title: Preparation of pH-sensitive beads for NSAID using three-component gel systems.
abstract: The aim of this study is to prepare novel pH-sensitive beads to obtain a gastric mucosa protective formulation and to ensure drug delivery into the intestine. Diclofenac sodium was used as a model drug. Bead formation was achieved by ionotropic gelation method using three-component gel system containing sodium alginate (Na-Alg), hydroxyethylcellulose (HEC) and hydroxypropylmethylcellulose (HPMC). Factors influencing the characteristics of beads (exposure time, cross-linking agent concentration, polymer ratio) were investigated by swelling and erosion tests based on gravimetric method. Drug release was tested in distilled water and/or artificial digestive fluids and evaluated with Korsmeyer-Peppas equation and Baker-Lonsdale model. The encapsulation behaviour was qualitatively indicated by differential scanning calorimetry (DSC) method. In vivo experiments were conducted to test ulcerogenicity and intestinal absorption in rats. HPMC increased the encapsulation efficiency (EE) and HEC improved the drug release in the intestinal fluids. The equilibrium water uptake (EWU) was correlated with exposure time, calcium chloride concentration and HEC amounts. Bead erosion increased proportionately to exposure time, while it reduced when calcium chloride concentrations were increased. Higher amounts of HEC increased, while higher pH values reduced the encapsulation efficacy. The in vivo experiments demonstrated that the studied encapsulation technology markedly reduced the ulcerogenic effect of diclofenac.
authors.affiliation: Department of Pharmaceutics, Semmelweis University, Hogyes E. Str. 7., H-1092 Budapest, Hungary. zsfenyvesi@gmail.com
authors.forename: Zsófia
authors.initials: Z
authors.lastname: Fenyvesi
authors.forename: Alíz
authors.initials: A
authors.lastname: Auner
authors.forename: Dirk
authors.initials: D
authors.lastname: Schmalz
authors.forename: Eszter
authors.initials: E
authors.lastname: Pásztor
authors.forename: Gabriella
authors.initials: G
authors.lastname: Csóka
authors.forename: Klára
authors.initials: K
authors.lastname: Gyires
authors.forename: Sylvia
authors.initials: S
authors.lastname: Marton
authors.forename: Imre
authors.initials: I
authors.lastname: Klebovich
authors.forename: István
authors.initials: I
authors.lastname: Antal
mesh_terms: D000464:Alginates / Q000737:chemistry; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D003460:Crystallization; D004008:Diclofenac / Q000737:chemistry; D004304:Dosage Forms; D016503:Drug Delivery Systems / Q000379:methods; D005782:Gels; D006863:Hydrogen-Ion Concentration; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D008863:Microspheres; D010316:Particle Size; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D000464:Alginates; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004304:Dosage Forms; D005782:Gels; D004008:Diclofenac; D065347:Hypromellose Derivatives; D008747:Methylcellulose