Biomedical subjects

Tonglei Li

Publications and source records attributed to Tonglei Li.

6 recordsLinked to original sources

PubMed2006

Empirically augmented density functional theory for predicting lattice energies of aspirin, acetaminophen polymorphs, and ibuprofen homochiral and racemic crystals.

PURPOSE: Lattice energies of drug crystals are closely associated with many important physicochemical properties including polymorphism of the crystals. Current quantum mechanical methods that can be applied to calculate the lattice energy of most drug crystals are not capable of fully considering the van der Waals interaction energy, a dominant component in the lattice energy. Herein, we report the results of using empirically augmented quantum mechanical methods for predicting the lattice energies of selected drug crystals. METHODS: Long-range van der Waals energies were evaluated by atom-atom pairwise C ( 6 ) R (-6 ) functions that were damped at short interatomic distance where interatomic interactions could be better evaluated by density functional theory (DFT). The atomic C ( 6 ) coefficients were taken from literature, and three damping functions were tested. For the quantum mechanical calculations, different basis sets were tested with aspirin as the model system. Basis set superposition error (BSSE) was considered. In addition to aspirin, acetaminophen Form I and Form II, and s(+)- and (+/-)-ibuprofen were calculated and the results were compared to experimental values. Experimentally determined single crystal structures were optimized prior to both empirical and DFT energy calculations. RESULTS: Lattice energies calculated by the empirically augmented quantum mechanical methods are in very good agreement with experimental values, suggesting the approach is acceptable. The results also indicate that the long-range van der Waals or dispersion energy is a significant part of the lattice energy, which cannot be accurately estimated by the DFT methods alone. CONCLUSIONS: Due to the empirical nature for estimating the dispersion energy, choosing the right empirical parameters is crucial. The methods and parameters tested seem to be able to produce reliable values of lattice energies of the drug crystals.

Acetaminophen↗

PubMed2005

Understanding solid-state reactions of organic crystals with density functional theory-based concepts.

Solid-state reactions are commonly observed in organic crystals, including pharmaceutical and agricultural materials, fine chemicals, dyes, explosives, optics, and many other substances. The fact that these reactions are in general highly anisotropic with regard to the initiation and propagation in a crystal has led to this study for investigating the effect of crystal packing on the reaction mechanism and kinetics of organic crystals. We have used electron density-based concepts, including nuclear Fukui function, developed from density functional theory, for elucidating the effect of electronic structures of different polymorphs on the difference in their chemical reactivity. Two polymorphs of flufenamic acid were studied. The calculation results on major reacting faces of the two forms support their reactivity difference with ammonia gas. In addition, we calculated surface energies of reacting faces to discuss how the mechanical difference may affect the propagation of solid-state reaction.

Crystallization↗

PubMed2005

Study of crystal packing on the solid-state reactivity of indomethacin with density functional theory.

PURPOSE: Solid-state reactions are highly anisotropic. Different polymorphs of the same compound may have remarkably different chemical reactivities. It was reported that two polymorphs of indomethacin single crystals, alpha- and gamma-forms, reacted with ammonia gas at dramatically different rates. In this study, the effect of crystal packing on their difference in chemical reactivity was investigated by examining the electronic structures and properties of the crystal forms. METHODS: Ab initio methods, including density functional theory, were used to calculate electronic structures of the alpha- and gamma-forms of indomethacin. In particular, nuclear Fukui functions were obtained to elucidate how a molecule in a crystal may respond to an electronic perturbation that can be caused by a chemical reaction. RESULTS: Different conformers in the two polymorphs showed different electronic structures. The carboxylic group of one symmetrically different molecule in the alpha-form had significantly larger nuclear Fukui functions than those of other molecules of either the alpha- or gamma-form, supporting the experimental observation that the alpha-form was much more reactive with ammonia than the gamma-form. In addition, the large nuclear Fukui functions associated with atoms other than those from the carboxylic group were attributed to the tension of two dislodged aromatic rings. CONCLUSIONS: Electronic calculations were able to provide insightful glimpses into the effect of crystal packing on the solid-state reaction of indomethacin. The nuclear Fukui function, which characterizes the physical stress on an atom due to perturbation in electron density, may provide a powerful means of studying the solid-state reactions of organic crystals at the electronic level.

