Pharmaceutical dosage forms granulation

Microcrystalline Cellulose. Microcrystalline cellulose is a purified, partially depolymerized cellulose that occurs as a white, odorless, tasteless, crystalline powder composed of porous particles. It is widely used in pharmaceutical dosage forms, primarily as a filler-binder in oral tablets and capsules with both wet granulation and direct compression processes. Microcrystalline cellulose was marketed first in 1964 by the FMC Corporation under name Avicel PH in four different particle size grades, each with different properties.37 Addition of Avicel into a spray-dried lactose-based formulation overcame compressibility problems. At the same time, the lactose enhanced the flowability of the Avicel products available at that time. The direct compression tableting process became a reality, rather than a concept, partially because of the availability of Avicel. As of 2007, Avicel PH is commercially available in 10 types with different particle size, density, and moisture grades that have different properties and applications (Table 7.6).38 Other brands of microcrystalline cellulose are also available on the pharmaceutical market, including Pharmacel 101 and 102 from DMV International and Emcocel 50 M and 90 M from JRS Pharma. 

Bandelin, F.J. Compressed tablets by wet granulation. In Pharmaceutical Dosage Forms Tablets, Lieberman, H.A., Lachman, L., Schwartz, J.B. Eds. Marcel Dekker, Inc. New York, 1989 I, 160-164. 

The chief reasons to granulate powders for the manufacture of pharmaceutical dosage forms are described by Kristensen and Schaefer. ... 

Martino PD. Censi R, Malaj L. et al. Influence of metronidazole particle properties on granules prepared in a high-.shear mixer-granulator. Drug Dev Ind Pharm 2(X)7 33(2) 121-31. Lantz RJ. Size reduction. In Licberman HA, Schwartz JB, eds. Pharmaceutical Dosage Forms, 2nd ed. Vol. 2. New York Marcel Dekker, Inc., 1990 107-2(X). 

Wide array of pharmaceutical dosage forms such as pellets, granules, sustained/controlled release, oral fast dissolving system, targeted release such as transdermal, transmucosal, and transungual delivery system and implants. 

Few materials used in the manufacture of pharmaceutical dosage forms exist in the optimum size, and most materials must be reduced in size at some stage during production. The advantages of sizing of granules in tablet formulation development are as follows ... 

Since the development of the Spansule brand (Smith Kline Beech am) of coated beads and granules in the late 1960s, various dmg product technologies have been developed and patented to achieve extended durations of therapeutic effects. Each of these does so by various mechanisms of control of dmg release from adrninistered dosage forms. Each method has its advantages and disadvantages, a discussion of which is available in the pharmaceutical hterature (see Drug delivery systems) (21). 

Manufacturing validation data, which should aim to identify the critical process steps, especially for nonstandard manufacturing processes such as for new dosage forms, should be discussed in the development pharmaceutics section of the application. Validation data may be accepted based on closely related products. In-process control tests and acceptance limits should be included for any aspect where conformity with the finished product tests cannot otherwise be guaranteed (e.g., mixing, granulation, emulsification and nonpharmacopeial sterilization processes). 

Figure 2 Process flow diagram for the manufacture of a tablet dosage form by wet granulation method. The arrows show the transfer of material into and out of each of the various unit operations. The information in parentheses indicates additions of material to specific unit operations. A list of useful pharmaceutical unit operations is presented in Table 6.

For process using existing technology, many of the potential variables and responses may have already been identified in previous product-development studies or in the pharmaceutical literature. Once properly identified, the list of variables and responses for the process is not likely to change appreciably. Typical variables and responses that could be expected in a granulated solid dosage form are listed in Table 1. 

Summers M, Aulton M. 2002. Granulations. In Aulton M, editor. Pharmaceutics science of dosage form design. London Churchill Livingstone. 

This is the place to start, since most often, analytical chemists are trying to help solve someone else s problem. We need to define the solute and its matrix as well as the nature of the analytical problem. For example, in the world of pharmaceuticals, there are raw material identification and purity determinations, in-process testing, dosage-form determinations, content uniformity, dissolution testing, stability studies, bioavailability, pharmacokinetics, and drug metabolism, to name a few. Each of these analytical problems has its own specific requirements. The matrix can be a raw material, granulation, tablet, capsule, solution, lotion, cream, syrup, dissolution medium, blood serum, urine, or various body tissues and fluids. Similar definitions can be described for virtually any industrial area and problem set. These definitions will help select sample preparation, separation, and detection techniques. 

Because of the interactions existing between different materials as well as between like materials, the performance of excipients in a formulation could be different from the performance of the excipients themselves. The most frequently used procedures in pharmaceutical processing for solid dosage formulations are mixing, granulation, and compaction, as well as storage of finished dosage forms. The effects of adsorption on these procedures have been studied, observed, and utilized widely in the pharmaceutical industry. 

Overall, factors that might affect the adsorption of actives on the carrier surface include surface properties, moisture content, the type and particle size/shape of carriers and actives, as well as the mixing ratio of actives and carriers. Pharmaceutical processes (i.e., milling and granulation) could affect the adsorption process by altering carrier and active properties (i.e., surface properties, size, and shape), hence the characteristics of blending and the quality of the final dosage form. 

Extrusion processes are applied within the pharmaceutical industry to produce a variety of dosage forms such as suppositories, implants, and granulations. 

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