Abstract
A hydrophilic matrix tablet containing 300 mg of propylthiouracil was formulated with several types of hydroxypropylmethylcellulose. The influence of polymer and drug granule particle size, polymer concentration, crystallinity and geometry of the polymer particles, the polymer incorporation outside or inside the granule, addition of a filler and tablet hardness were studied. Polymer concentration, polymer particle size and geometry, filler addition and type of the filler used had a major influence on in vitro drug dissolution profiles. The bioavailability of propylthiouracil in dogs from the hydrophilic matrices investigated was low, because of the short gastro-intestinal transit times of the matrix tablets in the dogs. The matrix tablets reached the colon in fasted dogs within 2–3 hours after administration. The results indicated the poor predictability of bioavailability experiments in dogs with hydrophilic matrices. Although the bioavailability data in pigs seemed promising, a transit time study revealed a long stomach residence time of the matrix tablets in pigs. These data suggested that pigs are an inappropriate animal model for bioavailability studies of erodible matrix tablets.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
REFERENCES
H. P. Ringhand, W. A. Ritschel, M. C. Meyer, A. B. Straughn and T. Hardt. Pharmacokinetics of propylthiouracil upon p.o. administration in man. Int. J. Clin. Pharmacol. Ther. Toxicol. 18:488–493 (1980).
D. A. Alderman. A review of cellulose ethers in hydrophilic matrices for oral controlled release dosage forms. Int. J. Pharm. Technol. 5:1–9 (1984).
J. E. Hogan. HPMC sustained release technology. Drug. Dev. Ind. Pharm. 15:975–999 (1989).
L. J. Lucisano, J. A. Breech, L. A. Angel and M. F. Robert. Evaluation of an alternate source of HPMC for use in sustained release tablet matrix. Pharm. Technol. Int. MAY/JUNE:34–46 (1989).
K. Ventouras, J. Boucherat and P. Buri. Influence des facteurs technologiques sur la libération de la vincamine incorporée dans des matrices hydrophiles. Pharm. Acta Helv. 52:119–123 (1977).
J. L. Ford, M. H. Rubinstein and J. E. Hogan. Dissolution of a poorly water soluble drug, indomethacin, from hydroxypropyl-methylcellulose controlled release tablets. J. Pharm. Pharmacol. 37:33P (1985).
L. Kabanda, C. De Muynck, R. A. Lefebvre and J. P. Remon. Validation of a HPLC method for the determination of propylthiouracil in plasma. J. Liquid. Chromatogr. 17(9):2069–2083 (1994).
R. C. Shumaker, H. Bauxenbaum and G. A. Thompson. ABSPLOTS: A LOTUS 123 spreadsheet for calculating and plotting drug absorption rates. Pharm. Res. 5:247–248 (1988).
S. Siegel and N. J. Castellan. Nonparametric statistics for the-behavioral sciences (Second Edition). McGraw-Hill international editions, 1988.
T. C. Dahl, T. Calderwood, A. Bormeth and K. Trimble. Influence of physico chemical properties of HPMC on naproxen release from sustained release matrix tablet. J. Control. Release. 14:1–10 (1990).
J. P. Kampmann and L. Skovsted. The pharmacokinetics of propylthiouracil. Acta Pharm. Toxicol. 35:361–369 (1974).
J. P. Kampmann. Pharmacokinetics of propylthiouracil in man after intravenous infusion. J. Pharmacokinet. Biopharm. 5:435–443 (1977).
P. C. Smith, P. N. J. Langendijk, J. A. Bosso and L. Z. Benet. Effect of probenecid on the formation and elimination of acyl glucuronides: Studies with zomepirac. Clin. Pharmacol. Ther. 38:121–127 (1985).
D. R. Abernethy, D. J. Greenblatt, B. Ameer and R. I. Shader. Probenecid impairment of acetaminophen and lorazepam clearance: direct inhibition of ether glucuronide formation. J. Pharmacol. Exp. Ther. 234:345–349 (1985).
J. B. Dressman and K. Yamada. Animal models for oral drug absorption. In P. G. Welling, F. L. S. Tse and S. V. Dighe (eds.), Pharmaceutical bioequivalences, Marcel Dekker, Inc., New York, 1991, pp 235–266.
M. Bialer, S. A. Kaplan and A. Yacobi. Animal models in the primary screening of controlled release formulations. In A. Yacobi and E. Halperin-Walega (eds.), Oral sustained release formulations. Design and Evaluation, Pergamon Press, New York, 1988, pp. 183–193.
J. Liaw, A. Rubinstein and J. R. Robinson. Bioavailability study of Theo-dur tablets in the fasted cannulated dog. Int. J. Pharm. 59:105–114 (1990).
W. A. Cressman and D. Sumner. The dog as a quantitative model for evaluation of nondisintegrating sustained-release tablets. J. Pharm. Sci. 60:132–134 (1971).
G. Hecht, J. E. Christian and G. S. Banker. In vivo pharmacodynamic evaluation of oral dosage form by whole body liquid scintillometry. J. Pharm. Sci. 55:678–684 (1966).
H. Nakagami, T. Yamao, E. Mafune and M. Takahashi. Evaluation of sustained release procainamide tablets made from micronized low-substituted hydroxypropylcellulose in dogs. Stp Pharm.[Sci]. 1:345–350 (1991).
M. Hossain, W. Abramowitz, B. J. Watrous, G. J. Szpunar and J. W. Ayres. Gastrointestinal transit of nondisintegrating, non-erodible oral dosage forms in pigs. Pharm. Res. 7:1163–1166 (1990).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kabanda, L., Lefebvre, R.A., Van Bree, H.J. et al. In Vitro and in Vivo Evaluation in Dogs and Pigs of a Hydrophilic Matrix Containing Propylthiouracil. Pharm Res 11, 1663–1668 (1994). https://doi.org/10.1023/A:1018982409661
Issue Date:
DOI: https://doi.org/10.1023/A:1018982409661