Current Advances in Drug Delivery Through Fast Dissolving/Disintegrating Dosage Forms

Fast Dissolving/Disintegrating Dosage Forms (FDDFs) have emerged as alternate dosage forms for patients who cannot swallow or who should not swallow or who refuse to swallow conventional tablets/capsules and liquid formulations. FDDFs include Fast Dissolving/Disintegrating Tablets (FDTs), Fast Dissolving/Disintegrating Oral Films (FDOFs), Fast Dissolving/Disintegrating Capsules (FDCs), Fast Dissolving/Disintegrating Pellets (FDPs), etc. These dosage forms dissolve/disintegrate quickly, when placed on tongue, resulting in solution/suspension, which can be swallowed easily and hence do not require water for their oral ingestion. This chapter introduces FDDFs rationale, their brief history, regulatory/pharmacopoeial aspects, advantages/disadvantages and their market potential.

Highly porous nature of freeze dried materials and their ability to retain shape and volume have motivated pharmaceutical scientists to explore application of freeze drying in manufacturing fast dissolving/disintegrating tablets (FDTs). The process of manufacturing lyophilised tablets as FDTs is extensively proprietary and patented. Zydis®, Lyoc®, QuickSolv® and NanoCrystal® NanomeltTM technologies have been successful in developing drug products and obtaining regulatory clearances from drug regulatory agencies for their marketing authorisations. This chapter aims to discuss formulation, processing and manufacturing aspects of FDTs prepared by freeze drying and also provides an overview on some of these patented FDT technologies.

Fast dissolving/disintegrating tablets (FDTs) can be manufactured by direct compression provided the challenge of fast disintegration with adequate mechanical strengths can be addressed. Superdisintegrants, directly compressible coprocessed excipients and water soluble excipients have opened up the flood gates of opportunities in designing and developing FDTs by direct compression. Unacceptable properties of active pharmaceutical ingredient (API), like poor solubility, bitter taste, low bioavailability, may be addressed by making granules, micro-particulates and/or using various coating methods. Such treated API can be used in preparing FDTs. Effervescent agents have also gained attention as disintegrating agents in tablets so as to fasten tablet disintegration time to achieve pharmacopoeial or regulatory compliance for disintegration time. This chapter describes various FDT technologies based on modifications of conventional tablet manufacturing methods. These techniques can be grouped into four categories, viz. direction compression, granulation methods, effervescent tablets and direct compression with subsequent treatments.

This chapter describes various developments in the designing, fabrication and manufacturing of FDTs using various technologies based on moulding, extrusion, floss, and three dimensional printing (3DP). Moulding has evolved from conventional moulding/tablet triturates to heat moulding, moulding methods involving use of compressed gases or low boiling point solvents, microwave drying, vacuum drying and compression of wet granules in especially designed moulding machine. Extrusion is not yet fully explored for developing FDTs. Floss techniques has moved ahead from Shearform® floss through liquiflash to creation of microparticulates. Rapid prototyping techniques, especially three dimensional printing (3DP), have enabled the use of computer aided designing (CAD) possibilities in manufacturing of highly porous dosage form offering immediate and complex drug release characteristics, tablets of any shape and dosage forms which can flash into a matter of seconds.

The conventional oral drug delivery system, in spite of ease of administration and convenience of therapy, is associated with certain limitations especially for paediatrics, geriatrics, unconscious and travelling patients. To make the safe and effective usage of drugs, fast dissolving/disintegrating dosage forms (FDDFs) serves as an effective approach for rapid delivery of drugs. The present chapter is an effort to describe the various aspects of FDDFs including the different patented products and technologies, which are either commercially available in the market or in development pipeline. A systematic study of various patents related to formulation, packaging and evaluation of FDDFs is also provided. Thus, this chapter provides most comprehensive insights on different FDDFs technologies through their patents and innovative steps described therein.

