(T1130-10-56) Understanding Friability Performance in Titanium-Free Film Coated Tablets as a Function of Tablet Shape and Core Composition

Purpose: This study showcases the potential of titanium-free (TF) film-coated tablets (FCTs) with calcium carbonate (CaCO₃)–based coatings as a promising alternative to those using titanium dioxide (TiO₂), addressing concerns regarding potential genotoxicity associated with TiO₂-based film coats (FCs). More specifically, this study aimed to investigate the friability performance of FCTs by varying several key variables. These variables include the core tablet formulation, tablet shape (specifically aspect ratio and cup depth), and film coating composition. Furthermore, this study focuses on evaluating TF CaCO₃–based FC formulations and their friability performance in FCTs in relation to tablet shape and composition variables. Two different core formulations were compared: a simplistic “conventional” placebo formulation and a formulation containing a high loading of Hypromellose Acetate Succinate – LG (HPMCAS), which mimics oral drug formulations containing a spray-dried dispersions (SDDs), as SSD enabled oral formulations grown in popularity.

Methods: Two core tablet placebo formulations were employed: a conventional formulation consisting of 96% 1:1 Microcrystalline Cellulose PH-102 (MCC PH-102) and Lactose FastFlo-316, 3% Croscarmellose Sodium (CCNa) as disintegrant, and 1% Magnesium Stearate (MgSt) as lubricant. The second formulation aimed to mimic a formulation containing a high loading of SDDs. This second placebo formulation, denoted “HPMCAS-based”, consisted of 50% HPMCAS-LG, 40% 1:1 MCC PH-102 and Lactose FastFlo-316, 9% CCNa as disintegrant, 0.5% Colloidal Silicone Dioxide as glidant, and 0.5% MgSt as lubricant. These core blends were compressed using a Korsch XM-12 Tablet Press with specialty tooling of varied tablet geometries. Geometry characteristics varied in cup depth (1.1 mm, 1.0 mm, and 0.9 mm) and aspect ratio (Length:Width, 194:97, 172:97), resulting in six unique geometries (Figure 1). All tablet conditions were film coated with a Thomas COMPULAB coater and utilized with one of seven different FCs, resulting in eighty-four different FCT conditions. All FC formulations used are commercially available. Six of the FCs examined all used calcium carbonate (CaCO₃) as an opacifier and were considered TF FCs. Only one of the seven FCs evaluated utilized titanium dioxide (TiO₂) as an opacifier and was used as a control. The aforementioned six TF FCs varied in polymer base and composition, ranging from: HPMC, HPMC+ Hydroxypropyl Cellulose (HPC), Polyethylene Glycol – Polyvinyl Alcohol Copolymer (PEG-PVA), Polyvinyl Alcohol (PVA), PEG+HPMC, and Copovidone (PVPVA). FCTs were tested using USP Friability standards on a Key FT-400 friabilator. Ten FCTs from each condition were selected at random and examined for any FC defects after a certain number of drops recorded. Friability performance was evaluated as the number of tablets out of ten exhibiting any FC damage (chipping, flacking, etc.) and denoted as defect rate.

Results: First, when holding tablet shape and FC variables constant, HPMCAS-based placebo core composition FCTs exhibited significantly better friability performance. These FCTs showed less damage at the same number of drops compared to FCTs with the conventional placebo core formulation (Figure 2). This finding indicates that the inclusion of HPMCAS in the core formulation positively affects the friability performance of the FCTs. Secondly, when holding core composition and FC variables constant, it was observed that FCTs with a smaller aspect ratio demonstrated better friability performance compared to those with a larger aspect ratio (Figure 2). Moreover, FCTs with a larger cup depth showed better friability performance than those with a smaller cup depth. From a tablet shape perspective, the optimal friability performance was achieved with tablets having a small aspect ratio and large cup depth, image “944” (Figure 1). Thirdly, it was evident that the type of coating had a significant influence on the friability performance of the FCTs (Figure 3). The FCTs with a PVPVA-based coat exhibited the poorest performance, with major FC defects observed after only 100 drops. The PEG-PVA-based coats showed approximately 50% of the FCTs displaying defects at 1,000 drops. Similarly, one of the HPMC-based TF coats and the HPMC-based TiO₂-containing coat also exhibited considerable defects at 1,000 drops. In contrast, FCTs with a PVA-based coat displayed no damage at 1,000 drops and showed no signs of damage until 3,000 drops. A similar observation was made for both the HPMC+HPC and PEG+HPMC-based coat, with tablets not showing any damage up to 4,000 drops.

Conclusion: This study identifies film-coating formulations that not only meet acceptable standards but also surpass the friability performance of the TiO₂-based gold standard. Overall, the study findings emphasize the importance of considering the core tablet formulation, tablet shape, and film coating composition in determining the friability performance of FCTs. Tablets containing HPMCAS in the core formulation and mimicking SDD-based formulations exhibited improved friability performance. Additionally, tablets with a smaller aspect ratio and larger cup depth showed better friability performance. The choice of the film coating composition also played a significant role, with PVPVA-based coatings displaying the poorest friability performance, while HPMC+HPC, PEG+HPMC, and PVA-based coatings offered better resistance in friability testing.

Acknowledgements: The main author of this work acknowledges Amy Neusaenger for her diligent work in carrying this study out as part of her internship position. The main author also acknowledges and thanks our internal film coating subject matter experts for their valuable insights into developing this project.

Figure 1: Tablet Geometry Summary

Figure 2: Quantified Defect Rate after 1,000 Standard USP Friability Drops. Friability of film coated placebo tablets as a function of Cup Depth (mm) and Aspect Ratio (L/W). Defect rates are shown for FCTs with a A) Conventional and B) HPMCAS-based placebo core formulation.

Figure 3: Quantified Defect Rate after 1,000 Standard USP Friability Drops on TF FCTs.