orally disintegrating tablets

The technology also incorporates taste-masking sweeteners and flavoring agents such as mint, cherry, and orange. The process works by removing water using an excess of alcohol (solvent extraction). S.R. 3 (6), 5861 (2001). Ghosh, "Intraoral Delivery Systems: An Overview, Current Status and Future Trends," in Drug Delivery to the Oral Cavity: Molecules to Market, T.K. D.J. M.C. Recent market studies indicate that more than half of the patient population prefers ODTs to other dosage forms (6) and most consumers would ask their doctors for ODTs (70%), purchase ODTs (70%), or prefer ODTs to regular tablets or liquids (>80%) (7). 38. In addition, several business needs are driving ODT technology development and the commercialization of new products such as the need for expanded product lines, improved life-cycle management, extended patent life, and marketing advantages. Copyright 2022 CompareNetworks, Inc. All rights reserved. P. Kearney and S.K. The Zydis freeze-dried oral solid dosage form typically dissolves in the mouth in under three seconds, which is significantly less than the other ODTs, and has a smooth mouthfeel. More than a billion of the ODTs are manufactured every year in Catalents UK facility in Swindon. Using otherwise standard ODT formulation technology, freeze dried ODTs, each containing 75mg of olive oil, were successfully made. This is important, as the larger the particles, the more gritty and unpleasant the mouthfeel will be in an ODT. 34. It also dilutes the dose, and the high molecular weight can lead to absorption problems. 40. Figure 5 shows the difference between a standard ODT and the Bio ODT. Gregory, "Solid Shaped Particles," US Patent 4,758,598 (1988). Syst. For example, several techniques for making compressed tablets (e.g., DuraSolv, CIMA Labs, Eden Prairie, MN; OraSolv, CIMA Labs; and WOWTAB, Yamanouchi, Norman, OK) produce tablets that are easy to handle and can be packaged in blister packs or bottles. L. Dobetti, "Fast-Melting Tablets: Developments and Technologies," Pharm. One drawback to the dispersion of a tablet in the mouth is its taste. This would permit very lipophilic APIs to be formulated via dissolution in oil before freeze drying. The technology can accommodate water-soluble and water-insoluble drugs in doses as large as 750 mg, which may contain multiple active ingredients. very bitter or otherwise unacceptable taste because taste masking cannot be achieved. As can be seen in Figure 3, the area under curve (AUC) over time is the same for the ODT taken both with and without water, and the standard capsule formulation. They cover a wide gamut of therapeutic areas, with the majority in areas that benefit from the fast onset of action. Most are relatively low doses of small molecule APIs, although doses up to 200mg have also been marketed and peptide and protein products have also been commercialized. Descriptions of orally disintegrating dosage forms. Because drugs delivered in ODTs may be absorbed in the pregastric sites of highly permeable buccal and mucosal tissues of the oral cavity, they may be suitable for delivering relatively low-molecular weight and highly permeable drugs. The reaction is allowed to proceed only to the extent of completing the base coating on organic acid crystals. 18. (CRC Press, New York, NY, 2005), pp. Ghosh and W.R. Pfister, Eds. Indeed, the site of absorption, the mouth, gives no extreme pH exposure as salivary pH is typically about 6.8, and no relevant proteases are present. 29. J. Hontz, "Development of a Rapidly Dissolving Famotidine Tablet," paper presented at the 41st Annual International Industrial Pharmaceutical Research Conference, Madison, WI, June 1999. The area under the curve for the low-dose ODT is equivalent to that of 10mg formulated conventionally. In contrast, some lyophilization manufacturing processes (e.g., Zydis, Cardinal Health, Dublin, OH) produce fragile freeze-dried tablets and compressed multiparticle tablets that can be packaged only in unit-dose blisters because of their high friability (8, 11, 12). R.H. Bogner, M.F. This is important for use in a developing world setting. The drug can be added, along with other standard tableting excipients, during the granulation or blending processes. Table II summarizes the main characteristics of various ODT technologies and products from several innovator companies in the oral fast-dissolve tablet arena (15). 33. The target population has expanded to those who want convenient dosing anywhere, anytime, without water. Careful selection of formulation options and ingredients, including the selection of the matrix component and the pH, can optimize inprocess stability. The filled trays are passed through a liquid nitrogen freeze channel, causing the API solution or suspension to freeze very rapidly. It is difficult to persuade infants and very young children to swallow them, and they may pose a choking hazard. K. Deepak, "Orally Disintegrating Tablets," Tablets and Capsules 7 , 3035 (2004). The blend is compressed into tablets using a conventional rotary tablet press. This situation may have implications for drug safety and efficacy, which may need to be addressed and assessed in a marketing application for an ODT (13). All of our sites are subject to annual review so we can remain in highest compliance with: CATALENTS BEST-IN-CLASS FAMILY OF FAST DISSOLVE TECHNOLOGIES. The other two technologies are both loosely compressed tablets, which take between 15 and 20 seconds to disperse. Technol. (CRC Press, New York, NY, 2005), pp. Floss-based tablet technology. Cherukuri and R. Fuisz, "Process and Apparatus for Making Tablets and Tablets Made Therefrom," US Patent 5,654,003 (1997). 