The Company has performed several pre-clinical trials with pigs and dogs in order to:
a. Design novel Accordion Pill™products based on unfolding multi-layer polymeric films;
b. Investigate the mechanism of gastric retention;
c. Assess the effect of the Accordion Pill™ on the drug's absorption properties;
d. Evaluate the safety profile of the Accordion Pill™ following repeated administration.

Dosage forms (DFs) with different dimensions and mechanical properties were administered to dogs together with an acidic buffer (pH=1.5). Gastric retention time (GRT) was determined by X-ray. The absorption of Riboflavin or L-DOPA from a prototype Accordion Pill™ was compared with a non-gastric-retentive controlled release DF, and an oral solution of the drug.

The extended absorption phase (>48h) of Riboflavin (100mg) administered in a Accordion Pill™ showed a 4-fold increase in oral bioavailability. The L-DOPA Accordion Pill™ maintained therapeutic L-DOPA concentrations (>500 ng/ml) for over 9 hours.

The Accordion Pill™ prolonged gastric retention and improved the absorption profile of typical narrow absorption drugs in animals.

Safety - experimental approach

The objective was to evaluate the safety of the Accordion Pill™ following long term repeated administration. For this purpose, four capsules were administered to pigs for 28 consecutive days. Following the last administration, a histopathological examination was performed on the gastrointestinal tract to evaluate possible signs of toxicity.