Tablet quality control

In the Phadebas TM amylase test (72) (Pharmacia Labs) the substrate was a water insoluble cross-TTnked blue starch in tablet form which also contains some inert ingredients, sodium and potassium phosphate buffer salts and sodium chloride. This polymer was hydrolyzed by amylase into water soluble blue starch fragments. After centrifugation the absorbance of the blue supernatant was proportional to the activity of amylase present in the test samples. The day to day variation on a quality control serum had a coefficient of variation of 2.7% based on 30 days of data in our laboratory. The method is simple, reproducible and uses microquantities of serum. 

ITMs provide a valuable service to all phases of tablet manufacture, from research to production and quality control [109 111]. As a research tool, ITMs allow in-depth study of the mechanism of tablet compaction by measuring the forces that develop during formation, ejection, and detachment of tablets. ITMs can also provide clues about how materials bond,... 

Release of drug independent of the environment of the system Systems can be much more expensive than conventional counterparts Quality control more extensive than most conventional tablets... 

It should be remembered that in 1970, when drug-release/dissolution tests first became official through the leadership of USP and NF, marketed tablets or capsules in general simply did not have a defined dissolution character. They were not formulated to achieve a particular dissolution performance, nor were they subjected to quality control by means of dissolution testing. Moreover, the U.S. Food and Drug Administration (FDA) was not prepared to enforce dissolution requirements or to even to judge their value. 

The decision to approve a new drug is made by a national regulatory body (Food Drug Administration in the U.S.A., the Health Protection Branch Drugs Directorate in Canada, UK Europe, Australia) to which manufacturers are required to submit their appUca-tions. AppUcants must document by means of appropriate test data (from predinical and clinical trials) that the criteria of efficacy and safety have been met and that product forms (tablet, capsule, etc.) satisfy general standards of quality control. 

In some Sub-Saharan African countries, a WHO study (WHO, 2003) shows a high failure rate in quality control testing on chloroquine tablets. Only 58% of the medicines tested had an acceptable levels of chloroquine content and only 25% had the correct dissolution rate (which is an indicator of the fact that the active substance is dissolved in the intestine and therefore can be absorbed by the body) (Figure 3). Treating patients with poor quality medicines may result in providing insufficient dosages, so promoting the development of resistance. 

Fig. 3. Percentage failures in ingredient content and dissolution in quality control tests on chloroquine tablets in seven...

In many pharmaceutical companies, quality control departments already use NIRS to identify formulations. Figure 23 illustrates a PLS calibration for the active content determination in a low-dose tablet. Once identity testing is passed, it is straightforward to consider as a next step the determination of active content in intact tablets. Thus, qualitative and quantitative analysis can be performed by acquiring a single NIR spectrum per sample. Two analytical techniques are replaced by one—nondestructive—NIR measurement. For this purpose near-infrared spectroscopy is a fast and powerful alternative to traditional analysis, which only remains necessary as reference analytics. 

If you are in charge of quality control laboratories in manufacturing companies, it is important to distinguish between the variability of a product and the variability of the analysis. When analyzing tablets on a pharmaceutical production line, variability in the results of an analysis has two contributions from the product itself and from the analytical procedure. Your bosses are interested in the former, and you, the analyst, must understand and control the latter. It is usually desired to use methods of analysis for which the repeatability is much less than the variability of the product, in which case the measured standard deviation can be ascribed entirely to the product. Otherwise, analysis of variance can be used to split the total variance of duplicate results into its components (chapter 2). In the discussion that follows, the emphasis is on measurement variability, but the principle is the same, and the equations and methods can be used directly to obtain information about the product or manufacturing process. 

For quality control, 25 tablets are removed at random from the manufacturing line each hour and analyzed. The mean value of vitamin C in the 25 tablets is shown by a data point on the control chart. 

Disintegration time and tablet hardness data could be collected from the manufacturing batch records however, for ease of administration these figures will be obtained from the quality control test results, which also contain individual tablet weighings. 

Specifications used by quality control to release drug A are found in a laboratory procedure. In addition to the previously discussed hardness and disintegration time requirements, the procedure calls for determining the average tablet weight by the United States Pharmacopeia (USP) procedure that is, 20 individual tablets are weighed. 

During compression, 1000 tablets were randomly selected for use by quality control. Inspection of the batch records revealed that all 30 batches were compressed on the same model press operating at approximately the same speed. All presses were fed by overhead delivery systems of the same design, thus tableting equipment will not be a source of variability from batch to batch. 

Let s next direct our attention to the testing done by quality control. The ATW at the core stage is based on the results from weighing 20 randomly selected tablets. The control chart in Figure 7 depicts a process with no single... 

A selective, sensitive, and rapid hydrophilic interaction liquid chromatography with electrospray ionization tandem mass spectrometry was developed for the determination of donepezil in human plasma [32], Donepezil was twice extracted from human plasma using methyl-ferf-butyl ether at basic pH. The analytes were separated on an Atlantis HILIC Silica column with the mobile phase of acetonitrile ammonium formate (50 mM, pH 4.0) (85 15, v/v) and detected by tandem mass spectrometry in the selective reaction monitoring mode. The calibration curve was linear (r = 0.9994) over the concentration range of 0.10-50.0 ng/ ml and the lower limit of quantification was 0.1 ng/ml using 200 /d plasma sample. The CV and relative error for intra- and inter-assay at four quality control levels were 2.7% to 10.5% and —10.0% to 0.0%, respectively. There was no matrix effect for donepezil and cisapride. The present method was successfully applied to the pharmacokinetic study of donepezil after oral dose of donepezil hydrochloride (10 mg tablet) to male healthy volunteers. 

Murakami et al. [82] developed and validated a sensitive HPLC technique to quantify omeprazole in delayed release tablets. The analysis was carried out using a RP-Cig column with UV-VIS detection at 280 nm. The mobile phase was diluted with phosphate buffer (pH 7.4) and acetonitrile (70 30) at a flow-rate of 1.5 ml/min. The parameters used in the validation process were linearity, range, quantification limit, accuracy, specificity, and precision. The retention time of omeprazole was about 5 min with symmetrical peaks. The linearity in the range of 10-30 ng/ml presented a correlation coefficient of 0.9995. The excipients in the formulation did not interfere with the analysis and the recovery was quantitative. Results were satisfactory and the method proved to be adequate for quality control of omeprazole delayed-release tablets. 

The automation of the HPLC determination of tablet content uniformity has been applied to the analysis of a variety of tablets and is used routinely for quality control purposes. The routine used is fairly typical of that described by other workers, in that the operator presents the samples to the robotic system in tubes. The system then continues the analysis as follows ... 

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. 

The absorption of pantoprazole at 295 nm was used for the quantitative determination, and the method validated and used for the analysis of pantoprazole in its tablets. The results of validation study indicated that the method is linear over the range of 1.0 to 3.0 mg/mL (r= 0.9999). The percent recovery and relative standard deviation were 99.3-101.5 (n=9), and less than 1.0%, respectively. This method can be used for quality control and routine analysis [5],... 

The product of the simpler synthesis was compared in detail with the product of the RR-amine process. In particular, the Research Quality Control Unit searched for the presence of different polymorphs and new impurities (e.g., the dialkylation byproduct from the first step). They compared the stabilities of both products and also compared the hardness and dissolution rates of tablets made from both products. Since the DBTA resolution, crystallization, and product isolation steps, as wll as the final dilevalol hydrochloride preparation step, were the same for both the RR-amine process and the simpler synthesis, it was anticipated that these steps should protect against the introduction of new impurities or changed physical parameters in the final crystalline product. Such proved to be the case. 

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