Small scale manufacturing and scintigraphic detection of pellet formulations

This research was designed to develop radiolabelling methods for pellets or mini-tablets so that their in vivo behaviour can be assessed using gamma scintigraphy. Eight different pellet formulation profiles were developed using paracetamol and indomethacin as partially and poorly water soluble model drugs respectively. Four different drug release profiles for each of the two model drugs were achieved by applying a film coat to the pellet formulations, which were manufactured using either extrusion-spheronisation or the drug-layering techniques. Pelletisation methods were developed on a small scale in order to minimise quantities of radioisotope required for manufacturing for scintigraphic studies.Extrusion-spheronisation used microcrystalline cellulose and lactose as the main components. Thermally controlled spheronisation at elevated temperature produced pellets within a narrow size distribution. It was found that the drug release rate from extrusion-spheronised pellets could be readily manipulated by changing the ratio of microcrystalline cellulose within the pellets. However, the drug-layering technique was required in order to achieve a rapid release of the poorly water soluble drug indomethacin.Two radiolabelling methods, the "incorporation" and the "soaking" methods, were successfully developed. In the "incorporation" method a 99mTc radioisotope is mixed into a powder blend prior to small scale extrusion-spheronisation and in the "soaking" method inert pellet cores are soaked in a solution containing a 99mTc radioisotope, which becomes attached to the pellet core prior to small scale drug-layering.The use of radiolabelled placebo pellets in gamma scintigraphic studies was validated. It was found that gastrointestinal transit of drug loaded formulations, which may include novel pellet formulations or mini-tablets, can be traced in vivo by mixing with radiolabelled placebo pellets.A faster and easier alternative to the "soaking" method, the "wet and dry" method, was optimised at a later stage.

Name dc:type.qualificationname

mphil

Level dc:type.qualificationlevel

masters-pg

Grantor dc:publisher.institution

University of Strathclyde

Year dc:date.issued

2014

Author dc:creator

• Jónsson, Toke

DOI

10.48730/qrvh-xc53

Identifier

T13816

OAI identifier oai:identifier

oai:strathclyde:12579s33h