Biomedical subjects

J K Guillory

Publications and source records attributed to J K Guillory.

At least 19 recordsLinked to original sources

PubMed1992

A high-performance liquid chromatographic method for the quantitative enantioselective analysis of mefloquine stereoisomers.

A rapid quantitative, enantioselective HPLC method for the analysis of the four stereoisomers, (+) and (-) erythro and (+) and (-) threo forms, of mefloquine has been developed using a Chiralpak Ad analytical column containing amylose tris-3,5-dimethylphenyl carbonate coated on silica gel and hexane/ethanol/diethylamine (96:4:0.1, v/v%) as the mobile phase. This method made it possible to quantitate small amounts of threo form in the presence of the erythro form of mefloquine, the form which is used as the active ingredient in commercial mefloquine tablets. Tablets from three sources were studied to estimate their optical purity, and it was found that tablets from one source contain 0.27 w/w% of the (-)-threo and 0.25 w/w% of the (+)-threo form, tablets from the second source contain 0.056 and 0.042 w/w% (-)- and (+)-threo, respectively, and tablets from the third source contain 0.052 w/w% (+)-threo, with the remainder erythro.

Chromatography, High Pressure Liquid↗

PubMed1991

Physical properties of the complexes formed between heptakis(2,6-di-O-methyl)-beta-cyclodextrin, beta-cyclodextrin, and chlorambucil.

The solid complex of chlorambucil (CHL) and heptakis-(2,6-di-O-methyl)-beta-cyclodextrin (DIMEB) has been isolated from ethanol and analyzed by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and powder X-ray diffractometry. The carbonyl stretching band of the complex, observed in the FTIR spectrum, was shifted to higher frequency, suggesting that intermolecular hydrogen bonds between CHL molecules are broken when the complex is formed. Since no melting endotherm was observed for CHL when the DSC thermogram of the complex was obtained, the crystal lattice of the compound must be disrupted upon complexation. X-ray diffraction patterns of the inclusion complex were different from those of the physical mixture and contained no peaks corresponding to free CHL, thus indicating the formation of a new crystalline material. The 1:1 CHL:beta-cyclodextrin (beta-CD) complex was isolated from aqueous solution at 3 degrees C. Results of analyses using FTIR and DSC were similar to those obtained with the CHL:DIMEB complex. The X-ray diffraction patterns of the complex suggest that its degree of crystallinity is higher than that of the CHL:DIMEB complex.

Calorimetry, Differential Scanning↗

PubMed1991

Microcalorimetric investigation of the complexation between 2-hydroxypropyl-beta-cyclodextrin and amine drugs with the diphenylmethyl functionality.

Solution calorimetry has been employed to evaluate the stability constants and standard-enthalpy changes (delta H degrees) associated with complex formation between 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and a group of amine compounds having the diphenylmethyl functionality in aqueous solution at 298.15 K. Data from microcalorimetric titrations of the compounds were analysed using a nonlinear least-squares method. Of the 12 compounds studied, only terfenadine.HCl formed a 1:2 (compound:HP-beta-CD) complex. All the others formed 1:1 complexes. The standard free energy decrease accompanying the formation of inclusion complexes is generally due to a negative delta H degrees. This exothermic delta H degrees can be interpreted as indicating that the binding forces for complexation include both the hydrophobic effect and strong van der Waals interactions. When a halogen substituent is in the aromatic ring, stability constants are higher and standard-entropy changes (delta S degrees) become positive, suggesting greater hydrophobic interaction. Both adiphenine.HCl and proadifen.HCl form more stable complexes, suggesting that hydrogen bonding to the carbonyl oxygen by the hydroxyl-group on the rim of the CD ring could be an important contributor to the complexation. Substitution on the aliphatic carbon of the diphenylmethyl group was also found to be important in determining the ability of compounds to bind with HP-beta-CD. The independence of the thermodynamic constants on the degree of protonation in the case of bifunctional amines indicates that the amine functional groups do not penetrate into the HP-beta-CD cavity.

