Tablet testing assay

Content uniformity is a USP test is designed to establish the homogeneity of a batch. Ten tablets are assayed individually after which the arithmetic mean and relative standard deviation (RSD) are calculated. USP criteria are met if the content uniformity lies within 85-115% of the label claim and the RSD is not greater than 6%. Provision is included in the compendium for additional testing if one or more units fail to meet the standards. 

In pharmaceuticals, NIR is used for, of course, moisture, polymorphic (drug) forms, percent crystallinity, isomer purity, tablet/capsule assay, coating levels, evaluation of dissolution times, and numerous process tests. It is a rapid means for the Food and Drug Administration to check for counterfeit drugs, and for the Drug Enforcement Agency to ascertain what type of materials are impounded in drug raids. ... 

Solid-handling techniqnes are typically physical methods, such as grinding and milling, that rednce solid dosage forms into small particles (i.e., fine powders) to facilitate extraction." Grinding multiple tablets (composite) into a homogeneons pnlverized form (typically 10-20 tablets for assay and >5 tablets for imparity testing) also provides a more representative sample for the batch. 

The use of common pharmaceutical ingredients and the tendency to gang test assays in the laboratory may prevent many of our end-product attributes from being in strict statistical control when measured over time. Therefore it is not recommended that a validation study or Annual Product Review require that a process be in statistical control to be considered acceptable, not even for in-process parameters such as tablet weight, thickness, and hardness. Processes that are not in a state of strict statistical control can be capable of consistently meeting specifications and can be validated. However, if processes are not in statistical control, efforts should always be made to eliminate special causes and get them into as near a state of statistical control as possible. The validation and Annual Product Review data can even be helpful in determining how processes can be improved. 

In the example found in Table 2, we have tests for a tablet product. Assay, dissolution, appearance, and degradation products are typical tests. For a moisture-sensitive product, there may be a need to test for moisture content as well. For a liquid product, a test for pH and microbiological tests are most often included. For a cream product the list of tests may also include a test for viscosity. 

Subcase b2 This case, called the paired f-test , is often done when two test procedures, such as methods A and B, are applied to the same samples, for instance when validating a proposed procedure with respect to the accepted one. In practicular, an official content uniformity" 5 assay might prescribe a photometric measurement (extract the active principle from a tablet... 

Note on GMPs The assays are conducted on individual dosage units (here tablets) and not on composite samples. The CU test serves to limit the variability from one dosage unit to the next (the Dissolution Rate test is the other test that is commonly used). Under this premise, outlier tests would be scientific nonsense, because precisely these outliers contain information on the width of the distribution that one is looking for. The U.S. vs. Barr Laboratories Decision makes it illegal to apply outlier tests in connection with CU and DR tests. This does not mean that the distribution and seemingly or truly atypical results should not be carefully investigated in order to improve the production process. 

Provide either in vitro or in vivo assay results for representative compounds, describe how the in vitro or in vivo assay protocol is performed, and describe how and why the test results demonstrate that the tested compounds exhibit a useful pharmaceutical property. Ideally, provide and link in vitro assay results to in vivo assay results that in turn demonstrate that the claimed compounds can be used to treat or prevent a disease. Describe how to administer the application s compounds and intended administration recipients (e.g., humans), including dosage amounts and dosage forms (e.g., pills, tablets, capsules), possible ways of administering the dosage... 

In contrast to aspirin itself, the U.S.P. monograph for aspirin tablets has undergone considerable changes. For some reason, U.S.P. does not use the ferric salt test for free salicylic acid, as does the British Pharmacopeia of 1973. Apparently, certain excipients such as citric and tartaric acid interfere with this reaction.77 Already in 1913, a double titration method was developed78 which was made an official method in 1926.79 This method was used as the assay method when the aspirin tablets monograph was introduced into U.S.P. XII in 1942. 

Sample preparation (SP) is generally not given adequate attention in discussions of pharmaceutical analysis even though its proper execution is of paramount importance in achieving fast and accurate quantification (see Chapter 5). Non-robust SP procedures, poor techniques, or incomplete extraction are the major causes of out-of-trend and out-of-specification results. The common SP techniques have been reviewed with a strong focus on tablets or capsules, as they are the primary products of the pharmaceutical industry. Detailed descriptions of SP methods for assays and impurity testing are provided with selected case studies of single- and multi-component products. 

Accuracy is defined as the bias of the method, it is a measure of how close the observed result is to the specified quantity. It is usually tested using a method of spiked placebos or of standard addition [3,4]. The expected performance of a method with respect to its accuracy varies enormously from sample to sample. A simple drug formulation, such as a tablet or injection, assayed by HPLC can expect an accuracy of around +/- 1%. 

Volume Displacement. This parameter is not a factor in dissolution testing but can prove to be a very important factor in automated assay, content uniformity, or degradation and impurities testing. It specifically addresses the volume displaced by the tablets in solution. Since manual sample preparations are often prepared utilizing volumetric flasks where the solution is diluted to the mark, the actual volume of solvent added to the flask is irrelevant. However, this actual volume... 

When attempting to convert a manual method into an automated method, there are certain elements, such as tablet size and solvent selection, which will have an impact on the ease of the conversion from manual to automated. For instance, some of the elements of an assay method that would make it easier to automate would be that the dosage form fits into a test tube the extraction uses neutral media or acid not more concentrated than 0.1 M makes use of nonvolatile, low-toxicity solvents does not use surfactants and uses premixed, room-temperature solvents. Some of the elements of a dissolution method that would make it easier to automate would be that the dosage form fits in the sample carousel, does not use media more concentrated than 0.1 M acid, does not use isopropanol or surfactant in large quantities, uses magnetic sinkers or no sinkers at all, and uses no or minimal reagent addition volumes for pH control. 

The Aria test is a routine assay in which a heat-treated milk sample is added to a well of a microtiter plate containing a freeze-dried tablet containing Bacillus subtilis ATCC 6633, nutrients, and triphenyltetrazoliumchloride as redox indicator (33). Following incubation, the normal growth of the organism is inhibited if antibacterials are present, and the uncolored indicator is not reduced into its red form. Detection of sulfonamides requires prior addition of trimethoprim in the milk samples analyzed. 

The CHARM inhibition assay (CIA), Charm farm test (CFT), and Valio TlOl test are all simple multiresidue screening tests based on microbial inhibition (34, 35). The CIA test is actually a disc assay using Bacillus stearothermophilus and specially formulated agar media to increase the sensitivity to sulfonamides. The CFT is a tube assay using the same test organism in a specific formulation, which, along with the nutrients, is in a tablet form. To roughly identify penicillins and sulfonamides with the CIA and CFT tests, positive samples should be reanalyzed after the addition of penicillinase and p-aminobenzoic acid. 

The determination of compound X and its related compounds in product X tablets will be validated according to the tests described in this protocol. The chromatographic parameters for these experiments are as stated in the method, HPLC Assay and determination of related compounds in product X tablets. ... 

The various applications of the analysis of tablets for dissolution testing, content uniformity, stability-indicating assays, and routine quality control assays have all been targets of automation using a robot system. 

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