Development of a dosage form for accelerated release.
OBJECTIVE
It was the aim of this study to develop an oral capsule delivery system capable of rapidly ejecting the incorporated payload in the small intestine.


METHODS
The capsule consists of four parts: a reaction mixture comprising of a basic and a corresponding acidic component, a plunger necessary to separate the reaction mixture from the inserted ingredients, capsule cap and body (made out of ethylcellulose (EC)), where at the bottom of the body a semipermeable filter membrane is mounted. As soon as water permeates through the membrane, the reaction mixture dissolves and carbon dioxide (CO2) is released resulting in a high speed liberation of inserted compounds onto the intestinal mucosa. Several filter membranes were investigated regarding water influx, capillary force and water retention capacity. CO2 release of sodium hydrogen carbonate (NaHCO3) was examined in presence of several acidic components in different morphological forms (powder, lyophilisate and granule) and the amount of CO2 liberation out of prepared capsules was determined. Furthermore, release of enteric coated capsules was tested within 0.1M HCl and 100mM phosphate buffer pH 6.8.


RESULTS
The rank order regarding membrane permeability was determined to be: cellulose acetate with a pore diameter of 12-15 μm>4-12 μm cellulose acetate>8 μm cellulose nitrate>8-12 μm cellulose acetate. NaHCO3 in combination with tartaric acid in form of a granule could be identified as the most promising reaction mixture with the highest amount of released CO2 compared to all other reaction mixture combinations. Stability of enteric coated capsules in HCl and a spontaneous release in phosphate puffer could be demonstrated within in vitro release studies.


CONCLUSIONS
In light of these results, the developed releasing system seems to be a promising tool for an accelerated delivery of several incorporated excipients.
Thiomatrix Forschungs-und Beratungs GmbH, Trientlgasse 65, Innsbruck 6020, Austria.
C
C
Waldner
Thiomatrix Forschungs-und Beratungs GmbH, Trientlgasse 65, Innsbruck 6020, Austria.
H E
HE
Friedl
Thiomatrix Forschungs-und Beratungs GmbH, Trientlgasse 65, Innsbruck 6020, Austria.
S
S
Dünnhaupt
Thiomatrix Forschungs-und Beratungs GmbH, Trientlgasse 65, Innsbruck 6020, Austria.
S
S
Köllner
Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-Universität of Innsbruck, Innrain 80-82, Innsbruck 6020, Austria.
G
G
Leonaviciute
Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-Universität of Innsbruck, Innrain 80-82, Innsbruck 6020, Austria. Electronic address: Andreas.Bernkop@uibk.ac.at.
A
A
Bernkop-Schnürch
D000268:Adhesiveness; D002214:Capsules / Q000008:administration & dosage* / Q000737:chemistry*; D002245:Carbon Dioxide / Q000737:chemistry; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods*; D065546:Drug Liberation; D005079:Excipients / Q000737:chemistry; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism; D008567:Membranes, Artificial
D002214:Capsules; D005079:Excipients; D008567:Membranes, Artificial; D002245:Carbon Dioxide; C013517:ethyl cellulose; D002482:Cellulose
Accelerated release; Capsule system; Mucoadhesion; Semipermeable membrane