A population growth model of dissolution

被引:30
作者
Dokoumetzidis, A
Macheras, P
机构
[1] UNIV ATHENS,DEPT PHARM,GR-15771 ATHENS,GREECE
[2] UNIV ATHENS,DEPT PHYS,ATHENS,GREECE
关键词
dissolution; model; growth; fraction absorbed; in vitro in vivo correlations;
D O I
10.1023/A:1012182102257
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Purpose. To develop a new approach for describing drug dissolution which does not require the presuppositions of time continuity and Fick's law of diffusion and which can be applied to both homogeneous and heterogeneous media. Methods. The mass dissolved is considered to be a function of a discrete time index specifying successive ''generations'' (n). The recurrence equation: Phi(n+1) = Phi(n) + r(1 - Phi(n))(1 - Phi(n)X(0)/theta) was derived for the fractions of dose dissolved Phi(n) and Phi(n+1) between generations n and n + 1, where r is a dimensionless proportionality constant, X-0 is the dose and theta is the amount of drug corresponding to the drug's solubility in the dissolution medium. Results. The equation has two steady state solutions, Phi(ss) = 1 when (X-0/theta) less than or equal to 1 and Phi(ss) = theta/X-0 when (X-0/theta) > 1 and the usual behavior encountered in dissolution studies, i.e. a monotonic exponential increase of Phi(n) reaching asymptotically the steady state when either r < theta/X-0 < 1 or r < 1 < theta/X-0. Good fits were obtained when the model equation was applied to danazol data after appropriate transformation of the time scale to ''generations''. The dissolution process is controlled by the two dimensionless parameters theta/X-0 and r, which were found to be analogous to the fundamental parameters dose and dissolution number, respectively. The model was also used for the prediction of fraction of dose absorbed for highly permeable drugs. Conclusions. The model does not rely on diffusion principles and therefore it can be applied under both homogeneous and non-homogeneous conditions. This feature will facilitate the correlation of in vitro dissolution data obtained under homogeneous conditions and in vivo observations adhering to the heterogeneous milieu of the GI tract.
引用
收藏
页码:1122 / 1126
页数:5
相关论文
共 21 条
  • [1] Abdou H., 1989, DISSOLUTION BIOAVAIL
  • [2] A THEORETICAL BASIS FOR A BIOPHARMACEUTIC DRUG CLASSIFICATION - THE CORRELATION OF IN-VITRO DRUG PRODUCT DISSOLUTION AND IN-VIVO BIOAVAILABILITY
    AMIDON, GL
    LENNERNAS, H
    SHAH, VP
    CRISON, JR
    [J]. PHARMACEUTICAL RESEARCH, 1995, 12 (03) : 413 - 420
  • [3] [Anonymous], PHARM DISSOLUTION TE
  • [4] Badawy SIF, 1996, INT J PHARM, V128, P45
  • [5] Davenport H.W, 1982, PHYSL DIGESTIVE TRAC
  • [6] TRANSIT OF PHARMACEUTICAL DOSAGE FORMS THROUGH THE SMALL-INTESTINE
    DAVIS, SS
    HARDY, JG
    FARA, JW
    [J]. GUT, 1986, 27 (08) : 886 - 892
  • [7] FRASER EJ, 1972, LANCET, V2, P541
  • [8] DISSOLUTION AND BIOAVAILABILITY OF DIGOXIN TABLETS
    FRASER, EJ
    LEACH, RH
    POSTON, JW
    BOLD, AM
    CULANK, LS
    LIPEDE, AB
    [J]. JOURNAL OF PHARMACY AND PHARMACOLOGY, 1973, 25 (12) : 968 - 973
  • [9] HAVLIN S, 1989, FRACTAL APPROACH HET, P251
  • [10] A CELLULAR-AUTOMATA MODEL OF DISSOLUTION
    KIER, LB
    CHENG, CK
    [J]. PHARMACEUTICAL RESEARCH, 1995, 12 (10) : 1521 - 1525