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Irregular absorption profiles observed from diclofenac extended release tablets can be predicted using a dissolution test apparatus that mimics in vivo physical stresses.
Eur J Pharm Biopharm. 2008 Oct; 70(2):421-8.EJ

Abstract

The prediction of the in vivo drug release characteristics of modified release oral dosage forms by in vitro dissolution tests is a prerequisite for successful product development. A novel dissolution test apparatus that mimics the physical conditions experienced by an oral formulation during gastrointestinal transit was developed. This included the simulation of pressure forces exerted by gut wall motility, shear forces generated during propagation, and loss of water contact when the dosage form is located in an intestinal air pocket. The new apparatus was evaluated using a diclofenac extended release (ER) tablet. The in vitro dissolution profiles were compared between the novel test apparatus and a conventional dissolution apparatus (USP II). These data were compared with the profiles of plasma concentration versus time that were obtained after the administration of an ER tablet to 24 healthy volunteers under fasting conditions. Multiple peaks were observed in individual plasma concentration-time profiles after the intake of the reference ER tablet. Standard dissolution testing showed typical characteristics of an almost continuous release for this formulation; however, dissolution testing with the novel apparatus suggested that the diclofenac release from the ER tablets would be extremely variable and dependent on the applied stress. The data suggest that the observed multiple peaks of plasma concentration after dosing of the ER diclofenac tablets are most probably caused by sensitivity to physical stress events during gastrointestinal transit.

Authors+Show Affiliations

Department of Biopharmaceutics and Pharmaceutical Technology, University of Greifswald, Greifswald, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18582568

Citation

Garbacz, Grzegorz, et al. "Irregular Absorption Profiles Observed From Diclofenac Extended Release Tablets Can Be Predicted Using a Dissolution Test Apparatus That Mimics in Vivo Physical Stresses." European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, vol. 70, no. 2, 2008, pp. 421-8.
Garbacz G, Wedemeyer RS, Nagel S, et al. Irregular absorption profiles observed from diclofenac extended release tablets can be predicted using a dissolution test apparatus that mimics in vivo physical stresses. Eur J Pharm Biopharm. 2008;70(2):421-8.
Garbacz, G., Wedemeyer, R. S., Nagel, S., Giessmann, T., Mönnikes, H., Wilson, C. G., Siegmund, W., & Weitschies, W. (2008). Irregular absorption profiles observed from diclofenac extended release tablets can be predicted using a dissolution test apparatus that mimics in vivo physical stresses. European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, 70(2), 421-8. https://doi.org/10.1016/j.ejpb.2008.05.029
Garbacz G, et al. Irregular Absorption Profiles Observed From Diclofenac Extended Release Tablets Can Be Predicted Using a Dissolution Test Apparatus That Mimics in Vivo Physical Stresses. Eur J Pharm Biopharm. 2008;70(2):421-8. PubMed PMID: 18582568.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Irregular absorption profiles observed from diclofenac extended release tablets can be predicted using a dissolution test apparatus that mimics in vivo physical stresses. AU - Garbacz,Grzegorz, AU - Wedemeyer,Ralph-Steven, AU - Nagel,Stefan, AU - Giessmann,Thomas, AU - Mönnikes,Hubert, AU - Wilson,Clive G, AU - Siegmund,Werner, AU - Weitschies,Werner, Y1 - 2008/06/07/ PY - 2008/03/25/received PY - 2008/05/29/revised PY - 2008/05/30/accepted PY - 2008/6/28/pubmed PY - 2008/12/17/medline PY - 2008/6/28/entrez SP - 421 EP - 8 JF - European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V JO - Eur J Pharm Biopharm VL - 70 IS - 2 N2 - The prediction of the in vivo drug release characteristics of modified release oral dosage forms by in vitro dissolution tests is a prerequisite for successful product development. A novel dissolution test apparatus that mimics the physical conditions experienced by an oral formulation during gastrointestinal transit was developed. This included the simulation of pressure forces exerted by gut wall motility, shear forces generated during propagation, and loss of water contact when the dosage form is located in an intestinal air pocket. The new apparatus was evaluated using a diclofenac extended release (ER) tablet. The in vitro dissolution profiles were compared between the novel test apparatus and a conventional dissolution apparatus (USP II). These data were compared with the profiles of plasma concentration versus time that were obtained after the administration of an ER tablet to 24 healthy volunteers under fasting conditions. Multiple peaks were observed in individual plasma concentration-time profiles after the intake of the reference ER tablet. Standard dissolution testing showed typical characteristics of an almost continuous release for this formulation; however, dissolution testing with the novel apparatus suggested that the diclofenac release from the ER tablets would be extremely variable and dependent on the applied stress. The data suggest that the observed multiple peaks of plasma concentration after dosing of the ER diclofenac tablets are most probably caused by sensitivity to physical stress events during gastrointestinal transit. SN - 0939-6411 UR - https://www.unboundmedicine.com/medline/citation/18582568/Irregular_absorption_profiles_observed_from_diclofenac_extended_release_tablets_can_be_predicted_using_a_dissolution_test_apparatus_that_mimics_in_vivo_physical_stresses_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0939-6411(08)00214-2 DB - PRIME DP - Unbound Medicine ER -