Purpose: Orally disintegrating tablets have become popular in recent years due to their improved compliance and greater patient preference. Companies in the nutraceutical and generic drug industries would like to take this opportunity for their product line extension by developing rapidly disintegrating tablets. However, the most available formulations for ODT are designed for low drug load with low compression forces. The current work is focused on studying the rapidly disintegrating formulations of vitamin B complex tablet, using Ludiflash®; a co-processed excipient consisting of mannitol, crospovidone (Kollidon® CL-SF) and polyvinyl acetate (Kollicoat® SR30D).
The slightly sweet taste of mannitol may help to minimize the bad taste of vitamin B. The smoothness of the super disintegrant Kollidon®CL-SF provides a better mouth feel while melting down the tablet. The insoluble binder Kollicoat® SR30D helps to create channels between the particles to promote water penetration. The highly porous microstructure of Ludiflash® may be suitable for preparing nutraceutical formulations with rapid disintegration.
Methods: There are several challenges in formulating Vitamin B complex rapidly disintegrating tablets.
1. Unfavorable vitamin taste. Taste-masking is needed to make it consumer-friendly
2. Very poor flowability and compressibility.
3. Hard to completely disperse the agglomerated B2 and B12 particles together with the other excipients, which makes the surface of the final tablet poor with yellowish spots
4. The drug load, including sweeteners and flavor is more than 53 mg per tablet. The rapid disintegration should be achieved in less than one minute with hardness about 90~110 N for packaging into a regular bottle.
The trial started with a simple direct compression formulation of Ludiflash® with sweetener / flavor. All the ingredients were weighed into a V-blender, and blending for 45 minutes before compression. The blend had bad flowability (Flodex index = 24) with strong vitamin taste and yellow/pink spots. The disintegrating time was much longer than one minute when the hardness was 90 ~110 N.
To improve the tablet properties, additional Kollidon® CL-SF was added, and the effect of ingredient blending sequence and blending time was studied. The ratio of ODT excipient (Ludiflash®) and disintegrant (Kollidon® CL-SF) was adjusted to study the relationship between tablet hardness and disintegrating time.
Results: Studies revealed the Kollidon® CL-SF has a unique function to disperse the agglomerated powders and improve the flowability. The agglomerated Vitamin B2 and B12 was first blended with Kollidon® CL-SF for 15 minutes before blending with the other ingredients. The yellow / pink spots disappeared, resulting in tablets with a uniform yellowish color. The flowability measured by Flodex index reduced to 14, indicating an improvement of flowability. Blending and dispersing of the fine Kollidon® CL-SF particles was just like the dry powder coating of vitamins, which helped the particle flow.
The same approach of dry powder coating was also applied on blending the taste blocker (NAT FLV), sucralose and orange flavor with the bitter vitamins (vitamins B5, and B6) before blending with Ludiflash®. The five-step blending procedure was summarized in Figure 1.
The final blend has no vitamin bitterness, while the flavor can be slightly adjusted by the ratio of sucralose and citric acid.
During the test, the amount of Kollidon® CL-SF was gradually increased to study the tablet properties. Since crospovidone is a super disintegrant as well as a binder, increasing the Kollidon® CL-SF amount not only reduces the disintegrating time, but also improves the hardness of the tablets. Under the same compression force (around 9 KN), increasing Kollidon® CL-SF amount from 5% to 10% significantly increased the hardness from 56 N to 110 N, while the disintegrating time reduced from 78 seconds to 58 seconds.
To further increase the tablet hardness, 10 mm convex tablet punches were used instead of the flat punches, which are popular in making ODTs.
The effect of lubricant was also studied. The disintegration time with 1% sodium stearyl fumarate was 52 seconds, as compared to 58 seconds with 1% magnesium stearate. The tablets hardness slightly increased when sodium stearyl fumarate was used.
The tablets which met both requirements on hardness and disintegrating time had a low friability of 0.16% with a creamy mouth feeling.
It is noticed that adding more Ludiflash® will further shorten the disintegrating time to less than 30 seconds,
Conclusion: The rapid disintegrating vitamin B complex tablets with high drug load and high tensile strength can be achieved by direct compression using Ludiflash® and Kollidon® CL-SF. Kollidon® CL-SF has a dual function as disintegrant and binder for rapid melting tablets. It also has an unusual ability to uniformly disperse the agglomerates within a blend. The sweetness of mannitol in Ludiflash®, together with the flavor and sweeteners, has successfully overcome the bad vitamin taste. The combination of Ludiflash® and Kollidon® CL-SF yields a hard tablet, which can be quickly disintegrated in saliva with a smooth and creamy mouth-feel.