(T1330-04-19) Non-Gelatin Film Coatings for Formulating Easy-to-Swallow Tablets

Purpose: About 40% population has trouble swallowing medicines [1]. Gelatin-based tablet coatings facilitate ease of swallowing; however, they could cause stomach upset, heartburn, allergies, and possibly interaction with the active pharmaceutical ingredient (API) [2]. The animal origin of gelatin variability in molecular weight, bloom strength, and functional properties as well as raising BSE/TSE concerns [3]. Aqueous solutions of gelatin can cause foaming during handling and may result in stability issues for moisture sensitive APIs. This study focuses on the use of compendial Kollicoat® IR (PEG-PVA graft copolymer - USP, EP) and Kollicoat® Protect (Kollicoat® IR + PVA), polymeric coating as effective alternatives to gelatin-based coating in formulating “easy-to-swallow” tablets. Additionally, such non-gelatin coatings offer good oxygen and moisture barrier properties without the risk of development of peroxides during storage.

Methods: Core tablet(s) (680 mg) consisting of 250 mg acetaminophen, 250 mg aspirin, 65 mg caffeine, povidone, lactose monohydrate, microcrystalline cellulose, and magnesium stearate, were manufactured by granulation followed by lubrication and compression. They were seal coated using PEG-PVA graft copolymer and PVA (6:4) (3% weight gain) followed by second layer of PEG-PVA graft copolymer (5% weight gain), both at 60 °C inlet temperature. Tablet slip performance, which evaluates ease of swallowing, was characterized using the method derived from static and dynamic friction test [4]. Each tablet was dipped into water for 1sec and placed on a Formica® laminated flat surface at different slope angles to evaluate the distance that each tablet slides down on the surface (Figure 1). Water vapor transmission rate (WVTR) and oxygen gas transmission rate (OGTR) were determined using isolated films of comparable thicknesses (70–75 μm), prepared using a Coatmaster™ (Figure 2). To prevent sedimentation during the drying phase, the dispersions were cast in 3-4 thin layers (one on top of the other) depending on the pigment content and the film density. The WVTR of PEG-PVA graft copolymer and PVA (6:4) was evaluated previously vs. PVA and HPMC using ASTM F 1249-20 [5] wherein a dry and wet chamber of known temperature and humidity are separated by the barrier film to be tested. Water vapor passing through the film mixes with gas in the dry chamber and is carried to a pressure modulated IR sensor, which generates an electrical signal proportional to the moisture content. The OGTR of PEG-PVA graft copolymer and PVA (6:4) and PEG-PVA graft copolymer were evaluated vs. PVA, HPC EF, and HPMC, using ASTM D 3985-17, in which the test sample is equilibrated in an environment with < 1% relative humidity. The specimen is then mounted as a sealed semi-barrier between two chambers at ambient atmospheric pressure. One chamber is purged by a stream of nitrogen and the other chamber contains oxygen. As oxygen permeates through the film into the nitrogen carrier gas, it is transported to the coulometric detector where it produces an electrical current, the magnitude of which is proportional to the amount of oxygen flowing into the detector per unit time.

Results: PEG-PVA graft copolymer and PVA (6:4) seal-coating with high pigment concentration provides good moisture barrier properties, ideal for improving stability of moisture-sensitive APIs [6]. It can hold up to 75% pigment relative to the polymer, which is significantly higher than HPMC based coatings and easier to formulate than PVA based coatings. In addition, this coating exhibits excellent oxygen barrier properties. Tablets coated with PEG-PVA graft copolymer and PVA (6:4) alone showed improved slip performance vs. uncoated tablets which didn’t slide at a slope of 45^o or lower. However, it was not equivalent to the marketed gelatin-coated tablet, possibly due to friction generated by talc present in the PEG-PVA graft copolymer and PVA (6:4) coating. To further improve the slip performance, a second coating layer of PEG-PVA graft copolymer was applied over the PEG-PVA graft copolymer and PVA (6:4) coated tablets. PEG-PVA graft copolymer is a water-soluble film former for instant release coatings. It is an excellent wet binder, and easily processed due to low solution viscosity (260 mPas of 25% solution), and very fast dissolution. When stored over 18 months under accelerated stability storage conditions, this polymer did not generate any peroxides (Data not shown). The two-layer coated tablets showed improved slip performance (slope as low as 15^o) compared to gelatin coated marketed tablets. The minimum sliding force for the two-layer coated tablet is also lower than that of gelatin-coated market standard (Figure 3).

Conclusion: Gelatin-based tablet coatings use complicated manufacturing process and present issues with handling, stability, and consumer acceptance. The proposed dual-layer coated tablets (copolymer of PEG-PVA graft copolymer and PVA (6:4) followed by PEG-PVA graft copolymer) may serves as an improved non-gelatin alternative for greater ease of swallowing. Additionally, it offers better moisture protection in contrast to a standard film-coating. Further studies in clinical set up will help confirm the ease of swallowing and patient compliance.

References: [1] DeRoche, C., Macclaren, G., & Sonies, B. (2000). Pill swallowing in America: A national survey of adults. In Poster, Dysphagia Research Society Annual Meeting, Savannah GA.
[2] https://www.rxlist.com/supplements/gelatin.htm
[3] Lis DM, Baar K. Effects of Different Vitamin C–Enriched Collagen Derivatives on Collagen Synthesis. International Journal of Sport Nutrition and Exercise Metabolism. 2019;29(5):526-531.
[4] Jeffrey Gimbel, Daniel to and Ali Rajabi-Siahboomi. Investigation of Optimum Coating Conditions for an Easy Swallow Coating System. Colorcon, Inc. AAPS 2018.
[5] T. Agnese, T. Cech and V. Geiselhart. 8th PBP World Meeting (2012); Istanbul, Turkey.
[6] T. Agnese, T. Cech, and V. Geiselhart. PBP World Meeting (2010); Valletta, Malta, G-EMP/MD277.

Figure 1: Tablet slippery performance comparison at 30 degrees (left) and 15 degrees (right) slope.

Figure 2: A) Water vapour permeation of Kollicoat Protect, PVA, HPMC and standard HPMC coating; B) Oxygen gas permeation of Kollicoat Protect, Kollicoat IR, PVA, HPC EF and HPMC.

Figure 3: Minimum force to slide comparison of uncoated, Kollicoat Protect coated, Kollicoat Protect + IR coated, and market standard tablets.