Optimisation de la concentration en électrolytes au sein des matrices à base de HASCA pour la libération prolongée
HASCA, High amylose sodium carboxymethyl starch (amylose-amylopectin 60% 40%), a hydrophilic ionic polymer used in sustained release matrix tablets, is characterized by the formation of a hydrogel when in contact with the dissolution medium. Fickian diffusion and relaxation of the polymer chains are the main mechanisms controlling the release of the active ingredients (AI). On the other hand, a common method for sustaining the release of a drug is to decrease its solubility. It’s known that the solubility of a drug depends on the form used, either the free base versus its salt or the free acid versus its salt. A combination of the salt and acid forms or the salt and base forms in the same HASCA matrix tablet was proposed. The objective of this work is to study the effect of the polymer’s nature on the release profile of AI in an aqueous medium with a pH gradient because HASCA is characterized by the presence of a carboxylic group, ionized or not according to the acidity of the dissolution medium. The influence of the nature of the AI, the salt or free base versus the free acid or its salt, on the release profile is also studied by selecting models of AI in each category. The influence of the proportion between the free form (acid or base) and the combination with its salt on the release profile is also investigated. Therefore tablets containing HASCA with different proportion of either naproxen acid and naproxen sodium (acid AI and its salt) or tetracycline and tetracycline hydrochloride (basic AI and it salt) are used. This will be evaluated during dissolution tests in a medium similar to the gastrointestinal environment according to the standards of USP (UV spectrophotometry). Intrinsic dissolution tests will also be conducted on pure AI for different studied pH.  This study shows that using HASCA, it’s possible to obtain sustained release tablets for administration once a day using a combination of acid and salt as AI.
tablets polymer matrix naproxen tetracycline