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1.  Parenteral Delivery of HPβCD: Effects on Drug-HSA Binding 
AAPS PharmSciTech  2010;11(3):1152-1158.
It is thought that cyclodextrins, such as 2-hydroxypropyl-β-cyclodextrin (HPβCD), will at high concentration affect pharmacokinetics of drugs through competitive binding with plasma proteins. Albumin is the major component of plasma proteins responsible for plasma protein binding. The purpose of this study was to evaluate in vitro the competitive binding of drugs between human serum albumin (HSA) and HPβCD in isotonic pH 7.4 phosphate buffer saline solution (PBS) at ambient temperature. Eight model drugs were selected based on their physicochemical properties and ability to form complexes with HSA and HPβCD. The drug/HPβCD stability constants (K1:1) were determined by the phase-solubility method and HSA/HPβCD competitive binding determined by an equilibrium dialysis method. Protein binding of drugs that are both strongly protein bound and have high affinity to HPβCD (i.e., have high K1:1 value) is most likely to be affected by parenterally administered HPβCD. However, this in vitro study indicates that even for those drugs single parenteral dose of HPβCD has to be as high as 70 g to have detectable effect on their protein binding. Weakly protein bound drugs and drugs with low affinity towards HPβCD are insensitive to the cyclodextrin presence regardless their lipophilic properties.
PMCID: PMC2974121  PMID: 20658211
2-hydroxypropyl-β-cyclodextrin; competitive binding; equilibrium dialysis; human serum albumin; parenteral delivery; stability constant
2.  Solvation and hydration characteristics of ibuprofen and acetylsalicylic acid 
AAPS PharmSci  2004;6(1):22-30.
Ibuprofen and acetylsalicylic acid were studied by thermoanalytical methods: sublimation calorimetry, solution calorimetry, and with respect to solubility. Upon measuring the temperature dependences of the saturated vapor pressure, enthalpies of sublimation, ΔHsub0, as well as the entropies of sublimation, ΔHsub0, and their respective relative fractions in the total process were calculated. The Gibbs energy of solvation in aliphatic alcohols as well as the enthalpic and entropic fractions thereof were also studied and compared with the respective properties of model substances and other nonsteroidal antiinflammatory drugs (benzoic acid, diflunisal, flurbiprofen, ketoprofen, and naproxen). In all cases, enthalpy was found to be the driving force of the solvation process. Correlations were derived between Gibbs energy of solvation in octanol, ΔGsolvOct, and the transfer Gibbs energy from water to octanol, ΔGtr0. Influence of mutual octanol and water solubilities on the driving force of partitioning is discussed. An enthalpy-entropy-compensation effect in octanol was observed, and consequences of deviation from the general trend are also discussed.
PMCID: PMC2750938  PMID: 18465255
ibuprofen; acetylsalicylic acid; NSAID; sublimation; solvation; hydration; plasma half-life

Results 1-2 (2)