Disintegrants factors affecting

The bioavailability of drugs from tablets can be markedly influenced by the rate and efficiency of the initial disintegration and dissolution process. Unfortunately, one is faced with a compromise situation — a structure that has both a durable structure prior to administration and the ability to readily break down when placed in the in vivo environment. One of the major factors affecting both these properties is the structure of the tablet, in particular its density (or porosity) and the pore structure. Study of the significance of such measurements and interpretation of the results is a relatively recent field of interest. 

Khalil, S. A., and Ali, M. M. Some formulation factors affecting disintegration and dissolution of chloramphenicol capsules. Acta. Pharm. Suec. 9 563-572, 1972. 

Dispersion of Particles—When lumpy material is mixed with a liquid, some measure of the rate at which the larger masses are disintegrated is necessary. What factors affect its breaking up into elemental units The size-distribution of the lumps is one factor, the solubility of the salts holding the particles together is another moisture-content may be a third. We shall discuss only those lumps easily disintegrated, and not those which are impermeable or so composed chemically and physically that the individual particles remain bound indefinitely. 

Lipid-based systems can achieve sustained release by providing a barrier to diffusion of water, necessary for dissolution of solid protein dispersed in a hydrophobic matrix, and by a subsequent barrier to diffusion or convection of protein solution entrapped within the matrix. The rate-limiting step for aqueous solute release is often dissolution or disintegration of the lipid mass or particle. Factors affecting release of proteins from various matrices have been reviewed in detail by Pitt (1990a) and Park et a/.(1993). 

Water Uptake. There is evidence to suggest that water uptake caused by capillary forces is the crucial factor in the disintegration process of many formulations. In such systems the pore structure of the tablet is of prime importance and any inherent hydrophobicity of the tablet mass will adversely affect it. Therefore, disintegrants in this group must be able to maintain a porous structure in the compressed tablet and show a low interfacial tension towards aqueous fluids. Rapid penetration by water throughout the entire tablet matrix to facilitate its breakup is thus achieved. Concentrations of disintegrant that ensure a continuous matrix of disintegrant are desirable and levels of between 5 and 20% are common. 

In practical fan sheet breakup processes, sheet thickness diminishes as the sheet expands away from the atomizer orifice, and liquid viscosity affects the breakup and the resultant droplet size. Dombrowski and Johns[238] considered these realistic factors and derived an analytical correlation for the mean droplet diameter on the basis of an analysis of the aerodynamic instability and disintegration of viscous sheets with particular reference to those generated by fan spray atomizers ... 

The type of drying technique (e.g., tray, fluid bed, microwave) required for the formulation needs to be determined and justified. The type of technique may be dependent on such factors as drug or formulation properties and equipment availability. Changing dryer techniques could affect such tablet properties as hardness, disintegration, dissolution, and stability. 

Pharmaceutical factors. The amount of drug that is released from a dose form (and so becomes available for absorption) is referred to as its bioavailability. This is highly dependent on its pharmaceutical formulation. With tablets, for example, particle size (surface area exposed to solution), diluting substances, tablet size and pressure used in the tabletting machine can affect disintegration and dissolution and so the bioavailability of the drug. 

More studies are necessary to elucidate the effect of other factors, such as the type of binder, the type of filler, and the solubility of the matrix, which may significantly affect the effectiveness of disintegrants in different modes of incorporation. For example, Becker, Rigassi, and Bauer-Brandl found that extragranular crospovidone was more effective in an acetaminophen tablet when the binder was maltodextrin (Licab DSH ), pregelatinized maize starch (Lycab PGS ), or low... 

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. 

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