A novel method to radiolabel gastric retentive formulations for gamma scintigraphy assessment.
OBJECTIVE
To develop a robust radiolabeling technique to enable evaluation of difficult to radiolabel gastric retentive formulations using gamma scintigraphy. The use of a successful radiolabel will allow accurate assessment of the gastric residence time of the formulations.


METHODS
The retention of two radionuclides, indium ((111)In) and samarium ((153)Sm), with and without further processing to improve radiolabel performance were evaluated in simulated gastric pH in vitro. The most successful formulation from the in vitro screening was further evaluated in preclinical and clinical studies.


RESULTS
In vitro evaluation revealed significant radionuclide leakage at pH 1.5 for most radiolabeling attempts. Radionuclide leakage at pH 4.5 was less pronounced. The most successful radiolabel was formulated by adsorbing indium chloride onto activated charcoal, followed by entrapment in a cellulose acetate polymer melt. This provided the best radiolabel retention under both pH conditions in vitro. The radiolabel also proved to be successful during preclinical and clinical evaluations, allowing evaluation of gastric retention performance as well as complete gastrointestinal transit.


CONCLUSIONS
A simple, yet robust radiolabel was developed for gastric retentive formulations to be evaluated pre-clinically or in a clinical setting by entrapping the radionuclide in an insoluble polymer through a simple polymer melt process.
Burke
Matthew D
MD
Product Development, Pharmaceutical Development, GlaxoSmithKline, Research Triangle Park, NC 27709, USA. matthew.d.burke@gsk.com
Staton
J Scott
JS
Vickers
Ann W
AW
Peters
Erin E
EE
Coffin
Mark D
MD
D000284:Administration, Oral; D000328:Adult; D000818:Animals; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D002606:Charcoal / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004285:Dogs; D004339:Drug Compounding; D004355:Drug Stability; D015902:Gamma Cameras; D005746:Gastric Emptying; D005772:Gastrointestinal Transit; D006207:Half-Life; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007204:Indium / Q000008:administration & dosage* / Q000737:chemistry; D007553:Isotope Labeling / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010087:Oxides / Q000008:administration & dosage* / Q000737:chemistry; D011868:Radioisotopes / Q000008:administration & dosage; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000008:administration & dosage* / Q000737:chemistry; D012493:Samarium / Q000008:administration & dosage* / Q000737:chemistry; D012995:Solubility; D013270:Stomach / Q000000981:diagnostic imaging*; D013678:Technology, Pharmaceutical / Q000379:methods*; D013997:Time Factors
D003692:Delayed-Action Preparations; D010087:Oxides; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D007204:Indium; D002606:Charcoal; C020758:indium trichloride; C005062:acetylcellulose; D012493:Samarium; D002482:Cellulose; C120592:samarium oxide