Wet granulation and direct compression

Ibrahim, Y. . E., and Olurinola, P. R. (1991), Comparitive microbiological contamination levels in wet granulation and direct compression methods of tablet production, Pharm. Acta Flelv., 66, 298. 

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. 

There are three methods of tablet manufacture designed to confer these essential attributes to a tablet formulation. Wet granulation and direct compression are the most important, with dry granulation (also known as precompression or slugging) used in some circumstances. Fig. 1 shows the processes of wet granulation and direct compression broken down into their constituent stages. 

Microcrystalline cellulose is widely used in pharmaceuticals, primarily as a binder/diluent in oral tablet and capsule formulations where it is used in both wet-granulation and direct-compression processes.In addition to its use as a binder/diluent, microcrystalline cellulose also has some lubricant and disintegrant properties that make it useful in tableting. 

Silicified microcrystalline cellulose is used as a filler in the formulation of capsules and tablets. It has improved compaction properties in both wet granulation and direct compression compared to conventional microcrystalline cellulose. " Silicified microcrystalline cellulose was specifically developed to address the loss of compaction that occurs with microcrystalline cellulose after wet granulation. 

In oral tablet formulations, P-cyclodextrin may be used in both wet-granulation and direct-compression processes. The physical properties of P-cyclodextrin vary depending on the manufacturer. However, P-cyclodextrin tends to possess poor... 

Marlow E, Shangraw R. Dissolution of sodium salicylate from tablet matrices prepared by wet granulation and direct compression. J Pharm Sci 1967 56 498-504. 

A. Khanum, D.S. Gayathri, Comparative evaluation of matrix tablet of diclofenac sodium employing wet granulation and direct compression method using blend of polymers. Res J Pharm and Technol, 1 (3), 265-269,2008. 

Wet granulation and direct compression are two methods used to manufacture tablets in the pharmaceutical industry. Zomer et al. used pyrolysis-gas chromatography-mass-spectrometry coupled with SVM classification to discriminate between the two tablet production methods.Mass spectra data were submitted to a PCA analysis, and the first principal components were used as input for SVM models having linear, polynomial, and Gaussian RBF kernels. SVM classifiers with polynomial and RBF kernels performed better in prediction than discriminant analysis. 

Development of solid dosage forms, more specifically tablets, involves three alternate processing methodologies—wet granulation, dry granulation, and direct compression (DC) (1). All these processes share the following common problems ... 

The manufacturing process used to make the test product should be described briefly to provide information on the method of manufacture (e.g., wet granulation vs. direct compression). A list of excipients used, the amount used, and their intended functions should be provided. Excipients used in the test product should have been used previously in FDA-approved IR solid oral dosage forms. 

Theophylline tablets made by both direct compression and wet granulation have been assessed. There is almost no difference between direct compression and wet granulation methods (see Figures 12-14) under the following conditions appropriate formulation (sufficient level of HPMC in the tablet) and precise control of the wet granulation process. Direct compression using Metolose SR is recognized as a suitable process for matrix tablets. 

Table 1 Typical unit operations involved in wet granulation, dry granulation, and direct compression...

Sorbitol is used as a diluent in tablet formulations prepared by either wet granulation or direct compression. It is particularly useful in chewable tablets owing to its pleasant, sweet taste and cooling sensation. In capsule formulations it is used as a plasticizer for gelatin. Sorbitol has been used as a plasticizer in film formulations. ... 

PDG Technology granules have excellent properties compared to wet grannlation, dry granulation, and direct compression. At the same time, the granules show both high compressibility and flowability. The results can be archived without using exotic and expensive excipients. 

The effect of UPF is verified by observing the similar pore size distributions of the wet granulation and the direct compression tablets in Frogerais, after 25% of the cumulative volume. 

The first component, which expresses the curve shape, exhibits an opposition of the release profiles obtained by wet granulation and by direct compression. The wet granulation profile has a sigmoid aspect while the direct compression profiles, particularly those for the tablets obtained in rotary machine, are nearly linear. 

In the plot of the first components (Fig. 5), the difference between the wet granulation and the direct compression profiles is confirmed. The first component discriminates between the shape profiles. The second component discriminates between the initial slopes of the release profiles. Then, it is possible to differentiate between the separate compaction and the other processes, because it has the highest initial slope. This is also observed in Fig. 3. 

The plots of two components obtained from PCA and lfom discriminant analysis, revealed an opposition between tablets obtained by wet granulation and by direct compression. In fact, the principal component represents the curve shape of the dissolution profiles (P), which, in these two processes, were quite different. 

Compared to wet granulation and roller compaction, the direct compression platform allows tablet manufacture with fewer unit operations, as listed in Table 7.1. The sections that follow discuss several advantages and disadvantages of using direct compression for tablet manufacture. 

TABLE 7.1 Comparative Unit Operations in Tablet Manufacture Using Wet Granulation, Roller Compaction, and Direct Compression... 

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