Novel Formulations and Mechanistic Insights into Gastroresistant Dosage Forms

The oral route is still the preferred route for the administration of active substances, being drugs,
nutraceuticals or food supplements. Capsules are the simplest oral dosage forms, allowing the
administration of different substances without the need of extensive formulation development.
Nevertheless, an additional coating step is normally necessary to provide gastroresistance to solid
dosage forms, which means added materials, equipment, time and consequently, costs. This thesis
shows the successful development of enteric hard capsules which do not require additional enteric
coating and subsequent mechanistic insights into polymer dissolution. The produced capsules are
fabricated using gastroresistant polymers, guaranteeing their efficacy in bypassing the stomach without
disintegration. The in-vitro success of these capsules may however not warrant in-vivo efficacy. This
occurs due to the clear differences between the commonly used in-vitro dissolution media and the
gastrointestinal fluids. During this thesis the mechanics of enteric polymer dissolution was studied,
alongside their ionisation proprieties and the effect of different buffers in their dissolution. The pKa of
synthetic and natural polymers was estimated using a novel application of electrophoretic light
scattering technique, through the study of zeta potential. Both the type and the number of functional
groups have shown to impact the estimated pKa, with phthalyl showing opposite effects to succinoyl
groups on polymer dissolution pH and pKa. A new technique was developed for the quantification of
HPMC-based polymers, adapted from the conventional phenol-sulfuric acid assay for carbohydrates.
Using this technique, the dissolution rate of enteric polymers was measured in compendial phosphate
and physiological bicarbonate buffers with varying buffer capacities. The microenvironmental pH of the
dissolving polymers was also measured on the surface of the dissolving films using the same buffers.
A link was observed between buffer capacity, buffer type and polymer dissolution rate, hinting at
possible reasons for the observed poor in-vitro/in-vivo correlation. The wettability of enteric polymeric
films was also studied using contact angle kinetics under different dissolution media, tracking contact
angle, drop volume and basal area over a period of time. Ultimately, the data from polymer dissolution
rate, microenvironmental pH, ionisation, pKa and wettability were correlated to better understand the
mechanics of enteric polymer dissolution under in-vitro physiological conditions.