betadex and n-hexadecane

The purpose of this study was to investigate the interaction of 2-hydroxypropyl-β-cyclodextrin (HPβCD) and 2,6-dimethyl-β-cyclodextrin (DMβCD) with the lipophilic drug nifedipine and to investigate the subsequent solubility-permeability interplay. Solubility curves of nifedipine with HPβCD and DMβCD in MES buffer were evaluated using phase solubility methods. Then, the apparent permeability of nifedipine was investigated as a function of increasing HPβCD/DMβCD concentration in the hexadecane-based PAMPA model. The interaction with nifedipine was CD dependent; significantly higher stability constant was obtained for DMβCD in comparison with HPβCD. Moreover, nifedipine displays different type of interaction with these CDs; a 1:1 stoichiometric inclusion complex was apparent with HPβCD, while 1:2 stoichiometry was apparent for DMβCD. In all cases, decreased apparent intestinal permeability of nifedipine as a function of increasing CD level and nifedipine apparent solubility was obtained. A quasi-equilibrium mass transport analysis was developed to explain this solubility-permeability interplay; the model enabled excellent quantitative prediction of nifedipine's permeability as a function of CD concentrations. This work demonstrates that when using CDs in solubility-enabling formulations, a trade-off exists between solubility increase and permeability decrease that must not be overlooked. This trade-off was found to be independent of the type of CD-drug interaction. The transport model presented here can aid in striking the appropriate solubility-permeability balance in order to achieve optimal overall absorption.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Absorption; Alkanes; beta-Cyclodextrins; Biological Transport; Calcium Channel Blockers; Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Cyclodextrins; Drug Delivery Systems; Drug Interactions; Humans; Intestinal Absorption; Intestines; Nifedipine; Permeability; Solubility

Soil was spiked with [9-(14)C]phenanthrene and [1-(14)C]hexadecane at 50 mg kg(-1) and aged for 1, 25, 50, 100 and 250 d. At each time point, the microcosms were amended with aqueous solutions of cyclodextrin (HP-beta-CD) at a range of concentrations (0-40 mM). Mineralisation assays and aqueous HP-beta-CD extractions were performed to assess the effect of the amendments on microbial degradation. The results showed that amendments had no significant impact on the microbial degradation of either of the (14)C-contaminants. Further, HP-beta-CD extractions were correlated with the mineralisation of the target chemicals in each of the soil conditions. It was found that the HP-beta-CD extraction was able to predict mineralisation in soils which had not been amended with cyclodextrin; however, in the soils containing the HP-beta-CD, there was no predictive relationship. Under the conditions of this study, the introduction of HP-beta-CD into soils did not enhance the biodegradation of the organic contaminants.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Alkanes; Bacteria; beta-Cyclodextrins; Biodegradation, Environmental; Carbon Radioisotopes; Environmental Restoration and Remediation; Isotope Labeling; Phenanthrenes; Soil Microbiology; Soil Pollutants

The preparation and formation mechanism of n-hexadecane/water emulsions using natural beta-cyclodextrin (beta-CD) and chemically modified beta-CDs (triacylated beta-cyclodextrins) as an emulsifier were investigated. The stable water/oil (W/O) emulsion was formed using tripropanoyl-beta-CD (TP-beta-CD). From observation using the contact angle (theta(ow)) of precipitates derived from CD, it was clarified that oil/water (O/W) emulsion at theta(ow)<90 degrees and (W/O) emulsion at theta(ow)>90 degrees are formed when the composition of each oil and water was mixed with natural beta-CD or triacylated beta-CDs.

Topics: Alkanes; beta-Cyclodextrins; Chemical Phenomena; Chemistry, Physical; Dimethyl Sulfoxide; Drug Compounding; Emulsions; Magnetic Resonance Spectroscopy; Molecular Conformation; Oils