No abstract

The features rendering orodispersible films (ODFs) patient-centric formulations are widely discussed in the scientific literature. However there is a lack of research studies exploring ODF characteristics with a potential impact on end-user acceptability. The aim of this study was to identify the key ODF characteristics affecting end-user acceptability by developing in vitro test methods for the prediction of ODFs acceptability and correlate these formulation characteristics with the data obtained from a human panel study. Four drug-free single-polymer films were prepared by solvent casting. Solutions of poly(vinyl) alcohol (PVOH) 39 KDa (P1), PVOH 197 KDa (P2), carboxymethylcellulose (CMC) 395 KDa (C1), and CMC 725 KDa (C2) were prepared. Texture analysis and Dynamic Mechanical Analysis (DMA) were used to assess film tack. Petri dish and drop methods were used to assess disintegration time. A human panel of 24 healthy young adults was employed to identify end-user acceptability criteria of the four study film samples. Texture analysis data of ODF tack were not found to be in agreement with the in vivo perceived stickiness in the mouth. However, measurement of the area under the adhesive force curve obtained by DMA correlated with in vivo perceived stickiness data for all samples. The disintegration times obtained by drop method were more comparable to human panel data than the petri dish method. Hence DMA and drop methods proved to be promising methodologies for the prediction of the end-user acceptability. The type and molecular weight of the film-forming polymer had a strong influence on stickiness perception, whereas only polymeric molecular weight influenced perceived disintegration time. The human panel study showed that Participant Reported Outcomes (PROs) for the perceived stickiness in the mouth and disintegration time of test films received significantly different scores between samples, and thus were identified as the key attributes with the potential to affect the end-user acceptability. ODF stickiness and disintegration time should therefore be evaluated at an early stage of the drug product design.

The impact of hydrodynamics and media composition on nifedipine dissolution profile from IR (immediate release) soft capsules was investigated using dissolution apparatus USP1, USP2, USP3 and USP4 (United State Pharmacopoeia). Media composition was varied in terms of pH and content, to mimic the dosage form intake with water or non-alcoholic beverages (orange juice) and alcoholic beverages (orange juice/ethanol mixture (47% v/v)). Through construction of in vitro-in vivo correlations (IVIVC) with corresponding in vivo data from the literature, it was possible to evaluate the in vitro conditions that are likely to simulate the in vivo formulation behaviour. Both linear and nonlinear correlations were obtained depending on experimental set-ups. Testing of 20mg nifedipine capsules in FaSSGFst (Fasted State Simulated Gastric Fluid pH 1.6; water administration) produced IVIVC with the USP3 (after time scaling) and USP4 apparatus. IVIVC were obtained for USP2, USP3 and USP4 in FaSSGFoj (Fasted State Simulated Gastric Fluid pH 3.4; orange juice administration). Linear and nonlinear correlations were obtained with the USP1, USP2 and USP3 apparatus when testing the capsules in FaSSGFoj/EtOH (orange juice/ethanol administration). This study highlighted that selection of physiologically relevant dissolution set-ups is critical for predicting the in vivo impact of formulations co-administration with water, non-alcoholic and alcoholic beverages.

No abstract

No abstract