title: Design of in situ dispersible and calcium cross-linked alginate pellets as intestinal-specific drug carrier by melt pelletization technique.
abstract: Conventional alginate pellets underwent rapid drug dissolution and loss of multiparticulate characteristics such as aggregation in acidic medium, thereby promoting oral dose dumping. This study aimed to design sustained-release dispersible alginate pellets through rapid in situ matrix dispersion and cross-linking by calcium salts during dissolution. Pellets made of alginate and calcium salts were prepared using a solvent-free melt pelletization technique that prevented reaction between processing materials during agglomeration and allowed such a reaction to occur only in dissolution phase. Drug release was remarkably retarded in acidic medium when pellets were formulated with water-soluble calcium acetate instead of acid-soluble calcium carbonate. Different from calcium salt-free and calcium carbonate-loaded matrices that aggregated or underwent gradual erosion, rapid in situ solvation of calcium acetate in pellets during dissolution resulted in burst of gas bubbles, fast pellet breakup, and dispersion. The dispersed fragments, though exhibiting a larger specific surface area for drug dissolution than intact matrix, were rapidly cross-linked by Ca(2+) from calcium acetate and had drug release retarded till a change in medium pH from 1.2 to 6.8. Being dispersible and pH-dependent in drug dissolution, these pellets are useful as multiparticulate intestinal-specific drug carrier without exhibiting dose dumping tendency of a "single-unit-like" system via pellet aggregation.
authors.affiliation: Particle Design Research Group, Faculty of Pharmacy, Universiti Teknologi MARA, 42300 Puncak Alam, Selangor, Malaysia.
authors.forename: Harjoh
authors.initials: H
authors.lastname: Nurulaini
authors.forename: Tin Wui
authors.initials: TW
authors.lastname: Wong
mesh_terms: D000085:Acetates / Q000737:chemistry; D000464:Alginates / Q000737:chemistry*; D002119:Calcium Carbonate / Q000737:chemistry; D017610:Calcium Compounds / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D003432:Cross-Linking Reagents / Q000737:chemistry*; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry*; D015195:Drug Design; D005750:Gastric Juice / Q000737:chemistry; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D007419:Intestinal Secretions / Q000737:chemistry; D007422:Intestines; D007700:Kinetics; D008855:Microscopy, Electron, Scanning; D008954:Models, Biological; D010316:Particle Size; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D000085:Acetates; D000464:Alginates; D017610:Calcium Compounds; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D006603:Hexuronic Acids; D020723:Glucuronic Acid; D002119:Calcium Carbonate; C120662:calcium acetate