2-Hydroxypropyl-beta-cyclodextrin↗

PubMed1991

Structural effects on the binding of amine drugs with the diphenylmethyl functionality to cyclodextrins. II. A molecular modeling study.

Molecular modeling has been used to study the complexation between alpha, beta, or gamma-cyclodextrin (CD) and a group of amine compounds having the diphenylmethyl functionality. The computer program SYBYL 5.3 and the Tripos force field (version 5.2) were used for all the calculations. Three-dimensional structures of 13 amine compounds were built individually from their atoms, and CDs were built based on the X-ray crystallographic coordinates. The diphenylmethyl derivative-CD complexes were constructed and optimized. Based on the calculated binding energies accompanying the inclusion process, the preferred method of approach of the compounds to the cavities of the CD molecules, and the structural effects on the binding between amine compounds and three CDs were explored. The calculated binding energies exhibited a good correlation with the stability constants obtained from solution calorimetric titrations. The present study shows that for similar ligand molecules, the molecular modeling technique should enable us to visualize the structure of the inclusion complexes and will also assist us in determining the ability of a potential drug molecule to form a stable complex with CDs.

Amines↗

PubMed1991

Structural effects on the binding of amine drugs with the diphenylmethyl functionality to cyclodextrins. I. A microcalorimetric study.

Solution calorimetry has been employed to evaluate the stability constants and enthalpy changes associated with complex formation between alpha-, beta, or gamma-cyclodextrin (CD) and a group of amine compounds having the diphenylmethyl functionality. Data from thermal titrations of the compounds were analyzed using nonlinear least squares. The standard free energy decrease accompanying the formation of inclusion complexes is generally due to a negative standard enthalpy change (delta H degrees). The standard entropy change (delta S degrees) was negative, except in the case of complexes formed with gamma-CD. Of the 13 compounds studied, only 2 formed complexes with 1:2 (compound:beta-CD) stoichiometry, terfenadine . HCl and cinnarizine . 2HCl. All the others formed 1:1 complexes. The structural effect on the stability constants, thermodynamics, and inclusion geometry was explored by relating the calorimetric results to the chemical structures of the guest molecules and the cavity sizes of the CD molecules. The results suggest that one of the phenyl groups of the diphenylmethyl functionality resides in the CD cavity and is in van der Waals contact with the inside wall of the CD cavity. In the case of alpha- and beta-CDs, van der Waals interaction dominates in the stabilization. On the other hand, the interaction between these compounds and gamma-CD is largely entropically driven. Adiphenine . HCl forms a more stable complex with beta-CD than proadifen . HCl, suggesting that hydrogen bonding to the carbonyl oxygen by the hydroxyl group on the rim of the CD ring can influence the strength of the binding interaction.

Calorimetry↗

PubMed1989

Physical characterization of the methanol solvate of urapidil.

The methanol solvate of urapidil was prepared and characterized by means of differential scanning calorimetry, thermogravimetric analysis, infrared spectroscopy, X-ray powder diffraction, intrinsic dissolution rate, and solution calorimetry. The stoichiometry of the urapidil:methanol solvate was found to be 1:1. The crystal and molecular structures were determined from three-dimensional X-ray data. The stability of the solvate under different storage conditions was also determined.

Calorimetry, Differential Scanning↗

PubMed1989

Heptakis(2,6-di-O-methyl)-beta-cyclodextrin complexation with the antitumor agent chlorambucil.

The effects of heptakis(2,6-di-O-methyl)-beta-cyclodextrin (DIMEB) and of beta-cyclodextrin (beta-CD) on the aqueous solubility and stability of chlorambucil (CHL) have been compared. In the presence of 1.3 x 10(-3) M DIMEB, there is a greater than 20-fold increase in the stability of chlorambucil at 37 degrees C, pH 4.13. Aqueous solubility of CHL is increased more than 40-fold in the presence of 1.74 x 10(-2) M DIMEB when the solubility is studied under conditions where degradation is minimized (3.0 degrees C, pH 4.13). In the presence of 1.3 x 10(-3) M beta-CD, there is a fourfold increase in the stability, and with 1.74 x 10(-2) M beta-CD, there is a threefold increase in the aqueous solubility of CHL under similar conditions. Stability constants of the CHL complex with DIMEB were determined kinetically and spectrophotometrically under various experimental conditions assuming 1:1 inclusion complex formation.

