(W0930-03-13) Impact of Film-Coating Excipient Selection on Tablet Performance and Stability

Purpose: Film-coating is a standard pharmaceutical approach for the development and manufacturing of oral solid dosages.¹ An immediate-release tablet was developed using a non-functional polyvinyl alcohol (PVA)-based film-coating (“PVA-Tablets”) and evaluated on stability studies at 25°C/60%RH and 40°C/75%RH. At 6-month timepoint of 40°C/75%RH and 24-month timepoint of 25°C/60%RH, the PVA-Tablets exhibited significantly slower dissolution compared with previous sampling timepoints (Figure 1). Therefore, the purpose of this study was to investigate the impact of film-coating excipient selection on the performance and stability (60°C and 40°C/75%RH) of an immediate-release tablet.

Methods: A roller compactor dry granulation process was used to produce milled granules that were blended and lubricated. A rotary tablet press compressed the lubricated blend into immediate-release core tablets, which were then film-coated with different types of film-coating excipients (hydroxypropyl methylcellulose [HPMC]- and PVA-based compositions) using a perforated pan. The film-coated tablets were packaged into induction-sealed HDPE bottles and stored in stability chambers set at 60°C, 40°C/75%RH and/or 25°C/60%RH. Tablet dissolution in water was evaluated at different storage timepoints and conditions using USP Apparatus 2 (paddle) method with a rotation speed of 100 rpm and temperature of 37°C.

Results: Immediate-release film-coated tablets were manufactured using HPMC-based and PVA-based film-coating (“HPMC-Tablets” and “PVA-Tablets,” respectively), and then the film-coated tablets were packaged into induction-sealed HDPE bottles. Both HPMC-Tablets and PVA-Tablets exhibited acceptable dissolution results upon release testing (average, minimum, and maximum at 45-minute timepoint for n=6 of HPMC-Tablets was 100%, 99%, and 102%, respectively, and PVA-Tablets was 99%, 98%, and 101%, respectively). HPMC-Tablets stored at 60°C for 3 weeks exhibited an average, minimum, and maximum dissolution release of 100%, 98%, and 100%, respectively, at 45 minutes (n=6), whereas PVA-Tablets stored at 60°C for 3 weeks exhibited an average, minimum, and maximum dissolution release of 53%, 11%, and 92%, respectively, at 45 minutes (n=6) (Figure 2). Dissolution slowdown was detected for PVA-Tablets stored at 40°C/75%RH for 5 months (average, minimum, and maximum were 22%, 18%, and 23%, respectively) but not for HPMC-Tablets stored under the same conditions (average, minimum, and maximum were 99%, 97%, and 100%, respectively) (Figure 3).

Conclusion: Although PVA-Tablets exhibited acceptable dissolution results through 18 months at 25°C/60%RH, there was a significant decrease in dissolution after 24 months. These results demonstrated that core tablet and film-coating interactions can result in physical (dissolution) changes to the product’s stability. Comparison of immediate-release tablets with different HPMC-based and PVA-based film-coatings showed that the dissolution slowdown could be mitigated by using an alternate film-coating composition. For this particular core tablet formulation, HPMC-Tablets were preferred because no dissolution slowdown in the accelerated conditions of 60°C and 40°C/75%RH was reported. In addition, the change in dissolution for PVA-Tablets that was identified in long-term (25°C/60%RH) storage conditions was also detected when using accelerated conditions of 60°C and 40°C/75%RH. Therefore, these studies also demonstrated the advantages of using accelerated stability studies to identify potential long-term dissolution issues.

References: 1. Sao K-S, Bajracharya R, Lee S-H, Han H-K. Pharmaceutics. 2020;12:853. doi:10.3390/pharmaceutics12090853.


Figure 1. Dissolution at 45 Minutes for PVA-Tablets Stored at 25°C/60%RH and 40°C/75%RH


Figure 2. Comparison of Dissolution at 45 Minutes for HPMC-Tablets and PVA-Tablets Stored at 60°C


Figure 3. Comparison of Dissolution at 45 Minutes for HPMC-Tablets and PVA-Tablets Stored at 40°C/75%RH