Engineered biodegradable polymeric nanoparticles injectable system of atorvastatin for improved therapeutic activity

Carrier-mediated drug delivery is one of the potential approaches employed to increase drug solubility and bioavailability. Atorvastatin (ATR), a HMG CoA reductase inhibitor, is a first-line medication prescribed for the treatment of hyperlipidemia and related cardiovascular diseases. The efficacy of ATR is highly limited due to its poor solubility and low oral bioavailability. In the present study, an injectable system of ATR-loaded polymeric nanoparticles was synthesized through the spray drying technique using chitosan polymer extracted in-house from a novel source of Portunus Sanguinolentus species shells. The effect of spray dryer nozzle diameter and polymer concentration on particle size, morphology, in vitro drug release, and ex vivo permeation was studied. The synthesized ATR-loaded chitosan particles were in the size range of 248.2 ± 17.58 nm to 329 ± 36.68 nm with homogeneous distribution. The average drug loading of all formulations was above 80%. The nozzle of 0.7 mm diameter produced smaller-sized particles with higher drug loading compared to the 1 mm diameter nozzle. Morphological analysis of the synthesized nanoparticles was performed using SEM, which revealed that particle size was increased linearly with increasing concentration of chitosan, with more flower-like structure deposition of polymer on the surface. The in vitro drug release and solubility study of the formulations on different bio-relevant media confirmed that the solubility of the drug was increased on all three different media as the concentration of chitosan increased. Also, the presence of chitosan improved the permeability of the drug through the membrane's adhesive property. Characterization of selected formulation with analytical techniques like FT-IR, XRD, TG-DSC confirmed that the drug was functionally active in the polymeric systems without significant alterations. Therefore, the synthesized formulation was proven to be effective in improving in vitro dissolution without significant loss, which could improve the in vivo bioavailability of Atorvastatin by enhancing solubility, absorption, and permeation in the physiological system.