Readings in Advanced Pharmacokinetics

This book, “Readings in Advanced Pharmacokinetics - Theory, Methods and Applications”, covers up to date information and practical topics related to the study of drug pharmacokinetics in humans and in animals. The book is designed to offer scientists, clinicians and researchers a choice to logically build their knowledge in pharmacokinetics from basic concepts to advanced applications. This book is organized into two sections. The first section discusses advanced theories that include a wide range of topics; from bioequivalence studies, pharmacogenomics in relation to pharmacokinetics, computer based simulation concepts to drug interactions of herbal medicines and veterinary pharmacokinetics. The second section advances theory to practice offering several examples of methods and applications in advanced pharmacokinetics

Toxicological profile for uranium

"A Toxicological Profile for Uranium, Draft for Public Comment was released in May 2011. This edition supersedes any previously released draft or final profile." - p iiiChemical manager(s)/author(s): Sam Keith, Obaid Faroon, Nickolette Roney, Franco Scinicariello, Sharon Wilbur, ATSDR, Division of Toxicology and Human Health Sciences, Atlanta, GA; Lisa Ingerman, Fernando Llados, Daneil Plewak, David Wohlers, Gary Diamond, SRC, Inc., North Syracuse, NY.201

Toxicological profile for chlorinated dibenzo-p-dioxins : (Update)

prepared by Research Triangle Institute ; prepared for U.S. Department of Health and Human Services, Public Health Service, Agency for Toxic Substances and Disease Registry."Under Contract No. 205-93-0606."--T.b."December 1998."Also available via the World Wide Web (accessed 2009 September 30).Includes bibliographical references (p. 543-672)

Benzene (update)

prepared by Syracuse Research Corporation under contract no. 200-2004-09793 ; prepared for U.S. Department of Health and Human Services, Public Health Service, Agency for Toxic Substances and Disease Registry."August 2007.""A Toxicological Profile for Benzene, Draft for Public Comment was released in August 2005. This edition supersedes any previously released draft or final profile"--P. iii.Chemical managers/authors: Sharon Wilbur, Sam Keith, Obaid Faroon, ATSDR, Division of Toxicology and Environmental Medicine, Atlanta, GA; David Wohlers, Julie Stickney,.Sari Paikoff,.Gary Diamond, Antonio Quin\ucc\u192ones-Rivera,.Syracuse Research Corporation, North Syracuse, NY --p. ix.Also available via the World Wide Web.Includes bibliographical references (p. 313-376) and index

Toxicological profile for iodine

prepared by Syracuse Research Corporation under contract no. 205-1999-00024 ; prepared for U.S. Dept. of Health and Human Services, Public Health Service, Agency for Toxic Substances and Disease Registry."April 2004.""A Toxicological Profile for Iodine, Draft for Public Comment was released in September 2001. This edition supercedes any previously released draft or final profile."--P. iii.Chemical manager(s)/author(s): John Rishe ... [et al.].Also available via the World Wide Web.Includes bibliographical references (p. 325-495)

Benzene (update)

prepared by Syracuse Research Corporation under contract no. 200-2004-09793 ; prepared for U.S. Department of Health and Human Services, Public Health Service, Agency for Toxic Substances and Disease Registry."August 2007.""A Toxicological Profile for Benzene, Draft for Public Comment was released in August 2005. This edition supersedes any previously released draft or final profile"--P. iii.Chemical managers/authors: Sharon Wilbur, Sam Keith, Obaid Faroon, ATSDR, Division of Toxicology and Environmental Medicine, Atlanta, GA; David Wohlers, Julie Stickney,.Sari Paikoff,.Gary Diamond, Antonio Quin\ucc\u192ones-Rivera,.Syracuse Research Corporation, North Syracuse, NY --p. ix.Also available via the World Wide Web.Includes bibliographical references (p. 313-376) and index

