Enhanced stability and oral bioavailability of erlotinib by solid self nano emulsifying drug delivery systems

The present investigation demonstrates the preparation of solid self nanoemulsfying drug delivery system (sSNEDDS) to enhance stability and bioavailability of Erlotinib (ERL) via the oral route. Capmul (R) MCM EP (CPM EP, oil), Cremophor (R) RH 40 (CMR RH 40, surfactant), and LBF CS (LBF CS, cosurfactant) were chosen as chief components for preparing Liquids SNEDDS (L-ERL-SNEDDS) based on solubility and emulsion forming ability. Pseudo ternary phase diagram and constrained mixture designs were applied to identify the self-emulsifying area and it was found that CPM EP, CMR RH 40, and LBF CS in the ratio of 59:11:30 showed optimized particle size (110.08 nm), with narrow PDI (0.114) and high ERL loading capacity (14.31 mg/g). Adsorption method was implemented for solidification of L-ERL-SNEDDS. Among various solid carriers were studied, Aerosil (R) 200 (A200) was finalized based on free flowing property and reconstitution ability. DSC and XRD studies revealed that crystallinity of drug was reduced in developed system. The developed formulation (named as, A200-ERLsSNEDDS) showed increased cytotoxicity and apoptosis in PANC-1 and MIA PaCa-2 cells. Pharmacokinetic studies revealed ~2.2 times increase in AUC0-infinity values in case of A200-ERL-sSNEDDS as compared to free ERL. Thus current strategy can be extrapolated for delivering of poorly soluble drugs via oral route.

Automated summary

This study demonstrates the preparation of solid self nanoemulsifying drug delivery system (sSNEDDS) to improve the stability and bioavailability of Erlotinib (ERL) via oral administration. The optimized formulation showed enhanced cytotoxicity and apoptosis in cancer cells, as well as increased drug exposure in pharmacokinetic studies. The results suggest that this strategy holds promise for delivering poorly soluble drugs orally.