Dosage description tests

Primary container-closure system-related data will need to cover storage, transportation, and use. The choice of materials of construction, their description, and the ability of the container-closure system to protect from moisture and/or light will need to be considered. The compatibility of the container-closure and its contents will need to consider sorption, leaching, and safety. The performance of the container-closure system will also need to be considered in terms of dose delivery from any associated device that is to be supplied as part of the product. Container-closure components will require adequate specifications covering description, identification, critical dimensional tolerances, and test methodology (including pharma-copeial and noncompendial methods). More data are likely to be required for liquid or semi-liquid products than for solid dosage forms. In the latter, product stability data and container-closure system specifications may suffice. 

Table 1 outlines the current status of scientific development for the dissolution or release testing from various dosage forms and recommends, where possible, the dissolution apparatus of first choice (13). Refer also to Chapter 2 for further description of the USP apparatus. 

Description of dilution procedures used to obtain recommended dosage. Was the admixture tested and approved ... 

Within a few years of the discovery of the extraordinary potency of LSD, a large number of close analogues were synthesized by Hofmann and his allies at Sandoz. Over the following decade many were tested in humans, both in patients and healthy subjects, with the qualitative descriptions and dosages published in the medical literature. 

If the chemical composition of the samples is known or at least partly known (in a stepwise TIE approach) or existing data allow for QSAR calculation, the samples can be ranked by TUs. Arts et al. (2006) studied, in 12 outdoor ditch mesocosms, the effects of sequential contamination with 5 pesticides in a regression design. They applied dosages equivalent with 0.2%, 1%, and 5% of the predicted environmental concentration (PEC) subsequently over 17 weeks. Endpoints recorded over 30 weeks included community composition of macroinvertebrates, plankton, and macrophytes, and leaf litter decomposition as functional ecosystem parameters. TUs were calculated in relation to acute toxicity data for the most sensitive standard species Daphnia magna and Lemna minor. Principal response curves (PRCs), a special form of constrained PCA, and Williams test (NOEC, class 2 LOEC) were used to identify the most sensitive taxa. Next to direct effects on certain species, also indirect effects, for example, how the change in abundance of a sensitive species affects the abundance of another, more tolerant species, can be detected only in mesocosm or in situ experiments. All observed effects were summarized in effect classes in a descriptive manner. 

Description of the number of test species groups, the dosage level to be administered to each group, the test article concentration or amount to be administered, the number of animals of each sex in each dose group Statement on how animals will be assigned or randomized to each of the dose groups... 

Tables 2-11 list the various compounds and the associated USP tests, together with their relevant chromatographic conditions. Drugs and related dosage forms have been arranged alphabetically, while descriptions of the various GC supports...

Specifications for excipients Pharmacopoeia copy of the monograph, test methods referenced Additional specifications Non-pharmacopoeia list of tests and for each excipient, including solvents, liquids to adjust pH, coatings, capsule shell, and inked imprint (on the dosage form), description of test methods, microbiological limits, colours EU/FDA/Japan ... 

Numerous methods are required to characterize drug substances and drug products (Chapter 10). Specifications may include description identification assay (of composite sample) tests for organic synthetic process impurities, inorganic impurities, degradation products, residual solvents, and container extractables tests of various physicochemical properties, chiral purity, water content, content uniformity, and antioxidant and antimicrobial preservative content microbial tests dissolution/disintegration tests hardness/friability tests and tests for particle size and polymorphic form. Some of these tests may be precluded, or additional tests may be added as dictated by the chemistry of the pharmaceutical or the dosage form. 

The written specification contains a description of the drug in dosage form, which includes all properties and qualities including identity, purity, and potency that are relevant to the fabrication and use of the drug, together with tolerances and a description of all tests or analyses used to determine those properties and qualities, in sufficient detail to permit performance by qualified personnel. All these tests are fully performed. 

Sulfur mustard (SM) is unique among chemical warfare agents because of the large number of reports of its effects in man. The majority of these reports are of its effects after release on the battle field, and give a description of the types of effect and their time course from exposure to resolution of the injury. However, SM is also one of the few chemicals that have been the subject of tests on humans to determine how toxic they are in terms of the doses or dosages that produce toxic effects. Unlike reports of accidental or battlefield exposures, these trials were carried out in chambers under controlled, or at least carefully recorded, conditions, usually with analytical confirmation of chamber concentrations. Many of the reports of these trials, which were elassified at the time they were produced, have now been released into the public record and are available for scientific review. This chapter reviews those reports that are now available to the general public in addition to the work already published. Volunteer trials were carried out in the USA, UK, India and Australia. The reports of these trials that have been released to the public record are held by the Defense Technical Information Service... 

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