Formulation and Evaluation of a Self-Microemulsifying Drug Delivery System (SMEDDS) of Atazanavir for Enhanced Solubility
TL;DR
The study confirmed that SMEDDS is a promising approach for enhancing Atazanavir solubility and dissolution.
Abstract
The present study was aimed at the formulation and evaluation of a Self-Microemulsifying Drug Delivery System (SMEDDS) of Atazanavir to enhance its solubility and dissolution performance. Atazanavir is a poorly water-soluble antiretroviral drug, and its pH-dependent solubility can limit oral dissolution and absorption. Therefore, a lipid-based SMEDDS approach was selected to improve drug solubilization and microemulsion formation after dilution.Preformulation studies confirmed that Atazanavir was an off-white to pale yellow crystalline powder with a melting point range of 193.4–194.3°C. The λmax was found at 249 nm in methanol. The calibration curve showed good linearity in the concentration range of 2–20 µg/mL with regression equation y = 0.0428x − 0.0045 and R² = 0.9995. Solubility screening showed maximum drug solubility in Capryol 90 among oils (73.14 ± 0.42 mg/mL), Labrasol among surfactants (96.74 ± 0.39 mg/mL), and Transcutol HP among co-surfactants (118.96 ± 0.36 mg/mL). Hence, these excipients were selected for SMEDDS development.Pseudo-ternary phase diagram studies showed that Labrasol:Transcutol HP at 2:1 produced the largest microemulsion region. Nine formulations were prepared, and formulation F5 containing 50 mg Atazanavir, 20% Capryol 90, 53.33% Labrasol, and 26.67% Transcutol HP was selected as optimized. F5 showed rapid self-emulsification, high transmittance (99.32 ± 0.14%), droplet size of 52.17 ± 0.65 nm, PDI of 0.184 ± 0.003, zeta potential of −23.17 ± 0.25 mV, viscosity of 122.53 ± 0.70 cP, conductivity of 186.43 ± 0.75 µS/cm, and drug content of 99.19 ± 0.28%.The optimized SMEDDS passed thermodynamic stability tests and showed improved dissolution, releasing 98.75 ± 0.32% drug in 0.1 N HCl and 96.05 ± 0.31% in phosphate buffer pH 6.8 within 60 min. Release kinetics followed first-order behavior. The study confirmed that SMEDDS is a promising approach for enhancing Atazanavir solubility and dissolution.