title: Drug release-modulating mechanism of hydrophilic hydroxypropylmethylcellulose matrix tablets: distribution of atoms and carrier and texture analysis.
abstract: Although release profiles of drug from hydrophilic matrices have been well recognized, the visual distribution of hydroxypropylmethylcellulose (HPMC) and atoms inside of internal structures of hydrophilic HPMC matrices has not been characterized. In this paper, drug release mechanism from HPMC matrix tablet was investigated based on the release behaviors of HPMC, physical properties of gelled HPMC tablet and atomic distributions of formulation components using diverse instruments. A matrix tablet consisting of hydroxypropyl methylcellulose (HPMC 6, 4,000 and 100,000 mPa·s), chlorpheniramine maleate (CPM) as a model and fumed silicon dioxide (Aerosil(®) 200) was prepared via direct compression. The distribution of atoms and HPMC imaging were characterized using scanning electron microscope (SEM)/ energy-dispersive X-ray spectroscopy (EDX), and near-infrared (NIR) analysis, respectively as a function of time. A texture analyzer was also used to characterize the thickness and maintenance of gel layer of HPMC matrix tablet. The HPMC matrix tablets showed Higuchi release kinetics with no lag time against the square root of time. High viscosity grades of HPMC gave retarded release rate because of the greater swelling and gel thickness as characterized by texture analyzer. According to the NIR imaging, low-viscosity-grade HPMC (6 mPa·s) quickly leached out onto the surface of the tablet, while the high-viscosity-grade HPMC (4000 mPa·s) formed much thicker gel layer around the tablet and maintained longer via slow erosion, resulting in retarded drug release. The atomic distribution of the drug (chlorine, carbon, oxygen), HPMC (carbon, oxygen) and silicon dioxide (silica, oxygen) and NIR imaging of HPMC corresponded with the dissolution behaviors of drug as a function of time. The use of imaging and texture analyses could be applicable to explain the release- modulating mechanism of hydrophilic HPMC matrix tablets.
authors.affiliation: Bioavailability Control Laboratory, College of Pharmacy, Ajou University, Suwon, Suwon 443-749, Korea. beomjinlee@gmail.com.
authors.forename: Jun-Bom
authors.initials: JB
authors.lastname: Park
authors.forename: Jisung
authors.initials: J
authors.lastname: Lim
authors.forename: Chin-Yang
authors.initials: CY
authors.lastname: Kang
authors.forename: Beom-Jin
authors.initials: BJ
authors.lastname: Lee
mesh_terms: D002626:Chemistry, Pharmaceutical; D002744:Chlorpheniramine / Q000008:administration & dosage* / Q000737:chemistry; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods; D005079:Excipients / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D012822:Silicon Dioxide / Q000737:chemistry; D013052:Spectrometry, X-Ray Emission; D019265:Spectroscopy, Near-Infrared; D013607:Tablets; D014783:Viscosity
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005079:Excipients; D013607:Tablets; D065347:Hypromellose Derivatives; D002744:Chlorpheniramine; D012822:Silicon Dioxide; D008747:Methylcellulose