Robust spatially resolved pressure measurements using MRI with novel buoyant advection-free preparations of stable microbubbles in polysaccharide gels

MRI of fluids containing lipid coated microbubbles has been shown to be an effective tool for measuring the local fluid pressure. However, the intrinsically buoyant nature of these microbubbles precludes lengthy measurements due to their vertical migration under gravity and pressure-induced coalescence. A novel preparation is presented which is shown to minimize both these effects for at least 25 min. By using a 2% polysaccharide gel base with a small concentration of glycerol and 1,2-distearoyl-sn-glycero-3-phosphocholine coated gas microbubbles, MR measurements are made for pressures between 0.95 and 1.44 bar. The signal drifts due to migration and amalgamation are shown to be minimized for such an experiment whilst yielding very high NMR sensitivities up to 38% signal change per bar

Evaluation of Dikamali as a Tablet Binder in Zidovudine Tablets

The aim of the present study is to evaluate the gum, Dikamali, as a tablet binder employing zidovudine as a model drug. Zidovudine tablets were prepared by wet granulation technique using Dikamali as a tablet binder. The Dikamali was used in wet form and dry form. Granules were evaluated for pre-compression parameters:  tapped density, bulk density, compressibility index, hausner ratio, and angle of repose. All the parameters were found to be within the acceptable limits. The tablets were evaluated for hardness, friability, weight variation, disintegration, content uniformity, and dissolution. For the formulations F1-F3D; F1-F3W; F4-F7 (see Table 1) the parameters of friability, disintegration time, and hardness were measured and their values range from 0.57-0.73% (w/w), 0.83-0.97% (w/w), 0.69-0.99% (w/w); 12-13 min, 10-12 min, 10-12 min; and 5-6.9 kg/cm2, 4.5-5.1 kg/cm2, 4.1-5.2 kg/cm2; respectively. The binding efficacy of Dikamali was compared with the standard binders, starch mucilage and polyvinyl pyrrolidone, using dissolution studies. The binders, Dikamali and starch, were compared at similar concentrations [2.5% (w/v), 5% (w/v), and 7.5% (w/v)], and the finalized formulation (F1D) was compared with a 10% (w/v) concentration of starch mucilage and a 10% (w/v) concentration of polyvinyl pyrrolidone (PVP). Dikamali [2.5% (w/v)] in dry form (i.e. F1D) showed the same percent drug release as that of the 10% (w/v) of starch mucilage and of polyvinyl pyrrolidone. In conclusion, Dikamali could well be used as a binding agent in the formulation of tablet dosage forms, and Dikamali is more effective in dry form than the wet form

TPX: Biomedical literature search made easy

TPX is a web-based PubMed search enhancement tool that enables faster article searching using an alysis and exploration features . These features include identification of relevant biomedical concepts from search results with linkouts to source databases, concept based article categorization, concept assisted search and filtering, query refinement. A distinguishing feature here is the ability to add user-defined concept names and/or concept types for named entity recognition. The tool allows contextual exploration of knowledge sources by providing concept association maps derived from the MEDLINE repository. It also has a full-text search mode that can be configured on request to access local text repositories, incorporating entity co-occurrence search at sentence/paragraph levels. Local text files can also be analyzed on-the-fly

Stability of Pharmaceutical Cocrystal During Milling: A Case Study of 1:1 Caffeine-Glutaric Acid

yesDespite the rising interest in pharmaceutical cocrystals in the past decade, there is a lack of research in the solid processing of cocrystals downstream to crystallization. Mechanical stress induced by unit operations such as milling could affect the integrity of the material. The purpose of this study is to investigate the effect of milling on pharmaceutical cocrystal and compare the performance of ball mill and jet mill, using caffeine-glutaric acid (1:1) cocrystal as the model compound. Our results show that ball milling induced polymorphic transformation from the stable Form II to the metastable Form I; whereas Form II remained intact after jet milling. Jet milling was found to be effective in reducing particle size but ball milling was unable to reduce the particle beyond certain limit even with increasing milling intensity. Heating effect during ball milling was proposed as a possible explanation for the difference in the performance of the two types of mill. The local increase in temperature beyond the polymorphic transformation temperature may lead to the conversion from stable to metastable form. At longer ball milling duration, the local temperature could exceed the melting point of Form I, leading to surface melting and subsequent recrystallization of Form I from the melt and agglomeration of the crystals. The findings in this study have broader implications on the selection of mill and interpretation of milling results for not only pharmaceutical cocrystals but pharmaceutical compounds in general

Formulation and corneal permeation of ketorolac tromethamine-loaded chitosan nanoparticles

