Pharmaceutical products moisture content

Table 33.5 presents a summary of the various types of dryers, together with examples of pharmaceutical products for which they are used commercially. It should be noted that in most cases alternate dryers are used in practice to dry the same product. Typical operating data for drying of selected pharmaceuticals are given in Table 33.6. The information contained in Table 33.6 is derived from operating dryer performance data as well as from laboratory-scale experiments. Laboratory and often pilot-scale tests are necessary before a commercial-scale dryer may be designed with confidence. For pharmaceutical products, laboratory tests are performed to provide data on the thermal sensitivity, oxidizability, stability, and final product moisture content. This forms the basis for the selection of a dryer and process parameters. If the product is produced in small quantities, a batch dryer may be selected. In large-scale production, energy losses, losses due to deterioration of the product quality, and other losses can be quite substantial if the dryer type and operating parameters are not optimally...

In many products it seems highly probable that there exists a narrow range of optimum moisture contents that should be maintained. More specifically, the effect of moisture on MCC-containing tablets has been the subject of an investigation that demonstrates the sensitivity of this important excipient to moisture content [10]. These researchers found that differences exist in both the cohesive nature and the moisture content to two commercial brands of MCC. A very useful report on the equilibrium moisture content of some 30 excipients has been compiled by a collaborative group of workers from several pharmaceutical companies and appears in the Handbook of Pharmaceutical Excipients [11,12],... 

The original applications of NIR were in the food and agricultural industries where the routine determination of the moisture content of foodstuffs, the protein content of grain and the fat content of edible oils and meats at the 1% level and above are typical examples. The range of industries now using the technique is much wider and includes pharmaceutical, polymer, adhesives and textile companies. The first in particular are employing NIR spectrometry for the quality control of raw materials and intermediates and to check on actives and excipients in formulated products. Figure 9.26(b) demonstrates that even subtle differences between the NIR spectra of enantiomers can be detected. 

Part—I has three chapters that exclusively deal with General Aspects of pharmaceutical analysis. Chapter 1 focuses on the pharmaceutical chemicals and their respective purity and management. Critical information with regard to description of the finished product, sampling procedures, bioavailability, identification tests, physical constants and miscellaneous characteristics, such as ash values, loss on drying, clarity and color of solution, specific tests, limit tests of metallic and non-metallic impurities, limits of moisture content, volatile and non-volatile matter and lastly residue on ignition have also been dealt with. Each section provides adequate procedural details supported by ample typical examples from the Official Compendia. Chapter 2 embraces the theory and technique of quantitative analysis with specific emphasis on volumetric analysis, volumetric apparatus, their specifications, standardization and utility. It also includes biomedical analytical chemistry, colorimetric assays, theory and assay of biochemicals, such as urea, bilirubin, cholesterol and enzymatic assays, such as alkaline phosphatase, lactate dehydrogenase, salient features of radioimmunoassay and automated methods of chemical analysis. Chapter 3 provides special emphasis on errors in pharmaceutical analysis and their statistical validation. The first aspect is related to errors in pharmaceutical analysis and embodies classification of errors, accuracy, precision and makes... 

Example 2 In a Pet Tabs (pet vitamin tablets) production, the pharmaceutical manufacturer is using milling and micronizing machines to pulverize raw materials into fine particles. These finished particles are combined and processed further in mixing machines. The mixed ingredients are then pressed into tablets, dried, and sealed in packages. A normally distributed quality characteristic, moisture content, is monitored. Samples of n = 4 tablets are taken from the manufacturing process every hour. The data after 25 samples have been collected are shown in Table 5. 

The authors concluded that water which cannot be removed at 100 °C is bound in such a way that it cannot jeopardize the pharmaceutical product. Only the free water can diffuse from the stopper to the product. The moisture content is measured by the Karl Fischer method with different temperatures in the oven, 100 °C to determine the free water content and up to 300 °C to measure the free and bound water. The authors suggested developing a similar program for other stoppers, since the time for such measurements is relatively short (1 week) instead of observing the RM in a product over long times. Table 1.15.2 summarizes the results with the stoppers described above. Table 1.15.3 lists the limits of the free moisture content in 2 types of stoppers and for different cake weights under the assumption that a maximum RM increase of 0.5% in the product is acceptable. 

Whatever the water requirement of a particular protein formulation, it is still important to maintain the residual moisture content of a pharmaceutical product within its stability specifications to maintain its quality. 

Because water provides the greatest extinction coefficient in the NIR for pharmaceutically relevant materials, it stands to reason that this is one of the most measured substances by the NIR technique. A recent application involves noninvasive measurement of water in freeze-dried samples. Derksen et al. [56], for instance, used NIR to determine water through the moisture content of samples with varying active content. Ka-met et al. applied NIR to moisture determination of lyophi-lized pharmaceutical products [57]. 

Apart from food industry (see Chapter 8), NIR chemical imaging has so far primarily been applied to qualitative and quantitative product characterization in the pharmaceutical industry. The ability to visualize and assess the compositional heterogeneity and structure of the end products is extremely important for both the development and manufacture of solid dosage forms [20]. Hence, NIR chemical images have been used to determine authenticity, content uniformity, particle sizes and distribution of sample components, polymorph distributions, moisture content and location, contaminations, coating and layer thickness, as well as a host of other structural details [21-29]. 

Spray drying is used to dry pharmaceutical fine chani-cals, foods, dairy products, blood plasma, numerous organic and inorganic chemicals, rubber latex, ceramic powders, detergents, and other products. Some of the spray-dried products are listed in Table 9.1, which also includes typical inlet and outlet moisture content and tanperatures together with the atomizer type and spray dryer layout used. 

This strategy is adopted because of the sheer complexity of the process and the unavailability in the past of suitable sensors for on-line quality moisture content measurement. The quality of the product such as final moisture content, thickness, porosity, wetting, and rehydration capability (for pregelatinized starch) as well as the right crystal structure (the right therapeutic form for pharmaceuticals) are complex functions of drum speed, temperature, nip width, feed material, feed concentration, and feed-spreading technique. In addition, the final moisture content and thickness of the sheet may not be uniform across the width of the drum dryer that can lead to problems in shelf life and packaging of the product, respectively. 

The dried vegetable products have shown the same organoleptic properties and moisture content as commercial vegetable powders for pharmaceutical use. Therefore, their active compounds do not lose their desirable characteristics after drying. 

Sorptive properties of the pharmaceutical products as represented by their sorption isotherms reflect their ability to absorb water from the air and are the source of valuable information for the selection of dryers as well as the packaging conditions. The sorption isotherm is the relationship between the relative humidity of the air and the moisture content of solid in equilibrium with this air. 

Relatively seldom used in the manufacture of final pharmaceutical products, band dryers find wide use in drying of raw materials, especially herbal and medicinal plants. Usually several bands in one-above-another configuration are used. Bands are made of stainless steel screens or perforated plates. Band speeds from several centimeters to about 0.5 m/min are used. Bandwidths vary from as low as 0.5 m up to 2 m. Drying air temperatures in the range 80°C-100°C, initial moisture contents of 45%-100%, (d.6) and drying rates of 5-18 kg/m h are usual in industrial practice. 

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