Floating gastroretentive drug delivery systems: Comparison of experimental and simulated dissolution profiles and floatation behavior

Veronika A Eberle; Joachim Schoelkopf; Patrick A C Gane; Rainer Alles; Jörg Huwyler; Maxim Puchkov

doi:10.1016/j.ejps.2014.03.001

Floating gastroretentive drug delivery systems: Comparison of experimental and simulated dissolution profiles and floatation behavior

Eur J Pharm Sci. 2014 Jul 16:58:34-43. doi: 10.1016/j.ejps.2014.03.001. Epub 2014 Apr 2.

Authors

Veronika A Eberle¹, Joachim Schoelkopf², Patrick A C Gane³, Rainer Alles¹, Jörg Huwyler⁴, Maxim Puchkov¹

Affiliations

¹ Department of Pharmaceutical Sciences, Division of Pharmaceutical Technology, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland.
² Omya International AG, 4665 Oftringen, Switzerland.
³ Omya International AG, 4665 Oftringen, Switzerland; School of Chemical Technology, Aalto University, FI-00076 Aalto, Helsinki, Finland.
⁴ Department of Pharmaceutical Sciences, Division of Pharmaceutical Technology, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland. Electronic address: joerg.huwyler@unibas.ch.

PMID: 24704154
DOI: 10.1016/j.ejps.2014.03.001

Abstract

Introduction: Gastroretentive drug delivery systems (GRDDS) play an important role in the delivery of drug substances to the upper part of the gastrointestinal tract; they offer a possibility to overcome the limited gastric residence time of conventional dosage forms.

Aims: The aim of the study was to understand drug-release and floatation mechanisms of a floating GRDDS based on functionalized calcium carbonate (FCC). The inherently low apparent density of the excipient (approx. 0.6 g/cm(3)) enabled a mechanism of floatation. The higher specific surface of FCC (approx. 70 m(2)) allowed sufficient hardness of resulting compacts. The floating mechanism of GRDDS was simulated in silico under simulated acidic and neutral conditions, and the results were compared to those obtained in vitro.

Methods: United States Pharmacopeia (USP) dissolution methods are of limited usefulness for evaluating floating behavior and drug release of floating dosage forms. Therefore, we developed a custom-built stomach model to simultaneously analyze floating characteristics and drug release. In silico dissolution and floatation profiles of the FCC-based tablet were simulated using a three-dimensional cellular automata-based model.

Results: In simulated gastric fluid, the FCC-based tablets showed instant floatation. The compacts stayed afloat during the measurement in 0.1 N HCl and eroded completely while releasing the model drug substance. When water was used as dissolution medium, the tablets had no floating lag time and sank down during the measurement, resulting in a change of release kinetics.

Conclusions: Floating dosage forms based on FCC appear promising. It was possible to manufacture floating tablets featuring a density of less than unity and sufficient hardness for further processing. In silico dissolution simulation offered a possibility to understand floating behavior and drug-release mechanism.

Keywords: Cellular automata; Dissolution testing; Drug release simulation; Floating tablets; Gastroretentive drug delivery; Release profiles.

Publication types

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

MeSH terms

Caffeine / chemistry
Calcium Carbonate / chemistry
Drug Delivery Systems*
Excipients / chemistry
Gastric Juice / chemistry
Hydrochloric Acid / chemistry
Hypromellose Derivatives / chemistry
Models, Biological*
Polyethylene Glycols / chemistry
Solubility
Tablets

Substances

Excipients
Polyox WSR-301
Tablets
Caffeine
Hypromellose Derivatives
Polyethylene Glycols
hypromellose 2208 (100 MPA.S)
Calcium Carbonate
Hydrochloric Acid