Factors Related to Manufacturing Processes

Many manufacturing process factors can have an impact on the dissolution characteristics of solid dosage forms. Very often, an appropriate unit operation is selected to enhance the dissolution rates of a drug product. Wet granulation, in general, has been shown to improve the wettability of poorly soluble drugs by incorporating hydrophilic properties into the surface of granules, hence resulting in a greater dissolution rate (Bandelin, 1990). Based upon the propensity for directly compressed tablets to deaggregate into finer drug particles, direct compression may be chosen over granulation for improving dissolution (Shangraw, 1990). Manufacturing variables may also have both positive and negative effects upon drug product dissolution. In tablet compression, there are always two competing factors: the positive effect due to the increase in the surface area by breaking into smaller particles, and the negative effect due to the enhancement in particle bonding that inhibits solvent penetration. For instance, high compression may reduce the wetta-bility of the tablet, since the formation of firmer and effective sealing layer by the lubricant is likely to occur under the high pressure that is usually accompanied by high temperature. The possible influences of the force used to compress a mixture of the drug and excipients into a tablet on the dissolution rate are summarized in Fig. 3.4.

Figure 3.4. Possible effects of compression force on the dissolution rate (modified from Finholt, 1974)

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