Formulation assessment

Fleishaker, J.C. et al., Psychomotor and memory effects of two adinazolam formulations assessed by a computerized neuropsychological test battery, J. Clin. Pharmacol., 33, 463, 1993. 

Kwong E. C., P. L. Lamarche, G. R. Down, S. A. McClintock, and M. L. Cotton. 1994. Formulation assessment of MK-886, a poorly water-soluble drug, in the beagle dbnjernational Journal of Pharmaceutips 103 259-265. 

If no, how could the tiers be defined, given the formulated assessment endpoint ... 

Conduct bioequivalence or bioavailability comparison studies for novel formulation assessment. 

Six scientific disciplines are involved in the developability characterization of a lead discovery candidate. As shown in Figure 4, these disciplines are in vivo pharmacology, bioanalytical method development, nonclinical formulation assessment, animal pharmacokinetics, drug metabolism, and toxicology. The following sections discuss each of these scientific disciplines in more detail. 

Formulation assessment, including solubility, stability, and delivery. 

Bagli, M. et al.. Mean input times of three oral chlorprothixene formulations assessed by an enhanced least-squares deconvolution method, J. Pharm. Set, 85 434-439, 1996. 

It is difficult to foresee all the potential problems that can be realized in a pan-coating process. Problems can be related to formulation shortcomings, process limitations, or suboptimal process parameters. Once a coat formulation has been established, there may not be opportunity to adjust composition depending on regulatory restrictions thus, it may be prudent to optimize to a robust formulation before the adjustment period passes. The following characteristics should be included in such a formulation assessment ... 

Model quality needs to be evaluated and communicated to interested parties in a structured way in order to ensure acceptance and usefulness. The MEG advises a stmcture consisting of three elements assessment, verification, and vahdation (EC, 1994b). In this chapter, we adopt the terminology as suggested by the MEG protocol, i.e., model evaluation includes the whole review of any model with respeet to proper scientific formulation (assessment), eorreet eoding (verifieation), and comparison with experimental data (validation). These stages are defined in Table 19.1. We are aware that other terms are sometimes used and that there is some philosophieal criticism of the use of the term validation. 

A conceptual model diagram shows the relationships between stressors and receptors in the context of the ecosystem where the stresses occnr. Because these relationships are often complicated, diagramming them is helpfnl in formulating assessment endpoints and in identifying specific measnres for use in exposure and effect analyses. 

The assessment of the contribution of a product to the fire severity and the resulting hazard to people and property combines appropriate product flammabihty data, descriptions of the building and occupants, and computer software that includes the dynamics and chemistry of fires. This type of assessment offers benefits not available from stand-alone test methods quantitative appraisal of the incremental impact on fire safety of changes in a product appraisal of the use of a given material in a number of products and appraisal of the differing impacts of a product in different buildings and occupancies. One method, HAZARD I (11), has been used to determine that several commonly used fire-retardant—polymer systems reduced the overall fire hazard compared to similar nonfire retarded formulations (12). 

The characteristics of interior paints that require testing and analysis include hiding and appearance, package stabiHty, adhesion, spatter resistance, flow and leveling, color and sheen uniformity, touch-up, stain removal, burnish resistance, and block and print resistance. A popular test that assesses the wet abrasion resistance of an interior paint is to measure its scmb resistance. A mechanical device is used to scmb a paint film of a specified thickness with a standard bmsh and abrasive cleanser suspension. The number of scmb cycles (back and forth movements of the weighted bmsh) at various end points (first cut through, or 50% removal of the film) is then recorded. Scmb resistance usually holds steady or decreases slightly as PVC is increased, but drops quickly once the CPVC is exceeded in a paint formulation. 

During process development, a model can be developed as soon as a conceptual flow sheet has been formulated. This model can be updated as more information about the process is obtained. Even at an early stage in the project, the model can be used to assess the preliminary economics of the process and the effect of technological changes on these economics. The model can aid in interpreting pilot-plant data and allows the study of many process alternatives. 

Performance. Consumer acceptance is a criterion on which cosmetic marketers caimot compromise. Whereas the likes and dislikes of consumers are in a state of constant flux, some product features are critical. A deodorant that does not deodorize or a hair coloring that fades in sunlight is unacceptable. Performance is tested by in vitro techniques during formulation, but the ultimate test of a product s performance requires in-use experience with consumers and critical assessment by trained observers. Performance tests can sometimes be combined with in-use safety tests, and protocols for such programs have been developed. 

It is obvious that the range of possible formulations based on poly(vinyl chloride) and related copolymers is very wide indeed. For each end-use the requirements must be carefully considered and a formulation devised that will give a compound of adequate properties at the lowest cost. In assessing cost it is not only important to consider the cost of the compound but also comparative processing costs, the possible cost of storing additional materials and many other cost factors. 

The Rijnmond area is that part of the Rhine delta between Rotterdam and the North Sea. The Commission for the Safety of the Population at large (COVO) commissioned the study for six chemicals and the operations associated with them acrylonitrile, liquid ammonia, liquid chlorine, LNG, propylene, and part of a separation process (diethanolamine stripper of a hydrodesulfurizer). The study objectives were to evaluate methods of risk assessment and obtain experience with practical applications of these methods. The results were to be used to decide to what extent such methods can be used in formulating safety policy. The study was not concerned with the acceptability of risk or the acceptability of risk reducing measures. 

In the USA, there is the ASTM standards and the well-known General Electric requirements. The total useful life of turbine oil is its most important characteristic. ASTM method D943 (IP 157) measures the life indirectly by assessing the useful life of the oxidation inhibitor contained in the formulation and are often referred to as the TOST life of the oil. Rust prevention is generally assessed by the ASTM D665 (IP 135) method. 

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