Disintegration time of orally dissolving films: various methodologies and in-vitro/in-vivo correlation

摘要

Orodispersible films (ODF) have gained a remarkable success in the market, especially in pediatric and geriatric populations. The time required for an ODF to disintegrate is an essential quality and safety feature, thus an appropriate methodology is crucial. The USP disintegration apparatus is not appropriate for ODFs, as the determination of the end point is challenging and may not predict in-vivo disintegration time. The aim of the present study was to design and evaluate new disintegration protocols as an attempt to select the best approach that would reflect the in-vivo disintegration time in comparison to formerly reported procedures. Novel methods were designed, namely; the frame, the cell, and the agar plate methods, and compared to the previously reported methods; clamp and modified USP disintegration methods. Different ODFs were formulated using various viscosity grades of hydroxypropylmethyl cellulose. The mechanical characteristics of the prepared films were studied using texture analyzer and film folding endurance test. The resultant disintegration time of the films measured by the aforementioned methods were compared and correlated with its in-vivo time. Interestingly, the results obtained through the use of the cell method for the low viscosity polymers did not vary significantly from that of their in-vivo results (p>0.05). Moreover, the disintegration time of all polymeric films determined by the cell method revealed independently on their viscosity the highest correlation with in-vivo disintegration time (R-2 = 0.999). Such findings indicated the suitability of the cell method in predicting in-vivo disintegration time of low viscosity polymeric films.