Tablet properties disintegration time

Determination of the time for a tablet to disintegrate when immersed in some test fluid has been a requirement in most compendia for many years. For many years, it was the only test available to evaluate the release of medicaments from a dosage unit. We now recognize the severe limitations of such tests in assessing this property—hence, the introduction of dissolution rate requirements. 

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. 

Time, Minutes Well Fluid Properties Disintegration State of Volclay Tablet Conventional Tetrapotassium Pyrophosphate ... 

When speaking about the optimisation of a (tablet) formulation then in most cases the attainment of preferable response values is meant, e.g. a high crushing strength, a low disintegration time, a certain dissolution profile etc. Another important desirable property of a formulation can be that the formulation is robust towards (small) deviations (errors) in process conditions or the proportions of the excipients this means that despite these errors the values of the responses considered remain at (almost) the same level or deviate with only an acceptable amount. It is of course desirable to maintain properties of any product on exactly the same value during production or use, but on the other hand this can be very expensive... 

The studies described in this chapter are restricted to the physical stability of tablets. Physical properties that are of interest are e.g. crushing strength, friability, disintegration time and dissolution profile. One of the causes of... 

Many papers have been published in which an experimental design is used to optimize tablet formulations. Both process variables as well as compositional variables (quantitative and qualitative) were used as independent (adjustable) variables. The studied dependent variables (factors to be optimized) are physical tablet properties directly after preparation such as weight variation, crushing strength, dissolution profile, disintegration time and friability. Doombos reviewed papers in which statistical methods were used to optimize tablet formulations [13]. 

Since the aim of this study was to evaluate the use of the change in the tablet properties during storage as a parameter to express the physical stability of tablet formulations, the Storage to Initial Ratio of the crushing strength (SIR(S)) and of the disintegration time (SIR(D)) were calculated and used as response values for equation (2). The calculations of SIR(S) and SIR(D) were performed as in equation (1). The mean of the measurements directly after preparation were used as initial value. 

The general instructions for the determination of the corresponding properties of tablets (hardness, disintegration, friability, dissolution) are contained the Pharmacopoeiae Ph.Eur. or USP. If it is not stated to the contrary, the disintegration time is measured in artificial gastric juice. The release is determined by the conditions laid down in the corresponding monographs for the tablets (usually USP) and in the prescribed medium. 

It has also been found with acetaminophen tablets that, compared with other disintegrants, the addition of 2% crospovidone gives harder tablets with a comparable, short disintegration time at a lower compression force [402]. Lactose gives tablets with similar properties [262]. 

Let us now identify the 2 levels (or states) of the factor as A and B. The factor or variable might be the choice of excipient, as in a previous example. Thus tablets may be formulated using 1% magnesium stearate (Fj = A) or another lubricant such as 2.5% hydrogenated castor oil (Fj = B). The disintegration time or other properties of the resulting tablets are then measured. 

Amounts of calcium phosphate up to 60% have little apparent effect on the properties. Increasing the concentration further gives soft and friable tablets with long disintegration times. These results suggest that calcium phosphate could be removed without a deleterious effect. 

The properties of all excipients present in the tablet must be considered for their possible effects on the final preparation, such as weight variation, disintegration time, dissolution characteristics and in vivo performance. The lower the proportion of the active substance present in the mixture, the more difficult it is to achieve a sufficient homogeneity. In Sects. 4.9 and 4.10, the formulation of tablets and the possibilities to process coated or modified-release tablets in capsules are discussed. 

---