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Pharmaceutical development of effervescent tablets
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Pharmaceutical development of effervescent tablets

Introduction

Pharmaceutical development of effervescent tablets focuses on creating oral dosage forms that dissolve rapidly in water and deliver active ingredients in a convenient and patient-friendly manner. Effervescent tablets contain an acidic component, commonly citric acid, and an alkaline component such as sodium bicarbonate. When these substances come into contact with water, they generate carbon dioxide and form a solution that patients can drink easily. As a result, effervescent formulations often improve drug dissolution, accelerate absorption, and enhance patient compliance. In addition, they provide an attractive option for pediatric, geriatric, and dysphagic patients who struggle to swallow conventional tablets.

The use of pellet technology further advances the pharmaceutical development of effervescent tablets. Pellets can separate incompatible ingredients, improve content uniformity, and increase formulation stability. Moreover, pellet-based systems can mask unpleasant tastes and protect sensitive active ingredients from degradation. Consequently, they can improve both product quality and the patient experience. These advantages make pellets an increasingly valuable platform for modern effervescent formulations.

Pharmaceutical Development of Effervescent Tablets Containing Acetylsalicylic Acid, Paracetamol, and Ascorbic Acid

The publication [1] entitled Pharmaceutical Development of Composition of Effervescent Tablets with Acetylsalicylic Acid, Paracetamol, and Ascorbic Acid presents the development of a fixed-dose combination effervescent tablet containing 300 mg acetylsalicylic acid, 200 mg paracetamol, and 300 mg ascorbic acid. The authors aimed to create a high-quality formulation for the Ukrainian pharmaceutical market while ensuring therapeutic efficacy, patient acceptability, and manufacturing feasibility.

To achieve this goal, the researchers applied a Quality-by-Design (QbD) approach. First, they defined the Quality Target Product Profile and identified critical quality attributes. Next, they investigated the influence of different excipients on powder flow, compressibility, tablet strength, disintegration behavior, and sensory properties. Furthermore, they used statistical methods, including regression analysis and utility-function optimization, to determine the most suitable formulation.

Excipient Groups and their Effects on Technological Performance

The study evaluated several excipient groups and their effects on technological performance. The researchers measured bulk density, tapped density, Carr’s index, flowability, hardness, friability, mass uniformity, and dissolution characteristics. In addition, they assessed organoleptic properties because consumer acceptance plays an important role in effervescent products. Among other excipients. microcrystalline cellulose micropellets (CELLETS® 100), are often utilized to enhance tablet hardness, which is frequently a weak point in effervescent systems [2,3].

A major outcome of the study was the identification of an optimal ratio between anhydrous citric acid and sodium bicarbonate. The authors determined that a ratio of 1:1.312 provided efficient carbon dioxide generation and rapid tablet disintegration. Consequently, the formulation achieved fast dissolution while maintaining acceptable mechanical strength. The researchers also found that the interaction between sorbitol and the binder system significantly influenced tablet performance. Therefore, careful excipient selection proved essential for balancing stability, manufacturability, and patient experience.

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Optimized Formulation

The optimized formulation contained acetylsalicylic acid, paracetamol, ascorbic acid, anhydrous citric acid, sodium bicarbonate, lactose, polyvinylpyrrolidone, crospovidone, sorbitol, sodium saccharin, lemon flavoring, and sodium stearyl fumarate. Subsequently, the team evaluated the final product against pharmacopoeial requirements and predefined quality criteria. The tablets met all quality specifications and demonstrated suitable technological characteristics.

The authors also conducted stability studies under long-term storage conditions. The results showed that the formulation remained stable for at least 24 months when stored in protective aluminum-polymer packaging. Therefore, moisture-resistant packaging emerged as a critical factor for preserving product quality. Overall, the study demonstrated that a systematic QbD strategy can successfully support the pharmaceutical development of effervescent tablets and generate a robust, patient-oriented product.

Active Pharmaceutical Ingredients

Acetylsalicylic Acid

Acetylsalicylic acid (ASA), commonly known as aspirin, is a non-steroidal anti-inflammatory drug (NSAID). It provides analgesic, antipyretic, anti-inflammatory, and antiplatelet effects. The compound is generally classified as a Biopharmaceutics Classification System (BCS) Class I drug because it exhibits high solubility and high permeability. Clinicians use ASA to treat pain, fever, inflammatory conditions, and cardiovascular disorders. In effervescent formulations, ASA dissolves rapidly and may reach therapeutic concentrations faster than conventional tablets. As a result, patients can experience quicker symptom relief.