Crystallization↗

PubMed2005

Face-integrated Fukui function: understanding wettability anisotropy of molecular crystals from density functional theory.

Wettability is one of the anisotropic surface properties of molecular crystals that exhibit the structural variance of chemical moieties on various growth faces. The divergence in liquid-solid interactions at different faces is thought to be related to the inherent responding capacity or sensitivity of a solid surface to the perturbation in electronic structures and atomic positions as a result of the contact by a liquid. Since the Fukui function, according to density functional theory (DFT), is a local function for describing such sensitivity to the structural perturbation and is directly related to local softness, it has been proposed and tested to use an integrated Fukui function over a crystallographic plane for describing the anisotropy of solid-liquid interactions. It is found that the contact angle of a polar solvent, such as water, on a crystal surface shows an intimate connection to the integrated Fukui functions of the surface, illustrating an extension of Pearson's HSAB (hard and soft acids and bases) to crystal systems. The concept of face-integrated Fukui function and the approach to apply the HSAB with the DFT-based concepts may provide a powerful means for describing anisotropic properties, including wettability of organic crystals.

Anisotropy↗

PubMed2003

Modeling of adhesion in tablet compression--I. Atomic force microscopy and molecular simulation.

Adhesion problems during tablet manufacturing have been observed to be dependent on many formulation and process factors including the run time on the tablet press. Consequently, problems due to sticking may only become apparent towards the end of the development process when a prolonged run on the tablet press is attempted for the first time. It would be beneficial to predict in a relative sense if a formulation or new chemical entity has the potential for adhesion problems early in the development process. It was hypothesized that favorable intermolecular interaction between the drug molecules and the punch face is the first step or criterion in the adhesion process. Therefore, the rank order of adhesion during tablet compression should follow the rank order of these energies of interaction. The adhesion phenomenon was investigated using molecular simulations and contact mode atomic force microscopy (AFM). Three model compounds were chosen from a family of "profen" compounds. Silicon nitride AFM tips were modified by coating a 20-nm iron layer on the surfaces by sputter coating. Profen flat surfaces were made by melting and recrystallization. The modified AFM probe and each profen surface were immersed in the corresponding profen saturated water during force measurements using AFM. The work of adhesion between iron and ibuprofen, ketoprofen, and flurbiprofen in vacuum were determined to be -184.1, -2469.3, -17.3 mJ. m(-2), respectively. The rank order of the work of adhesion between iron and profen compounds decreased in the order: ketoprofen > ibuprofen > flurbiprofen. The rank order of interaction between the drug molecules and the iron superlattice as predicted by molecular simulation using Cerius(2) is in agreement with the AFM measurements. It has been demonstrated that Atomic Force Microscopy is a powerful tool in studying the adhesion phenomena between organic drug compounds and metal surface. The study has provided insight into the adhesion problems occurring during tablet compression and a direction for continued study.

Adhesiveness↗

PubMed2003

A statistical support for using spectroscopic methods to validate the content uniformity of solid dosage forms.

The advent of PAT, Process Analytical Technologies, offers the possibility of large scale monitoring of tablets as they come off the press. The most rapid techniques allowing the largest sample sizes are based on reflectance spectroscopy. As these techniques sample only a portion of the tablet, it is critical to prove that sampling a portion has a larger (and, therefore, more conservative) statistical variance than sampling the entire. Once demonstrated, a partial sampling technique, for example, a Near Infrared (NIR) sensor, should be able to provide a safe bracket for content uniformity evaluation. It is the purpose of this report to support the claim that the coefficient of variance (CV) from sampling a part of a dosage form cannot be smaller than the CV from sampling the whole dosage form. This hypothesis will be supported in this study by both a statistical proof and experimental data acquired from a model tablet system.

Chromatography, High Pressure Liquid↗