title: α-Glucosyl hesperidin induced an improvement in the bioavailability of pranlukast hemihydrate using high-pressure homogenization.
abstract: The α-glucosyl hesperidin (Hsp-G)-induced improvement of both the dissolution and absorption properties of pranlukast hemihydrate (PLH) was achieved by means of a high-pressure homogenization (HPH) processing. The average particle size in the HPH-processed suspension was decreased significantly after 50 cycles of processing and reached a constant size of ca. 300 nm. The amount of dissolved PLH gradually increased with the pass number of HPH processing, and was extremely higher than the PLH solubility (0.8 μg/mL at 37°C) after the HPH processing. On a dissolution study of the freeze-dried sample of HPH-processed PLH/Hsp-G (1/10), the apparent solubility of PLH was at least 2.5-fold more than that of untreated PLH crystals. The transport study showed that the amount of PLH that had permeated through the Caco-2 cell monolayers was improved in the case of HPH-processed PLH/Hsp-G (1/10). The bioavailability of PLH from HPH-processed PLH/Hsp-G (1/10) showed a 3.9- and 2.2-fold improvement over the PLH crystal in terms of C(max) and AUC values, respectively. Hsp-G formed an associated structure in aqueous media. High-pressure homogenization provides a good opportunity for molecular-level interaction of PLH and the associated structure of Hsp-G to occur. The use of Hsp-G under HPH processing was a promising way to enhance the dissolution and absorption of PLH without using an organic solvent.
authors.affiliation: Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Uchiyama
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Tozuka
authors.forename: Fusatoshi
authors.initials: F
authors.lastname: Asamoto
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Takeuchi
mesh_terms: D019540:Area Under Curve; D001682:Biological Availability; D001692:Biological Transport; D018938:Caco-2 Cells; D002867:Chromones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000737:chemistry*; D005612:Freeze Drying; D005960:Glucosides / Q000737:chemistry*; D006569:Hesperidin / Q000031:analogs & derivatives* / Q000737:chemistry; D006801:Humans; D007408:Intestinal Absorption; D020024:Leukotriene Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010316:Particle Size; D010539:Permeability; D012995:Solubility
chemical_list: D002867:Chromones; D004337:Drug Carriers; D005960:Glucosides; D020024:Leukotriene Antagonists; C487382:glucosyl hesperidin; D006569:Hesperidin; C047681:pranlukast