Novel In-Situ Liquefying Carbonated SNEDDS Loaded with Atorvastatin Calcium: An Approach for Overcoming Dosage and Stability Challenges

Abstract

Although self nanoemulsifying drug delivery system (SNEDDS) enhances atorvastatin calcium bioavailability, formulation leakage from capsules and drug degradation limits its pharmaceutical application. The traditional solidifying adsorption approach failed to overcome the instability issue and produced a powder with a high dosage. Combining in-situ liquefying (poloxamer 188) and pH-modifying agents (sodium bicarbonate) was invented to address these challenges while maintaining dissolution performance. Therefore, five formulations were prepared, namely: liquid SNEDDS (L-SNEDDS), solid SNEDDS (S-SNEDDS), carbonated SNEDDS (C-SNEDDS), in-situ liquefying SNEDDS (IL-SNEDDS), and in-situ liquefying carbonated SNEDDS (IL-C-SNEDDS). Oil and cosurfactant ingredients were selected based on the solubility of the drug and poloxamer 188, respectively, while surfactant was selected based on transmittance measurement. Moreover, the prepared formulations were characterized using a Zetasizer, pH meter, thermal behavior, SEM, FTIR, PXRD, and dissolution apparatus. Finally, the stability of prepared formulations was studied to assess the impact of formulation type on drug stability. Results showed that atorvastatin calcium exhibited the highest solubility in imwitor 308 (181.4 mg/g) among tested oils. The optimized SNEDDS formulation displayed a transmittance value of 98.62%, indicating excellent emulsification with a particle size of 10.5 nm. The optimized L-SNEDDS formulation comprises tween 80, propylene glycol, and imwitor 308 (2: 1: 1). The results showed that Syloid successfully adsorbed L-SNEDDS, which was present in an amorphous state. In vitro dissolution studies demonstrated that all SNEDDS formulations achieved > 90% drug dissolution. However, notable drug degradation was observed with liquid and solid SNEDDS (> 10%) compared to < 5% in IL-C-SNEDDS. The present study demonstrates that IL-C-SNEDDS effectively addresses dosage and stability challenges without increasing the total dosage.

Graphical Abstract