DEVELOPMENT AND EVALUATION OF POMALIDOMIDE SUPERSATURABLE SELF-NANOEMULSIFYING DRUG DELIVERY SYSTEM FOR IMPROVED SOLUBILITY AND DISSOLUTION RATEAbstract
Background: Pomalidomide belongs to BCS class IV drug with low solubility and undergoes first-pass metabolism leads to reduced bioavailability of 15%. Objective: The current study aimed to develop pomalidomide Super saturable-SNEDDS to enhance solubility. Methods: Preliminary solubility studies were performed to identify oil, surfactant, and co-surfactant ratios. Pseudo tertiary phase diagram constructed to select the areas of nanoemulsion and based on monophasic region. Nineteen ratios were selected for drug loading study having oil: Smix ratio in 3:1, from which 15 formulations of pomalidomide SNEDDS were prepared with 4mg drug loading and screened for visual observation and turbidity measurement studies. These SNEDDS are further characterized for robustness, content of drug, entrapment efficiency, and in-vitro dissolution analysis. The optimized SNEDDS formulation was selected for screening of precipitation inhibitor by adding 2% precipitation inhibitors, and concentration-time profiles were studied under non-sink conditions from which best PI was selected and then in-vitro dissolution studies conducted for the super saturable SNEDDS (S-SNEDDS). The optimized final formulation S-SNEDDS with the highest drug release was analyzed for FTIR, particle size, Z average, zeta potential, SEM analysis, and stability studies. Results: Based on pseudo tertiary phase diagram, Akomed E oil – Caprol PGE 860 – and PEG 600 as oil, surfactant, and co-surfactant selected, respectively. All the formulations were stable with no phase separation and maximum % transmittance. The formulation F11 was selected as optimized one based on maximum drug release of 99.04% within 60 min. By adding PVP K17 as a precipitation inhibitor to conventional SNEDDS, a super saturable system was prepared. Firstly, the prepared SNEDDS played an important role in increasing the aqueous solubility and hence oral absorption due to nano-range size. Secondly, the S-SNEDDS found to be advantageous over SNEDDS for having a higher drug load and inhibition of dilution precipitation of pomalidomide. Formulated S-SNEDDS (F11) showed drug release of 99.98%. The particle size, PDI and zeta potential of the optimized formulation F11 S-SNEDDS were 49.0 nm, 0.318, and -24.4 mV, respectively. The FTIR and SEM studies did not indicate any drug excipient interaction and confirmed nanosized which is stable. Conclusion: Pomalidomide-loaded S-SNEDDS could potentially be exploited as a delivery system for improving solubility and increase drug release.