP crystallinity in ASDs and the dissolution study of NDP have been performed to compare the dissolution profiles. The ASDs were kept for 6 months to investigate the stability. In the X-ray diffraction pattern, no peak was observed in all samples of ASDs. No peak was found in sample of all ASDs from the thermograms. These results suggest that the drug may be molecularly dispersed in matrix of amino methacrylate copolymer. The drug dissolution at 120 min, from ASDs without surface-active agent and NDP powder were 58.31% and 17.95%, respectively. The dissolved NDP from ASDs composed of SLS, polysorbate 80 and PEG400 were 96.25%, 88.86% and 75.32%, respectively. These results may occur due to the reduction of surface tension, the addition of the low amount of high efficiency of surface-active agent e.g., SLS (compared with PEG400 and polysorbate 80) provided the higher NDP dissolution. The content analysis of NDP in selected ASDs was studied at the end of 3 and 6 months, the NDP content remained unchanged after storage.

Improvement in Solubility and Absorption of Nifedipine Using Solid Solution: Correlations between Surface Free Energy and Drug Dissolution

Ternary solid solutions composed of nifedipine (NDP), amino methacrylate copolymer (AMCP), and polysorbate (PS) 20, 60, or 65 were prepared using a solvent evaporation method. The dissolution profiles of NDP were used to study the effect of the addition of polysorbate based on hydrophilic properties. A solid solution of NDP and AMCP was recently developed; however, the dissolution of NDP was <70%. In the present study, polysorbate was added to improve the dissolution of the drug by altering its hydrophilicity. The suitable formulation contained NDP and AMCP at a ratio of 1:4 and polysorbate at a concentration of 0.1%, 0.3%, or 0.6%. Differential scanning calorimetry and powder X-ray diffraction were used to examine the solid solutions. No peak representing crystalline NDP was observed in any solid solution samples, suggesting that the drug was molecularly dispersed in AMCP. The NDP dissolution from NDP powder and solid solution without PS were 16.82% and 58.19%, respectively. The highest dissolution of NDP of approximately 95.25% was noted at 120 min for the formulation containing 0.6% PS20. Linear correlations were observed between the surface free energy and percentages of dissolved NDP (R2 = 0.7115–0.9315). Cellular uptake across Caco-2 was selected to determine the drug permeability. The percentages of cellular uptake from the NDP powder, solid solution without and with PS20 were 0.25%, 3.60%, and 7.27%, respectively.