betadex and tartaric-acid

Haloperidol (HALO) is a weak base with very low aqueous solubility that is used as an antipsychotic drug. This study aimed to improve its solubility by forming HALO/β-cyclodextrin (β-CD)-based ternary complexes with organic acids. The solubility of HALO/β-CD binary and HALO/β-CD/organic acid ternary complexes in different media (i.e. citrate buffer pH 3 and 6) was explored. The stoichiometric ratio between the drug and β-CD was 1:1 in all complexes formed. The solubility of HALO/β-CD binary complexes significantly increased in citrate buffer pH 3 compared with citrate buffer pH 6. For the ternary complexes, HALO/β-CD/tartaric acid and HALO/β-CD/lactic acid in citrate buffer pH 3 increased HALO solubility compared with HALO/β-CD/succinic acid due to their higher unionized species. The highest stability constant and complexation efficiency values in citrate buffer pH 3 were shown by the ternary complexes with lactic acid followed by tartaric acid and succinic acid, respectively. Results indicated that lactic acid provided the greatest binding strength and solubilization efficiency for the complex.

Topics: Antipsychotic Agents; beta-Cyclodextrins; Drug Carriers; Drug Compounding; Haloperidol; Lactic Acid; Solubility; Succinic Acid; Tartrates; Water

In this study, a triple recognition chiral extraction process has been developed to separate (S)-amlodipine from racemic raw medicine, based on the combination of molecularly imprinted hollow fiber membrane and cross-flow biphasic recognition extraction. The chiral separation process was operated in a dismountable hollow fiber module coated with molecularly imprinted polymer, and the cross-flow extraction was applied with d-tartaric acid in feed phase and sulfobutyl ether-β-cyclodextrin in stripping phase. The synergistic effect of molecularly imprinted polymer and dual chiral additives was investigated, and excellent enantioseparation ability with a selectivity factor of 1.98 was obtained. Mathematical model of S/R=0.598e

Topics: Amlodipine; beta-Cyclodextrins; Chemical Fractionation; Molecular Imprinting; Stereoisomerism; Tartrates

The purpose of this study was to develop a new delivery system based on drug cyclodextrin (CD) complexation and loading into nanostructured lipid carriers (NLC) to improve the oral bioavailability of vinpocetine (VP). Three different CDs and three different methods to obtain solid vinpocetine-cyclodextrin-tartaric acid complexes (VP-CD-TA) were contrasted. The co-evaporation vinpocetine-β-cyclodextrin-tartaric acid loaded NLC (VP-β-CD-TA COE-loaded NLC) was obtained by emulsification ultrasonic dispersion method. VP-β-CD-TA COE-loaded NLC was suitably characterized for particle size, polydispersity index, zeta potential, entrapment efficiency and the morphology. The crystallization of drug in VP-CD-TA and NLC was investigated by differential scanning calorimetry (DSC). The in vitro release study was carried out at pH 1.2, pH 6.8 and pH 7.4 medium. New Zealand rabbits were applied to investigate the pharmacokinetic behavior in vivo. The VP-β-CD-TA COE-loaded NLC presented a superior physicochemical property and selected to further study. In the in vitro release study, VP-β-CD-TA COE-loaded NLC exhibited a higher dissolution rate in the pH 6.8 and pH 7.4 medium than VP suspension and VP-NLC. The relative bioavailability of VP-β-CD-TA COE-loaded NLC was 592% compared with VP suspension and 92% higher than VP-NLC. In conclusion, the new formulation significantly improved bioavailability of VP for oral delivery, demonstrated a perspective way for oral delivery of poorly water-soluble drugs.