Excipients play important functional roles in dosage form manufacturing. Disintegration and dissolution of dosage form and sometimes the active ingredient is greatly influenced by the use of excipient(s) like diluents and superdisintegrants in the formulation. With the advent of FDDF technologies, several directly compressible excipient systems have been introduced by excipient industry to ease fast disintegrating/dissolving tablet (FDT) manufacturing by the process of direct compression. These excipient systems have supplied a royalty free, licensee free and a low cost solution for FDT manufacturing to drug product manufacturers. Advancements in disintegrants and disintegration enhancers have also helped in formulating quicker disintegrating dosage forms. Some new excipients have been used to overcome bitter taste of drugs, improve compressibility of saccharides and as diluents in formulating FDTs. Some excipients have been modified and provided in special for their exclusive use in formulating FDTs. This chapter provides an updated review on some of the excipient/excipient for their potential use formulating FDTs.

Fast dissolving/disintegrating dosage forms (FDDFs) comprise dosage forms meant for dissolution/disintegration in saliva and subsequent swallowing of the formulation. FDDFs include fast dissolving/disintegrating tablets (FDTs), fast dissolving/disintegrating films (FDFs), fast dissolving/disintegrating pellets (FDPs) or fast dissolving/disintegrating granules (FDGs), etc. Drug release from such dosage forms starts from the oral cavity itself and, therefore, a part of total drug may be absorbed much before the drug reaches in the stomach. Early release of the drug in saliva, in close proximity to taste buds, makes it desirable that the drug shall be presented in a taste masked form and palatability shall be improved to an extent that dosage form is highly acceptable among patients. Therefore, bitter or other unpleasant taste of the drug is a great challenge to formulate a taste masked FDDF formulation. An ideal taste masking technique should provide a good refreshing mouthfeel, pleasant taste and appealing flavour. On the other hand, an ideal taste masking technique shall not impart grittiness, reduction in bioavailability and a large increase in the size of the dosage form. Approaches for taste masking are generally categorised into physical, chemical and organoleptic (physiological). The technology of taste masking is highly proprietary and extensively patented. Physical/chemical methods of masking the undesirable taste work synergistically with organoleptic approaches for improving the overall palatability of pharmaceutical formulations. Hence, several proprietary taste masking technologies utilise synergistic/additive effect of two or more approaches for taste masking. This chapter provides a comprehensive overview on taste masking methods, proprietary and/or patented technologies, giving special emphasis on their application in FDDFs.

Quality assurance and evaluation of fast dissolving/disintegrating dosage forms (FDDFs) require conduct of various pharmacopoeial and non-pharmacopoeial tests and their compliance to acceptance limits. Dosage forms specific and non-specific tests include assessment for hardness, weight variation, assay, content uniformity, friability, disintegration, dissolution, etc. Highly porous nature of fast disintegrating/ dissolving tablets (FDTs) makes them brittle and fragile. Friability limits for FDTs are generally higher than the friability limits of conventional tablets. Newer tests, methodologies and equipments have been devised for evaluation of in vitro disintegration/ dissolution and to simulate in vivo conditions of the oral cavity. Drug dissolution/release studies are also required to be conducted in a manner so as to simulate in vivo oral conditions to ensure reproducibility of batches. The developed drug release tests and explored methodologies are correlated to in vivo disintegration/ dissolution for their wider acceptance and future incorporation in pharmacopoeia. Taste masking and palatability of FDDFs are evaluated during drug development and stability studies. Some of these evaluation tests have been incorporated in regulatory guideline and/or pharmacopoeia, while some others are in development phases. This chapter provides a comprehensive overview on various quality control/assurance tests for evaluation of FDTs and capsules.

