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Biomedical subjects

J L Lach

Publications and source records attributed to J L Lach.

At least 19 recordsLinked to original sources
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↗
PubMed1977

Sustained-release applications of montmorillonite interaction with amphetamine sulfate.

Urinary recovery studies showed that montmorillonite significantly affects the initial therapeutic levels of amphetamine sulfate. The combination of a 1:20 drug-montmorillonite complex with pure drug in a 1:1 ratio, based on amphetamine content, resulted in recovery profiles resembling those obtained from prolonged-release dosage forms. The 1:20 complex, pure drug, and combination formulations showed comparable bioavailability after 48 hr.

Adult↗
PubMed1977

PH-dependent drug release from certain commercial tablets.

A dissolution-dialysis profile for each of several brands of nitrofurantoin, hydrochlorothiazide and sulfisoxazole tablets was developed at three pH levels. The study used a two-compartment diffusion cell with a semipermeable cellophane membrane. Nitrofuratoin tablets were tested at pH values of 7.2, 4.7 and 1.2; sulfisoxazole tablets at 7.2, 5.5 and less than 1. Studies with hydrochlorothiazide tablets were terminated because the pH of the dissolution medium had no effect of practical significance on dissolution or dialysis rates. The dissolution rates of the nitrofurantoin and sulfisoxazole tablets were highly brand-individualized and complex. The effects of pH upon a particular formulation were unpredictable. The results suggest that dissolution testing at one fixed pH, as commonly practiced, may be insufficient for some products. This pH-dependent release characteristic may not correspond to a change in bioavailability in all cases, but it represents a potential problem which should be considered by the formulator.

Biological Availability↗
PubMed1976

Evaluation of emulsion stability by diffuse reflectance spectroscopy.

A new method is described for evaluating the stability of emulsion bases and active components contained within such emulsions. Diffuse reflectance spectroscopy (DRS) is a technique that has the capability of detecting changes in particle size, surface properties, or drug quality of emulsions as a function of time without disturbance of the system. Such physical or chemical changes are monitored by changes in the visible and UV wavelength spectral characteristics of the emulsified systems. Four basic emulsion systems were prepared and analyzed for physical stability for 6 months by three techniques: visible coalescence, particle counting measurement, and DRS. Two drugs, aspirin and ascorbic acid, were then incorporated within stable emulsion bases, and the chemical stability of these drugs was monitored by DRS for 6 months. Results were compared with concomitant quantitative drug assay procedures. Good agreement was observed when data from DRS and analytical measurements were compared. The DRS technique may be used as a supportive method, offering simplicity and expedience, with other methods of evaluating emulsion stability and drug stability within emulsified systems.

Ascorbic Acid↗
PubMed1976

In vitro adsorption of various pharmaceutical to montmorillonite.

Dissolution and dialysis studies showed that cationic drugs and certain nonionic drugs bind strongly to montmorillonite clay. The quantity of drug bound by one unit of clay varied considerably. Anionic drugs were weakly bound, and less bioavailabilty problems would be anticipated with these medicinals. The mechanism of binding of cationic drugs to montmorillonite was proposed as a two-step process: a cation-exchange reaction followed by strong surface chemisorption.

Adsorption↗
PubMed1975

Drug diffusion and bioavailability: tetracycline metallic chelation.

The effects of chelation on the in vitro diffusion rate of tetracycline at variable pH values and concentrations was studied. A two-compartment diffusion cell using a semipermeable cellophane membrane was used to determine diffusion rates. Tetracycline in solution was mixed with aluminum, magnesium, copper, calcium and cobalt ions and analyzed by ultraviolet spectrophotometry. Diffusion rates were determined at pH 1, 5.5 and 8. Tetracycline chelate formation is pH-dependent. The diffusion rate of tetracycline chelates is concentration-dependent and is reduced even if the chelate is water soluble.

Biological Availability↗