(T1430-11-72) Evaluation of Stability and Physical Parameters of Sitagliptin IR Tablets Coated with Different Titanium Dioxide Free Coating Systems

Purpose: To address concerns around the use of titanium dioxide (TiO2) in certain nutraceutical markets and the potential impact on pharmaceutical products, Opadry^® TF, TiO2 Free Formulated Film Coatings have been developed¹. This range of coating formulations, though similar in functionality, may contain additional ingredients such as calcium carbonate that are not present in existing TiO2 containing formulations in order to impart opacity to the film coatings. The dispersion pH for such formulations could be slightly on the alkaline side. New best-in-class TiO2 free formulations such as Opadry TF 276U is designed to provide higher opacity at standard coating weight gains, while Opadry TF 277U is a calcium carbonate free coating. The objective of this study was to study the impact of various Opadry TF coating systems as shown in Table 1 on physicochemical properties such as assay, impurity, color difference, DT and dissolution performance of immediate release (IR) tablets using a model drug, sitagliptin.

Methods: Sitagliptin IR tablets were produced using direct compression with StarTab^®, a novel directly compressible starch and microcrystalline cellulose as diluents, magnesium stearate was added as lubricant. Compressed tablets were film coated using a TiO2 containing Opadry system and several different Opadry TF (TiO2 free) coating formulations. Tablet coating was performed in a 12.5" perforated coating pan (O’HARA Labcoat™ M5), using 900 g batch size. The coated tablets were stored in 75 cc HDPE containers at accelerated storage conditions of 40°C/75% RH and 30°C/65% RH for 3 months. Coated tablets were evaluated for surface roughness, assay, impurity, and dissolution.

Results: The sitagliptin content of the uncoated and film coated tablet formulations (Trials 1-5) was within acceptable limits of 95-105% at both the initial and end of 3M accelerated stability condition. Impurity profile was NMT 0.2% (limit = 1%) up to 3M stability time point in all film coated tablet formulations (Trials 1-5) indicating Opadry TF film coating system did not impact drug degradation (Figure 1). No significant difference in drug release was observed for all Opadry and Opadry TF film coated tablets at initial and accelerated stability conditions of 40⁰C / 75% RH (Figure 2).

Conclusion: The study showed sitagliptin tablets coated with Opadry TF had comparable physicochemical performance when applied at 3% weight gain. At the end of 3M accelerated stability studies, coated tablets complied with all the analytical tests suggesting Opadry TF does not have any adverse effect on sitagliptin tablet formulation.

Table 1: Tio2 Free Coating Systems Evaluated

Figure 1: Assay Test Results for Sitagliptin Tablets at Initial and Accelerated Stability Conditions

Figure 2: Drug Release Profiles of Sitagliptin Tablets at Initial and Accelerated Stability Condition