Solidified SNEDDS for the oral delivery of rifampicin: Evaluation, proof of concept, in vivo kinetics, and in silico GastroPlusTM simulation

Publication date: Available online 24 May 2019Source: International Journal of PharmaceuticsAuthor(s): Afzal Hussain, Faiyaz Shakeel, Sandeep Kumar Singh, Ibrahim A. Alsarra, Abdul Faruk, Fars K. Alanazi, G.V. Peter ChristoperAbstractThe present investigation was performed to develop a rifampicin (RIF)-loaded solidified self-nanoemulsifying drug delivery system (SNEDDS) (solidified RIF-OF1) for in vitro and in vivo evaluations. Optimized formulations were tested for their powder flow characteristics, loading efficiency, and in vitro dissolution (at pH-1.2, 6.8 and 7.4). Compatibility studies were also performed. The formulations were also tested for hemocompatibility, intestinal permeation, histopathological effects, and in vivo pharmacokinetics. Additionally, an in silico simulation study using GastroPlus was performed. At different varied pH values, we observed immediate release (T85% within 15 min) based on the dissolution profile. This could be due to labrasol-assisted RIF solubilization. In vitro hemolysis study of the reconstituted RIF-OF1 revealed normal architecture of erythrocytes compared to the positive control (lysed and fragmented). Through in vivo permeation and biopsy studies, a rationale for facilitated intestinal permeation of RIF with components deemed physiological safe (normal anatomy of mucosal membrane evidenced from biopsy study) could be established. The in vitro-in vivo correlation (IVIVC) plus module of GastroPlusTM simulation showed a good IVIVC bet...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research