title: pH-independent drug release of an extremely poorly soluble weakly acidic drug from multiparticulate extended release formulations.
abstract: Extended release mini matrix tablets for 8-Prenylnaringenin (8-PN), an extremely poorly soluble weakly acidic drug, were developed by using polyvinylacetate/polyvinylpyrrolidone as matrix former. Mini matrix tablets were manufactured by direct compression or wet granulation technique. With conventional modified release formulations, the drug demonstrated pH-dependent release due to pH-dependent solubility of the drug substance (i.e., increasing solubility at higher pH-values). In order to achieve pH-independent drug release two classes of pH-modifying agents (water-soluble vs. water-insoluble) were studied with respect to their effect on the dissolution of 8-PN. Addition of water-soluble salts of weak acids (sodium carbonate and sodium citrate) failed in order to achieve pH-independent 8-PN release. In contrast, addition of water insoluble salts of a strong base (magnesium hydroxide and magnesium oxide) was found to maintain high pH-values within the mini matrix tablets during release of 8-PN at pH 1 over a period of 10 h. The micro-environmental conditions for the dissolution of the weakly acidic drug were kept almost constant, thus resulting in pH-independent drug release. Compound release from mini matrix tablets prepared by wet granulation was faster compared to the drug release from tablets prepared by direct compression.
authors.affiliation: Pharmaceutical Development, Schering AG, Berlin, Germany.
authors.forename: Therese
authors.initials: T
authors.lastname: Riis
authors.forename: Annette
authors.initials: A
authors.lastname: Bauer-Brandl
authors.forename: Torsten
authors.initials: T
authors.lastname: Wagner
authors.forename: Heiko
authors.initials: H
authors.lastname: Kranz
mesh_terms: D002130:Calcium Phosphates / Q000737:chemistry; D002254:Carbonates / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D002951:Citrates / Q000737:chemistry; D003692:Delayed-Action Preparations; D005079:Excipients / Q000737:chemistry*; D044950:Flavanones / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D007785:Lactose / Q000737:chemistry; D008276:Magnesium Hydroxide / Q000737:chemistry; D008277:Magnesium Oxide / Q000737:chemistry; D017633:Magnesium Silicates / Q000737:chemistry; D011205:Povidone / Q000737:chemistry; D000077559:Sodium Citrate; D012995:Solubility; D013213:Starch / Q000737:chemistry; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods; D014867:Water / Q000737:chemistry
chemical_list: C119737:8-prenylnaringenin; D002130:Calcium Phosphates; D002254:Carbonates; D002951:Citrates; D003692:Delayed-Action Preparations; D005079:Excipients; D044950:Flavanones; D017633:Magnesium Silicates; D013607:Tablets; D014867:Water; D000077559:Sodium Citrate; D008277:Magnesium Oxide; C005686:sodium carbonate; D013213:Starch; C020243:calcium phosphate; C001671:magnesium trisilicate; D011205:Povidone; D007785:Lactose; D008276:Magnesium Hydroxide