Capsaicin loaded solid SNEDDS for enhanced bioavailability and anticancer activity: In-vitro, in-silico, and in-vivo characterization.

Bhagwat, Durgacharan A; Swami, Pratik A; Nadaf, Sameer J; Choudhari, Prafulla B; Kumbar, Vijay M; More, Harinath N; Killedar, Suresh G; Kawtikwar, Pravin S

In this investigation, the fabrication of capsaicin loaded self nano emulsifying drug delivery system (SNEDDS) was attempted to improve the effectiveness of capsaicin through the oral route. A pseudo-ternary phase diagram was constructed at different km values (1:1, 2:1, & 3:1). Nine liquid formulations (L-CAP-1 to L-CAP-9) were prepared at km= 3, evaluated & converted to solid free-flowing granules using neusilin® US2. L-CAP-3 comprising of 15% isopropyl myristate, 33.75% Labrafil, & 11.25% ethanol exhibited higher % transmittance (98.90 ± 1.24%) & lower self-emulsification time (18.19 ± 0.46 seconds). FT-IR spectra showed no incompatibility whereas virtual analysis confirmed hydrogen bond interaction between amino hydrogen in the capsaicin & oxygen of the neusilin. DSC & XRD study revealed the amorphization & molecular dispersion of capsaicin in S-SNEDDS. TEM analysis confirmed the nano-sized spherical globules. Within 15 min, L-SNEDDS, S-SNEDDS, & pure capsaicin showed 87.36 ± 3.25%, 85.19 ± 4.87%, & 16.61 ± 3.64% drug release respectively. S-CAP-3 significantly (p<0.001) inhibited the proliferation of HT-29 colorectal cancer cells than capsaicin. Apoptosis assay involving Annexin V/PI staining for S-CAP-3 treated cells demonstrated a significant (p<0.001) apoptotic rate. Remarkably, 3.6 fold increase in bioavailability was observed after oral administration of capsaicin-SNEDDS than plain capsaicin.