A novel, fast-dissolving delivery system that releases active ingredients in seconds is one of the fastest-growing segments of the supplements marketplace. Andaleeb Ahmed explains how this breakthrough can offer greater convenience and safety for both paediatric and geriatric populations
Advances in technology continue to break the barriers of conventional encapsulation methods. Today, active ingredients can be delivered with a level of convenience, performance and bioavailability never before seen in the marketplace. And, as our scientific understanding of the prevention and management of diseases continues to grow, companies find themselves in ever-greater competition—investing millions of dollars to develop novel ways of delivering nutrients orally to patients.
Such companies are constantly focusing on delivery systems that offer greater patient compliance, effective dosages and minimal chances of side effects. Fast-dissolving tablets or rapid-melt tablets are one such innovation; it is one of the fastest-growing segments in the pharmaceutical market, as evidenced by an estimated $28 billion in 2002 sales.
This novel type of delivery system offers convenience for treatment-resistant populations who have difficulty swallowing oral dosage forms. The demand for these formulations has gone up significantly for children and older populations. They are particularly convenient for paediatric and geriatric segments of the population because they rapidly disintegrate in the mouth without the need for chewing or drinking water.
The disintegration times of these tablets depend largely on the size of the dosage form and hardness parametersFast-melting formulations even offer advantages for drug-compliant patients who take other orally administered pills, such as chewable, suspensions and effervescent tablets. When placed in the mouth, these tablets disintegrate in a few seconds, resulting in quick absorption of the actives through the buccal and oesophageal mucous, thus offering faster bioavailability of active ingredients with minimal side effects. Fast-melting tablets can also serve as carriers for a wide range of nutritional and dietary supplements including calcium, caffeine, antioxidants and folic acid.
Key ingredients to use
Important ingredients that are used in the formulation of fast-melting tablets should allow quick release of the drug, resulting in faster dissolution. This includes both the actives and the excipients.
Excipients balance the properties of the actives in fast-melting tablets. This demands a thorough understanding of the chemistry of these excipients to prevent interaction with the actives. Determining the cost of these ingredients is another issue that needs to be addressed by formulators. The role of excipients is important in the formulation of fast-melting tablets. These inactive food-grade ingredients, when incorporated in the formulation, impart the desired organoleptic properties and product efficacy. Excipients are general and can be used for a broad range of actives, except some actives that require masking agents.
Binders keep the composition of these fast-melting tablets together during the compression stage. The right selection of a binder or combination of binders is essential to maintain the integrity and stability of the tablet. The temperature of the excipient should be preferably around 30?35C for faster melting properties. Further, its incorporation imparts smooth texture and disintegration characteristics to the system. Binders can either be liquid, semi solid, solid or mixtures of varying molecular weights such as polyethylene glycol. The choice of a binder is critical in a fast- dissolving formulation for achieving the desired sensory and melting characteristics, and for the faster release of active ingredients. Commonly available fats such as cocoa butter and hydrogenated vegetable oils can also be used.
Emulsifying agents are important excipients for formulating fast-melting tablets. They aid in rapid disintegration and drug release without chewing, swallowing or drinking water. In addition, incorporating emulsifying agents is useful in stabilising the immiscible blends and enhancing bioavailability. A wide range of emulsifiers is recommended for fast-tablet formulation, including alkyl sulfates, propylene glycol esters, lecithin, sucrose esters and others. These agents can be incorporated in the range of 0.05 per cent to about 15 per cent by weight of the final composition. Lubricants, though not essential excipients, can further assist in making these tablets more palatable after they disintegrate in the mouth. Lubricants remove grittiness and assist in the drug transport mechanism from the mouth down into the stomach.
Bulking materials are significant in the formulation of fast-melting tablets. The material contributes functions of a diluent, filler and cost reducer. Bulking agents improve the textural characteristics that in turn enhance the disintegration in the mouth. Besides, adding bulk also reduces the concentration of the active in the composition. The recommended bulking agents for this delivery system should be more sugar-based such as mannitol, polydextrose, lactitol and starch hydrolysate for higher aqueous solubility and good sensory perception. Lactitol in particular has high aqueous solubility and good sensory perception. Bulking agents are added in the range of 10 per cent to about 90 per cent by weight of the final composition.
Flavours and taste-masking agents make the products more palatable and pleasing for patients. The addition of these ingredients assists in overcoming bitterness and undesirable tastes of some active ingredients. Both natural and synthetic flavours can be used to improve the organoleptic characteristic of fast-melting tablets. Formulators can choose from a wide range of sweeteners including sugar, dextrose and fructose, as well as non-nutritive sweeteners such as aspartame, sugar alcohols and sucralose. The addition of sweeteners contributes a pleasant taste as well as bulk to the composition.
Widely known technologies that are applied in the formulation of these fast-melting tablets are freeze-drying, direct compressions and moulding. There are advantages and limitations associated with each technology.
Freeze-drying is based on the principle of sublimation that imparts much faster dissolution characteristics to the tablets. The processing is carried at a non-elevated temperature that eliminates temperature severity. The finished products are relatively stable and can be stored in a dry environment. However, this is a costly operation and involves the use of a freeze dryer, and freeze-drying technology has limitations due to factors such as time, costly equipment and processing conditions. Besides, tablets formulated by this technology lack physical resistance and need special handling and packaging.
Direct compression is the most cost-effective technology for formulating fast-melting tablets because it requires no special equipment. Besides, using conventional equipment also has a limited number of processing steps. Fast-melting tablets manufactured by this method have satisfactory disintegration time. The disintegration times of these tablets depend largely on size and hardness parameters.
Moulding is one simple and efficient method that can be used by formulators. Moulding technology can use both conventional and non-conventional equipment. However, tablets manufactured by moulding cannot have faster disintegration times like freeze-dried ones. The ingredients are first solubilised in the solvent before being compressed into mould plates. The quality parameter of fast-melting tablets such as disintegration time, mouth feel, dissolution time and other sensory perceptions depend on the type of dispersion. Because the most commonly used solvent in moulding is water, tablets formulated in this way disintegrate much faster and with better taste. However, tablets formulated using this technology are not resistant to breakage during handling of the finished tablets.
Fast-melting formulations need continued evolution to offer line extension for major oral products. Another challenging goal is to overcome existing manufacturing, disintegrating and handling obstacles.
Andaleeb Ahmed was involved in the development of rapid-melt tablets at Capricorn Pharma.