Testing of turbulent seals for rotordynamic coefficients

A facility has been developed for dynamic testing of straight and convergent tapered seals with the capability of measuring the radial and tangential force components which result from a circular centered orbit. The test apparatus causes the seal journal to execute small-eccentricity centered circular orbits within its clearance circle. Dynamic measurements are made and recorded of the seal displacement-vector components, and of the pressure field. The pressure field is integrated to yield seal tangential and radial reaction-force components. Representative test data are provided and discussed for straight seals

A high-Reynolds-number seal test facility: Facility description and preliminary test data

A facility has been developed for testing the leakage and rotordynamic characteristics of interstage-seal configurations for the HPFTP (High Pressure Fuel Turbopump) of the SSME (Space Shuttle Main Engine). Axial Reynolds numbers on the order of 400,000 are realized in the test facility by using a Dupont freon fluid called Halon (CBrF3). The kinematic viscosity of Halon is of the same order as the liquid hydrogen used in the HPFTP. Initial testing has focused on the current flight configurations (a three-segment, stepped unit) and a convergent-taper candidate

Particle diffusional layer thickness in a USP dissolution apparatus II: A combined function of particle size and paddle speed

This work was to investigate the effects of particle size and paddle speed on the particle diffuisonal layer thickness h app in a USP dissolution apparatus II. After the determination of the powder dissolution rates of five size fractions of fenofibrate, including <20, 20–32, 32–45, 63–75, and 90–106 µm, the present work shows that the dependence of h app on particle size follows different functions in accordance with the paddle speed. At 50 rpm, the function of h app is best described by a linear plot of $h_{{rm app}} = 9.91sqrt d - 23.31$ ( R 2  = 0.98) throughout the particle diameter, d , from 6.8 to 106 µm. In contrast, at 100 rpm a transitional particle radius, r , of 23.7 µm exists, under which linear relationship h app  = 1.59 r ( R 2  = 0.98) occurs, but above which h app becomes a constant of 43.5 µm. Thus, h app changes not only with particle size, but also with the hydrodynamics under standard USP configurations, which has been overlooked in the past. Further, the effects of particle size and paddle speed on h app were combined using dimensionless analysis. Within certain fluid velocity/particle regime, linear correlation of h app / d with the square-root of Reynolds number $(dvarpi /upsilon )^{1/2}$ , that is, $h_{{rm app}} /d = 1.5207 - 9.25 times 10^{ - 4} (dvarpi /nu )^{1/2}$ ( R 2  = 0.9875), was observed. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:4815–4829, 2008Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/61209/1/21345_ftp.pd

Physicochemical and physiological mechanisms for the effects of food on drug absorption: The role of lipids and pH

Drugs are absorbed after oral administration as a consequence of a complex array of interactions between the drug, its formulation, and the gastrointestinal (GI) tract. The presence of food within the GI tract impacts significantly on transit profiles, pH, and its solubilization capacity. Consequently, food would be expected to affect the absorption of co‐administered drugs when their physicochemical properties are sensitive to these changes. The physicochemical basis by which ingested food/lipids induce changes in the GI tract and influence drug absorption are reviewed. The process of lipid digestion is briefly reviewed and considered in the context of the absorption of poorly water‐soluble drugs. The effect of food on GI pH is reviewed in terms of location (stomach, upper and lower small intestine) and the temporal relationship between pH and drug absorption. Case studies are presented in which postprandial changes in bioavailability are rationalized in terms of the sensitivity of the physicochemical properties of the administered drug to the altered GI environment.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97269/1/1_ftp.pd

Biowaiver monographs for immediate release solid oral dosage forms: prednisolone.

Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing prednisolone are reviewed. Data on its solubility, oral absorption, and permeability are not totally conclusive, but strongly suggest a BCS Class 1 classification. Prednisolone's therapeutic indications and therapeutic index, pharmacokinetics, and the possibility of excipient interactions were also taken into consideration. Available evidence indicates that a biowaiver for IR solid oral dosage forms formulated with the excipients tabulated in this article would be unlikely to expose patients to undue risks

Effect of Intragastric pH on the Absorption of Oral Zinc Acetate and Zinc Oxide in Young Healthy Volunteers

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142255/1/jpen0393.pd

Biowaiver monographs for immediate release solid oral dosage forms: acetaminophen (paracetamol).