The clinical development of rectal microbicides for HIV prevention

Introduction: Individuals practicing unprotected receptive anal intercourse are at particularly high risk of HIV infection. Men who have sex with men in the developed and developing world continue to have disproportionate and increasing levels of HIV infection. The last few years have seen important progress in demonstrating the efficacy of oral pre-exposure prophylaxis, vaginal microbicides, and treatment as prevention but there has also been significant progress in the development of rectal microbicides. The purpose of this thesis is to summarise the status of rectal microbicide research, to identify opportunities, challenges, and future directions in this important field of HIV prevention, and to describe the results of a recently completed Phase 1 rectal microbicide study (MTN-007). Methods: MTN-007, a Phase 1, randomised, partially blinded, rectal safety study was undertaken to determine whether a reduced glycerin formulation of tenofovir 1% gel was safe and acceptable to men and women with a history of practicing receptive anal intercourse. The study was conducted at three clinical trial sites in the United States (Pittsburgh, Pennsylvania; Boston, Massachusetts; and Birmingham, Alabama). Study participants were randomized to one of three gel arms (tenofovir gel, a hydroxyethyl cellulose placebo gel, or a 2% Nonoxynol gel) or a no treatment arm and received a total of eight rectal daily doses of the study product. In addition to collecting conventional clinical safety and acceptability data, the study also included extensive mucosal safety assays to determine whether product administration was associated with changes in mucosal biology that might predispose to increased risk of HIV acquisition associated with unprotected receptive anal intercourse. Results: Sixty-five participants (45 men and 20 women) were recruited into the study. There were no significant differences between the numbers of ≥ Grade 2 adverse events across the arms of the study. Likelihood of future product use (acceptability) was 87% (reduced glycerin formulation of tenofovir 1% gel), 93% (hydroxyethyl cellulose placebo gel), and 63% (Nonoxynol-9 gel). Fecal calprotectin, rectal microflora, and epithelial sloughing, did not differ by treatment arms during the study. Suggestive evidence of differences was seen in histology, mucosal gene expression, protein expression, and T cell phenotype. These changes were mostly confined to comparisons between the Nonoxynol-9 gel and other study arms. Microarray analysis of the mucosal transcriptome provided preliminary evidence that topical application of tenofovir 1% gel was associated with decreased mitochondrial function within the rectal mucosa. Conclusions: The MTN-007 study demonstrated that, using conventional criteria, tenofovir gel is safe and acceptable and should be advanced to Phase 2 development as a potential rectal microbicide. However, microarray analysis of mucosal tissue suggested that use of tenofovir gel may modulate mucosal mitochondrial function. This observation will require further evaluation in future studies

Fabrication of solid dispersion based patches using hot melt injection moulding and fused deposition modelling 3D printing

The poor aqueous solubility of many APIs, such as felodipine, are significant dissolution rate limiting factors that often lead to poor oral systemic bioavailability. Solid dispersions have been used as a formulation approach to improve drugs dissolution properties. Most of the reported solid dispersion formulations in the literature are binary mixtures with limited functionalities (with enhancing dissolution being the primary function). The aim of this study is to design, characterise and evaluate complex solid dispersions with intentionally designed microstructures (in the form of phase separations). The potential functionalities of these microstructures were explored by this project. In our view, the complex formulations are more representative of real pharmaceutical products in their final forms. HME-IM is a single processing technique for fabricating formulations with high geometric precision in a rapid, efficient and environmentally friendly way. It was used as the main processing method to produce the solid dispersion based buccal patches in this project. The patches were thoroughly characterised using conventional techniques including DSC, MTDSC, TGA, DVS, ATR-FTIR, PXRD, SEM, EDS, IR imaging, mucoadhesion and in vitro dissolution testing. In order to address the spatial distribution of the phase separations, two non-conventional characterisation methods, thermal analysis by structural characterisation and X-ray microcomputed tomography, were introduced to provide novel insights into the heterogeneity and phase distribution of these formulations. The results revealed that HME-IM patches with 10% drug loading were unsaturated while those with 20-30% w/w drug concentration were saturated or even supersaturated. HME-IM patches containing TPGS were more solubilising to felodipine and more stable compared to Tween 80 containing systems. Thermal analysis by structural characterisation provided rapid detection of heterogeneity and the thermal dissolution of crystalline drug fraction while XμCT provided microscale spatial distribution of different phases. Having shown the advantages of using polymeric blends to formulate solid dispersions that were demonstrated by the felodipine buccal patches, we further explored the use of polymer blends for improving the FDM 3D printability of pharmaceutical solid dosage forms with the potential applications in personalised medicine. This project demonstrated the potential and formulation principles of using HME-IM and FDM 3D printing as formulation methods for production of polymer blend based complex solid dispersions for the purposes of enhanced bioavailability of poorly soluble drugs and providing personalised medicines