Preparation and characterization of pH-independent sustained release tablet containing solid dispersion granules of a poorly water-soluble drug. 2011

Huyen Thi Thanh Tran, and Jun Bom Park, and Ki-Hyuk Hong, and Han-Gon Choi, and Hyo-Kyung Han, and Jaehwi Lee, and Kyung Taek Oh, and Beom-Jin Lee
Bioavailability Control Laboratory, College of Pharmacy, Kangwon National University, Chuncheon 200-701, Republic of Korea.

Sustained release (SR) tablets containing solid dispersions (SD) granules of a poorly water-soluble drug were prepared to investigate the controlled pH-independent release of the drug. Losartan potassium (LST), an anti-hypertensive agent was chosen as a model drug because of its pH-dependent solubility and short elimination half-life. Poloxamer 188 was used as an SD carrier. A free-flowing SD granule was prepared by adsorbing the melt of the drug and poloxamer 188 onto the surface of an adsorbent, Aerosil 300 (fumed silicon dioxide), followed by direct compression with polyethylene oxide (PEO, 5 × 10(6)) to obtain an SD-loaded SR (SD-SR) matrix tablet. Differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) revealed partially amorphous structures of the drug in the SD granules. Scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS) images indicated adsorption of SD granules onto the surface of the adsorbent. The SD granules dissolved completely within 10 min, a dissolution rate much higher than that of pure LST. Moreover, pH-independent sustained release of LST from the SD-SR tablet was achieved for 2h in gastric fluid (pH 1.2) and for 10h in intestinal fluid (pH 6.8). A combination of SD techniques using surface adsorption and SR concepts is a promising approach to control the release rate of poorly water-soluble drugs in a pH-independent manner.

UI MeSH Term Description Entries
D007419 Intestinal Secretions Fluids originating from the epithelial lining of the intestines, adjoining exocrine glands and from organs such as the liver, which empty into the cavity of the intestines. Intestinal Secretion,Secretion, Intestinal,Secretions, Intestinal
D008855 Microscopy, Electron, Scanning Microscopy in which the object is examined directly by an electron beam scanning the specimen point-by-point. The image is constructed by detecting the products of specimen interactions that are projected above the plane of the sample, such as backscattered electrons. Although SCANNING TRANSMISSION ELECTRON MICROSCOPY also scans the specimen point by point with the electron beam, the image is constructed by detecting the electrons, or their interaction products that are transmitted through the sample plane, so that is a form of TRANSMISSION ELECTRON MICROSCOPY. Scanning Electron Microscopy,Electron Scanning Microscopy,Electron Microscopies, Scanning,Electron Microscopy, Scanning,Electron Scanning Microscopies,Microscopies, Electron Scanning,Microscopies, Scanning Electron,Microscopy, Electron Scanning,Microscopy, Scanning Electron,Scanning Electron Microscopies,Scanning Microscopies, Electron,Scanning Microscopy, Electron
D002152 Calorimetry, Differential Scanning Differential thermal analysis in which the sample compartment of the apparatus is a differential calorimeter, allowing an exact measure of the heat of transition independent of the specific heat, thermal conductivity, and other variables of the sample. Differential Thermal Analysis, Calorimetric,Calorimetric Differential Thermal Analysis,Differential Scanning Calorimetry,Scanning Calorimetry, Differential
D003692 Delayed-Action Preparations Dosage forms of a drug that act over a period of time by controlled-release processes or technology. Controlled Release Formulation,Controlled-Release Formulation,Controlled-Release Preparation,Delayed-Action Preparation,Depot Preparation,Depot Preparations,Extended Release Formulation,Extended Release Preparation,Prolonged-Action Preparation,Prolonged-Action Preparations,Sustained Release Formulation,Sustained-Release Preparation,Sustained-Release Preparations,Timed-Release Preparation,Timed-Release Preparations,Controlled-Release Formulations,Controlled-Release Preparations,Extended Release Formulations,Extended Release Preparations,Slow Release Formulation,Sustained Release Formulations,Controlled Release Formulations,Controlled Release Preparation,Controlled Release Preparations,Delayed Action Preparation,Delayed Action Preparations,Formulation, Controlled Release,Formulations, Controlled Release,Prolonged Action Preparation,Release Formulation, Controlled,Release Formulations, Controlled,Sustained Release Preparation,Timed Release Preparation,Timed Release Preparations
D004337 Drug Carriers Forms to which substances are incorporated to improve the delivery and the effectiveness of drugs. Drug carriers are used in drug-delivery systems such as the controlled-release technology to prolong in vivo drug actions, decrease drug metabolism, and reduce drug toxicity. Carriers are also used in designs to increase the effectiveness of drug delivery to the target sites of pharmacological actions. Liposomes, albumin microspheres, soluble synthetic polymers, DNA complexes, protein-drug conjugates, and carrier erythrocytes among others have been employed as biodegradable drug carriers. Drug Carrier
D004339 Drug Compounding The preparation, mixing, and assembly of a drug. (From Remington, The Science and Practice of Pharmacy, 19th ed, p1814). Drug Formulation,Drug Preparation,Drug Microencapsulation,Pharmaceutical Formulation,Compounding, Drug,Formulation, Drug,Formulation, Pharmaceutical,Microencapsulation, Drug,Preparation, Drug
D005750 Gastric Juice The liquid secretion of the stomach mucosa consisting of hydrochloric acid (GASTRIC ACID); PEPSINOGENS; INTRINSIC FACTOR; GASTRIN; MUCUS; and the bicarbonate ion (BICARBONATES). (From Best & Taylor's Physiological Basis of Medical Practice, 12th ed, p651) Gastric Juices,Juice, Gastric,Juices, Gastric
D006863 Hydrogen-Ion Concentration The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH pH,Concentration, Hydrogen-Ion,Concentrations, Hydrogen-Ion,Hydrogen Ion Concentration,Hydrogen-Ion Concentrations
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000959 Antihypertensive Agents Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS. Anti-Hypertensive,Anti-Hypertensive Agent,Anti-Hypertensive Drug,Antihypertensive,Antihypertensive Agent,Antihypertensive Drug,Anti-Hypertensive Agents,Anti-Hypertensive Drugs,Anti-Hypertensives,Antihypertensive Drugs,Antihypertensives,Agent, Anti-Hypertensive,Agent, Antihypertensive,Agents, Anti-Hypertensive,Agents, Antihypertensive,Anti Hypertensive,Anti Hypertensive Agent,Anti Hypertensive Agents,Anti Hypertensive Drug,Anti Hypertensive Drugs,Anti Hypertensives,Drug, Anti-Hypertensive,Drug, Antihypertensive,Drugs, Anti-Hypertensive,Drugs, Antihypertensive

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