Disintegrants compression force, effect

FIG. 12. The averaged effect of disintegrant, compression force, and lubricant on the release of hydrochlorothiazide from anhydrous lactose-based capsules. Control = 0% disintegrant. (Replotted from Ref. 47.)... 

Fig. 22 Averaged effect of disintegrant, lubricant, and compression force on hydrochlorothiazide dissolution from dicalcium phosphate-based capsules. (From. Ref. 133.)...

The effect that compression force can have on the disintegration efficiency seems, therefore, largely dependent on the mechanism of the disintegrant action. The effectiveness of swelling or structure recovery may well be dependent on attaining a compression force that achieves a critical porosity in the matrix. On the other hand, the capillary uptake of liquid, which is a necessary precursor to these mechanisms could be compromised if the tablet matrix is compressed to a porosity too low. 

Riippi, M., Antikainen, O., Niskanen,T., and Yliruusi, J. (1998),The effect of compression force on surface structure, crushing strength, friability, and disintegration time of erythromycin acistrate tablets, Eur. J. Pharm. Biopharm., 46, 339-345. 

The addition of crospovidone has no adverse effect on tablet hardness. The hardness often remains proportional to the compression force over a wide range [404, 390], so that tablets of high hardness and rapid disintegration can be obtained. The performance of crospovidone, starch and carboxymethyl starch in hydrochlorothiazide is compared in Fig. 76. 

Fig. 77. Effect of compression force on the disintegration time of drug-containing tablets with different disintegrants [390]...

Hill PM. Effect of compression force and corn starch on tablet disintegration time. J Pharm Sci 1975 65(11) 1694-1696. 

Within the realm of physical reality, and most important in pharmaceutical systems, the unconstrained optimization problem is almost nonexistent. There are always restrictions that the formulator wishes to place or must place on a system, and in pharmaceuticals, many of these restrictions are in competition. For example, it is unreasonable to assume, as just described, that the hardest tablet possible would also have the lowest compression and ejection forces and the fastest disintegration time and dissolution profile. It is sometimes necessary to trade off properties, that is, to sacrifice one characteristic for another. Thus, the primary objective may not be to optimize absolutely (i.e., a maxima or minima), but to realize an overall pre selected or desired result for each characteristic or parameter. Drug products are often developed by teaching an effective compromise between competing characteristics to achieve the best formulation and process within a given set of restrictions. 

After arriving at the maximum pressing force, pressure is released. If as shown in Fig. 8.1, compaction is performed by a punch in a die, the direction of travel of the piston reverses and, when no expansion of the densified body occurs, the pressing force should drop to zero immediately (vertical line). In reality, there is always a more or less pronounced spring-back which is caused by the expansion of compressed gas and the relaxation of elastic deformation. As mentioned before, this effect becomes more pronounced with increasing speed of densification until, at a certain compression rate, the compacted body disintegrates partially or totally upon depressurization. Therefore, it is often necessary to find an optimal compromise between densification speed (= capacity) and product integrity (= quality). 

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