Tabletted samples

Tablet samples were pulled according to the same protocol at different times into the conditioning cycle because the same pattern of results emerged repeatedly, enough information has been gained to permit mechanical and operational modifications to be specified that eliminated the observed inequalities to such a degree that a more uniform product could be guaranteed. The groups are delineated on the assumptions that the within-group distributions are normal and the between-group effects are additive. The physicochemical reasons for the differentiation need not be similarly stmctured.

Often the character of materials in a mixture undergoes solid-state rearrangements due to the pressures associated with compaction, which may or may not be polymorphic in nature. Consider the pre-compression powder blend, whose DSC thermogram is shown in Fig. 4.16, and which features the presence of four endothermic transitions. In the postcompression, ground tablet sample whose DSC thermogram is shown in Fig. 4.17, the endotherms having maxima at 86.5 and 106°C remain relatively constant (maxima at 85.3 and 104.2°C). On the other hand, the third endotherm in the pre-compression thermogram shows considerable attrition in the post-compression sample, and an additional endotherm (not previously observed in the pre-compression sample)... 

To demonstrate the ability to evaluate intersample variations, an over-the-counter (OTC) pain relief medication from two different manufacturers was compared. The samples contain three APIs each acetaminophen, aspirin and caffeine. Pure acetaminophen, aspirin and caffeine samples are obtained in either tablet form or powder compact and included within the same FOV as the tablets to provide simultaneous reference materials for the tablet samples. The tablets and pure components were arranged as shown in Plate 8.1a. Measurements on all samples were collected simultaneously. Tablet A samples from one manufacturer have a reported label concentration of 37%, 37%, and 10%, for the three API components, respectively. Tablet B samples from the second manufacturer contain the same three APIs, at label concentrations of 39%, 39%, and 10 %, respectively. In addition to these samples, tablet C samples are included in the array of tablets. These samples contain only acetaminophen as the API with a reported label concentration of 79%, and are made by the manufacturer who produces tablet A. The remaining mass of all three tablet types represents the excipient (binder, disintegrant, and lubricant) materials. 

The authors would like to thank Dr. Robbe C. Lyon of the FDA for providing the furosemide tablet samples. References... 

Friability was determined with 20 tablet samples in a friability tester (Erweka TA3R 15 min, 25 rev min-1). 

Precision Intermediate Precision. Sets of six dissolution samples that are prepared using different instruments and by different analysts are used to determine intermediate precision. However, this procedure will not be able to differentiate method variation versus tablet-to-tablet variation. It will predict the worst-case precision that includes tablet-to-tablet, sampling, and analysis variations. 

Tablet weight uniformity will provide a measure of the efficiency of the powder flow, tlie force feeder, or the automated weight control system. Weight monitoring by the press operator is usually the weight of a 5- or 10-tablet sample. Uniformity of individual tablets, which after all does relate to dose, will be more informative. The powder flow may not be sufficiently good, even with forced feeders.

Ore samples were provided by the Smithsonian Institution National Museum of Natural History, Department of Mineral Science Division of Mineralogy, and Breakwater Resources Limited. Dr. N. Norman, Department of Classics, University of Georgia provided the curse tablet samples. 

To demonstrate the ability to evaluate inter-sample variations, tablet groups from two different manufacturers in an over-the-counter (OTC) pain relief medication were compared. Pure acetaminophen, aspirin, and caffeine samples are obtained in either tablet form or powder compact and included within the same FOV as the tablets to provide simultaneous reference materials for the tablet samples. The tablets and pure components were arranged as shown in Plate la. This FOV contains 20 tablets and the... 

TABLE 6.7 Analytical Results for Stratified Tablet Samples... 

HPLC analysis with photodiode array detection confirmed that retention times as well as the UV spectra of the impurity peak in tablet samples and desiccant extract were identical. Mass spectrometric analysis of the samples for the structural elucidation of this peak was inconclusive. 

The impurity peak at RRT 0.40 was observed in all film-coated active and placebo tablets. The structural identification of this peak in the tablet samples was confirmed by both mass spectrometric and UV spectral analyses to be glyceryl triacetate, commonly known as triacetin, a component in the film coating used in these formulations. 

