Dual-drug co-crystal synthesis for synergistic in vitro effect of three key first-line antiretroviral drugs

Two pharmaceutical solid state co-crystals EFZA and NEF of two non-nucleoside reverse transcriptase inhibitors (efavirenz, EFV and nevirapine, NVP) and a nucleoside reverse transcriptase inhibitor, zidovudine (AZT) were prepared. Currently, these drugs are essential in various front-line HIV treatment regimens due to their potential in the management of HIV infection. Solid-state principles and solvent-assisted grinding were used for screening of co-crystal preparation. Characterization was carried out using DSC, HSM and TGA, then complimented by FT-IR spectral data and powder X-ray diffraction. HPLC analysis was used for a solubility assays. Both co-crystals indicated different thermal behaviour compared to the individual drug components. Differences in vibrational modes within the spectral region and the unique powder X-ray patterns confirmed the identity of EFZA and NEF as new molecular derivatives. Quantitative studies using HPLC indicated an enhanced solubility of the co-crystals at different pH values compared to the parent compounds; thus making these interesting candidates for future formulation6

Towards the design of new and improved drilling fluid additives using molecular dynamics simulations

During exploration for oil and gas, a technical drilling fluid is used to lubricate the drill bit, maintain hydrostatic pressure, transmit sensor readings, remove rock cuttings and inhibit swelling of unstable clay based reactive shale formations. Increasing environmental awareness and resulting legislation has led to the search for new, improved biodegradable drilling fluid components. In the case of additives for clay swelling inhibition, an understanding of how existing effective additives interact with clays must be gained to allow the design of improved molecules. Owing to the disordered nature and nanoscopic dimension of the interlayer pores of clay minerals, computer simulations have become an increasingly useful tool for studying clay-swelling inhibitor interactions. In this work we briefly review the history of the development of technical drilling fluids, the environmental impact of drilling fluids and the use of computer simulations to study the interactions between clay minerals and swelling inhibitors. We report on results from some recent large-scale molecular dynamics simulation studies on low molecular weight water-soluble macromolecular inhibitor molecules. The structure and interactions of poly(propylene oxide)-diamine, poly(ethylene glycol) and poly(ethylene oxide)-diacrylate inhibitor molecules with montmorillonite clay are studied.<br>Durante a exploração de óleo e gás um fluido de perfuração é usado para lubrificar 'bit' da perfuradora, manter a pressão hidrostática, transmitir sensores de leitura, remover resíduos da rocha e inibir o inchamento da argila instável baseada nas formações dos folhelhos. O aumento das preocupações ambientais bem como a legislação resultante levou à procura de novos fluidos de perfuração com componentes biodegradáveis. No caso dos aditivos para inibir o inchamento das argilas o entendimento das interações entre os aditivos e as argilas tem que ser adquirido para permitir o projeto de moléculas commelhores propriedades. Devido à natureza desordenada da dimensão nanoscópica dos nano poros dos minerais argilosos, simulações computacionais têm se tornado uma ferramenta poderosa para estudar as interações entre o inchamento da argila e o inibidor. Neste trabalho revisamos brevemente o histórico do desenvolvimento de fluidos técnicos de perfuração, o impacto ambiental dos fluidos de perfuração e o uso de simulações computacionais para estudar as interações entre os fluidos de perfuração e os inibidores do inchamento. Nós reportamos resultados para alguns estudos baseados em simulações de dinâmica molecular em larga escala em uma solução aquosa de baixo peso molecular com solutos compostos por macromoléculas inibidoras. A estrutura e as interações entre inibidores compostos por polipropileno óxido, polietileno óxido e moléculas e a argila montmorilonita são estudadas