title: Investigation of Need of Natural Bioenhancer for a Metabolism Susceptible Drug-Raloxifene, in a Designed Self-Emulsifying Drug Delivery System.
abstract: Bioenhancers can increase the bioavailability of metabolism susceptible drugs. The present study was designed to understand the impact of bioenhancer on permeability and bioavailability of a biopharmaceutical drug disposition classification system (BDDCS) class II drug raloxifene (RLX). RLX undergoes extensive first pass metabolism by UGT enzymes in gastrointestinal tract (GIT) and has an oral bioavailability of about 2%. Self-emulsifying drug delivery system (SEDDS) of RLX was developed using a designed approach and this formulation was loaded with reported bioenhancers: quercetin and piperine. These formulations were tested for improvement in permeability and bioavailability of the RLX. The apparent permeability using everted gut sac (Papp) for SEDDS (5.26 ± 1.10 × 10-8cm/s) was found to be similar to that of SEDDS with bioenhancers (5.11 ± 1.05 × 10-8cm/s). In oral bioavailability study in rat, SEDDS demonstrated a 4-fold and 2.5-fold higher AUC0-∞than RLX suspension (control) and marketed product, respectively. No additional improvement in permeability and bioavailability was offered by inclusion of piperine and quercetin (bioenhancers) in the SEDDS.
authors.affiliation: Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Mohali, Punjab, 160062, India.
authors.forename: Poonam Singh
authors.initials: PS
authors.lastname: Thakur
authors.affiliation: Rekitt Benckiser, Gurgaon, India.
authors.forename: Narinder
authors.initials: N
authors.lastname: Singh
authors.affiliation: Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Mohali, Punjab, 160062, India.
authors.forename: Abhay T
authors.initials: AT
authors.lastname: Sangamwar
authors.affiliation: Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Mohali, Punjab, 160062, India. akbansal@niper.ac.in.
authors.forename: Arvind Kumar
authors.initials: AK
authors.lastname: Bansal
mesh_terms: D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004655:Emulsions; D005260:Female; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry
chemical_list: D004655:Emulsions; D013501:Surface-Active Agents; D020849:Raloxifene Hydrochloride
keywords: SEDDS; UGT; bioenhancer; design of experiment; permeability