In silico prediction coupled with in vitro experiments and absorption modeling to study the inclusion complex of telmisartan with modified beta-cyclodextrin

Telmisartan (TEL) is a poorly bioavailable antihypertensive drug candidate owing to its low solubility in all the biofluids. The present study is aimed to enhance the solubility of TEL by forming an inclusion complex with sulfobutylether beta-cyclodextrin (SBE-β-CD), discover its mode of inclusion and predict the bioavailability of the prepared complexes. The formation of the inclusion complex is explained based on the hydrogen bond propensities and molecular dynamics simulations. Freeze-drying method was employed for the preparation of inclusion complexes. These complexes were subsequently characterized by powder X-ray diffraction, differential scanning calorimetry, and Fourier transform-infrared spectroscopy. The spatial configuration of the drug inside the cyclodextrin cavity is probed using ¹H and ¹³C NMR. The in silico docking results are in good agreement with the experimental data and reveal that the hydrogen bond is formed as a part of the guest molecule enters from the broader end of the ring and the protons at the interior portion of the molecule interact with the carboxylic acid (–COOH) group of TEL leading to the formation of a hydrogen bond. The phenyl moiety of TEL occupies the central core and forms multiple Van-der-Waals interactions with the glucopyranose units of the SBE-β-CD. The inclusion complex demonstrates significantly higher in vitro dissolution profile as compared with plain TEL. The GastroPlus? simulation software generated parameters of inclusion complex in comparison to plain TEL show a seven fold increase in C_max and 18 fold increase in bioavailability.     

The Use of Models for Environmental Forecasting and Corporate Planning

This paper presents briefly, the forecasting and planning activities which have evolved over the years in Esso Petroleum Company. It describes three computer models developed in the Corporate Planning Department for these activities an econometric model for short-term environmental forecasting and economic analysis; a horizon year optimization model for long-range corporate objectives setting; and a multi-time period simulation model for financial forecasting and planning both in short and long term. The structure, use and limitations of each of the models are discussed.     

The Formation of DNA Photodamage: The Role of Exciton Localization

The electronic structure during the formation of a cyclobutane pyrimidine dimer (CPD) between two thymine bases is investigated using semi‐empirical and first‐principles approaches. The dimerization of two isolated thymine bases is found to have no barrier or a very small barrier in agreement with previous studies suggesting low photostability of DNA. The well‐known high photostability of DNA can only be explained taking other factors into account. We investigate the role of the exciton location in the particular environment. Different model systems, from isolated thymine bases to an oligonucleotide in aqueous solution, are discussed. Analysis of the frontier orbitals allows one to understand the connection between the location of the exciton, the relative orientation of the thymine bases, and the observed reactivity.     

Ionic Liquids Can Permanently Modify Porous Silicon Surface Chemistry

To develop ionic liquid/porous silicon (IL/pSi) microarrays we have contact pin‐printed 20 hydrophobic and hydrophilic ionic liquids onto as‐prepared, hydrogen‐passivated porous silicon (ap‐pSi) and then determined the individual IL spot size, shape and associated pSi surface chemistry. The results reveal that the hydrophobic ionic liquids oxidize the ap‐pSi slightly. In contrast, the hydrophilic ionic liquids lead to heavily oxidized pSi (i.e., ox‐pSi). The strong oxidation arises from residual water within the hydrophilic ILs that is delivered from these ILs into the ap‐pSi matrix causing oxidation. This phenomenon is less of an issue in the hydrophobic ILs because their water solubility is substantially lower.