As an example, tablet samples for a product were prepared in an 85% organic medium and transferred into HPLC vials. An impurity peak was observed in some, but not all, of the tablet samples, blanks and standards. It was suspected that the solution in some of the vials may have come in contact with the HPLC Teflon caps and extracted a component from the cap. To evaluate this possibility, dissolving solvent was transferred into similar HPLC vials. These vials were capped with the Teflon caps and were kept inverted overnight to allow maximum contact of the solvent with the vial caps. A set of control samples were also prepared in which the vials were only filled halfway with dissolving solvent and care was taken not to allow the dissolving solvent to come into contact with the vial caps. These samples were analyzed by HPLC and, as shown in Fig. 10.3, confirmed the origin of the peak in question as being from the vial caps. In addition, the UV spectral analyses of the... 

Tablet sample preparation involved adding methanol to the tablets to extract the low-dose active ingredient from the HPMC. Methanol helped with the disintegration of the HPMC but did not cause the immediate release portion of the tablet to disintegrate. After using methanol, an acetate buffer, pH 4.5, was added to the sample solution to extract the high-dose active ingredient from the immediate release layer of the tablet. The sample solution was centrifuged to separate the larger particles...

Different types of syringe filters were then evaluated to try to remove the problematic excipients. Figure 10.4c shows that the use of an Amicon Ultra-4 centrifugal filter (Millipore, Billerica, MA) removed the residual HPMC from the sample solution but did not remove the starch. The Amicon Ultra-4 filter, however, does introduce later eluting filter-related peaks that fortunately do not interfere with any components of interest. Starch was not removed by any of the filters tested. As a result, excipient placebo samples were used as part of the method. These placebo samples were extracted and injected onto the HPLC system to confirm which peaks in the fixed combination tablet samples were excipient-related and these peaks were not quantitated or reported as drug-related degradants. 

Figure 10.4 Representative HPLC chromatograms (a) excipient placebo for the high dose active IR portion of the bilayer tablet (b) excipient placebo for the low-dose active sustained release portion of the bilayer tablet (c) Amicon Ultra-4 filtered fixed combination tablet sample. Annotation 1 = low-dose active ingredient 2 = high-dose active ingredient = pregelatinized starch-related peak = HPMC-related peak = filter-related peaks.

Deltamethrin is extracted from the water-dispersible tablet sample with a mixture of dioxane and water. The suspension is further diluted five times with iso-octane and filtered. The deltamethrin content is determined by comparing the response of the sample with that of a deltamethrin standard by high-performance liquid chromatography (HPLC), using a Nucleosil column (or equivalent) and a mixture of dioxane and iso-octane as the mobile phase. 

Another example includes the recovery (mass %) of API and degradation products of API from two 100-mg tablet (5 tablets) sample solution clarified by filtration and clarified by means of centrifugation. The data in the Table 8-5 demonstrates that the two methods of sample clarification are equivalent and that the filtration procedure (0.2-pm Nylon filter, with 5 mL pre-wet) is... 

Figure 19 (A) QUV/cw, cool white photostability tester (B) a cross sectional view of the test chamber before modification for pharmaceutical testing and (C) their tablet sample holder tor the unit. Source. Courtesy of Q-Lab Corporation.

The influence of variations in the film layer thickness on photo protection was investigated using uncoated nifedipine tablets. Samples of the tablets were completely covered with yellow transparent blister films of layer thicknesses ranging from 30-300 pm. The photostabilizing effect of the yellow blister film was found to increase with film layer thickness. After six hours irradiation the loss of drug content was 24% for the 30 pm films and only 6% for the 300 pm films, (Fig. 6) a substantial improvement in the photo protection of the product (21). 

Conventional rotary tablet presses are controlled by periodically taking tablet samples from the discharge chute and checking their tablet weight, thickness, and... 

FIGURE 3 Positive-ion atmospheric pressure chemical ionization mass spectrum at retention time approximately 13.7 minutes for nitroglycerin tablet sample. 

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