Pharmacokinetic study of solid-lipid-nanoparticles of altretamine complexed epichlorohydrin-β-cyclodextrin for enhanced solubility and oral bioavailability.
Altretamine is a synthetic drug approved for treatment of ovarian cancer. The only drawback with its formulation is poor aqueous solubility and low oral bioavailability. In the present work an attempt has been made to prepare inclusion complex of altretamine with epichlorohydrin beta cyclodextrin. The complexes were prepared by kneading, co-evaporation and freeze-drying method and were confirmed by FTIR, XRD, DSC, drug content and dissolution study. Kneaded complex possess maximum solubilizing efficiency of 82.63 in 25mM Epi-β-CD solution. SLNs of pure altretamine and ALT complexed with Epi-β-CD were prepared by modified emulsification-ultrasonication method. The particle size and zeta potential was found to be 151.5nm and -21.3mV. The drug release pattern of SLNs was bi-phasic in nature; with an initial burst release followed by sustained drug release. Pharmacokinetic study showed that the average Cmaxwas found to be 0.94μg/ml, which was 2.47 times higher as compared to the pure drug. The AUCt for SLNs was 150minμgh/ml and 54minμgh/ml for pure ALT suspension which proved that the SLNs exhibited greater absorption compared to the pure drug. Thus, smaller particle size, higher entrapment efficiency and enhanced aqueous solubility led to improvement in oral bioavailability of ALT.
University Institute of Pharmacy, Pt. R. S.S.U., Raipur, Chhattisgarh, India; Shri Rawatpura Sarkar Institute of Pharmacy, Kumhari, Durg, Chhattisgarh, India. Electronic address: beenagidwani@gmail.com.
Bina
B
Gidwani
University Institute of Pharmacy, Pt. R. S.S.U., Raipur, Chhattisgarh, India; Shri Rawatpura Sarkar Institute of Pharmacy, Kumhari, Durg, Chhattisgarh, India; University of Minnesota, Minneapolis, MN, United States. Electronic address: ambervyas@gmail.com.
Amber
A
Vyas
D000284:Administration, Oral; D006585:Altretamine / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D000818:Animals; D001682:Biological Availability; D004337:Drug Carriers / Q000737:chemistry*; D004811:Epichlorohydrin / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D047392:beta-Cyclodextrins / Q000737:chemistry*
D004337:Drug Carriers; D008055:Lipids; D047392:beta-Cyclodextrins; D004811:Epichlorohydrin; C031215:betadex; D006585:Altretamine
Altretamine; Epichlorohydrin beta cyclodextrin; Pharmacokinetics