The roles of acidifiers in solid dispersions and physical mixtures.
The roles of acidifiers in polyvinylpyrrolidone-based solid dispersions and physical mixtures were originally investigated on dissolution rate of drug, acidifier release, structural crystallinity and micro-environmental pH. A poorly water-soluble and weakly basic isradipine was used as a model drug. The solid dispersion and physical mixtures were prepared with drug and polyvinylpyrrolidone without or with pH modifiers using the solvent evaporation method and then compressed into tablet. The dissolution rate of drug from solid dispersions containing acidifiers were more pronounced when compared to physical mixtures. The dissolution rate of isradipine from solid dispersion was ranked by acidifiers in a decreasing order: fumaric acid, citric acid, glycolic acid and malic acid. In contrast, the acidifiers in physical mixtures had no significant difference in drug dissolution rate. It was attributed by the rank of acidifiers leading to the decrease of micro-environmental pH and slower release rate of acidifier as well as the maintenance of structural amorphousness. The selection of acidifiers with optimal micro-environmental pH, retarded release rate and maintaining structural amorphousness of drug could maximize the dissolution rate of weakly basic drug in solid dispersion.
Bioavailability Control Laboratory, College of Pharmacy, Kangwon National University, 192-1 Hyoja-Dong, Chuncheon 200-701, Republic of Korea.
Thao Truong-Dinh
TT
Tran
Phuong Ha-Lien
PH
Tran
Han-Gon
HG
Choi
Hyo-Kyung
HK
Han
Beom-Jin
BJ
Lee
D002626:Chemistry, Pharmaceutical / Q000379:methods*; D019343:Citric Acid / Q000737:chemistry / Q000493:pharmacokinetics; D003460:Crystallization / Q000379:methods; D004304:Dosage Forms; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism*; D012995:Solubility
D004304:Dosage Forms; D004364:Pharmaceutical Preparations; D019343:Citric Acid