Biomedical subjects

Mahmoud Mirmehrabi

Publications and source records attributed to Mahmoud Mirmehrabi.

5 recordsLinked to original sources

PubMed2006

Thermodynamic modeling of activity coefficient and prediction of solubility: Part 1. Predictive models.

A new activity coefficient model was developed from excess Gibbs free energy in the form G(ex) = cA(a) x(1)(b)...x(n)(b). The constants of the proposed model were considered to be function of solute and solvent dielectric constants, Hildebrand solubility parameters and specific volumes of solute and solvent molecules. The proposed model obeys the Gibbs-Duhem condition for activity coefficient models. To generalize the model and make it as a purely predictive model without any adjustable parameters, its constants were found using the experimental activity coefficient and physical properties of 20 vapor-liquid systems. The predictive capability of the proposed model was tested by calculating the activity coefficients of 41 binary vapor-liquid equilibrium systems and showed good agreement with the experimental data in comparison with two other predictive models, the UNIFAC and Hildebrand models. The only data used for the prediction of activity coefficients, were dielectric constants, Hildebrand solubility parameters, and specific volumes of the solute and solvent molecules. Furthermore, the proposed model was used to predict the activity coefficient of an organic compound, stearic acid, whose physical properties were available in methanol and 2-butanone. The predicted activity coefficient along with the thermal properties of the stearic acid were used to calculate the solubility of stearic acid in these two solvents and resulted in a better agreement with the experimental data compared to the UNIFAC and Hildebrand predictive models.

Butanones↗

PubMed2006

Thermodynamic modeling of activity coefficient and prediction of solubility: Part 2. Semipredictive or semiempirical models.

The solubility of stearic acid, ranitidine hydrochloride, and stavudine were predicted in selected organic solvents. The experimental solubility data of stearic acid and ranitidine hydrochloride were reported in previous work of the authors and stavudine's solubility was measured in this work. Equilibrium aqueous solubility of crystalline stauvudine was determined at controlled temperatures by stirring and filtration, with spectrophotometric quantification. The new model developed in Part 11 of this communication was modified as a semipredictive model with two adjustable parameters. Predicting the solubility data with the NRTL model using just one experimental point resulted in a big error while the modified new model and the UNIQUAC model showed much smaller errors. A new method was proposed in this work for predicting the solubility data of all polymorphs of a given compound using the experimental solubility data of one of the polymorphs of the same chemical compound. Although in general, the UNIQUAC model predictions were marginally superior, the new model is simpler and does not require the molecular parameters such as Van der Waals area and volume. The solubility prediction in a mixture of solvents using the NRTL and UNIQUAC models was also discussed.

2-Propanol↗

PubMed2005

Stavudine.

The crystal structure of the title compound (systematic name: 2',3'-didehydro-2',3'-deoxythymidine), C10H12N2O4, consists of two molecules in the asymmetric unit bound together by hydrogen bonds. The conformational geometry differentiates this form of stavudine from its two previously published polymorphs. In addition, a different hydrogen-bonding scheme is observed compared with the previous two structures. This polymorph is the thermodynamically most stable form of the antiviral drug, as evidenced by differential scanning calorimetry (DSC) and IR data.

Anti-HIV Agents↗

PubMed2005

An approach to solvent screening for crystallization of polymorphic pharmaceuticals and fine chemicals.

It is desirable to have a systematic approach for predicting or interpreting the effect of the solvents on the production of polymorphs. A method based on the atomic electronegativity is suggested that calculates the partial charge distribution in the solute and solvent molecules. Using the calculated partial charges, correlations are developed to predict the hydrogen bonding ability of the solute and/or solvent molecules. The predictive capability of the proposed correlations is compared with the results of a quantum mechanics approach. Selection of the right solvent may play a significant role in the formation of a desirable polymorph or solvate. The most important properties of class 2 and 3 solvents of International Conference on Harmonization (ICH) for crystallization of polymorphic compounds are listed in this paper. The partial charge calculation has been used as a tool for analyzing the solvent impact on polymorphic isolation of two compounds: ranitidine hydrochloride (H2 receptor antagonist) and stearic acid (used as excipients or in coating the tablets).

Algorithms↗

PubMed2004

Improving the filterability and solid density of ranitidine hydrochloride Form 1.

Ranitidine hydrochloride Form 1 produced by the original method (Price et al., 1978 US patent) has poor filtration and drying characteristics, which make it less desirable commercially in comparison with Form 2. This article shows that the operating parameters have significant influence on the final properties of Form 1. In terms of filterability and solid bulk density, it was found that at a higher temperature (approximately 48 degrees C), the viscosity of the slurry decreased and improved product quality as compared with operating at room temperature (approximately 25 degrees C). It was found that the rapid addition of acid to the ranitidine base increased product density but led to higher residual solvent inclusion. The presence of excess ranitidine base in the solution and also the manner of reactant addition had a significant influence on the onset of nucleation and the rate of crystallization. The best results in terms of filterability and bulk solid density were obtained using an initial pH of 5.3 and then increasing it to 6.3-6.4 after the onset of nucleation.

Chemistry, Pharmaceutical↗