Title : Self-nanoemulsifying drug delivery system (SNEDDS) of apremilast: In-vitro evaluation and pharmacokinetic studies
Abstract:
Psoriatic arthritis is an autoimmune disease of the joints; it can lead to persistent inflammation, joint damage and disability. Apremilast (APR) was the first FDA-approved oral anti-psoriatic arthritis drug. It APR immediate release tablets Otezla® have 20-33% bioavailability compared to APR absolute bioavailability 73%. APR-SNEDDS were formulated to enhance APR’s solubility, dissolution and oral bioavailability. The assay of drug was carried out using a validated HPLC method. The standard plot obtained linearity in the concentration range of (0.1 to 100 µg/ml) with R2= 0.9991. Using Lauraglycol-FCC as the oil phase, de-ionized water as the aqueous phase, tween-80 as the surfactant and transcutol-HP as the cosurfactant, nine APR-SNEDDS were developed namely (F1-F9) by spontaneous emulsification method. Various thermodynamic tests were carried out on APR-SNEDDS. Stable SNEDDS were characterized then subjected to in-vitro drug release studies via dialysis membrane. The optimum formulation was F9 which showed the maximum in-vitro drug release (94.9%) over 24h was furtherly investigated in in-vivo studies. F9 was composed of 15% oil, 60% Smix, and 25% water had the lowest droplet size (17.505 ± 0.247 nm), low PDI (0.147 ± 0.014), low ZP (-13.35 mV), highest %T (99.15 ± 0.131) and optimum increases in the relative bioavailability (703.66%) compared to APR suspension (100%) over 24h. These findings represented APR-SNEDDS as a possible alternative delivery system for APR and for future studies to evaluate the major factors that influence the encapsulation efficiency and stability of APR. Moreover, the application of APR-SNEDDS for oral delivery, efficacy and safety assessments.
