Thermoresponsive Solid Dispersion to Enhance Dissolution Profile of Atorvastatin Calcium: An Industrially Sustainable Alternative to Conventional Approaches.

Background

Poor aqueous solubility of therapeutic molecules remains a limitation in the pharmaceutical development of lipophilic drugs. This requires formulation approaches that provide the desired therapeutic efficacy while being industry-friendly. This study aimed to optimize a thermoresponsive solid dispersion containing atorvastatin calcium to enhance its dissolution performance.

Methods

Various nonaqueous solvents were screened to select a thermo-modulating agent. A central composite design was employed to investigate the impact of Pluronic F-68 concentration (5-15% w/w) and atorvastatin calcium concentration (5-10% w/w) on phase transition temperature and phase transition interval. Molecular interactions were assessed by Fourier-transform infrared spectroscopy. The in vitro dissolution of the optimized thermoresponsive solid dispersion was assessed using a USP Apparatus II dissolution test.

Results

Propylene glycol was identified as the optimal thermo-modulating agent, forming a rigid carrier through hydrogen bonding with Pluronic F-68. The optimized thermoresponsive solid dispersion consisted of 10.07% w/w Pluronic F-68 and 9.98% w/w atorvastatin calcium. It converted to a solution state at 32 °C. At physiological temperature, the phase transition interval was 111.66 s. Dissolution studies demonstrated that the thermoresponsive solid dispersion enhanced the dissolution profile of atorvastatin calcium within 5 min, 96.6 ± 1.2% compared to 13.8 ± 4.2% for the raw drug. A comparison of process characteristics indicated fewer unit operations and no organic-solvent requirement relative to conventional techniques.

Conclusions

This approach enhances dissolution performance and eliminates the need for organic solvents through simple manufacturing processes.