The Most Efficient Directly Compressible Excipient for Effervescent Tablets Formulation

Situation

Effervescent formulations are produced as solids with intent to transform into a liquid form just before administration. In water, effervescent reaction produces carbon dioxide (CO2) – the fizzing that appeals to consumers along with flavorful additives, providing multi-sensory experience. Effervescent formulations are gaining popularity in prescribed and over-the-counter medications, dietary supplements, as well as energy products. Carbonated liquid dosage forms can speed up adsorption and bioavailability, leading to faster onset of action. Liquid dosage forms are also better tolerated by consumers with dysphagia (children or elderly). Active ingredients upsetting to stomach or difficult to digest, pH-sensitive, or that requiring a large dose may also benefit from administration in a liquid form. However, formulation production as liquids is not practical and is subject to accelerated degradation. In addition, moisture, light, and oxygen sensitive actives may take advantage of effervescent manufacturing and storage requirements. Effervescent reaction is highly sensitive to any moisture; thus formulations are designed to contain less than 1% of residual moisture, they are typically produced in dehumidified environments (10% RH), and packaged in either aluminum or plastic tubes with desiccants or heavy-gauge aluminum foil packets. It is advisable to invest in appropriate packaging for a proper shelf life of effervescent products. Majority of effervescent products are tablets. Effervescent tablets are mainly made by a granulation process (labor and energy intensive). The growing pipeline of commercially available direct compressible excipients provides an opportunity for effervescent tablet production by cost-effective direct compression processes. Binders in effervescent tablets should be water-soluble but at the same time non-hygroscopic, as well as bring the tablet hardness to appropriate handling point. Polyols (sugar alcohols) are frequently used as filler/binders. Sorbitol is the most commonly used polyol in effervescent tablet formulation. However, bulk sorbitol powder contains residual moisture and its high aqueous solubility restricts use of water-based granulation process. Lactose (milk sugar) is also offered commercially as effervescent filler, though about 65% of the human population has a reduced ability to digest lactose.

Challenge

Water-soluble, non-hygroscopic, digestible, and direct compressible filler/binder for effervescent tablet manufacturing is in great need.

Solution

SweetPearl® P300 DC is a granulated maltitol specifically designed for direct compression. Distinctive physicochemical properties of maltitol make it an excellent excipient for effervescent formulations. It is low hygroscopic, chemically stable, inert, but at the same time, water soluble. Nutritionally, this non-sugar sweetener has good digestive tolerance.

SweetPearl® P300 DC maltitol key benefits:

• Key physicochemical properties: good compressibility and flowability; high density (allowing tablet to stay at the bottom of the glass for faster disintegration); water-soluble; less hygroscopic (ability to attract moisture) than other polyols; chemically inert (does not easily react with other compounds).
• Nutritional characteristics: sweetness equivalent to sucrose that combines especially well with fruit flavors; cooling effect; non-cariogenic – does not contribute to tooth decay, hence it is not metabolized by oral bacteria; good gastrointestinal tolerance.
• Product information: commercially produced of high purity from natural sources; meets regulatory requirements of major markets for pharmaceutical and dietary applications.

Results

Tablets (weight of 2400 mg) formulated with SweetPearl® P300 DC (direct compressible maltitol) were compressed in a Korsch XP1 tablet press to around 100 N hardness. Tablets passed friability test. Tablets were designed to stay at the bottom of the glass throughout the effervescent period and completely effervesced in less than 2 minutes, providing a clear solution in 200 mL of water. Stability of active ingredient ascorbic acid (Vitamin C), prone to oxidation and hydrolysis, in the effervescent tablets stored in plastic bottles and aluminum pouches under standard (25°C/60% RH) and accelerated (40°C/75% RH) conditions up to 6 months, was superior in tablets formulated with SweetPearl® P300 DC maltitol in comparison to tablet analog formulated with sorbitol as a filler.

Formulation Example

Conclusion

SweetPearl® P 300 DC maltitol contains the features desired to make an effervescent tablet solution attractive and palatable to patients, stable in the formulation, and quickly dissolvable, all in a cost-effective and efficient manner.

References

1. Popescu C, Zhou L, Nienow C, Lefevre P. Ascorbic Acid Stability in Effervescent Tablets Formulated with Direct Compressible Maltitol. AAPS Annual Meeting, San Diego, California, November 2014. 

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