Yu LX, Ellison CD, Conner DP, Lesko LJ and Hussain AS Influence of Drug Release Properties of Conventional Solid Dosage Forms on the Systemic Exposure of Highly Soluble Drugs AAPS PharmSci 2001;
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article 24
(https://www.pharmsci.org/scientificjournals/pharmsci/journal/01_24.html).
Figures and Tables
Figure 1.A schematic of disintegration and dissolution processes, where the disintegration is considered as a first-order process and the dissolution from drug particles is proportional to the concentration difference between the particle surface and bulk solution. The disintegration considers the effect of formulations and manufacturing process variables, whereas the dissolution from drug particles mainly considers the effect of solubility and particle size.
Table 1.
Figure 2A.(A) The percent drug in the dosage form, in particles, and dissolved as a function of time, where Kf = 5 h-1 , Kd = 1600 mL/h.
Figure 2B.(B) Effect of disintegration on drug release, where Kd = 1600 mL/h. The disintegration time can be calculated by 1/Kf . Thus, the Kf values of 1, 2, and 6 h-1 correspond to the disintegration (residence) times of 1, .5, and .17 hours.
Figure 2C.(C) In vitro drug release, characterized by percent dissolved at 30 minutes, as a function of disintegration and dissolution constants (Kf and Kd ). The figure shows the percent dissolved at 30 minutes given the values of the disintegration and dissolution rate constants.
Figure 3A.(A) The total exposure of area under the curve (AUC) and
Figure 3B.(B) peak exposure (Cmax ) ratios of solid dosage forms in reference to an oral solution as a function of the disintegration and dissolution rate constants for highly soluble (.4 mg/mL) and highly permeable (1.0 x 10-3 cm/sec) compounds. The figure shows the requirements of Kf and Kd values to make a solid dosage form to be bioequivalent to an oral solution formulation. When compared with Figure 2(C), the requirements of in vitro dissolution can be determined based on the assumption of the same Kf and Kd in vivo and in vitro.
Figure 4A.(A) The total exposure of area under the curve (AUC)
Figure 4B.(B) peak exposure (Cmax ) ratios of solid dosage forms in reference to an oral solution as a function of the disintegration and dissolution rate constants for highly soluble (.4 mg/mL) and poorly permeable (2.0 x 10-5 cm/sec) compounds. The figure shows the requirements of Kf and Kd values to make a solid dosage form to be bioequivalent to an oral solution formulation. When compared with Figure 2(C), the requirements of in vitro dissolution can be determined based on the assumption of the same Kf and Kd in vivo and in vitro.
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