Tablet disintegration mechanism

Water uptake has been implicated as a mechanism of action for tablet disintegrants. Khan and Rhodes studied the adsorption and absorption properties of various disintegrants [56]. They concluded that the... 

MOLECULAR STRUCTURE. In their attempts to identify the mechanism(s) of action of tablet disintegrants, researchers recently have turned their... 

Although water penetration is a neeessary first step for disintegration, swelling is probably the most widely aceepted mechanism of action for tablet disintegrants. Indeed, most disintegrants do swell to some extent, but the variability of this property between disintegrants reduces its plausibility as a sole meehanism. 

Guyot-Hermann, A.M., and Ringard, J., Disintegration mechanisms of tablets eontaining starches. Hypothesis about the particle-particle repulsive force. Drug Dev. Ind. Pharm., 7 155-177 (1981). 

Tablets require a certain amount of strength, or hardness and resistance to friability, to withstand mechanical shocks of handling in manufacture, packaging, and shipping. Adequate tablet hardness and resistance to powdering and friability are necessary requisites for consumer acceptance while immediate-release tablets should readily disintegrate in the stomach as quick possible. For this reason, the relationship of harness to tablet disintegration and drug dissolution has been described.

Ingram JT, Lowenthal W. Mechanism of action of starch as a tablet disintegrant I factors that affect the swelling of starch grains at 37°. ] Pharm Sci 1966 55 614-617. 

Lowenthal W. Mechanism of action of tablet disintegrants. Pharm Acta Helv 1973 48 589-609. 

Cellulose-based disintegrants are widely used in tablet formulations. Although the exact disintegration mechanism is still subject to controversy, capillary water penetration and swelling seem to be involved most of the time. Table 26 lists some characteristics of tablet disintegrating agents that are either low-substituted or crosslinked derivatives, or CMC divalent salts. 

For most tablets, it is necessary to overcome the cohesive strength introduced into the mass by compression. It is therefore common practice to incorporate an excipient, called a disintegrant, which induces this process. Several types, acting by different mechanisms, may be distinguished (a) those that enhance the action of capillary forces in producing a rapid uptake of aqueous liquids, (b) those that swell on contact with water, (c) those that release gases to disrupt the tablet... 

The USP disintegration test is typical of most and is described in detail in a monograph of that volume. Briefly, it consists of an apparatus in which a tablet can be introduced into each of six cylindrical tubes, the lower end of which is covered by a 0.025 in.2 wire mesh. The tubes are then raised and lowered through a distance of 5.3-5.7 cm at a rate of29-32 strokes per minute in a test fluid maintained at 37 2°C. Continuous agitation of the tablets is ensured by this stroking mechanism and by the presence of a specially designed plastic disk, which is free to move up and down in the tubes. 

The rate at which selected liquids penetrate into tablets can be used to study their pore structure. A knowledge of the rate of liquid penetration should also provide information on the disintegration/dissolution behavior of a tablet on administration. Such investigations are capable of forming a valuable link between physico-mechanical characteristics and in vivo performance. 

Infusion of fat into the ileum has been shown to cause a lengthening of the SITT—a phenomenon known as the ileal brake (27,28). However, the effect is generally modest (causing a delay of 30-60 min) and attempts to exploit this mechanism in drug delivery have had limited success. Dobson et al. (29,30) studied the effect of co-administered oleic acid on the small intestinal transit of non-disintegrating tablets. They showed a delay in SITT in over half of all cases, and a doubling of SITT in some instances, but in the other cases SITT was either unaffected or even reduced. Lin et al. (31) have also showed slowed GI transit in patients with chronic diarrhea by administration of emulsions containing 0, 1.6, and 3.2 g of oleic acid. Small intestinal transit in normal subjects was measured at 102 11 min, while the transit times in the patients treated with the three emulsions were, respectively, 29 3, 57 5 and 83 5 min. 

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. 

Matsumara, H., Studies on the mechanism of tablet compression and disintegration. IV. Evolution of wetting heat and its reduction by compressional force, Yakugaku Zasshi, 79 63-68 (1959). 

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