36. Under this circumstance, it is assumed that the absorption of a drug molecule from the ODT occurs in the postgastric GIT segments, similar to the conventional oral dosage form. Other patented ODT technologies based on lyophilization include Lyoc (Farmalyoc, now Cephalon, Franzer, PA) and QuickSolv (Janssen Pharmaceutica, Beerse, Belgium). 2. The Zydis technology requires specific characteristics for drug candidates and matrix-forming materials. G.L. 25. As an example, the 32 amino acid peptide calcitonin, which has a molecular weight of 3432, was formulated as an ODT. Only one of the three other methods outlined in Table 1 uses lyophilization, and tablets made this way typically take more than a minute to disperse. The result is a fast-disintegrating tablet that has adequate hardness for packaging in bottles and easy handling. DeRoche et al., "Consumer Preference for Orally Disintegrating Tablets Over Conventional Forms of Medication: Evolving Methodology for Medication Intake in Dysphagia," lecture presented at the 12th Annual Meeting of the Dysphagia Research Society, San Francisco, CA, Oct. 24, 2003. Only a few technologies can produce tablets that are sufficiently hard and durable to allow them to be packaged in multidose bottles (e.g, DuraSolv, AdvaTab [Eurand, Vandalia, OH], and WOWTAB). 1. Table I lists several ODT products that are marketed in the United States. The graph in Figure 1 shows a comparison between 10mg doses of selegeline in both traditional tablet and ODT formats, and a 1.25mg Zydis ODT. 9. The rapid onset of action is of benefit in drugs designed to treat acute conditions, such as migraines and psychiatric incidents, as well as conditions like insomnia. Rev.Therap. The Bio ODT also holds out promise for oral vaccines. This can either contain two different APIs, or an API and a necessary excipient that is otherwise incompatible. This pre-gastric absorption can reduce side effects caused by metabolites formed by liver enzymes. Technol. In addition, ODTs may be suitable for the oral delivery of drugs such as protein and peptide-based therapeutics that have limited bioavailability when administered by conventional tablets. Though the appropriate particle size for insoluble drugs is ~50 m, drugs with larger particle sizes also can be formulated into freeze-dried wafers using suspending agents such as gelatin and flocculating agents such as xanthan gum (8, 31). The AUC was almost identical to that for a regular cetirizine tablet. 21. Furthermore, any minor damage to the package may cause the wafer to collapse because of moisture absorption (34). These products usually degrade rapidly in the stomach. Freeze-dried ODTs are manufactured and packaged in polyvinyl chloride or polyvinylidene chloride plastic packs, or they may be packed into laminates or aluminum multilaminate foil pouches to protect the product from external moisture (8). Ghosh and W.R. Pfister, Eds. Other ODT products made with conventional tableting processes include Frosta (Akina Inc., West Lafayette, IN), ProMelt (aaiPharma, Wilmington, NC), EasyTec Tablets (Antares Pharma, Exton, PA), Fast Oral Technology, D-Zolv (Capricorn Pharma Inc., Frederick, MD), and Oro-dispersible tablets (Grupo vita, Barcelona, Spain) (15). The aluminum packaging provides a high moisture barrier and good environmental protection, and acceptable storage has been demonstrated at room temperature for multiple peptide and protein compounds. Stage 4 Sealing Such collapse sometimes can be prevented by using various matrix-forming excipients such as mannitol that can induce crystallinity and hence, impart rigidity into the amorphous composite. Ghosh, "Quick Dissolving Oral Dosage Forms: Clinical Pharmacology, Biopharmaceutical, and Regulatory Considerations," paper presented at the annual meeting of the American Association of Pharmaceutical Scientists (AAPS), Salt Lake City, UT, Oct. 29, 2003. 61 , 3637 (1990). The DuraSolv ODT technology is a second-generation technique based on the OraSolv technology. Furthermore, if the drug is absorbed within the oral cavity rather than being digested, it avoids the first pass of the liver. A lower dose is required as the active is not metabolized by the liver before it reaches the bloodstream. 