PURPOSE: To investigate the relationship between mean dissolution time (MDT) and dose/solubility ratio (q) using the diffusion layer model. METHODS: Using the classic Noyes-Whitney equation and considering a finite dose, we derived an expression for MDT as a function of q under various conditions. q was expressed as a dimensionless quantity by taking into account the volume of the dissolution medium. Our results were applied to in vitro and in vivo data taken from literature. RESULTS: We found that MDT depends on q when q < 1 and is infinite when q > 1 and that the classic expression of MDT = 1/k. where k is the dissolution rate constant, holds only in the special case of q = 1. For the case of perfect sink conditions, MDT was found to be proportional to dose. Using dissolution data from literature with q < 1, we found better estimates of MDT when dependency on dose/ solubility ratio was considered than with the classic approach. Prediction of dissolution limited absorption was achieved for some of the in vivo drug examples examined. CONCLUSION: The mean dissolution time of a drug depends on dose/ solubility ratio, even when the model considered is the simplest possible. This fact plays an important role in drug absorption when absorption is dissolution limited.
PURPOSE: To investigate the relationship between mean dissolution time (MDT) and dose/solubility ratio (q) using the diffusion layer model. METHODS: Using the classic Noyes-Whitney equation and considering a finite dose, we derived an expression for MDT as a function of q under various conditions. q was expressed as a dimensionless quantity by taking into account the volume of the dissolution medium. Our results were applied to in vitro and in vivo data taken from literature. RESULTS: We found that MDT depends on q when q < 1 and is infinite when q > 1 and that the classic expression of MDT = 1/k. where k is the dissolution rate constant, holds only in the special case of q = 1. For the case of perfect sink conditions, MDT was found to be proportional to dose. Using dissolution data from literature with q < 1, we found better estimates of MDT when dependency on dose/ solubility ratio was considered than with the classic approach. Prediction of dissolution limited absorption was achieved for some of the in vivo drug examples examined. CONCLUSION: The mean dissolution time of a drug depends on dose/ solubility ratio, even when the model considered is the simplest possible. This fact plays an important role in drug absorption when absorption is dissolution limited.
Authors: Lawrence X Yu; Gordon L Amidon; James E Polli; Hong Zhao; Mehul U Mehta; Dale P Conner; Vinod P Shah; Lawrence J Lesko; Mei-Ling Chen; Vincent H L Lee; Ajaz S Hussain Journal: Pharm Res Date: 2002-07 Impact factor: 4.200
Authors: Oluwatoyin A Adeleke; Yahya E Choonara; Pradeep Kumar; Lisa C du Toit; Lomas K Tomar; Charu Tyagi; Viness Pillay Journal: AAPS PharmSciTech Date: 2013-08-30 Impact factor: 3.246
Authors: Carolina Ameijeiras Rodríguez; Sara Carolina Henriques; Aymara Sancho-Araiz; Iñaki F Trocóniz; Luis Almeida; Nuno Elvas Silva Journal: Pharm Res Date: 2021-12-21 Impact factor: 4.200