ABSTRACT
Gastric emptying of oral silicone dosage forms was studied in humans by gamma-scintigraphy. To achieve a constant and predictable residence time in the stomach, three different formulations based on known concepts such as controlled swelling were investigated. The importance of physical parameters such as size or shape were also examined to assess the feasibility of designing a dosage form for gastric retention. Three shapes: minimatrices, extruded rods and moulded slabs were screened. To label the silicone polymer, two isotopes, used routinely in nuclear medicine departments, were selected: iodine-123 and indium-111. To select the most suitable isotope, the yield and the stability of the labelling were determined in vitro on the pharmaceutical dosage forms. The residence time of these silicone formulations, labelled with iodine and administered in hard gelatine capsules, was monitored in 12 subjects with a gamma camera. The study was performed under fed conditions after ingestion of a standardised meal labelled with indium. The minimatrices provided at least 3 h retention, slabs exhibited 4 h 40 min retention. For the rods the mean residence time in the stomach was around 4 h 20 min. In addition, a correlation was established between the gastric emptying of rods and the half-gastric residence time of meal. On the contrary, such a correlation was not observed for the slabs.
Subject(s)
Silicones/pharmacokinetics , Stomach/diagnostic imaging , Administration, Oral , Adult , Dosage Forms , Female , Gastric Emptying , Humans , Hydrogen-Ion Concentration , Indium Radioisotopes , Iodine Radioisotopes , Male , Particle Size , Radionuclide ImagingABSTRACT
The objective of this work was to evaluate the ability of appropriate silicone elastomers to encapsulate hydrophilic compounds in microspheres prepared according to a multiphase emulsion-polymerization process. The particle size of the microspheres can be modified by controlling the usual emulsification parameters, such as the viscosity of the different phases, shear rates and surface activity properties of additives. The encapsulation efficiencies of a hydrophilic drug, propranolol hydrochloride, were very high but its release rates were very slow. Osmotic agents such as glycerol and propylene glycol did not enhance the release rate, whereas it was slightly increased by both sodium chloride addition and higher drug loading.
