Dissolution number

Equations (25) and (26) show that the dissolution number will also influence the drug absorption in addition to the absorption and dose numbers. Assuming that the initial amount of drug in solution is insignificant compared to the amount of solid drug, the fraction of dose absorbed can be estimated by... 

Crison and Amidon [47,48] recently used the mass balance approach to study the variability in absorption due to intestinal transit time for water-insoluble drugs. As expected, for low dose drugs, such as digoxin, the variability in absorption sharply decreases with the increase of dissolution number via micronization. For high dose drugs, such as griseofulvin, little effect was observed when the dissolution number was increased by micronization. 

Further predictions of in vivo drug absorption could be obtained by using fundamental dimensionless groups such as Do (dose number), Dn (dissolution number), and An (absorption number). The three dimensionless numbers are combinations of physiochemical and physiological parameters and represent the most fundamental view of GIT drug absorption and are the foundation principles of the BCS [3], Do is calculated using Eq. 2.26 ... 

An = absorption number = Do = dose number = Dn = dissolution number =... 

The importance of dissolution on drug absorption and bioavailability may be described in relation to the concept of dissolution number, Dn, introduced by Amidon et al.67 Dn may be defined as... 

From these simple data on a single-stroke research press, a formulator can begin to generate relationships between tablet properties and the compressional forces used to compact them. Thus, one could plot tablet hardness as a function of compaction force or pressure (see Fig. 2). The same would be true for disintegration tune, thickness, a dissolution number, etc. In fact, any dependent variable (tablet property) can be related to the independent variable (compaction force.) It is important to remember that force is the parameter one can control and, therefore, the independent variable. 

This equation can be used in conjunction with (6.9) for the estimation of Fa. The microscopic approach points out clearly that the key parameters controlling drug absorption are three dimensionless numbers, namely, absorption number An, dissolution number Dn, and 9. The first two numbers are the determinants of membrane permeation and drug dissolution, respectively, while 9 reflects the ratio of the dose administered to the solubility of drug. 

The dissolution number (Dn) is the ratio of the residence time and the dissolution time (toiss)j which comprises the equilibrium solubility (Cs), diffusivity (D), density (p), the initial particle radius (r0), and the intestinal residence time (tres) ... 

Figure 3.2 Graph of estimated fraction dose absorbed (F) vs dissolution number (Dn) and dose number (Do) for a high permeability drug [6], The dose number and the dissolution number ofdigoxin and griseofulvin are marked in the figure.

Figure 3.2. It can be seen that for high An, the critical range of the dose number and the dissolution number is around 1, where sharp changes in the fraction of drug absorbed are obtained due to small changes in D0 and Dn [6].

Figure 2. Estimation of DCS class based on the GastroPlus software of SimulationPlus. Based on the dimensionless Dose, Absorption and Dissolution Numbers, drugs can be defined as DCS Class 1 (A), 11 (B), 111 (C) and IV (D) based solely on structural information. The program gives predicted values for solubility, pKa and effective human intestinal permeability in order to suggest a fraction absorbed into the portal vein. (See color insert after Index.)...

Dissolution number (D ) is characterized by the time required for drag dissolution which is the ratio of the intestinal residence time < T g> and the dissolution... 

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