Disintegrates surface response

FIG. 11. Surface response of disintegration time as fimctions of compression pressure and percentage disintegrant. (From Ref 35, reproduced with permission from the copyright owner.)... 

Surface area and moisture uptake have been related to the disintegration properties of excipients such as crosspovidone, starch, and alginic acid [17]. The surface areas of the three materials were measured, and a linear correlation was found between the maximum moisture sorption and specific surface area for the three disintegrants. The greater the surface area of the material, the more numerous were the sites for capillary attraction of water to its surface. It was postulated that the capillary action appears to be responsible for the disintegration properties of the materials. 

To motivate the response surface approach, suppose that there is some response of interest (for example, crushing strength in the tablet formulation example of Section 2.1.1), and a set of quantitative, continuous design variables that are of interest to the researcher (for example, the quantities of glidant, lactose, and disintegrant for the tablet formulation example). One possible objective for the researcher might be to understand and describe the relationship between the design variables and the response. This relationship can be described mathematically by... 

Figure 2.2 Response surface showing the effect of lactose and disintegrant...

FIGURE 8.13 Response-surface diagram for the time of 100% in vitro enzymatic disintegration of albumin microparticles prepared by variation of glutaraldehyde concentration and duration of cross-linking. (From Oner, L. and Groves, MJ. (1993b). J. Pharm. Pharmacol., 45, 866-870. With permission.)... 

Among many benefits of press instrumentation, formulation fingerprinting is perhaps the most obvious. Compressibility and ejection profiles, as well as dissolution and disintegration curves related to compression force, are unique for each formulation and can be used as a batch record. For process optimization, one can include compression or precompression force and speed factors in experimental design. Compactibility and ejection profiles can be used for excipient and lubricant evaluation. Other useful product development and optimization tools include response surface, Heckel, and force-thickness plots. 

The smart response capability of polysaccharides upon application of stress allows polar and apolar domains to easily form or disintegrate due to variation of the order/disorder ratio at the molecular level. This finally results in variation of specific crystallinity index or crystalline/amorphous ratio at the macroscopic level. Significant variation of interactive properties may even be achieved by minor variation of branching characteristics, which changes surface/volume ratio and, hence, preferences for inter- or intramolecular stabilization. Additionally, a rather effective response option is variation of relative percentages of molar and mass fractions by limited degradation/ reorganization or precipitation/dissolution transition. 

Figure 5.18 Use of the 3 design to study a granulation process, with response surface of disintegration time in minutes [adapted from reference (17), with permission].

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