10- Circumventing the Thermal Degradation of Atorvastatin Calcium to Facilitate its Production by Melt Extrusion

Abstract

Atorvastatin (ATV), a widely used lipid-lowering agent, faces significant formulation challenges due to its poor aqueous solubility and thermal instability. This study aims to develop a melt-extrudable formulation of ATV while mitigating the risk of its thermal degradation. Through the use of hot-melt extrusion (HME) method, various formulations were prepared and evaluated, with Formulation A4 (20% ATV, 70% hydroxypropyl Cellulose (HPC), 5%, polyethylene glycol (PEG) 600, 5% polyethylene oxide (PEO) 10k) emerging as the optimal solution. Differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) were used to confirm the formation of the ATV solid dispersion. In vitro drug release studies were conducted to compare the optimal formulation (A4) against the pure drug. The thermal stability evaluation revealed that ATV in pure drug does not degrade when held at 100 ºC for 40 minutes, achieving a recovery rate of 102.29% ± 1.22%. Formulation A4, extrudable at 100 ºC without any degradation, demonstrated a recovery rate of 100.84% ± 1.33%, and uniform distribution of ATV along the extrudate. In vitro drug release study showed that A4 Formulation released approximately 61% of ATV after 240 minutes in a buffer solution, compared to the pure drug's rapid release of ~100%. The reported formulation was therefore successfully prepared into a solid dispersion by Melt Extrusion without inducing any ATV degradation.