Characteristics of drug substances in oily solutions. Drug release rate, partitioning and solubility.
In vitro rate of drug release from oil solutions was investigated in a rotating dialysis cell. A log linear correlation was established between the rate constant (k(obs)) for attainment of equilibrium and apparent partition coefficient (P(app)) between oil vehicle and release media using various weak acids and bases and non-electrolytes. Collander like linear free energy relationships were observed allowing various oil-aqueous buffer partition coefficients to be calculated from known octanol-aqueous buffer partition coefficients. Solubility of the various drug substances in oil vehicles were investigated. A linear correlation was observed between log molar solubility and melting point of the solutes. Release profiles obtained for release of two local anaesthetics dissolved in the same oil vehicle exhibited an unexpected behavior involving an initial delayed release of the most lipophilic local anaesthetic.
Larsen
Dorrit Bjerg
DB
Department of Analytical and Pharmaceutical Chemistry, The Royal Danish School of Pharmacy, Universitetsparken 2, DK-2100, Copenhagen, Denmark. dola@dfh.dk
Parshad
Henrik
H
Fredholt
Karin
K
Larsen
Claus
C
D000779:Anesthetics, Local / Q000737:chemistry*; D002045:Bupivacaine / Q000737:chemistry*; D003692:Delayed-Action Preparations; D009821:Oils / Q000737:chemistry*; D011318:Prilocaine / Q000737:chemistry*; D012995:Solubility
D000779:Anesthetics, Local; D003692:Delayed-Action Preparations; D009821:Oils; D011318:Prilocaine; D002045:Bupivacaine