Multicomponent Solid Forms in Pharma, Hair Care and Dental Care

This work covers multicomponent solid forms including co-amorphous solid forms with active pharmaceutical ingredients (APIs) and, co-crystals, salts, hydrates and solvates to help model intermolecular interaction taking place in larger systems including polymers and proteins. A new prediction model was created to help identify which combinations of APIs and small molecule co-formers were likely to form co-amorphous systems. The prediction model suggests co-amorphous formation is related to the average molecular weight of the two components and the strength of the intermolecular interactions formed. A new co-amorphous screen containing mebendazole with 29 co-formers was performed and compared to the predicted results, which showed a predictive hit rate of 90%. The dimer of vinylcaprolactam (bisVCap) was used in a co-amorphous screen with 13 APIs. The experimental results were compared to the predicted results with 11 out of 13 systems correctly predicted. The co-amorphous systems found were analysed by FTIR which identified new intermolecular interactions formed between bisVCap and the APIs, stabilising the co-amorphous state. Crystals of a hydrogenated dimer of vinylpyrrolidone and hydrogen peroxide were grown by cooling crystallisation and characterised by SXRD. The structures were used to identify the bonding models present in a polyvinylpyrrolidone hydrogen peroxide complex. The crystal structures were combined with DFT calculations to produce two new proposed structures of the hydrogen bonding in the polyvinylpyrrolidone hydrogen peroxide complex. A hair care mixture formed from a gluconamide and a gluconate and 3-hydroxypropyl ammonium salt, is known to strengthen hair fibres; however, the process is unknown. To identify potential interactions between the mixture and hair fibres, a range of crystals were grown. The crystals were identified by SXRD as two polymorphic forms of the gluconamide and three salts of 3-hydroxypropylammonium with sulfuric acid, methane sulfonic acid and oxalic acid. The new crystal structures and structures from the Cambridge structural database were used to speculate potential interactions formed. The gluconamide was identified to be a supramolecular gelator in aniline and benzyl alcohol. The gels were characterised by rheology, scanning electron microscopy, 1H NMR, FTIR and XRPD

Alexander Cumming - King or Pawn? An Englishman on the Colonial Chessboard of the Eighteenth-century American Southeast

A review of the actions of Alexander Cummning in South Carolina

The Structure and Expression of the Murine Glutathione Peroxidase Gene

The literature relating to the cell biology of the murine haemopoietic system, particularly the erythropoietic lineage has been reviewed, as have current ideas relevant to the regulation of cell-specific gene transcription. A series of experiments analysing the structure and expression of the murine gene encoding a polypeptide of approximately 19kD present in reticulocytes is then presented. These show that the gene encodes the selenium-dependent enzyme glutathione peroxidase (GSHPx) which contains the unusual amino acid selenocysteine in its polypeptide backbone. This amino acid has been shown by sequencing of the GSHPx gene and mRNA to be encoded by the "termination" codon, UGA. The significance of this finding is discussed. The GSHPx mRNA is detectable in every cell type and tissue examined, although at varying levels. Thus in erythroid cells, liver and kidney, the GSHPx mRNA level is 20-50 fold higher than in other cells. These differences have been shown not to be due to nuclear retention of the mRNA or pre-mRNA in low expressing cells. Furthermore, the levels of pre-mRNA in a low and a high expressing cell line vary in the same way as the mRNA. It therefore seems that the different levels of GSHPx mRNA arise through differences either in the stability of the GSHPx mRNA or in the rate of transcription of the GSHPx gene in different tissues. Indirect support for the involvement of the latter mechanism has come from an analysis of the chromatin structure of the GSHPx gene in tissues expressing the mRNA at a high or low level. Thus a broad DNAse I hypersensitive site is seen downstream from the gene. In addition, two erythroid specific DNAse I hypersensitive sites are also located 3' to the GSHPx gene. Functional studies, involving short term transfection assays using fragments of the GSHPx gene linked to the chloramphenicol acetyltransferase (CAT) gene, showed that the region of DNA immediately upstream of the GSHPx gene transcription initiation site functions equally well as a promoter of transcription in both a low expressing and a high expressing cell line. In addition, a DNA fragment from the 3' end of the GSHPx gene, shown by sequence analysis to contain elements homologous to cis-acting viral and cellular DNA transcription regulatory sequences, did not have any effect upon the transcription from the GSHPx or other promoters when linked in cis to them

Rapid appraisal to improve canal irrigation performance: experience and options

As more priority is given to improving performance on existing canal irrigation systems, it becomes more important to understand and improve the process of identifying precisely what to do. Many types and combinations of actions are possible, but how to identify which are best has been neglected. Each irrigation system is unique and requires a specially tailored program. Detailed appraisals of the large numbers of existing projects impose impossible demands for high-level specialists and lead to long delays in the delivery of information. Cost-effective approaches and methods are needed which make manageable demands on staff and lead to implementable actions with early benefit. This paper assists in the search for such methods. It draws on experience with rapid rural appraisal (RRA) in other fields1 and on experience with canal irrigation mainly in Asia. Appraisal is used in the general sense to mean investigation and analysis. Primary attention is given to practical investigation, i.e., finding out about existing canal irrigation systems. Diagnostic analytical approaches are treated in detail in a separate paper (Chambers and Carruthers 1985)