Literature data are reviewed on the properties of acetaminophen (paracetamol) related to the biopharmaceutics classification system (BCS). According to the current BCS criteria, acetaminophen is BCS Class III compound. Differences in composition seldom, if ever, have an effect on the extent of absorption. However, some studies show differences in rate of absorption between brands and formulations. In particular, sodium bicarbonate, present in some drug products, was reported to give an increase in the rate of absorption, probably caused by an effect on gastric emptying. In view of Marketing Authorizations (MAs) given in a number of countries to acetaminophen drug products with rapid onset of action, it is concluded that differences in rate of absorption were considered therapeutically not relevant by the Health Authorities. Moreover, in view of its therapeutic use, its wide therapeutic index and its uncomplicated pharmacokinetic properties, in vitro dissolution data collected according to the relevant Guidances can be safely used for declaring bioequivalence (BE) of two acetaminophen formulations. Therefore, accepting a biowaiver for immediate release (IR) acetaminophen solid oral drug products is considered scientifically justified, if the test product contains only those excipients reported in this paper in their usual amounts and the test product is rapidly dissolving, as well as the test product fulfils the criterion of similarity of dissolution profiles to the reference product

Effects of medicines used to treat gastrointestinal diseases on the pharmacokinetics of coadministered drugs:A PEARRL Review

Background: Drugs used to treat gastrointestinal diseases (GI drugs) are widely used either as prescription or over23 the-counter (OTC) medications and belong to both the ten most prescribed and ten most sold OTC medications worldwide. Current clinical practice shows that in many cases, these drugs are administered concomitantly with other drug products. Due to their metabolic properties and mechanisms of action, the drugs used to treat gastrointestinal diseases can change the pharmacokinetics of some co27 administered drugs. In certain cases, these interactions can lead to failure of treatment or to the occurrence of serious adverse events. The mechanism of interaction depends highly on drug properties and differs among therapeutic categories. Understanding these interactions is essential to providing recommendations for optimal drug therapy. Objective: To discuss the most frequent interactions between GI and other drugs, including identification of the mechanisms behind these interactions, where possible. Conclusion: Interactions with GI drugs are numerous and can be highly significant clinically. Whilst alterations in bioavailability due to changes in solubility, dissolution rate and metabolic interactions can be (for the most part) easily identified, interactions that are mediated through other mechanisms, such as permeability or microbiota, are less well understood. Future work should focus on characterizing these aspects

Biowaiver monographs for immediate release solid oral dosage forms: Aciclovir

Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing (biowaiver) for the approval of immediate release (IR) solid oral dosage forms containing aciclovir are reviewed. Aciclovir therapeutic use and therapeutic index, pharmacokinetic properties, data related to the possibility of excipient interactions and reported BE/bioavailability (BA) studies were also taken into consideration in order to ascertain whether a biowaiver can be recommended. According to the Biopharmaceutics Classification System (BCS) and considering tablet strengths up to 400 mg, aciclovir would be BCS Class III. However, in some countries also 800 mg tablets are available which fall just within BCS Class IV. Aciclovir seems not to be critical with respect to a risk for bio in equivalence, as no examples of bio in equivalence have been identified. It has a wide therapeutic index and is not used for critical indications. Hence, if: (a) the test product contains only excipients present in aciclovir solid oral IR drug products approved in ICH or associated countries, for instance as presented in this article; and (b) the comparator and the test product both are very rapidly dissolving , a biowaiver for IR aciclovir solid oral drug products is considered justified for all tablet strengths. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:5061–5073, 2008Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/61316/1/21392_ftp.pd

Findings from the Longitudinal CINRG Becker Natural History Study

BACKGROUND: Becker muscular dystrophy is an X-linked, genetic disorder causing progressive degeneration of skeletal and cardiac muscle, with a widely variable phenotype. OBJECTIVE: A 3-year, longitudinal, prospective dataset contributed by patients with confirmed Becker muscular dystrophy was analyzed to characterize the natural history of this disorder. A better understanding of the natural history is crucial to rigorous therapeutic trials. METHODS: A cohort of 83 patients with Becker muscular dystrophy (5-75 years at baseline) were followed for up to 3 years with annual assessments. Muscle and pulmonary function outcomes were analyzed herein. Age-stratified statistical analysis and modeling were conducted to analyze cross-sectional data, time-to-event data, and longitudinal data to characterize these clinical outcomes. RESULTS: Deletion mutations of dystrophin exons 45-47 or 45-48 were most common. Subgroup analysis showed greater pairwise association between motor outcomes at baseline than association between these outcomes and age. Stronger correlations between outcomes for adults than for those under 18 years were also observed. Using cross-sectional binning analysis, a ceiling effect was seen for North Star Ambulatory Assessment but not for other functional outcomes. Longitudinal analysis showed a decline in percentage predicted forced vital capacity over the life span. There was relative stability or improved median function for motor functional outcomes through childhood and adolescence and decreasing function with age thereafter. CONCLUSIONS: There is variable progression of outcomes resulting in significant heterogeneity of the clinical phenotype of Becker muscular dystrophy. Disease progression is largely manifest in adulthood. There are implications for clinical trial design revealed by this longitudinal analysis of a Becker natural history dataset