(T1230-02-08) Application of Ac-Di-Sol® SD-711 in Orally Disintegrating Tables (ODTs): Performance Comparison of Croscarmellose Sodium and Crospovidone

Purpose: Orally disintegrating tablets (ODTs) generally have the appropriate dissolving or disintegrating performance in the mouth without additional water for easy administration. ODTs have many advantages, including 1) Improving patients’ compliance, 2) Rapid onset of action, and 3) Effectiveness for pediatric, geriatric, and psychiatric patients without changing pharmacodynamics from film coating tablet. Croscarmellose sodium (CCS) and Crospovidone (PVPP) are two of the most widely used superdisintegrants in ODTs. CCS is a cross-linked sodium salt of carboxymethyl cellulose, and it presents long, fibrous particles. PVPP is a polyvinylpyrrolidone derivative, which is insoluble in water. PVPP usually exists in granular and porous particles. The main proposed disintegrating mechanism of CCS and PVPP are coming with wicking and swelling. Thus, although their respective disintegration mechanisms are well known, few data based on actual studies have been reported to clarify the differences in disintegration mechanisms, usage levels, and drug elution performance in the same experimental condition. In this study, we present comparative data on the formulation of ODTs with either CCS or PVPP.

Methods: All CCS and PVPP experimental data were performed using representative products Ac-Di-Sol® SD-711 (ADS) and Polyplasdone™ XL-10 (PVPP XL-10), respectively. In this study, a vildagliptin ODT was prepared. At first, vildagliptin granules were prepared via high shear granulation, which started from mixing with hydroxypropyl cellulose, silicon dioxide, and Ethanol, followed by dry screening and collecting granules through the screens between 50 mesh and 120 mesh. After these vildagliptin granules were coated by fluid bed with ETHOCEL™ STD 7 ethyl cellulose and METHOCEL™ VLV Hypromellose grade, vildagliptin ODT was formulated by direct compression of Pearlitol® 200 SD (Mannitol) with either ADS or PVPP XL-10. The disintegration time of both ODT was tested using a texture analyzer (TA XT. Plus) [1]. Drug dissolution test of vildagliptin ODT was evaluated with reference to a doctoral dissertation [2], because there is no specific reference of vildagliptin. In short, Sotax dissolution system with the USP apparatus 2 at paddle speed of 50 rpm was employed for the dissolution test. The stability of vildagliptin ODT with different superdisintegrants was observed under 75% RH condition on day 5 and day 10 with monitoring tablet weight and hardness.

Results: Disintegration performance (Onset time and End point) was analyzed with Texture Analyzer (Figure 1). ADS-based ODTs were found to have much shorter Onset time and End point at 2% usage level compared to PVPP XL-10-based ODTs. In addition, the ADS-based ODTs always had a shorter Onset time, while the PVPP XL-10-based ODTs showed a reversal with a shorter End point at 5% or greater use level. No synergistic effect with ADS and PVPP XL-10 was observed in this trial. Drug release performance was evaluated in a pH 7.0 solution simulating saliva (Figure 2). Similar to the disintegration performance of the previous experiment, the use of 2% ADS, 5% ADS and 5% PVPP XL-10 showed faster disintegration performance than the use of 2% PVPP XL-10. The drug release after 2 minutes for all four tested formulations was less than 20%, which is expected to provide a good taste masking effect. Vildagliptin ODT-hardness decreased with storage time at 75% RH day by day, especially for at 5% PVPP XL-10 usage, tablet hardness of the ODTs decreased by almost 50% after 10 days at 75% RH (Figure 3). Remarkably, tablet hardness of PVPP XL-10-based ODTs was clearly reduced, although no dramatic increase in tablet hygroscopicity was observed. On the other hand, ADS based-ODTs were much less sensitive to high humidity and are expected to have better stability in terms of tablet hardness.

Conclusion: When vildagliptin is used as model drug for ODT, ADS based-ODTs at 2-5% use level showed excellent disintegration performance with quick swelling and disintegration. On the other hand, PVPP XL-10 based ODTs would be disintegrated at more than 5% use level with rapidly disintegration. In high humidity condition, ADS-based ODTs would be more stable than PVPP XL-10-based ODTs.

References: [1] Abdelbary G., Eounai C., Prinderre P., et al, Determination of the In Vitro Disintegration Profile of Rapid Disintegrating tablets and Correlation with Oral Disintegration. Int. J. Pharm. 2005,292: 29-41
[2] Gu YL. Preparation of Vildagliptin tablets. Hebei China. Univ. of Hebei medical. 2015

Acknowledgements: No Conflict of Interest

Figure 1. Disintegration performance in Vildagliptin ODT

Figure 2. Drug release of vildagliptin ODT in pH 7.0 (simulated saliva)

Figure 3. Hardness and moisture absorption of ODT stored in 75 %RH