Swallowing medication has always been a major problem among 50% of the population, especially in cases of elderly and children due to a fear of choking, resulting to an inappropriate medication adherence and in turn to non-compliance of dosage regimen. Swallowing problems are also seen in adult people who are bed-ridden or those who are busy in working or travelling, which makes them to forget or miss their doses as it requires water to swallow. This issue can be overcome by using FDDFs (Fast Dissolving/Disintegrating Dosage Forms), which have gained an immense popularity worldwide and a specific position in the field of novel drug delivery systems due to their easier administration and excellent palatability. FDDF has characteristics of both solid as well as liquid dosage form, as during storage and before administration it is solid in nature, a stability factor and as soon as it is placed in the mouth or beneath the tongue it rapidly gets transformed into its liquid form in the presence of saliva within a few seconds of its administration. The buccal mucosa is well supplied with both vascular and lymphatic systems and most importantly avoidance of intestinal or hepatic metabolism. The site and extent of absorption through buccal cavity are the important factors to be considered in developing FDDFs. The other factors like meta-bolising enzyme transporters involved, bioavailability and physicochemical properties of the drug are also important properties to be considered in developing FDDFs. FDDFs, as delivery systems, are widely used in treatment of allergies or emergency conditions which require a rapid therapeutic effect of the drug, e.g. sublingual tablet of nitroglycerin in case of angina attack. The disintegration time is also the important factor for classifying a drug product as FDDF, as generally, it is below 60 s in case of FDDF. Several FDDF drug products belonging to Fast Dissolving/Disintegrating tablets (FDTs), Fast Dissolving/Disintegrating Oral Films (FDOFs) have been introduced in the market as a result of an increased patient demands and their market presence is expected to expand in the forthcoming years.

Ease of administration and patient compliance makes the oral route as the most popular route of administration, but difficulty in swallowing or dysphagia may limit the use of oral route in special populations like paediatrics, geriatrics, psychotics, cancer patients, etc. Unavailability of water and episodic attack of allergy also contributes to difficulties in swallowing tablets and capsules. Here the novel fast dissolving oral film (FDOF) technology gives new hope to overcome these problems. Oral films made from active ingredient and hydrophilic polymers are capable of rapidly dissolution/disintegration in the buccal cavity. A part of the drug is absorbed from buccal route providing the advantages of quicker onset, bypassing first pass effect and reducing gastric degradation or metabolism. These qualities have made oral film a very popular and convenient dosage form for paediatric, geriatric as well as adult populations. This chapter describes formulation aspects, preparation technologies and some important patents of FDOFs.

Fast disintegrating tablets (FDTs) were initially developed for immediate drug delivery, quicker onset of action and as age appropriate dosage form for special populations like geriatrics, paediatrics, psychotics, etc. Their quick dissolution/ disintegration in the oral cavity has made them suitable for incorporating microparticles/pellets for developing controlled drug delivery systems. Furthermore, advancement in manufacturing technologies and dosage forms have led to the introduction of newer dosage forms like oral disintegrating mini tablets (ODMTs), fast disintegrating capsules (FDCs), fast disintegrating pellets (FDPs) and orodispersible or to dissolve in oral powders. ODMTs are small size (2-3 mm in diameter) tablets prepared with characteristics of faster dissolution/disintegration. ODMTs have been found suitable and well acceptable in children. Perforation and vacuum drying methods have been used to convert traditional capsules into FDCs to overcome disadvantages of other FDDFs like expensive manufacturing, low payload, lengthy processes and insufficient masking of undesirable taste. Extrusion spheronisation and spray coating of drug with suitable excipients can led to FDPs, while orodispersible/effervescent powders can be filled in a unit dose packing. This chapter details about these novel FDDFs vis a vis to some novel advancements in their compositions.

Websites of various drug regulatory agencies like US FDA, EMA, MHRA, PMDA and CDSCO were visited and information about approval and market authorisations of FDDF drug products’ was collected with an aim to provide updated lists. Additionally, information about marketed FDDF drug products was also retrieved from websites of pharmaceutical companies and other literature sources. This chapter comprehensively enlists various drug products approved and marketed in US, UK, Europe, Japan and India.