(T1430-06-40) Design and Evaluation of a Taste-Masked Sustained Release Effervescent Formulation of Caffeine

Purpose: Caffeine has been widely studied for its effects on alertness, cognitive function, and physical performance. As caffeine consumption increases, exploring innovative ways to enhance efficacy and minimize side effects is important. One approach is the development of sustained release formulations, delivering caffeine gradually over time. This could lead to sustained cognitive and physical performance while alleviating adverse side effects, such as jitteriness and insomnia, improving overall consumer experience. The objective of this research was to develop a sustained release system using a hydrophobic polymer, ethyl cellulose (Ethocel®), which also effectively mitigated API bitterness. The final dosage form was an effervescent tablet, maximizing consumer experience and promoting hydration, which is also essential to overcome caffeine diuretic effects.

Methods: The study was executed in three steps: 1. Caffeine granulation: Fluidized bed granulation was used to increase caffeine particle size and formulation compactibility. Particle size is also important to ensure good flow during the coating process. Caffeine granules were prepared using following procedure: caffeine, fumed silica, and sorbitol were sifted prior to adding to the fluid bed. Povidone K30 was dissolved in water and used as granulation liquid via top spray. Drying process was done until the moisture was not more than 1%. 2. Granule coating with ethyl cellulose: caffeine granules were coated as follows: ethyl cellulose standard 10 was dissolved in a hydroalcoholic mixture of ethanol-water (9:1). Triethyl citrate was dispersed in part of the hydroalcoholic mixture (9:1) with homogenizer prior mixing into ethyl cellulose solution. The coating dispersion was filtered with mesh 60 before spraying onto caffeine granules. 3. Effervescent tablet formulation: caffeine sustained release granules, citric acid, sodium bicarbonate, sucralose, cola flavor, fumed silica, and polyethylene glycol 6000 were mixed and then compacted using 25 mm round tooling. Effervescent tablet physical parameters were measured and recorded.

Results: The water quantity required during fluid bed granulation was found to be 29.3%.w/v or w/w Preliminary trials were performed using several polymers, such as carbomer, methacrylate based, and ethyl cellulose with the latter showing better performance on active release. This is consistent with the theory that the hydrophobic polymer would act better as a physical barrier as it would not easily dissolve. The weight gain during coating process was 40% to ensure that granule dissolution profile would reach 8 hours. The caffein granules had a bulk density of 0.332 g/ml, tapped density of 0.39 g/ml, Carr's Index of 15%, and Hausner Ratio of 1.18, indicating good flow characteristics. Study of particle size effect on sustained release also was performed with the results showing granules with 841 µm size having slower release compared to smaller particle size. Physical testing results for effervescent tablets are within specifications with tablet thickness 4.5 – 4.8 mm, tablet hardness 4 – 7 kP, tablet weight 2900 – 3200 mg and disintegration time below 3 minutes.

Conclusion: The successful incorporation of sustained release caffeine granules into an effervescent tablet matrix presents a viable strategy to enhance therapeutic efficacy while potentially reducing side effects. The use of hydrophobic polymer coating enabled a controlled release profile extending up to 8 hours, effectively prolonging caffeine’s stimulant effect. The formulated tablets exhibited adequate hardness and acceptable disintegration time, supporting their suitability for oral administration. These findings suggest that effervescent tablets can serve as a consumer-friendly platform for sustained caffeine delivery. Further investigation into long-term effects and consumer acceptability will be instrumental in advancing this formulation toward commercialization, paving the way for enhanced caffeine products in the market.

References: 1. Khan, M. I., & Ranjha, M. F. (2016). "Ethyl cellulose-based sustained release drug delivery systems: A review." Journal of Drug Delivery Science and Technology, 31, 50-58.
2. Kumar, S., & Kumar, A. (2014). "Effervescent tablets: A review." International Journal of Pharmaceutical Sciences and Research, 5(7), 2537-2545.


Figure 1: Caffeine Released as a Function of Time


Figure 2: Tablet Mechanical Strength - % Elongation


Figure 3: Tablet Mechanical Strength - Peak Stress