Topics: Administration, Oral; Animals; beta-Cyclodextrins; Biological Availability; Calorimetry, Differential Scanning; Chemistry, Pharmaceutical; Drug Carriers; Hydrogen-Ion Concentration; Lipids; Male; Nanostructures; Nanotechnology; Rabbits; Solubility; Tartrates; Technology, Pharmaceutical; Vinca Alkaloids; Water

(1)H NMR spectrometry, FT-IR spectroscopy, as well as molecular modeling at the AM1 level and normal mode analysis were used to characterise the interactions and the formation of inclusion complexes between three organic acids: maleic, fumaric, L-tartaric acids and betaCD. In aqueous medium, the complexation was confirmed by (1)H NMR spectroscopy using two-dimensional technique. The stable geometries of the complexes were determined by molecular modeling. Experimental infrared frequencies were assigned on the base of the vibrational normal mode calculation at the fully optimized geometry for the inclusion complexes. All the results point out the presence of stable inclusion complexes between acids and betaCD at the solid state. These results show the double role of the acid. Correlated with the theoretical and experimental data previously obtained for the miconazole/CD/acids complexes, in function of both acids and CDs structures, the acids can either stabilize the complexes by formation of a multicomponent complex or form acid/CD inclusion complexes, hindering the guest inclusion.

Topics: beta-Cyclodextrins; Dicarboxylic Acids; Fumarates; Hydrogen Bonding; Magnetic Resonance Spectroscopy; Maleates; Miconazole; Models, Molecular; Pharmaceutical Vehicles; Spectroscopy, Fourier Transform Infrared; Tartrates; Thermodynamics

The objective of this study was to investigate the effect of multicomponent complexation (MCC) of vinpocetine (VP), a poorly soluble base-type drug, with beta-cyclodextrin (betaCD), sulfobutylether beta-cyclodextrin (SBEbetaCD), tartaric acid (TA), polyvinylpyrrolidone (PVP) and hydroxypropylmethylcellulose (HPMC), on the design of controlled release hydrophilic HPMC tablets and to evaluate their in vitro release profiles by a pH gradient method. Multicomponent complexation led to enhanced dissolution properties of VP both in simulated gastric and intestinal fluids, and became possible the development of HPMC tablet formulations with more independent pH dissolution profiles. Drug release process was investigated experimentally using USP apparatus 3 and by means of model-independent parameters. Responses studied included similarity of dissolution profiles, time for 60% of the drug to dissolve (T(60%)), percent of VP released after 7 h (PD(7 h)) and the dissolution efficiency parameter at 12 h (DE(12 h)). Influence of multicomponent complexation was proved to increase the release of VP from HPMC tablets and superior PD(7 h) and DE(12 h) values were obtained in formulations containing VP-CD-TA complexes. Results supported the use of HPMC matrices to provide a useful tool in retarding the release of VP and that dissolution characteristics of the drug may be modulated by multicomponent complexation in these delivery systems, suggesting an improvement on VP bioavailability.

Topics: beta-Cyclodextrins; Body Fluids; Drug Compounding; Gastric Mucosa; Humans; Hydrogen-Ion Concentration; Hypromellose Derivatives; Intestinal Mucosa; Kinetics; Methylcellulose; Models, Biological; Solubility; Tablets, Enteric-Coated; Tartrates; Vinca Alkaloids

1H NMR spectroscopy was used for determining the optical purity of cis-ketoconazole enantiomers obtained by fractional crystallization. The chiral analysis was carried out using beta-cyclodextrin in the presence of (+)-L-tartaric acid. The mechanism of the chiral discrimination process, the stability of the complexes formed, and their structure in aqueous solution were also investigated by 1H and 13C chemical shift analysis, two-dimensional NOE experiments, relaxation time measurements, and mass spectrometry experiments. Theoretical models of the three-component interaction were built up on the basis of the available NMR data, by performing a conformational analysis on the relevant fragments on ketoconazole and docking studies on the components of the complex. The model derived from a folded conformation of ketoconazole turned out to be fully consistent with the molecular assembly found in aqueous solution, as inferred from NOE experiments. An explanation of the different association constants for the complexes of the two enantiomers is also provided on the basis of the interaction energies.

Topics: Antifungal Agents; beta-Cyclodextrins; Cyclodextrins; Drug Interactions; Drug Stability; Ketoconazole; Mass Spectrometry; Models, Molecular; Molecular Conformation; Nuclear Magnetic Resonance, Biomolecular; Protons; Solutions; Stereoisomerism; Tartrates; Thermodynamics; Water