Paracetamol

Paracetamol, also known as acetaminophen, is an analgesic and antipyretic agent. It is commonly classified as a BCS Class III drug due to its high solubility and relatively low permeability. Physicians frequently prescribe paracetamol for mild-to-moderate pain and fever. In this combination product, paracetamol complements the analgesic action of acetylsalicylic acid. Furthermore, its established safety profile supports its widespread use in over-the-counter therapies. The effervescent dosage form improves dissolution and simplifies administration for many patients.

Ascorbic Acid

Ascorbic acid, or vitamin C, is a water-soluble vitamin with strong antioxidant properties. It generally displays characteristics associated with high solubility and high permeability. Therefore, it is often considered to exhibit BCS Class I-like behavior. Clinicians use ascorbic acid to prevent or treat vitamin C deficiency and to support immune function. In addition, the antioxidant activity of vitamin C may complement the therapeutic effects of analgesic combinations. Effervescent formulations are particularly suitable for ascorbic acid because they provide rapid dissolution and pleasant sensory characteristics.

Conclusion and Outlook

The pharmaceutical development of effervescent tablets offers significant opportunities to improve oral drug delivery. The reviewed study demonstrates how a structured Quality-by-Design approach can optimize formulation performance, product stability, and patient acceptance. Moreover, the combination of acetylsalicylic acid, paracetamol, and ascorbic acid provides a multifunctional therapy for pain and fever management. The results also highlight the importance of excipient selection, effervescent component ratios, and protective packaging.

Looking ahead, pellet-based technologies could further strengthen the pharmaceutical development of effervescent tablets. For example, pellets can improve stability, separate incompatible ingredients, and enable modified-release profiles. In addition, they can support the development of personalized medicines and complex combination products. Consequently, pellet-containing effervescent tablets will likely play an increasingly important role in future pharmaceutical innovation.

References

[1] O. Panysheva, Pharmaceutical Science Advances 4 (2026) 100123. doi: 10.1016/j.pscia.2026.100123

[2] V. Nikam, et al., Design, development and physicochemical evaluation of effervescent tablets of antihistamine drug
Int. J. Drug Deliv.Technol., 13 (4) (2023), pp. 1520-1526, 10.25258/ijddt.13.4.61

[3] P. Kaur, et al., Formulation, development and evaluation of effervescent tablet of green tea (Camellia sinensis), Cent. Nerv. Syst. Agents Med. Chem., 25 (4) (2025), pp. 579-590, 10.2174/0118715249333134250116112001

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Multilayered pharmaceutically active compound-releasing microparticles in a liquid dosage form

Introduction to Multilayered Pharmaceutically Active Compound Technology

Multilayered pharmaceutically active compound-releasing microparticles in a liquid dosage form represent an innovative approach to oral drug delivery. This technology combines the benefits of coated pellets with the convenience of liquid administration. Effervescent tablets are solid dosage forms that release carbon dioxide when they dissolve in water. This reaction results from the interaction between an acid source, such as citric acid, and a carbonate or bicarbonate salt. Patients consume the resulting solution or suspension immediately after preparation. Consequently, effervescent tablets improve ease of administration and often enhance patient compliance.

Pellets play an increasingly important role in modern effervescent tablet formulations. Unlike conventional powder blends, pellets can carry individual functional coatings that protect active pharmaceutical ingredients (APIs) from degradation. In addition, pellets can separate incompatible ingredients within the same dosage form. They also improve taste masking and enable modified-release properties. As a result, formulators can develop more stable and effective products. Furthermore, pellet-containing effervescent tablets often reduce gastrointestinal irritation and improve dose uniformity. These advantages benefit both the final pharmaceutical product and the patient.

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Summary of EP3117824A1

The European patent EP3117824A1 describes a drug delivery platform based on multilayered pharmaceutically active compound-releasing microparticles suspended in a liquid dosage form. The invention addresses a major challenge in pharmaceutical formulation. Many controlled-release and enteric-coated particles lose functionality when they remain in contact with water for extended periods. Therefore, maintaining stability during storage becomes difficult.

The patented technology uses microparticles that contain an API-loaded core surrounded by multiple functional coating layers. A controlled-release or enteric coating forms the intermediate layer. An additional outer protective layer surrounds this coating. The inventors designed this outer layer from a combination of hydrophilic and hydrophobic materials. Consequently, the layer protects the underlying release-controlling membrane from premature exposure to the liquid environment.

