Tablet assay

In Fig. 4.39, results for spiked placebo and for the verum tablets are given for compound A (bold lines) and B all horizontal bars should be at 100%, and the vertical lines should be centered at the same height. The gray trendlines, particularly for the LO- and Hl-range A-values indicate a systematic difference in response between tbe calibration solutions and the spiked placebo tablets (extraction efficiency, interference, etc.). For same ranges, the verum-tablets assays either underestimate the content of A by 4—5%, or A is underdosed. For compound A the repeatability figures are as follows (%-of-nom-inal, see file Fig4 39.dat), see Table 4.36. 

The near-IR technique has been used very successfully for moisture determination, whole tablet assay, and blending validation [23]. These methods are typically easy to develop and validate, and far easier to run than more traditional assay methods. Using the overtone and combination bands of water, it was possible to develop near-IR methods whose accuracy was equivalent to that obtained using Karl-Fischer titration. The distinction among tablets of differing potencies could be performed very easily and, unlike HPLC methods, did not require destruction of the analyte materials to obtain a result. 

Vol. 1. Staphylococcus aureus (ATCC 9144) is used for the turbidimetric procedure. The bulk raw material official assay is found in 21CFR -452.10 and the official tablet assay is found in 21CFR452.110. The sample is diluted from 0.3 to 2.0 Mg./ml. in pH 7.0 buffer and comparison is made to a standard curve of 0, 0.3, 0.4, 0.6,... 

SPE, chromatography (i.e., thin-layer chromatography, gel-permeation chromatography and HPLC) and on-line multi-dimensional chromatography. These techniques are rarely used in routine tablet assays due to their technical difficnlties, labor intensity and problems with recovery. 

The method yielded >99% label claim of the API for the composite tablet assay. Table 3 lists the results of a filter validation study showing the quantitative recovery of the API from most membrane media. 

TABLE 10 Results of a Gage R R Study for a Typical Oral Film-coated Tablet Assay Procedure... 

A typical example of a straightforward tablet assay is the analysis of frusemide tablets ... 

Farmer, S., McCauslin, L., Burns, P. K., and Velagaleti, R. (2004, Aug.), Photosensitivity of internal standard valerophenone used in USP ibuprofen bulk drug and tablet assay and its effect on quantitation of ibuprofen and its impurities, Pharm. Technol, 68-74. 

D. Complex configurable SCADA system Automated workstations for tablet assay... 

The final mix blending time was reported as either 10 or 15 min. Twenty-one of the 30 batches were tumbled for 10 min and the remainder were mixed for 15 min. The mixing time is not mechanically controlled or automatically recorded it is left to the operator to interpret elapsed time. Because of the importance of the step to distribution of the therapeutic agent, a comparison was made between the distribution of the percentage of relative tablet potency [(tablet assay/tablet weight) x 100] for the two mixing times. The frequency distributions of the two populations are shown in Figure 3. 

Figure 3 Histogram of drug A granulation uniformity resulting from different blending times. Percentage of relative potency = (tablet assay/tablet weight) X 100.

Figure 8 x-control chart for drug B tablet assay (ingredient Bl). 

Control charts similar to the hand-drawn ones used earlier to illustrate the evaluation of processing data are also easily prepared using readily available software. Figure 16 is an x chart of tablet assay for active ingredient 2. Note that minimum maximum specification limits have been included. Figure 17 depicts a traditional x control chart for dissolution to which error bars have been added to denote individual tablet assays for each batch. 

Figure 16 Drug F computer-generated x-control chart of tablet assay (AI 1).

One problem that has been encountered in grinding tablets is the physical separation of the analyte of interest in the matrix. This phenomenon helps explain discrepancies that occur between the average of the individual tablet assay values prepared by direct dissolution and those of the corresponding tablet composites. Table 2.1 outlines various advantages and disadvantages of sample preparation procedures for overcoming segregation of tablet components [9-11]. 

Although sharing similarities with the tablet procedures, this differs from the typical tablet assay by using organic solvents and having two evaporation steps [68]. The unit operations carried out by the system are the following ... 

Process Powder Blending Liquid Addition Rate, mL/min Granulation Time, min Minimum Mean Tablet Assay (%) Maximum Mean Tablet Assay (%) /(RSI)... 

Mean weight and weight variability Tablet assay... 

Since the response of the detector (and the separation) is a function of a flow rate, it is essential that the standard response curve be determined at the same flow rate as the tablet assay. If retention times differ significantly from the runs of the standards, there is a need to troubleshoot the HPLC to determine where the problem resides. Refer to Chapter 3 for a discussion of retention time precision. 

M. R. Smith, R. D. Jee, A. C. Moffat, D. R. Rees, and N. W. Broad, A procedure for calibration transfer between near-infrared instruments—a worked example using a transmittance single tablet assay for piroxicam in intact tablets. Analyst 129... 

Poor values for linearity are usually the result when only production samples are used for development of quantitative calibrations. The low R values are a result of the narrow range of active concentrations due to the quality that is inherent in pharmaceutical processes. A typical pharmaceutical process gives samples that vary little from the nominal value. Typical ranges for tablet assays fall within a range of 97 to 102% of label claim. This 5% range, coupled with errors in the HPLC analysis, lead to a poor correlation line. In HPLC or UV/VIS spectroscopic methods, an R value approaching unity is common the U.S.P. recommends a value no lower than 0.995. A typical NIR linearity, based solely on actual production samples, is often closer to 0.8 than 1.0 due primarily to the narrow range. 

The number of tablets assayed is given by Sample weight... 

The near-IR technique has been used very successfully for moisture determination, whole tablet assay, and blending validation. These methods are typically easy to develop and validate and far easier to run than more traditional assay methods. It is possible to use the overtone and combination bands... 

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