title: Gastroretentive extended-release floating granules prepared using a novel fluidized hot melt granulation (FHMG) technique.
abstract: The objective of this work was to investigate the feasibility of using a novel granulation technique, namely, fluidized hot melt granulation (FHMG), to prepare gastroretentive extended-release floating granules. In this study we have utilized FHMG, a solvent free process in which granulation is achieved with the aid of low melting point materials, using Compritol 888 ATO and Gelucire 50/13 as meltable binders, in place of conventional liquid binders. The physicochemical properties, morphology, floating properties, and drug release of the manufactured granules were investigated. Granules prepared by this method were spherical in shape and showed good flowability. The floating granules exhibited sustained release exceeding 10 h. Granule buoyancy (floating time and strength) and drug release properties were significantly influenced by formulation variables such as excipient type and concentration, and the physical characteristics (particle size, hydrophilicity) of the excipients. Drug release rate was increased by increasing the concentration of hydroxypropyl cellulose (HPC) and Gelucire 50/13, or by decreasing the particle size of HPC. Floating strength was improved through the incorporation of sodium bicarbonate and citric acid. Furthermore, floating strength was influenced by the concentration of HPC within the formulation. Granules prepared in this way show good physical characteristics, floating ability, and drug release properties when placed in simulated gastric fluid. Moreover, the drug release and floating properties can be controlled by modification of the ratio or physical characteristics of the excipients used in the formulation.
authors.affiliation: The Drug Delivery and Biomaterials Group, School of Pharmacy, Medical Biology Centre, Queen's University Belfast , 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, U.K.
authors.forename: H
authors.initials: H
authors.lastname: Zhai
authors.forename: D S
authors.initials: DS
authors.lastname: Jones
authors.forename: C P
authors.initials: CP
authors.lastname: McCoy
authors.forename: A M
authors.initials: AM
authors.lastname: Madi
authors.forename: Y
authors.initials: Y
authors.lastname: Tian
authors.forename: G P
authors.initials: GP
authors.lastname: Andrews
mesh_terms: D002152:Calorimetry, Differential Scanning; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D004339:Drug Compounding; D005079:Excipients / Q000737:chemistry*; D005223:Fats / Q000737:chemistry; D005227:Fatty Acids / Q000737:chemistry; D008795:Metronidazole / Q000737:chemistry; D008962:Models, Theoretical; D009821:Oils / Q000737:chemistry; D017693:Sodium Bicarbonate / Q000737:chemistry; D013818:Thermogravimetry
chemical_list: D005079:Excipients; D005223:Fats; D005227:Fatty Acids; D009821:Oils; C071184:Gelucire 50-13; D008795:Metronidazole; C086409:glyceryl behenate; D017693:Sodium Bicarbonate; D002482:Cellulose; C008079:hydroxypropylcellulose
keywords: FMHG; floating granules; gastroretention; granulation; metronidazole; oral drug delivery