Unveiling the Superiority of Innovative Carbonated Self-Nanoemulsifying Drug Delivery Systems in Improving the Stability of Acid-Labile Drugs: Atorvastatin as a Model Drug

Abstract

Atorvastatin (AT) is widely prescribed by physicians during the treatment of hyperlipidemia. The self-nanoemulsifying drug delivery system (SNEDDS) is used to overcome its low drug solubility and bioavailability. However, the presence of free fatty acids in SNEDDS formulation resulted in remarkable AT degradation. This study explores innovative carbonated SNEDDS to enhance the stability of AT within SNEDDS formulation. Various types of SNEDDS formulations were prepared and evaluated. In vitro dissolution was performed to examine the ability of SNEDDS formulation to enhance AT dissolution. The solidified SNEDDS formation was prepared using Syloid adsorbent (AT-SF6). In addition, sodium bicarbonate was loaded within the best formulation at various concentrations to prepare carbonated SNEDDS (AT-CF6). Kinetics of drug degradation were studied over 45 days to assess AT stability in SNEDDS formulations. It was found that the SNEDDS formulation was able to enhance the dissolution of AT by about 1.5-fold compared with the pure drug formulation. AT-SF6 did not reduce the degradation rate of the drug compared with AT-F6. However, AT-CF6 formulations showed that increasing the concentration of incorporated sodium bicarbonate significantly reduced the degradation rate of AT. It was found that sodium bicarbonate in AT-CF6 significantly reduced the degradation rate of AT (0.00019) six-fold compared with AT-F6 (0.00115). The obtained results show that carbonated SNEDDS is a promising approach to enhance the stability of acid-labile drugs and their pharmaceutical application.