Impact of oral gavage technique of drug-containing microcontainers on the gastrointestinal transit and absorption in rats
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Oral gavage is the most common way to administer drug formulations orally to rats. Yet, the technique applied and its influence on gastrointestinal (GI) transit receive little attention. This study aims to investigate the impact of three oral gavage techniques on GI transit and drug absorption utilizing microcontainers (MCs). The MCs were filled with paracetamol and BaSO4 (1:1 w/w ratio), coated with Eudragit S100, and filled into size-9 gelatin capsules. An in vitro study confirmed the intactness of the coating, and the capsules were administered to rats with air, water, or a piston. X-ray imaging determined the locations of the MCs, and the corresponding plasma concentration of paracetamol established a correlation with the location. The fastest GI transit occurred with air-dosing, while water-dosing caused delayed gastric emptying for 3 h with non-quantifiable paracetamol absorption. Piston-dosed MCs were retained in the stomach for up to 1 h, though for 3 h in one rat. Air-dosing caused discomfort and stress in rats, thus limiting its ethical and physiological relevance. Water-dosing confined its use due to delayed gastric emptying. In conclusion, the oral gavage technique affected the GI transit of MCs and, consequently, drug absorption. Piston-dosing appeared to be the superior dosing technique.
|Journal||International Journal of Pharmaceutics|
|Publication status||Published - 2022|
The research is funded by the Danish National Research Foundation ( DNRF122 ) and Villum Fonden (Grant No. 9301 ), Center for intelligent drug delivery and sensing using microcontainers and nanomechanics (IDUN). Jacob Rune Jørgensen is acknowledged for the collaboration in the development of the piston device for oral gavage, and Lasse Højlund Eklund Thamdrup is thanked for microcontainer manufacturing. The authors also thank Anne-Marie Heegaard for giving access to the IVIS Lumina XR. The graphical abstract was created with Biorender.com.
- Animal studies, Dosing technique, Gastrointestinal transit, Microcontainers, Paracetamol, X-ray imaging