Chemico-calorimetric analysis of amorphous granules manufactured via continuous granulation process

The current study explores the first case of the implementation of solution calorimetry (SolCal) in order to determine the amorphous content of crystalline benzoyl-methoxy-methylindol-acetic acid (BMA)—a model poorly soluble drug, in the amorphous granules prepared via single-step continuous twin-screw dry granulations (TSG). Amorphous magnesium aluminometasilicate (Neusilin®) (US2) was used as a novel inorganic carrier via a TwinLab 10 mm twin-screw extruder. The BMA/US2 blends were processed at 180 °C and varying drug: carrier ratios of 1:4, 1:2.5 and 1:1 (w/w). Physico-chemical characterisation conducted via SEM, DSC and XRPD showed amorphous state of the drug in all granulated formulations. Reverse optical microscopy revealed a meso-porous structure of US2 in which the drug particles are adsorbed and/or entrapped within the porous network of the carrier. This phenomenon can be the underlying reason for the increase of the amorphous content in the extruded granules. Solution calorimetry (SolCal) study revealed amorphous content of the drug in all formulations quite precisely, whereas the dynamic vapour sorption (DVS) analysis complemented the results from SolCal. Furthermore, an attempt has been made for the first time to interrelate the findings from the SolCal to that of the release of the drug from the amorphous granules. It can be concluded that SolCal can be used as a novel technique to precisely quantify and interrelate the amorphous content to its physico-chemical performances such as drug release from the granulated formulations processed via TS

The T1405N Carbamoyl Phosphate Synthetase Polymorphism Does Not Affect Plasma Arginine Concentrations in Preterm Infants

A C-to-A nucleotide transversion (T1405N) in the gene that encodes carbamoyl-phosphate synthetase 1 (CPS1) has been associated with changes in plasma concentrations of L-arginine in term and near term infants but not in adults. In preterm infants homozygosity for the CPS1 Thr1405 variant (CC genotype) was associated with an increased risk of having necrotizing enterocolitis (NEC). Plasma L-arginine concentrations are decreased in preterm infants with NEC.To examine the putative association between the CPS1 T1405N polymorphism and plasma arginine concentrations in preterm infants.Prospective multicenter cohort study. Plasma and DNA samples were collected from 128 preterm infants (<30 weeks) between 6 and 12 hours after birth. Plasma amino acid and CPS1 T1405N polymorphism analysis were performed.Distribution of genotypes did not differ between the preterm (CC:CA:AA = 55.5%:33.6%:10.9%, n = 128) and term infants (CC:CA:AA = 54.2%:35.4%:10.4%, n = 96). There was no association between the CPS1 genotype and plasma L-arginine or L-citrulline concentration, or the ornithine to citrulline ratio, which varies inversely with CPS1 activity. Also the levels of asymmetric dimethylarginine, and symmetric dimethylarginine were not significantly different among the three genotypes.The present study in preterm infants did not confirm the earlier reported association between CPS1 genotype and L-arginine levels in term infants

A proprietary alpha-amylase inhibitor from white bean (Phaseolus vulgaris): A review of clinical studies on weight loss and glycemic control

Obesity, and resultant health hazards which include diabetes, cardiovascular disease and metabolic syndrome, are worldwide medical problems. Control of diet and exercise are cornerstones of the management of excess weight. Foods with a low glycemic index may reduce the risk of diabetes and heart disease as well as their complications. As an alternative to a low glycemic index diet, there is a growing body of research into products that slow the absorption of carbohydrates through the inhibition of enzymes responsible for their digestion. These products include alpha-amylase and glucosidase inhibitors. The common white bean (Phaseolus vulgaris) produces an alpha-amylase inhibitor, which has been characterized and tested in numerous clinical studies. A specific and proprietary product named Phase 2® Carb Controller (Pharmachem Laboratories, Kearny, NJ) has demonstrated the ability to cause weight loss with doses of 500 to 3000 mg per day, in either a single dose or in divided doses. Clinical studies also show that Phase 2 has the ability to reduce the post-prandial spike in blood glucose levels. Experiments conducted incorporating Phase 2 into food and beverage products have found that it can be integrated into various products without losing activity or altering the appearance, texture or taste of the food. There have been no serious side effects reported following consumption of Phase 2. Gastro-intestinal side effects are rare and diminish upon extended use of the product. In summary, Phase 2 has the potential to induce weight loss and reduce spikes in blood sugar caused by carbohydrates through its alpha-amylase inhibiting activity

Root Canal Anatomy of Maxillary and Mandibular Teeth

It is a common knowledge that a comprehensive understanding of the complexity of the internal anatomy of teeth is imperative to ensure successful root canal treatment. The significance of canal anatomy has been emphasized by studies demonstrating that variations in canal geometry before cleaning, shaping, and obturation procedures had a greater effect on the outcome than the techniques themselves. In recent years, significant technological advances for imaging teeth, such as CBCT and micro-CT, respectively, have been introduced. Their noninvasive nature allows to perform in vivo anatomical studies using large populations to address the influence of several variables such as ethnicity, aging, gender, and others, on the root canal anatomy, as well as to evaluate, quantitatively and/or qualitatively, specific and fine anatomical features of a tooth group. The purpose of this chapter is to summarize the morphological aspects of the root canal anatomy published in the literature of all groups of teeth and illustrate with three-dimensional images acquired from micro-CT technology.info:eu-repo/semantics/publishedVersio

Evaluation of Griseofulvin Binary and Ternary Solid Dispersions with HPMCAS

The stability and dissolution properties of griseofulvin binary and ternary solid dispersions were evaluated. Solid dispersions of griseofulvin and hydroxypropyl methylcellulose acetate succinate (HPMCAS) were prepared using the spray drying method. A third polymer, poly[N-(2-hydroxypropyl)methacrylate] (PHPMA), was incorporated to investigate its effect on the interaction of griseofulvin with HPMCAS. In this case, HPMCAS can form H bonds with griseofulvin directly; the addition of PHPMA to the solid dispersion may enhance the stability of the amorphous griseofulvin due to greater interaction with griseofulvin. The X-ray powder diffraction results showed that griseofulvin (binary and ternary solid dispersions) remained amorphous for more than 19 months stored at 85% RH compared with the spray-dried griseofulvin which crystallized totally within 24 h at ambient conditions. The Fourier transform infrared scan showed that griseofulvin carbonyl group formed hydrogen bonds with the hydroxyl group in the HPMCAS, which could explain the extended stability of the drug. Further broadening in the peak could be seen when PHPMA was added to the solid dispersion, which indicates stronger interaction. The glass transition temperatures increased in the ternary solid dispersions regardless of HPMCAS grade. The dissolution rate of the drug in the solid dispersion (both binary and ternary) has significantly increased when compared with the dissolution profile of the spray-dried griseofulvin. These results reveal significant stability of the amorphous form due to the hydrogen bond formation with the polymer. The addition of the third polymer improved the stability but had a minor impact on dissolution