Variazioni significative delle caratteristiche di rilascio di una forma farmaceutica gastroresistente in funzione delle condizioni di conservazione

A stability test was carried out on an oral dosage form designed for the modified release of cloricromene hydrochloride. The drug is formulated in film coated pellets contained in hard gelatine capsules. The coating is made of cellulose acetate trimellitate, a pH-dependent polymer insoluble in the gastric environment. For this reason the dissolution test is carried out in hydrochloride medium at pH=1 for 2 hours and then in phosphate buffer at pH=6.8. For the first two hours no more than 40% of the dose should be released while, after the pH change, all the drug content (at least 85%) should be released within the third hour. To verify the reproducibility of the controlled release dosage form performance, an accelerated stability test was carried out on the blistered capsules in their final packaging for one month. The product was stored in controlled conditions at 40°C and 75% R.H. and tested at 7 days' intervals. The dissolution profiles obtained during the accelerated stability test, evidence a remarkable and progressive loose of efficiency of the film coating (pH-dependent protection) during storage. In fact the percentage of drug released during the first two hours is less than 30% in the case of the original product, while it increases progressively to reach more than 60% after only one month of storage at 40°C and 75% R.H. although, after the pH change, the remaining drug content is released completely within the following hour. This accelerated stability test evidences how critical could be the storage conditions on the performance of a controlled release dosage form in particular when a cellulose acetate trimellitate film coating is chosen to obtain the modulation of the drug delivery profile.