Physicochemical testing

Since the U.S. vs. Barr decision in 1993 (relevant to pharmaceuticals and related fields, rules applied by the Federal Food Drug Administration, FDA), outlier tests may no longer be applied to physicochemical tests, under the assumption that such test methods, having been optimized and validated for the particular set of circumstances, rarely produce outliers. These tests may not be applied to CU results at all. Good manufacturing practices mandate that operators work according to pre-set procedures and write down any observed irregularities as they... 

Physicochemical tests—plastics Polyethelene containers PET and PETG bottles... 

In addition to the tests described above, other chemical, biological, physical, and physicochemical tests were performed (16) which are not reported in this paper because of space limitation. These tests are mainly concerned with product safety, chemical stability and sensory perception. 

Physicochemical tests are required in essential oil monographs published in standards, pharmacopoeias and codices. Chromatospectral techniques are modern methods used to assess the quality of essential oils. The most important technique for the analysis of essential oils is GC. Several detectors may... 

Methods to determine the potential biological activity of products obtained through recombinant DNA techniques are of fundamental importance. Despite the existence of numerous physicochemical techniques to characterize the protein product structure and the presence of contaminants, they provide little, if any, information about its biological potency. A bioassay is defined as a functional test, and no physicochemical test can measure the function. However, for some peptide hormones, which are less complex in structure than most cytokines, well defined physicochemical tests may be used to estimate biological activity for instance, the capillary electrophoresis analysis of a protein s isoform content if the specific activity of each one is known. 

A subtle distinction can be made between QSARs and the PMs associated with physicochemical tests. The distinction is that while any PM (associated with a physicochemical test) could also be called a QSAR, not all QSARs could also be called PMs. For example, QSARs can also be based on theoretical descriptors (e.g., topological indices) or on experimental properties that are themselves more easily predicted than measured (e.g., the octanol-water partition coefficient). Furthermore, QSARs developed for the prediction of physicochemical and in vitro end points would not be regarded as PMs. 

Information on the physicochemical properties of the substance. The testing information required on the substance depends on the volumes manufactured or imported. All substances will require a base set of testing information and as the tonnage bands increase the amount of information increases. All substances will need physicochemical testing and the amount of information will change as the tonnages increase ... 

Physicochemical Analysis In terms of complexity, HGH is fairly simple and well-characterized. Human growth hormone is a single-chain, 191-amino-acid, nonglyco-sylated protein with two intramolecular disulfide bonds. Sandoz used a variety of physicochemical tests and analytical methods to confirm the primary, secondary, and... 

Some potential extractable chemicals from packaging materials are water soluble, while others are soluble only in nonpolar environments. The USP includes physicochemical tests for plastics based on water extracts, while water, alcohol, and hexane extracts are required for polyethylene containers under controlled temperature and time parameters (70°C for 24h for water and alcohol and 50°C for 24h for hexane). 

The USP physicochemical tests for extractables should be a part of all suitability programs, regardless of the criticality of the drug dosage form. USP elastomeric closures for injections should also be a part of the extractables study to establish safety. These USP tests, which have evolved over many years, are relevant, sensitive, rapid, and inexpensive. They help establish material safety. 

The chemical composition should also be evaluated by performing the simple but informative USP physicochemical tests using water, drug product vehicle, and alcohol extractions of plastic components. Specifications should be set for nonvola-... 

With this approach, WHO and FAO specifications would have equal standing and equal transparency in development, and their acceptance would be enhanced. They could be used throughout the world with the same requirements concerning, for example, the tolerances on active ingredient content, impurities and the physicochemical tests required. 

The Committee expressed concern at the fact that different chemical and physicochemical test methods are recommended by WHO and FAO. The FAO specifications give references to official and collaboratively tested methods adopted by the Collaborative International Pesticide Analytical Council (CIPAC) or by AO AC International (AOAC) and published by these organizations but do not provide full texts of the methods. In WHO specifications published up to 1997, the chemical and physicochemical methods are described in full, with the specifications, or under the heading WHO test methods in the same document. In some new Interim Specifications... 

