title: Enhanced dissolution and oral bioavailability of nifedipine by spontaneous emulsifying powders: effect of solid carriers and dietary state.
abstract: The objective of this study was to prepare spontaneous emulsifying powder (SEP) for improving dissolution and enhancing oral bioavailability of a poorly water-soluble drug, nifedipine (NDP). In order to investigate the effects of solid carrier properties, such as surface area and pore size, and a concurrent food intake on absorption of NDP in rats, different SEP formulations were prepared by adsorbing liquid spontaneous emulsifying formulation (SEF), composing of polyoxyl 35 castor oil, caprylic/capric glyceride and diethylene glycol monoethyl ether at a ratio of 1:1:8, onto various solid carriers (i.e., silica (FS), porous calcium silicate (PCS) and porous silicon dioxide). The solid characterization by scanning electron microscopy, differential scanning calorimetry and powder X-ray diffraction revealed the absence of crystalline NDP in the formulations. SEP also demonstrated excellent spontaneous emulsification properties similar to SEF. The droplet size of emulsions formed after dilution was less than 200 nm. The solid carriers (particularly PCS) had significant and positive effect in drug dissolution; the mean dissolution time of SEP containing PCS was considerably improved. SEP also provided a good stability after storage in accelerated and long-term conditions for 6 months. The bioavailability study resulted in enhanced values of C(max) and AUC for SEP formulations, when tested in both fasted and fed rats. Furthermore, comparing the AUC in fasted and fed rats, NDP powder exhibited a significant food effect. The difference in bioavailability of NDP in fed compared to fasted state can be avoided by using SEP.
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, Thailand; Pharmaceutical Biopolymer Group (PBiG), Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, Thailand.
authors.forename: Yotsanan
authors.initials: Y
authors.lastname: Weerapol
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, Thailand; Pharmaceutical Biopolymer Group (PBiG), Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, Thailand.
authors.forename: Sontaya
authors.initials: S
authors.lastname: Limmatvapirat
authors.affiliation: Department of Thai Medicine, Faculty of Traditional Thai Medicine, Prince of Songkla University, Songkhla, Thailand.
authors.forename: Chaweewan
authors.initials: C
authors.lastname: Jansakul
authors.affiliation: Laboratory of Pharmaceutical Engineering, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Takeuchi
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, Thailand; Pharmaceutical Biopolymer Group (PBiG), Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, Thailand. Electronic address: sriamornsak_p@su.ac.th.
authors.forename: Pornsak
authors.initials: P
authors.lastname: Sriamornsak
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002121:Calcium Channel Blockers / Q000008:administration & dosage* / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics; D017610:Calcium Compounds / Q000737:chemistry*; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000008:administration & dosage* / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics; D065546:Drug Liberation; D004355:Drug Stability; D004356:Drug Storage; D004655:Emulsions; D018565:Food-Drug Interactions; D007408:Intestinal Absorption; D008297:Male; D009543:Nifedipine / Q000008:administration & dosage* / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics; D010316:Particle Size; D016062:Porosity; D011208:Powders; D017208:Rats, Wistar; D017640:Silicates / Q000737:chemistry*; D012822:Silicon Dioxide / Q000737:chemistry*; D013499:Surface Properties
chemical_list: D002121:Calcium Channel Blockers; D017610:Calcium Compounds; D004337:Drug Carriers; D004655:Emulsions; D011208:Powders; D017640:Silicates; D012822:Silicon Dioxide; D009543:Nifedipine; C031293:calcium silicate
keywords: Nifedipine; Poorly water-soluble drug; Porous calcium silicate; Silica derivatives; Spontaneous emulsifying formulation; Spontaneous emulsifying powder