Characterization of heterogeneity and spatial distribution of phases in complex solid dispersions by thermal analysis by structural characterization and X-ray micro computed tomography

Purpose: This study investigated the effect of drug-excipient miscibility on the heterogeneity and spatial distribution of phase separation in pharmaceutical solid dispersions at a micron-scale using two novel and complementary characterization techniques, thermal analysis by structural characterization (TASC) and X-ray micro-computed tomography (XCT) in conjunction with conventional characterization methods. Method: Complex dispersions containing felodipine, TPGS, PEG and PEO were prepared using hot melt extrusion-injection moulding. The phase separation behavior of the samples was characterized using TASC and XCT in conjunction with conventional thermal, microscopic and spectroscopic techniques. The in vitro drug release study was performed to demonstrate the impact of phase separation on dissolution of the dispersions. Results: The conventional characterization results indicated the phase separating nature of the carrier materials in the patches and the presence of crystalline drug in the patches with the highest drug loading (30% w/w). TASC and XCT where used to provide insight into the spatial configuration of the separate phases. TASC enabled assessment of the increased heterogeneity of the dispersions with increasing the drug loading. XCT allowed the visualization of the accumulation of phase separated (crystalline) drug clusters at the interface of air pockets in the patches with highest drug loading which led to poor dissolution performance. Semi-quantitative assessment of the phase separated drug clusters in the patches were attempted using XCT. Conclusion: TASC and XμCT can provide unique information regarding the phase separation behavior of solid dispersions which can be closely associated with important product quality indicators such as heterogeneity and microstructure

Effect of a vitamin/mineral supplement on children and adults with autism

<p>Abstract</p> <p>Background</p> <p>Vitamin/mineral supplements are among the most commonly used treatments for autism, but the research on their use for treating autism has been limited.</p> <p>Method</p> <p>This study is a randomized, double-blind, placebo-controlled three month vitamin/mineral treatment study. The study involved 141 children and adults with autism, and pre and post symptoms of autism were assessed. None of the participants had taken a vitamin/mineral supplement in the two months prior to the start of the study. For a subset of the participants (53 children ages 5-16) pre and post measurements of nutritional and metabolic status were also conducted.</p> <p>Results</p> <p>The vitamin/mineral supplement was generally well-tolerated, and individually titrated to optimum benefit. Levels of many vitamins, minerals, and biomarkers improved/increased showing good compliance and absorption. Statistically significant improvements in metabolic status were many including: total sulfate (+17%, p = 0.001), S-adenosylmethionine (SAM; +6%, p = 0.003), reduced glutathione (+17%, p = 0.0008), ratio of oxidized glutathione to reduced glutathione (GSSG:GSH; -27%, p = 0.002), nitrotyrosine (-29%, p = 0.004), ATP (+25%, p = 0.000001), NADH (+28%, p = 0.0002), and NADPH (+30%, p = 0.001). Most of these metabolic biomarkers improved to normal or near-normal levels.</p> <p>The supplement group had significantly greater improvements than the placebo group on the Parental Global Impressions-Revised (PGI-R, Average Change, p = 0.008), and on the subscores for Hyperactivity (p = 0.003), Tantrumming (p = 0.009), Overall (p = 0.02), and Receptive Language (p = 0.03). For the other three assessment tools the difference between treatment group and placebo group was not statistically significant.</p> <p>Regression analysis revealed that the degree of improvement on the Average Change of the PGI-R was strongly associated with several biomarkers (adj. R²= 0.61, p < 0.0005) with the initial levels of biotin and vitamin K being the most significant (p < 0.05); both biotin and vitamin K are made by beneficial intestinal flora.</p> <p>Conclusions</p> <p>Oral vitamin/mineral supplementation is beneficial in improving the nutritional and metabolic status of children with autism, including improvements in methylation, glutathione, oxidative stress, sulfation, ATP, NADH, and NADPH. The supplement group had significantly greater improvements than did the placebo group on the PGI-R Average Change. This suggests that a vitamin/mineral supplement is a reasonable adjunct therapy to consider for most children and adults with autism.</p> <p>Trial Registration</p> <p><b>Clinical Trial Registration Number: </b><a href="http://www.clinicaltrials.gov/ct2/show/NCT01225198">NCT01225198</a></p

Pediatric DXA: clinical applications

Normal bone mineral accrual requires adequate dietary intake of calcium, vitamin D and other nutrients; hepatic and renal activation of vitamin D; normal hormone levels (thyroid, parathyroid, reproductive and growth hormones); and neuromuscular functioning with sufficient stress upon the skeleton to induce bone deposition. The presence of genetic or acquired diseases and the therapies that are used to treat them can also impact bone health. Since the introduction of clinical DXA in pediatrics in the early 1990s, there has been considerable investigation into the causes of low bone mineral density (BMD) in children. Pediatricians have also become aware of the role adequate bone mass accrual in childhood has in preventing osteoporotic fractures in late adulthood. Additionally, the availability of medications to improve BMD has increased with the development of bisphosphonates. These factors have led to the increased utilization of DXA in pediatrics. This review summarizes much of the previous research regarding BMD in children and is meant to assist radiologists and clinicians with DXA utilization and interpretation