H bonding can be detected more or less easily by practically any physicochemical test method. Tests applied to the liquid state, which are of most practical interest, suffer from knotty and incomplete theoretical treatment. At present, and not considering spectral studies,... 

Milano, C.J. Bailey, L.C. Evaluation of current compendial physicochemical test procedures for pharmaceutical elastomeric closures and development of an improved hplc procedure, PDA. J. Pharm. Sci. Tech. 1999, 53, 202-210. 

Based on physicochemical testing, a different approach to the manipulation of the chemical is needed ... 

Physicochemical testing is performed to characterize the physical and chemical properties of a plastic to insure that the composition of the synthetic medium will not compromise the quality of the drug being stored within it. To perform these tests, samples of plastic identical to the material being used in the primary package are subjected to an extraction procedure—to dissolve in an extraction solution leachable compounds that are at risk of entering the pharmaceutical preparation. This extraction solution is then subjected to analysis to evaluate the identity and quantity of leachants. For most plastics, the appropriate extraction medium is purified water, but elastomeric closures for use with injections should include extraction with three different extraction... 

For the first two tests, extracts that are similar to those used during physicochemical testing are used. The extraction process, which differs somewhat from previous extractions, is explained in the USP. The first test, the systemic injection test, uses a sample of extract injected intravenously or intraperitoneally (as indicated in the test protocol) into each of five albino mice. Note that a control solution is used to inject five mice in a control group as well. Animals are evaluated over the next three days and monitored for death, abnormal behavior, or weight loss. If the test results are inconclusive, the protocol can be repeated on groups of 10 mice each. 

Containers that require classification but are not being used for prescription dispensing are categorized based on their material. The same three substances are considered as were explored during physicochemical testing PE (e.g., HDPE and LDPE), PET and PETG, and PP. 

A number of tests are available for the chemical characterization of medical device materials to establish material safety and biocompatibility. These tests include infrared analysis, aqueous and non-aqueous physicochemical tests, high-performance liquid and gas chromatography, atomic absorption spectroscopy and inductively coupled plasma spectroscopy, and a variety of mechanical/physical tests. 

These aqueous physicochemical tests are designed to determine the presence of water-soluble substances without regard to their identity. Results are presented as a set of four values, showing the results for test type together with the corresponding USP limits (see Table 5). These aqueous extract tests are intended to serve as the basis for design specifications. 

The USP recommends isopropyl alcohol (IPA) for conducting physicochemical tests of elastomeric closures used for pharmaceutical containers. IPA can dissolve many chemicals that are insoluble in water. The extract is analyzed for nonvolatile residue and residue on ignition. Turbidity and ultraviolet absorption tests are performed to detect the presence of extractables without specifically identifying their chemical makeup. Results are presented as a set of five values for each of the end points (see Table 6). USP limits do not yet exist for these tests, but they are not necessary for establishing specifications for the acceptance of materials. 

Note. Results of aqueous extraction physicochemical testing on polymers commonly used in medical devices. ... 

Table 6 Physicochemical tests for polymer contaminants using isopropanol extraction ...

Physicochemical analysis has evaluated the particular chemical properties of test substances, which have been identified as key structural components contributing to penetration, irritation, or sensitization. Absence of absorption in the ultraviolet (UV) range also has been used to suggest lack of photoirritant potential. Physicochemical tests are rapid, cost-effective, easily standardized, and transferable to outside laboratories. 

A new drug development program should include a series of physicochemical tests to fully define the impurity profile of a pharmaceutical compound prior to performance of extensive pharmacologic and toxicologic studies. This is necessary to assure that observed toxicologic or pharmacologic profiles are in fact due to the compound of interest and not to impurities. 

The quality control tests can be divided into two categories physicochemical tests and biological tests. Refer to Saha (2004) for detailed description of these methods. These tests are briefly outlined below. 

Physicochemical Tests Physicochemical tests include the tests for the physical and chemical parameters of a PET radiopharmaceutical, namely physical appearance, isotonicity, pH, radionuclidic purity, chemical purity, and radiochemical purity. 

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