The aim of this work was to formulate chitosan (CS)-based nanoparticles (NPs) loaded with ketorolac tromethamine (KT) intended for topical ocular delivery. NPs were prepared using ionic gelation method incorporating tri-polyphosphate (TPP) as cross-linker. Following the preparation, the composition of the system was optimized in terms of their particle size, zeta potential, entrapment efficiency (EE) and morphology, as well as performing structural characterization studies using Fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). The data suggested that the size of the NPs was affected by CS/TPP ratio where the diameter of the NPs ranged from 108.0 ± 2.4 nm to 257.2 ± 18.6 nm. A correlation between drug EE and the corresponding drug concentration added to the formulation was observed, where the EE of the NPs increased with increasing drug concentration, for up to 10 mg/mL. FT-IR and DSC revealed that KT was dispersed within the NPs where the phosphate groups of TPP were associated with the ammonium groups of CS. The in vitro release profile of KT from CS NPs showed significant differences (p < 0.05) compared to KT solution. Furthermore, mucoadhesion studies revealed adhesive properties of the formulated NPs. The KT-loaded NPs were found to be stable when stored at different storage conditions for a period of 3 months. The ex vivo corneal permeation studies performed on excised porcine eye balls confirmed the ability of NPs in retaining the drug on the eye surface for a relatively longer time. These results demonstrate the potential of CS-based NPs for the ocular delivery of KT

Thermal and in situ x-ray diffraction analysis of a dimorphic co-crystal 1:1 caffeine-glutaric acid

YesSpurred by the enormous interest in co-crystals from the pharmaceutical industry, many novel co-crystals of active pharmaceutical ingredients have been discovered in recent years and this has in turn led to an increasing number of reports on polymorphs of co-crystals. Hence, a thorough characterization and understanding of co-crystal polymorphs is a valuable step during drug development. The purpose of this study is to perform in situ structural analysis and to determine thermodynamic stability of a dimorphic co-crystal system, 1:1 caffeine-glutaric acid (CA-GA, Forms I and II). We performed thermal and structural characterizations by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), hot-stage microscopy (HSM), slurry and in situ variable temperature X-ray diffraction (VTXRD). For completeness, we have also re-determined crystal structures of CA-GA Forms I and II at 180 K using single crystal X-ray diffraction. Our results revealed that Form II is stable and Form I is metastable at ambient conditions. Further, the results suggest that the dimorphs are enantiotropically related and the transition temperature is estimated to be 79 Celcius degrees.This work was supported by Science and Engineering Research Council of A*STAR (Agency for Science, Technology and Research), Singapore

Fostering Community Preparedness to Cope with Drought: new initiatives and results from a study involving ODL and ICT from South Central India

Drought has emerged as a key concern in the context of climate variability induced by Climate Change processes and over a billion people are vulnerable, according to UN estimates. Drought preparedness is recognized as the preferred way to cope over relief, and information is the key. Improved access to contemporary ICT in the form of mobile phones and the Internet can help address the challenge of information deficiency in this matter. We have tried to develop an integrated approach for improving the capacity of rural communities by bringing together agricultural information with methods of ODL and effective exchange or delivery using video- conferencing. This has also enabled skill building among vulnerable rural communities in the use of color-coded maps derived from satellite imagery and GIS platforms. ICRISAT in partnership with a community based all- women micro-credit organization, the Adarsha Mahila Samaikhya (AMS), in South Central India has developed this blend of techniques to help the AMS and rural communities to anticipate how vulnerable their villages would be to drought in a season. This is an ongoing partnership, and we report here on joint studies carried out during March 2008- September 2009

Intriguing High Z'' Cocrystals of Emtricitabine

YesEmtricitabine (ECB) afforded dimorphic cocrystals (Forms I, II) of benzoic acid (BA), whereas with p-hydroxybenzoic acid (PHBA), p-aminobenzoic acid (PABA) are resulted in as high Z'' cocrystals. Intriguingly, the Z'' of cocrystals are trends from two to fourteen based on the manipulation of functional groups on the para position of BA (where H atom is replaced with that of OH or NH2 group). ECB‒PABA cocrystal consists of six molecules each and two water molecules in the asymmetric unit (Z''=14) with 2D planar sheets represents the rare pharmaceutical cocrystal. The findings suggest that the increment of H bond donor(s) systematically via a suitable coformer are in correspondence with attaining high Z'' cocrystals. Further, solid state NMR spectroscopy in conjunction with single crystal X-ray diffraction are demonstrated as significant tools to enhance the understanding of the number of symmetry independent molecules in the crystalline lattice and provide insights to the mechanistic pathways of crystallization.Department of Science and Technology (DST) Fund for improvement of S & T Infrastructure (FIST) with grant no. SR/FST/CST-266/2015(c) to PS and VP. AN and VV acknowledge the Government of India under National Overseas Scholarship (2012-13) and High Commission of India, London UK for PhD studentship