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


OBJECTIVE
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.
Department of Pharmaceutical Sciences, Division of Pharmaceutical Technology, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland.
Veronika A
VA
Eberle
Omya International AG, 4665 Oftringen, Switzerland.
Joachim
J
Schoelkopf
Omya International AG, 4665 Oftringen, Switzerland; School of Chemical Technology, Aalto University, FI-00076 Aalto, Helsinki, Finland.
Patrick A C
PA
Gane
Department of Pharmaceutical Sciences, Division of Pharmaceutical Technology, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland.
Rainer
R
Alles
Department of Pharmaceutical Sciences, Division of Pharmaceutical Technology, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland. Electronic address: joerg.huwyler@unibas.ch.
Jörg
J
Huwyler
Department of Pharmaceutical Sciences, Division of Pharmaceutical Technology, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland.
Maxim
M
Puchkov
D002110:Caffeine / Q000737:chemistry; D002119:Calcium Carbonate / Q000737:chemistry; D016503:Drug Delivery Systems; D005079:Excipients / Q000737:chemistry; D005750:Gastric Juice / Q000737:chemistry; D006851:Hydrochloric Acid / Q000737:chemistry; D065347:Hypromellose Derivatives / Q000737:chemistry; D008954:Models, Biological; D011092:Polyethylene Glycols / Q000737:chemistry; D012995:Solubility; D013607:Tablets
D005079:Excipients; C098305:Polyox WSR-301; D013607:Tablets; D002110:Caffeine; D065347:Hypromellose Derivatives; D011092:Polyethylene Glycols; C584694:hypromellose 2208 (100 MPA.S); D002119:Calcium Carbonate; D006851:Hydrochloric Acid
Cellular automata; Dissolution testing; Drug release simulation; Floating tablets; Gastroretentive drug delivery; Release profiles