Tests for Physical Dependence

Reduced effectiveness of a fixed dose and/or the need for larger doses to obtain a constant response indicates the development of tolerance. ED50 values obtained before and after repeated daily treatment are compared to assess the magnitude of tolerance. 

MODIFICATIONS OF THE METHOD Other authors (e.g. Glassman 1971) injected the dose which induced a full antinociceptive effect in mice twice daily for a period of 21 days and evaluated the stepwise decay of effectiveness. After 21 days, the effect of 10 mg/kg morphine or 30 mg/kg meperidine i.p. decreased to approximately 50 % of the value of the first day. 

Langerman et al. (1995) evaluated the acute tolerance to continuous morphine infusion up to 8 h in the rat with various doses using the hot plate and the tail flick assay. Tolerance was observed with the hot plate assay but not with the tail flick assay suggesting tolerance development at a supraspinal site. 

Smith et al. (2003) used twice daily injections of morphine and implantation of morphine-containing pellets to study mechanisms of opioid tolerance in mice. 

Riba et al. (2002) showed that the role of opioid receptors in modifying the antinociceptive effects of x opioid agonists changes during morphine tolerance. 

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Test for physical dependence, tolerance and substitution potential... 

VonVoigtlander PF, Lewis RA (1983) A withdrawal hyperalgesia test for physical dependence evaluation of p. and mixed-partial opioid agonists. J Pharm Meth 10 277-282 Way EL (1993) Opioid tolerance and physical dependence and their relationship. In Herz A, Akil H, Simon EJ (eds) Handbook of Experimental Pharmacology, Vol 104/ Opioids II, chapter 53. Springer Berlin Heidelberg New York, pp 573-596... 

TESTING DRUGS FOR PHYSICAL DEPENDENCE POTENTIAL AND ABUSE LIABILITY. Joseph V. Brady, Ph.D., and Scott E. Lukas, Ph.D., eds. 

TESTING DRUGS FOR PHYSICAL DEPENDENCE POTENTIAL AND ABUSE... 

Brady, J.V. and Lukas, S.E., Testing Drugs for Physical Dependence Potential and Abuse Liability. NIDA Research Monograph 52, 1984. 

As a conclusion, JUPITER experiment and analysis was found to possess sufficient consistency on the whole, especially for the prediction of criticality, space-dependency of C/Es in core region, and sodium void reactivity, which were persistent problems in the past JUPITER evaluations. It was also recognized that there is, however, some room for further improvements about the C28/F49 ratio, reaction rate distribution in blanket region, and Doppler reactivity. Efforts are now being conducted from various viewpoints such as re-evaluation of experimental and analytical errors, application of new most-detailed analytical tools, comparisons with other experimental cores, and refrnement of statistical tests for physical consistency. 

The idea of using mathematical modeling for describing materials behavior under loads is well known. Some physical phenomena, which can be observed in materials during testing, have time dependent quantitative characteristics. It gives a possibility to consider them as time series and use well developed models for their analysis [1, 2]. Usually applied... 

Estimating Minimum Sample Quantity for Moisture Measurement Estimates of material quantity for testing moisture content depend on mechanisms of moisture distribution in the material. Moisture is physically retained on particle surfaces, chemically adsorbed on surfaces and within pores of particulate solids, and contained as an internal constituent of solids. Significant internal moisture is most often encountered in organic and agricultural source materials. 

T Urethanes not shown because of great differences in physical properties, depending on formulations. Adhesion characteristics should he related by actual test data. Any system which shows concrete failure when tested for surfacing adhesion should he rated excellent with decreasing rating for systems showing failure in cohesion or adhesion below concrete failure. 

All packing materials produced at PSS are tested for all relevant properties. This includes physical tests (e.g., pressure stability, temperature stability, permeability, particle size distribution, porosity) as well as chromatographic tests using packed columns (plate count, resolution, peak symmetry, calibration curves). PSS uses inverse SEC methodology (26,27) to determine chromatographic-active sorbent properties such as surface area, pore volume, average pore size, and pore size distribution. Table 9.10 shows details on inverse SEC tests on PSS SDV sorbent as an example. Pig. 9.10 shows the dependence... 

The elements are obtainable in a state of very high purity but some of their physical properties are nonetheless variable because of their dependence on mechanical history. Their colours (Cu reddish, Ag white and Au yellow) and sheen are so characteristic that the names of the metals are used to describe them. Gold can also be obtained in red, blue and violet colloidal forms by the addition of vtirious reducing agents to very dilute aqueous solutions of gold(III) chloride. A remarkably stable example is the Purple of Cassius , obtained by using SnCla as reductant, which not only provides a sensitive test for Au but is also used to colour glass and ceramics. Colloidal silver and copper are also obtainable but are less stable. 

Elastomer samples are cast in molds, the size and shape of which depend on its purpose. Samples for physical properties can be produced using a custom-made book mold designed to create a thin sheet (0.1 in.) containing premolded test parts, such as those for die-C tear, flexural modulus, and so on. Alternatively, a flat plaque mold may be used to create a 6 x 6 x 0.1-in. sheet from which may be cut samples for testing. Thicker samples for hardness measurements may... 

For nonpharmacopeial materials a full specification should be included in the application. This should include appropriate tests and requirements for physical characteristics, identification, relevant purity tests, and performance-related tests. Characteristics likely to influence bioavailability of the finished product should be controlled. Routine tests and specifications should be described. Methods should be validated. The material should be fully characterized, with full data on the chemistry concerned and including consideration of the safety of the excipient. Any relevant European Directive requirements or other international specifications should be met, but additional requirements might apply depending on the intended use of the product—e.g., for materials to be used in sterile products. 

The mathematical relations of gas-liquid reactions are like those for physical absorption but the equilibria and mass transfer coefficients are much more complex because they depend on the chemical nature of the reactant and its remaining concentration at each location in the reactor. Such data are not plentiful or well correlated in print, and the main reliance for particular reactions is on laboratory or pilot plant testing. 

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