TY - JOUR

T1 - Direct visualizing of paracetamol immediate release tablet disintegration in vivo and in vitro

AU - Fredholt, Freja

AU - Di Meo, Camilla

AU - Sloth, Stine

AU - Müllertz, Anette

AU - Berthelsen, Ragna

N1 - Funding Information: Thanks to each volunteer participating in the clinical study. Thanks to the Danish distributor, Neovalitis for free colon endoscopic camera capsules (Given Imaging) used in the in vitro studies and for enabling the conduction of said studies. Thanks to Stefen Fjellander for technical support with the data recorder used for obtaining images from the camera capsule. Thanks to Herlev Hospital for making the needed equipment and support available for the visualization studies in vivo. Furthermore, a big thanks to nurse Iben Nielsen for help with administration of the endoscopic camera capsules and support during the in vivo study.

PY - 2022

Y1 - 2022

N2 - The purpose of the present study was to study tablet disintegration by direct visualization, in vivo and in vitro. Based on literature data, a standard conventional paracetamol (CP) tablet, Panodil®, and a rapidly absorbed paracetamol (RP) tablet, Panodil® Zapp, were chosen as model systems to study tablet disintegration in the human stomach. Based on the obtained in vivo results, an in vitro disintegration method was designed to reproduce the visualized disintegration process occurring in the human stomach. For the clinical study, CP and RP tablets fastened to digital endoscopic camera capsules were administered to fasted human volunteers (n = 4). The disintegration time and process were visualized by the real time video recordings, using the endoscopic camera capsule. The average disintegration time was found to be 26 ± 13 min and 10 ± 7 min, for CP (n = 4) and RP (n = 4) tablets, respectively. It was possible to reproduce the in vivo disintegration data in vitro using a USP 2 dissolution apparatus with 250 mL of viscous Fasted State Simulated Gastric Fluid (vFaSSGF*), simulating the rheological profile of human fasted state gastric fluid following administration of a glass of water. The viscosity of the simulated fasted state gastric fluid was found to have a large impact on the disintegration time of the tested immediate release tablets. Therefore, it is recommended to mimic gastric fluid viscosity during in vitro tablet disintegration studies.

AB - The purpose of the present study was to study tablet disintegration by direct visualization, in vivo and in vitro. Based on literature data, a standard conventional paracetamol (CP) tablet, Panodil®, and a rapidly absorbed paracetamol (RP) tablet, Panodil® Zapp, were chosen as model systems to study tablet disintegration in the human stomach. Based on the obtained in vivo results, an in vitro disintegration method was designed to reproduce the visualized disintegration process occurring in the human stomach. For the clinical study, CP and RP tablets fastened to digital endoscopic camera capsules were administered to fasted human volunteers (n = 4). The disintegration time and process were visualized by the real time video recordings, using the endoscopic camera capsule. The average disintegration time was found to be 26 ± 13 min and 10 ± 7 min, for CP (n = 4) and RP (n = 4) tablets, respectively. It was possible to reproduce the in vivo disintegration data in vitro using a USP 2 dissolution apparatus with 250 mL of viscous Fasted State Simulated Gastric Fluid (vFaSSGF*), simulating the rheological profile of human fasted state gastric fluid following administration of a glass of water. The viscosity of the simulated fasted state gastric fluid was found to have a large impact on the disintegration time of the tested immediate release tablets. Therefore, it is recommended to mimic gastric fluid viscosity during in vitro tablet disintegration studies.

KW - Capsule endoscopy

KW - Direct visualization

KW - Dissolution

KW - Immediate release tablets

KW - Paracetamol

KW - Tablet disintegration

U2 - 10.1016/j.ejpb.2022.09.007

DO - 10.1016/j.ejpb.2022.09.007

M3 - Journal article

C2 - 36122785

AN - SCOPUS:85139019257

VL - 180

SP - 63

EP - 70

JO - European Journal of Pharmaceutics and Biopharmaceutics

JF - European Journal of Pharmaceutics and Biopharmaceutics

SN - 0939-6411

ER -