The most important drug delivery route is undoubtedly the oral route. It offers advantages of convenience of administration and potential manufacturing cost savings. Of drugs that are administered orally, solid oral dosage forms in general and tablets in particular represent the preferred class of product. Today drug delivery companies are focusing on solid oral drug delivery systems that offer greater patient compliance and effective dosages. Melt in mouth tablet (MMT), which is known to be one of the most innovative methods in oral drug delivery, is rapidly growing area in the pharmaceutical industry. This kind of melt in mouth tablet is good for those patients who have difficulty to swallow oral dosage forms, especially the elderly and children. These tablets are also suitable for the mentally ill, the bedridden, population where the underlying disease disrupts swallowing ability (e.g. migraine, Parkinsonism), the patients with persistent nausea, who are travelling, and who do not have easy access to water.
What are melt in mouth tablets?
They are solid dosage forms that dissolve or disintegrate within a minute in the oral cavity without the need of water or chewing and have a pleasant taste. They are popularly known as orally disintegrating tablets (ODT) and also called fast-dissolving, fast-melting or fast-disintegrating. The CDER, FDA defines an ODT to be solid dosage form containing medicinal substance(s), which disintegrates rapidly, usually within a matter of seconds, when placed upon the tongue. The European Pharmacopoeia recognizes the MMTs as orodispersible tablets or tablets intended to be placed in the mouth that subsequently disperses rapidly before being swallowed. Various terminologies with their acronyms are being used to describe an MMT by various drug delivery researchers and inventor companies. These are: melt in mouth/ (mouth melt) tablet (MMT); fast-melting tablet (FMT); fast-dissolving/ disintegrating tablet (FDT); orally disintegrating tablet (ODT); mouth dissolve tablet (MDT); rapidly disintegrating tablet (RDT); and orodispersible tablet (OT). The MMTs have received ever-increasing demand during last decade as evidenced by multi billion dollar sales, which is forecast to grow at 7-9% per annum. This booming market can be attributed to the benefits of the MMTs (Table 1).
Table 1: Benefits of melt in mouth tablets
Benefit Reasons
Therapeutic
advantage Time from symptom appearance to drug action may be shorter for MMT as, unlike conventional tablets, they can be taken instantly in almost any situation. In addition enhanced buccal absorption results in increased bioavailability.
Patient comfort &
compliance MMT is the most convenient for all patients, can be taken readily without water whenever symptoms appear and together with convenience of good taste enhance compliance.
Production cost The total manufacturing cost of the MMTs could be comparable to that of conventional tablets. With low development costs and market risk, the overall success of the company in fulfilling intended functions would be increased.
Life cycle management Pharmaceutical companies benefit from the product differentiation provided by the MMTs, ideal for either a line extension for existing drugs that the company already owns, or for drugs that no longer have patent protection.
Technology of MMT manufacture
The MMTs now on the market are made using one of two established methods: by freeze drying a liquid dosage into solid dosage form or by making tablets, including direct compressed tablets, compression molded tablets, using conventional tablet machines. Other methods include cotton candy, spray drying, and sublimation. The moulding, lyophilization or freeze-drying, and direct compression technologies have led to products that are approved by the US FDA. Freeze dried (lyophilized) tablets impart much faster dissolution characteristics to the tablets due to their very high porous network. However, lyophilized forms lack physical resistance and therefore need special handling and packaging (must be packaged individually). Direct compression is the most cost-effective technology for formulating the MMTs. Because it uses existing high-speed tablet machines and common excipients, it is often favoured over other manufacturing processes for the MMTs. A direct compression tablet will typically take longer time to disintegrate than freeze dried product. This problem can be overcome to some extent by making tablet with lower compression forces than conventional tablets to obtain a higher porosity. Moulding technology can use both conventional and non-conventional equipment. Because the most commonly used solvent in moulding is water, tablets formulated in this way disintegrate slightly faster than compressed tablets. Currently, four patented fast-dissolving/disintegrating technologies are utilized by the companies in the US. They are Zydis, OraSolv, WOWTAB and DuraSolv. Other technologies like FlashDose, Flashtab, Orodis and OraQuick have also gained importance in the international market. Zydis, a freeze dried formulation, was the first marketed new technology tablet that commercialized in 1986.
Success of the MMT
The MMT industry was historically dominated by the innovator of Zydis. Improvements in this technology, especially with taste masking and good mouth feel have emerged more recently with new products. The market success of the MMT is evident from the fact that there are about 50 products presented in this dosage form in therapeutic areas as varied as schizophrenia, migraine, nausea, pain, allergies, Parkinson disease, Alzheimer disease, diarrheas, hypertension, anxiety and even erectile dysfunction. Recent market research has shown that patients prefer the convenience of an MMT to conventional medicines, in addition patients prefer good-tasting formulations to bland or non-flavoured products.
Challenges ahead
The problem of MMTs is their low physical resistance and high friability. Taste-masking is of critical importance in the formulation of an acceptable MMT. The ideal MMTs must disintegrate in the saliva, while maintaining a pleasant taste and good mouth feel. Most MMTs are often less robust, many are very lightweight and fragile requiring them to be individually packaged. Rapid disintegration but less friable robust tablets, overall bioavailability, effective taste masking, good mouth feel, easy to handle and standard packaging (push through blister) are the requirements of envisioned MMTs.
Conclusion
The MMT offers the combined benefits of a liquid formulation and a solid dosage form. The tablets are obviously handled as solid but ingestible as liquid dosage form. The future of the MMTs is promising. The development of the MMTs continues to be a big success for the pharmaceutical drug delivery companies. Majority of the people, based on market survey in western countries, indicated they would prefer an MMT over a conventional tablet. Researchers are developing many MMTs that improve the ways in which current tablets are administered. Considering all these, days are not far away when patients will taste drugs like candy, which will come in mint, strawberry, vanilla and other fruity flavours and melt in their mouth.
(The author is reader in Pharmacy,
Annamalai University, Annamalainagar 608 002, (TN).
Email: cdl_scbasak@sancharnet.in