Chemistry, Pharmaceutical↗

PubMed1989

Quantitative Fourier transform-infrared/attenuated total reflectance (FT-IR/ATR) analysis of trimethoprim and sulfamethoxazole in a pharmaceutical formulation using partial least squares.

An alternative procedure for the simultaneous determination of trimethoprim and sulfamethoxazole in an intravenous pharmaceutical formulation is presented. Infrared spectra of 14 calibration and 6 validation samples were collected using Fourier transform-infrared/attenuated total reflectance (FT-IR/ATR). Partial least-squares (PLS) analysis of the spectral data yielded an average relative error of prediction of 0.69% for trimethoprim and 0.38% for sulfamethoxazole. Analysis of a commercial formulation gave concentration values for sulfamethoxazole and trimethoprim in close agreement with those obtained by a modification of the high-performance liquid chromatography (HPLC) assay listed in the United States Pharmacopeia (USP).

Chromatography, High Pressure Liquid↗

PubMed1988

Physical characterization of the hydrates of urapidil.

Three hydrates of urapidil were prepared and characterized by means of differential scanning calorimetry, thermogravimetric analysis, infrared spectroscopy, X-ray powder diffraction, intrinsic dissolution rates, and solution calorimetry. The stoichiometry of the urapidil hydrates was found to be 1:5, 1:3, and 1:1 (urapidil:water). The crystal and molecular structures of urapidil pentahydrate were determined from three-dimensional X-ray data. The stability of the pentahydrate and monohydrate under different storage conditions was also determined.

Chemical Phenomena↗

PubMed1979

Physical characterization of solid iopanoic acid forms.

Three solid forms of iopanoic acid were characterized by X-ray diffraction, differential scanning calorimetry, scanning electron microscopy, thermal microscopy, IR spectroscopy, and dissolution studies. X-ray analysis demonstrated that two solid forms were crystalline and that the third was amorphous. The amorphous form had been reported previously as crystalline. Enthalpies and entropies of transition were calculated using differential scanning calorimetry. A fourth form, a benzene solvate, also was isolated but proved to be too unstable at room temperature to permit conclusive characterization. The amorphous form demonstrated a 10-fold greater intrinsic dissolution rate than the commercially available form (Form I). Form II's intrinsic dissolution rate was 1.5 times greater than that of Form I. In powder dissolution studies, the peak solubilities of the different forms followed the same rank order as their intrinsic dissolution rates. Form II was relatively stable in aqueous saturated solutions, but the amorphous form was rapidly converted to Form I under similar conditions.

Calorimetry, Differential Scanning↗

PubMed1976

Effect of sulfasalazine on digoxin bioavailability.

Low levels of digoxin were noted in a patient receiving digoxin and sulfasalazine (SSA). Discontinuation of SSA resulted in a significant increase in serum digoxin levels. To determine whether or not SSA consistently interfered with the therapeutic effect of digoxin, both drugs were administered to 10 normal subjects in a crossover study. Each received 2 doses of digoxin (0.5 mg, elixir): one dose given alone, and a second dose after 6 days of treatment with SSA. When digoxin was given with SSA, the average area under the serum digoxin curve fell from the control value of 8.79 ng-hr-ml(-1) to 6.66 ng-hr-ml(-1) (p less than 0.05), fell and total urinary excretion decreased from 278 mcg/10 days to 228 mcg/10 days (p less than 0.025). These changes suggest interference with the bioavailability of digoxin by SSA. Studies were conducted to determine whether SSA inhibited digoxin absorption by physically absorbing the glycoside from solution. In vitro tests failed to reveal any significant adsorptive properties for SSA.

Absorption↗

PubMed1976