16. A structure former, usually mannitol chosen for its high compatibility and its well-known documented properties - is also added. ODTs release drug in the mouth for absorption through local oromucosal tissues and through pregastric (e.g., oral cavity, pharynx, and esophagus), gastric (i.e., stomach), and postgastric (e.g., small and large intestines) segments of the gastrointestinal tract (GIT). Furthermore, it could help to generate a mucosal response, which is important for certain infections such as influenza, pneumonia and human papillomavirus (HPV). (CRC Press, New York, NY, 2005), pp. This would almost certainly improve compliance, and offer an improved safety profile compared to an injectable vaccine. 12. Despite these advantages, the application of this technology is limited by the amount of drug that can be incorporated into each unit dose. Matrix formation and its characteristics are equally important for freeze-drying technology. (CRC Press, New York, NY, 2005), pp. The future potential for ODTs is promising because of the availability of new technologies combined with strong market acceptance and patient demand. This strategy has been successfully applied to the antihistamine cetirizine, which has a very bitter taste. FDA, Electronic Orange Book: Approved Drug Products With Therapeutic Equivalence Evaluations Current Through February 2005, http://www.fda.gov/cder/ob/default.htm, accessed March 18, 2005. All rights reserved. 27 (10 Supp), 2229 (2003). J.A. The freeze drying process then proceeds as normal, followed by packaging. Stage 2 Filling and freezing 42. These tablets are distinguished from conventional sublingual tablets, lozenges, and buccal tablets which require more than a minute to dissolve in the mouth. Pharmacol. Tapash K. Ghosh is a senior clinical pharmacology and biopharmaceutics reviewer at the US Food and Drug Administration (HFD 880), 9201 Corporate Blvd., Room N224, Rockville, MD 20850. Ghosh and W.R. Pfister, Eds. By sequentially dosing two separate matrix solutions with different gelling or density characteristics in this way, a single ODT with acceptable quality characteristics can be achieved. 32. The frozen units are then transferred to large-scale freeze dryers for the lyophilization process. S.R. More than 35 products have been launched using this technology in more than 60 countries around the world. 291336. D. Brown, "Orally Disintegrating Tablets: Taste Over Speed," Drug Deliv. Prescription ODT products initially were developed to overcome the difficulty in swallowing conventional tablets with water among pediatric, geriatric, and psychiatric patients with dysphagia. Common matrix-forming agents include gelatin, dextran, or alginates which form glassy amorphous mixtures for providing structural strength; saccharides such as mannitol or sorbitol for imparting crystallinity, hardness, and elegance; and water, which functions as a manufacturing process medium during the freeze-drying step to induce the porous structure upon sublimation. If significantly higher plasma levels and systemic exposure have been observed, pregastric absorption leading to the avoidance of first-pass metabolism may play an important role. Although it is still early days for ODT formulation of biologics, the model studies already carried out indicate its clear potential. Select products to compare by checking the boxes next to the items. Chemical analysis of API in support of preformulation studies (e.g., solubility determinations, compatibility testing). An additional advantage is the potential to avoid the need for cold-chain storage. This review article discusses orally disintegrating tablets and their manufacturing technologies, development issues, and future trends. 37. All rights reserved. G.K.E. Freeze-drying tablet process. For example, safety profiles may be improved for drugs that produce significant amounts of toxic metabolites mediated by first-pass liver metabolism and gastric metabolism and for drugs that have a substantial fraction of absorption in the oral cavity and segments of the pregastric GIT. Examples are cited in the literature in which the pharmacokinetic profiles and bioavailabilities of the same dose of drug in an ODT are not bioequivalent to the conventional oral dosage form. Not all APIs can be formulated in such a way that pre-gastric absorption is possible. This floss is commonly composed of saccharides such as sucrose, dextrose, lactose, and fructose. 5 (3), 5054 (2005). At present, ODTs are the only quick-dissolving dosage form recognized by FDA and listed in Approved Drug Products with Therapeutic Equivalence Evaluations (also called the Orange Book) (3, 9). Optical microscopy R. Fuisz, "Ulcer Prevention Method Using a Melt-Spun Hydrogel," US Patent 5,622,717 (1997). Keep up with our latest articles, news and events. As previously mentioned, fragile products require special unit-dose packaging, which may add to the cost. K. Sharma, W.R. Pfister, and T.K. The lyophilization based manufacturing process and its low temperatures reduces the potential for heat damage to the biologics. Cherukruri and R. Fuisz, "Process and Apparatus for Making Tablets and Tablets Made Therefrom," European Patent 0,677,147 A2 (1995). 27 (10 Suppl), 1013 (2003). No official support or endorsement of this article by FDA is intended or should be inferred. As the water is vaporized without going through the liquid state, it does not redissolve the solid ingredients, instead, leaving behind a porous gelatin framework.