title: Formulation optimization of Docetaxel loaded self-emulsifying drug delivery system to enhance bioavailability and anti-tumor activity.
abstract: Poor bioavailability of Docetaxel (DCT) arising due to its low aqueous solubility and permeability limits its clinical utility. The aim of the present study was to develop DCT loaded self-emulsified drug delivery systems (D-SEDDS) and evaluate its potential ability to improve the oral bioavailability and therapeutic efficacy of DCT. D-SEDDS were characterized for their in vitro antitumor activity, in situ single pass intestinal perfusion (SPIP), bioavailability, chylomicron flow blocking study and bio-distribution profile. The D-SEDDS were prepared using Capryol 90, Vitamin E TPGS, Gelucire 44/14 and Transcutol HP with a ratio of 32.7/29.4/8.3/29.6 using D-Optimal Mixture Design. The solubility of DCT was improved upto 50 mg/mL. The oral bioavailability of the D-SEDDS in rats (21.84 ± 3.12%) was increased by 3.19 fold than orally administered Taxotere (6.85 ± 1.82%). The enhanced bioavailability was probably due to increase in solubility and permeability. In SPIP, effective permeability of D-SEDDS was significantly higher than Taxotere. D-SEDDS showed 25 fold more in vitro cytotoxic activity compared to free DCT. Chylomicron flow blocking study and tissue distribution demonstrated the intestinal lymphatic transport of D-SEDDS and higher retention in tumor than Taxotere. The data suggests that D-SEDDS showed desired stability, enhanced oral bioavailability and in vitro antitumor efficacy.
authors.affiliation: Pharmacokinetics and Metabolism Division, CSIR-Central Drug Research Institute, Lucknow, India.|Academy of Scientific and Innovative Research, New Delhi, India.
authors.forename: Guru R
authors.initials: GR
authors.lastname: Valicherla
authors.affiliation: Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Raibarelly, India.
authors.forename: Kandarp M
authors.initials: KM
authors.lastname: Dave
authors.affiliation: Pharmacokinetics and Metabolism Division, CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Anees A
authors.initials: AA
authors.lastname: Syed
authors.affiliation: Pharmacokinetics and Metabolism Division, CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Riyazuddin
authors.affiliation: Pharmacokinetics and Metabolism Division, CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Anand P
authors.initials: AP
authors.lastname: Gupta
authors.affiliation: Biochemistry Division, CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Akhilesh
authors.initials: A
authors.lastname: Singh
authors.affiliation: Pharmacokinetics and Metabolism Division, CSIR-Central Drug Research Institute, Lucknow, India.|Academy of Scientific and Innovative Research, New Delhi, India.
authors.lastname: Wahajuddin
authors.affiliation: Sophisticated Analytical Instrumental Facility, CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Kalyan
authors.initials: K
authors.lastname: Mitra
authors.affiliation: Biochemistry Division, CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Dipak
authors.initials: D
authors.lastname: Datta
authors.affiliation: Pharmacokinetics and Metabolism Division, CSIR-Central Drug Research Institute, Lucknow, India.|Academy of Scientific and Innovative Research, New Delhi, India.
authors.forename: Jiaur R
authors.initials: JR
authors.lastname: Gayen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D001682:Biological Availability; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D000077143:Docetaxel; D004339:Drug Compounding; D016503:Drug Delivery Systems; D004355:Drug Stability; D004655:Emulsions; D005026:Ethylene Glycols / Q000737:chemistry; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D008297:Male; D008807:Mice, Inbred BALB C; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D011409:Propylene Glycols / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D043823:Taxoids / Q000493:pharmacokinetics* / Q000494:pharmacology; D014810:Vitamin E / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004655:Emulsions; D005026:Ethylene Glycols; D011108:Polymers; D011409:Propylene Glycols; D043823:Taxoids; C584816:capryol propylene glycol monocaprylate; C104509:gelucire 44-14; D014810:Vitamin E; D000077143:Docetaxel; D011092:Polyethylene Glycols; C010111:carbitol; C014225:tocophersolan