During storage, the protective coating minimizes drug leakage and preserves the integrity of the controlled-release system. As a result, the microparticles maintain their desired release characteristics for extended periods. Once the patient administers the formulation, the outer coating dissolves rapidly in the stomach. Subsequently, the underlying controlled-release coating resumes its intended function. This mechanism allows the formulation to deliver the API at a predefined location or rate within the gastrointestinal tract.

The invention offers particular advantages for drugs that require modified release, intestinal targeting, or protection from acidic gastric conditions. In addition, the technology supports the development of patient-friendly liquid formulations. This feature benefits pediatric, geriatric, and dysphagic patients who often struggle to swallow tablets or capsules. Overall, the patent combines the flexibility of pellet-based drug delivery with improved stability in aqueous dosage forms. Therefore, it represents an important advancement in oral pharmaceutical technology.

Impact of MCC spheres in this Patent

In EP3117824A1, CELLETS® or similar spherical starter cores serve as the fundamental substrate for producing the multilayered pharmaceutically active compound-releasing microparticles. These inert pellet cores, commonly composed of microcrystalline cellulose, provide a highly uniform and mechanically stable surface onto which drug-containing layers and subsequent functional coatings can be applied with high precision.

Their excellent sphericity promotes uniform coating thickness, which is critical for achieving reproducible controlled-release performance and minimizing variability between pellets. Furthermore, Cellets enable high drug loading while maintaining robust processing characteristics during fluid-bed coating operations.

Pellet size also plays an important role in the final product performance. Smaller pellets, typically in the range of 100–500 µm (such as CELLETS® 100, 200, 350), offer a larger surface area and can provide faster or more uniform drug release, whereas larger pellets, often between 500–1500 µm (such as CELLETS® 500, 700, 1000), facilitate the application of multiple coating layers and may support more sophisticated release profiles.

In addition, smaller pellets generally improve content uniformity and patient acceptability, especially in liquid and effervescent dosage forms, because they create a smoother mouthfeel and more homogeneous suspension. Therefore, selecting the appropriate Cellet size represents a key formulation parameter that influences coating efficiency, drug release kinetics, stability, and overall patient experience.

Acetylsalicylic Acid, Paracetamol, and Ascorbic Acid in Pellet-Based Effervescent Formulations

Although EP3117824A1 does not specifically focus on acetylsalicylic acid, paracetamol, or ascorbic acid, the technology applies well to these APIs. Acetylsalicylic acid, commonly known as aspirin, belongs to the nonsteroidal anti-inflammatory drug (NSAID) class. It treats pain, fever, inflammation, and cardiovascular disorders. Depending on the classification source and physiological conditions, aspirin generally falls within BCS Class I or Class III. Because aspirin can irritate the gastric mucosa, pellet-based controlled-release systems may improve gastrointestinal tolerability.

Paracetamol is an analgesic and antipyretic agent that treats pain and fever. It is generally classified as a BCS Class I compound due to its high solubility and permeability. Furthermore, pellet technology can improve taste masking and provide modified-release options. These properties make paracetamol formulations more suitable for pediatric and elderly patients.

Ascorbic acid, also known as vitamin C, functions as a water-soluble vitamin and antioxidant. Healthcare professionals use it to prevent and treat vitamin C deficiency. It exhibits high aqueous solubility and frequently appears in effervescent products. Moreover, pelletization can improve formulation stability by separating ascorbic acid from reactive ingredients. This approach may reduce degradation during storage and improve product quality.

Conclusion and Outlook

Multilayered pharmaceutically active compound technology offers a sophisticated solution for modern oral drug delivery. It combines coated pellet systems with liquid dosage forms while maintaining controlled-release functionality. Moreover, the technology supports improved stability, enhanced patient convenience, and flexible formulation design. When formulators incorporate pellets into effervescent tablets, they can protect sensitive APIs, reduce gastrointestinal side effects, and optimize therapeutic performance. As pharmaceutical research advances, multilayered pharmaceutically active compound systems will likely support more complex formulations and personalized treatment strategies. Consequently, this technology may become an increasingly important platform for next-generation oral medicines.

Patent Summary

  • Name of Patent: Multilayered pharmaceutically active compound-releasing microparticles in a liquid dosage form
  • Patent Number: EP3117824A1
  • Year of Patent: 2015
  • Patent Holders: Federica Ronchi, Jonathan Goole, Karim Amighi, Georges Guillaume, Vincent Stephenne
  • Affiliation: Be Pharbel Manufacturing
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