Content uniformity assay testing

Repeatability. Repeatability expresses the precision under the same operating conditions over a short interval of time. The recommended testing for automated content uniformity, assays, degradation and impurity methods, and dissolution methods are listed in Table 5.1. 

Equivalency. This test compares the results of the automated procedure with the results of the validated manual method. If accuracy of the automated procedure has been proven, it may not be necessary to perform the equivalency study. However, if the manual method does not exist, then accuracy and reproducibility data should be used to assess the suitability of the automated method. The recommended testing for content uniformity, assays, degradation and impurity methods and dissolution methods are listed in Table 5.4. 

Finished product test results to include content uniformity, assay, hardness, friability, etc. 

Content Uniformity/Assay. The question most often asked is when NIR will be able to be used as a release test. In the earliest NIR assays, tablets and capsules were not analyzed intact. Prior to scanning, the active was extracted and scanned in a clear liquid. The first use of NIR for tablets was reported in 1968. Sherken assayed the meprobamate content in tablet mixtures and commercial preparations. Allen used NIR to analyze a three-component mix carisoprodol, phenacetin, and caffeine. The powder was extracted with chloroform and scanned in the NIR. Several other publications took advantage of the dissolve and scan approach.t ... 

Tablets must meet the U.S.P. requirement for content uniformity testing (62). The content uniformity assay is performed by assaying ten tabiets individually. The samples are...

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... 

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. 

Several in vitro tests are currently employed to assure drug product quality. These include purity, potency, assay, content uniformity, and dissolution specifications. For a pharmaceutical product to be consistently effective, it must meet all of its quality test criteria. When used as a QC test, the in vitro dissolution test provides information for marketing authorization. The dissolution test forms the basis for setting specifications (test, methodology, acceptance criteria) to allow batch release into the market place. Dissolution tests also provides a useful check on a number of physical characteristics, including particle size distribution, crystal form, etc., which may be influenced by the manufacturing procedure. In vitro dissolution tests and QC specifications should be based on the in vitro performance of the test batches used in in vivo studies or on suitable compendial specifications. For conventional-release products, a single-point dissolution... 

The information in this chapter applies specifically to the first element sample preparation. The sample preparation steps are usually the most tedious and labor-intensive part of an analysis. By automating the sample preparation, a significant improvement in efficiency can be achieved. It is important to make sure that (1) suitable instrument qualification has been concluded successfully before initiation of automated sample preparation validation [2], (2) the operational reliability of the automated workstation is acceptable, (3) the analyte measurement procedure has been optimized (e.g., LC run conditions), and (4) appropriate training in use of the instrument has been provided to the operator(s). The equipment used to perform automated sample preparation can be purchased as off-the-shelf units that are precustomized, or it can be built by the laboratory in conjunction with a vendor (custom-designed system). Off-the-shelf workstations for fully automated dissolution testing, automated assay, and content uniformity testing are available from a variety of suppliers, such as Zymark (www.zymark.com) and Sotax (www.sotax.com). These workstations are very well represented in the pharmaceutical industry and are all based on the same functional requirements and basic principles. 

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... 

Individual assay results from content uniformity testing... 

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. 

Quantitative tests for the assay of major components (e.g., drug substance and preservatives) in samples of drug substance or drug product (assay, content uniformity, dissolution rate, etc.)... 

Identity Weight Percent/Assay/Content Uniformity/Dissolution Impurity Testing Quantitative TesP... 

Identity is a general requirement for dosage forms. When determining specificity for identity, the assay and related substances or the content uniformity methods can be used. Assay and content uniformity methods are quantitated by external reference standard. This identity test confirms that the correct active ingredient (s) is present and is present in correct ratio if multiple variants are available. The method could also be used for post-packaging analysis. The general requirements are that the sample and standard chromatograms should correspond in retention time and normalized peak area within 10%. 

There are two types of analysis needed for cleaning verification (1) active (2) soap. Since residual amounts of active and soap are to be determined, the methods need to be very sensitive. For measuring the active, the assay or the content uniformity method can be employed (if the sensitivity of the existing method is acceptable). If the sensitivity of the current assay or content uniformity method is not acceptable, then modifications can be made to an existing method or a more sensitive test method is developed. 

---