title: In situ controlled crystallization as a tool to improve the dissolution of Glibenclamide.
abstract: For pharmaceutical purpose, micro-sized drugs are needed for many delivery systems, such as pulmonary and oral drug delivery systems. Many strategies have been employed to reduce the particle size of poorly water soluble drugs. Microcrystals could be produced by controlled association of drug in order to obtain naturally grown particles. The aim of this work was to increase the aqueous solubility and dissolution of Glibenclamide. The in situ controlled crystallization process was conducted in the presence of the non-ionic surfactants, Cremophor RH40 and Solutol HS-15 (0.75 and 1.5%, w/v), as protective stabilizing agents against agglomeration. In addition, these surfactants inhibit P-glycoprotein that reduces intestinal absorption of Glibenclamide by efflux transportation. Crystal shape was changed and particle size was reduced by about 15-folds, compared to control untreated drug. Differential Scanning Calorimetry (DSC) results indicated no interaction between the drug and the stabilizer. Microcrystals showed marked increase in the drug dissolution, Solutol HS-15 at 1.5% (w/v) concentration showing the highest dissolution efficiency. It could be concluded that in situ controlled crystallization using surfactants are promising method to improve dissolution of Glibeclamide as a model poorly water soluble drug.
authors.affiliation: University of Sunderland, Department of Pharmacy, Health and Well-being, Sunderland, SR1 3SD, UK. amal.elkordy@sunderland.ac.uk
authors.forename: Amal Ali
authors.initials: AA
authors.lastname: Elkordy
authors.forename: Ayobami
authors.initials: A
authors.lastname: Jatto
authors.forename: Ebtessam
authors.initials: E
authors.lastname: Essa
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors; D001692:Biological Transport / Q000187:drug effects; D002152:Calorimetry, Differential Scanning / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003460:Crystallization / Q000379:methods*; D005079:Excipients / Q000737:chemistry; D005905:Glyburide / Q000737:chemistry*; D007408:Intestinal Absorption / Q000187:drug effects; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D012995:Solubility; D013229:Stearic Acids / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods*; D014867:Water / Q000737:chemistry
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D005079:Excipients; D013229:Stearic Acids; D013501:Surface-Active Agents; D014867:Water; C022131:cremophor; D011092:Polyethylene Glycols; C067028:Solutol HS 15; D005905:Glyburide