Jiantao Zhang, Yidan Lan, Ashish Joshi,Nigel Langley
Coenzyme Q10 (CoQ10) is an effective antioxidant that plays a fundamental role in cellular bioenergetics, offers cardiac health benefits, and prevents cell damage from free radicals. However, many commercial CoQ10 dietary supplements are capsule products that can be hard to swallow for geriatric patients1. Orally disintegrating tablets (ODTs) offer nutraceutical manufacturers a solution for patients that experience dysphagia and other swallowing difficulties when taking solid oral dosage products. ODTs dissolve rapidly in contact with saliva, eliminating the need to chew or swallow the tablet, which can improve compliance among the geriatric population. The drawback of poorly formulated ODTs is that they often have a sandy/gritty mouthfeel and lack the organoleptic properties (taste and aftertaste) that patients desire. To fully meet consumers’ needs and improve patient compliance, a CoQ10 ODT should disintegrate quickly without compromising taste and mouthfeel.
This article describes a study that compared a commercial CoQ10 ODT product with a formulation designed to exhibit improved taste and disintegration characteristics.
Reformulation methods and results
The reformulated ODTs were of similar size and shape as the commercial ODT using 12-millimeter punches with a compound cup profile on a Korsch XL 100 tablet press. As Photo 1 shows, the surface of the commercial tablets had a significant number of yellow spots that may have been a result of insufficient blending. Because the reformulated ODT formulation was initially blended for 20 minutes with Kollidon CLSF, which is known for dispersing agglomerated powders and improving flowability [2], the reformulated product had a smoother, more uniform tablet surface than the commercial product.
Tablet hardness was measured using a Key International HT-300 tablet tester. Figure 1 shows the hardness of the reformulated ODTs pressed at several different compression forces versus the hardness of the commercial CoQ10 ODT (88 newtons). When the compression force was increased from 5 to 20 kilonewtons, the hardness of the reformulated CoQ10 ODT increased from 60 to 150 newtons. A compression force of 10 kilonewtons resulted in a hardness of 95 newtons, which was close to the 88-newton tablet hardness of the commercial product. Increasing the percentage of Kollidon CLSF in the reformulated ODTs increased the tablet hardness, because the excipient also functions as a direct compression binder [3]. For example, at 10 kilonewtons of compression force, 10 percent Kollidon CLSF produced ODTs with a hardness of 89 newtons while 15 percent Kollidon CLSF produced ODTs with a hardness of 95 newtons.
Next, the friability of the ODT products was measured using a model 10801 Vankel Vanderkamp friability tester. Reformulated ODTs made using 5 kilonewtons of compression force produced 0.5 percent friability, similar to reformulated ODTs pressed at several different compression forces versus the hardness of the commercial CoQ10 ODT (88 newtons). When the compression force was increased from 5 to 20 kilonewtons, the hardness of the reformulated CoQ10 ODT increased from 60 to 150 newtons. A compression force of 10 kilonewtons resulted in a hardness of 95 newtons, which was close to the 88-newton tablet hardness of the commercial product. Increasing the percentage of Kollidon CLSF in the reformulated ODTs increased the tablet hardness, because the excipient also functions as a direct compression binder [3].
For example, at 10 kilonewtons of compression force, 10 percent Kollidon CLSF produced ODTs with a hardness of 89 newtons while 15 percent Kollidon CLSF produced ODTs with a hardness of 95 newtons. Next, the friability of the ODT products was measured using a model 10801 Vankel Vanderkamp friability tester. Reformulated ODTs made using 5 kilonewtons of compression force produced 0.5 percent friability, similar to that of the commercial ODT (0.4 percent). At 10 to 20 kilonewtons of compression force, the friability of reformulated ODTs was much lower than that of the commercial ODT, ranging from 0.13 percent to 0.03 percent (Figure 2).
This low friability is a result of the strong binding effect of Kollidon CLSF, which generates a robust ODT that can withstand handling and transportation [3]. Finally, the ODTs’ disintegration times were compared using water as a medium. As shown in Figure 3, the reformulated ODTs disintegrated in 10 to 40 seconds, depending on the compression force, while the commercial ODT took 42 seconds to disintegrate. Kollidon CLF can also be used as a disintegrant in this formulation at 15 percent, resulting in similar properties as Kollidon CLSF at 15 percent; however, the super-fine particle size of Kollidon CLSF offers an exceptionally creamy mouthfeel, which makes it ideal for use in ODT formulations.
Panel in-vivo tests showed that the reformulated ODT had a smooth, pleasant, and creamy mouthfeel; dissolved quickly; and was easy to swallow. In comparison, the commercial ODT product had a sandy/gritty texture, and a scratchy feel on the tongue, mouth, and throat that persisted long after swallowing.
Conclusion
The reformulated CoQ10 ODTs were the same dosage strength and of a similar size, weight, and shape as the commercial CoQ10 ODTs but demonstrated increased hardness, decreased friability, and faster disintegration. The addition of Kollidon CLSF improved the disintegration time, mouthfeel, and uniform dispersion of colored ingredients, preventing a speckled tablet surface. The improved organoleptic properties and physical appearance of the reformulated CoQ10 tablets may help to greatly improve patients’ product experience as well as compliance.
References
1. P Desai, C Liew, P Heng; Review of Disintegrants and the Disintegration Phenomena, J Pharma Sci, 2016, 105, 2545.
2. Y Lan, A Joshi, J Shang, N Langley; Formulation of rapidly disintegrating tablets with high bitter drug load and high tensile strength, AAPS 2018, Washington DC.
3. F Bang, T Cech, V Geiselhart; Investigating the impact of crospovidone particle size on the characteristics of an orally disintegrating tablet, 4th Conference on Innovation in Drug Delivery, 2016, Antibes, France.
Jiantao Zhang, Yidan Lan, and Ashish Joshi are technical service managers, and Nigel Langley is a director of technical service at BASF, Tarrytown, NY (800 526 1072, www.basf.com).