Preparation, characterization and in vitro evaluation of atorvastatin nanosuspensions

Poorly water-soluble drugs present a significant challenge for pharmaceutical development, particularly affecting the pharmacokinetics of orally administered drugs due to their poor dissolution. This study aimed to enhance the dissolution of a low water solubility drug atorvastatin using nanosuspension technology. Antisolvent technique was utilized to prepare atorvastatin calcium nanosuspensions. Different stabilizers were used including Cremophor, HPMC, pluronics (F127, F108, and F68), PEG400, PEG600, PEG 1k, PEG8k, PVA, PVP k30, PVP k10, PVP 44k, SLS, sodium alginate, Tween 20, and Tween 80. The prepared nanosuspensions were lyophilized using mannitol or trehalose as a lyoprotectant. Several optimum formulations were obtained. The selected best optimum formulation was 2% pluronic F127, 80 mg mannitol, and 2 min sonication time. It exhibited a mean particle size of 54.5 nm, a zeta potential of -0.809, and 0.141 PDI after reconstitution. The crystalline state of the nanoparticles was evaluated using differential scanning calorimetry (DSC) and X-ray diffraction (XRD). Fourier-transform infrared spectroscopy (FTIR) was used to assess interactions between the drug substance and the additives. In vitro drug release study was conducted for lyophilized nanosuspension in comparison to the innovator product Lipitor® in two different media, 0.05M potassium phosphate buffer pH 6.8 and 0.1N HCL. The XRD analyses indicated that the lyophilized nanosuspension was partially crystalline with some amorphization and this confirmed by DSC. FTIR results suggested that there was a physical interaction between atorvastatin and the additives. The polymer and lyoprotectant successfully preserved and coated the drug nanoparticles. The lyophilized nanosuspension exhibited superior dissolution in 0.1N HCl. However, the innovator was faster in 0.05 M phosphate buffer. In conclusion, successful preparation of lyophilized nanosuspension of atorvastatin calcium was achieved. The current findings revealed that excipient functionality in terms of stabilization, effect on solid state properties, and drug release were critical for development of stable and efficient nanosuspension.