J.A. Characterizes moisture sorption properties and physical stability of lyophilized formulation in humidity, Characterization of hydrates and polymorphs, X-ray powder diffraction (XRPD) C.C. J. Aurora and V. Pathak, "Oral Disintegrating Technologies: Oral Disintegrating Dosage Forms: An Overview," Drug Deliv. 27 (11), 92100 (2003). partially nonionized at the oral cavity's pH; ability to diffuse and partition into the epithelium of the upper GIT (log. 291336. Today, ODTs are more widely available as over-the-counter products for the treatment of allergies and cold and flu symptoms. 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). This pre-gastric absorption can reduce side effects caused by metabolites formed by liver enzymes. There are many patients for whom traditional tablets and capsules are not ideal dosage forms. No official support or endorsement of this article by FDA is intended or should be inferred. This would permit very lipophilic APIs to be formulated via dissolution in oil before freeze drying. QuickSolv disintegrates very rapidly but is limited to low drug content and can be used only with active ingredients that are insoluble in the extraction solvent (36). R. Fuisz, "Ulcer Prevention Method Using a Melt-Spun Hydrogel," US Patent 5,622,717 (1997). G.K.E. S.V.

Although it is still early days for ODT formulation of biologics, the model studies already carried out indicate its clear potential. Table II: Orally disintegrating tablet manufacturers and technology characteristics (18). Technol. 17 , 6172 (2000). Development work has been carried out using influenza as a model vaccine antigen. Many APIs have an unpleasant taste or create other unappealing sensations as they are solubilized. The formed matrix structure is very porous in nature and rapidly dissolves or disintegrates upon contact with saliva (16). K. Deepak, "Orally Disintegrating Tablets," Tablets and Capsules 7 , 3035 (2004).

It is difficult to persuade infants and very young children to swallow them, and they may pose a choking hazard. The filled trays are passed through a liquid nitrogen freeze channel, causing the API solution or suspension to freeze very rapidly. 140. Then, the excipient is mixed with the active ingredient or active microparticles and with other standard tableting excipients and then compressed into tablets. 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. T.K. All rights reserved. Cherukuri and R. Fuisz, "Process and Apparatus for Making Tablets and Tablets Made Therefrom," US Patent 5,654,003 (1997).

The coating technology involves the API particles and micronized polymer agglomerates being placed in a mixing vessel equipped with an acoustic vibrator.

Optical microscopy N. Sharma et al., "Manufacturing Technology Choices for Mouth Dissolving Tablets," Pharm. In the literature, ODTs also are called orally disintegrating, orodisperse, mouth-dissolving, quick-dissolve, fast-melt, and rapid-disintegrating tablets and freeze-dried wafers (see sidebar, "Descriptions of orally disintegrating dosage forms") (35). This review article discusses orally disintegrating tablets and their manufacturing technologies, development issues, and future trends. Gole et al., "Preparation of Pharmaceutical and Other Matrix Systems by Solid-State Dissolution," US Patent 5,215,756 (1993). William R. Pfister, PhD,* is a senior director of preclinical affairs at NexMed (USA), Inc., (Robbinsville, NJ). 10. 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. 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. One drawback to the dispersion of a tablet in the mouth is its taste. This would almost certainly improve compliance, and offer an improved safety profile compared to an injectable vaccine. This strategy has been successfully applied to the antihistamine cetirizine, which has a very bitter taste. J. Chu, "Product Development, Scale-Up and Technology Transfer Aspects of Fast Dispersing Dosage FormsWOWTAB," paper presented at the annual meeting of the AAPS, Salt Lake City, UT, Oct. 29, 2003. K. Cremer, "Orally Disintegrating Dosage Forms Provide Drug Life Cycle Management Opportunities," Pharm. 21. 34. Technol. Both ibuprofen and acetaminophen have been successfully formulated in this way to date. Parakh and A. Gothoskar, "A Review of Mouth Dissolving Tablet Technologies," Pharm. Body weight loss, which is an indicator of the extent of the disease, was greatest for the unvaccinated and infected control group, which is demonstrated by the results shown on the lowest set of data points on the graph and shows rapid weight loss after day 2 of the study. M.C. Over the past three decades, orally disintegrating tablets (ODTs) have gained much attention as a preferred alternative to conventional oral dosage forms such as tablets and capsules. Scher's (now Cardinal Health's) Zydis freeze-drying manufacturing process for ODT products (8, 28) has been the most commercially successful ODT technique. As an example, the drug selegeline is a monoamine oxidase B inhibitor used to treat Parkinsons disease and depression, but its active metabolites include methamphetamine, which leads to side-effects. ODTs also offer clinical advantages such as improved safety and, in some cases, improved efficacy and other broader indications. Ghosh and W.R. Pfister, Eds. (CRC Press, New York, NY, 2005), pp. 4. The particle size of the organic acid crystals is carefully chosen to be larger than the base excipient to ensure uniform coating of the base excipient onto the acid crystals. Several drug delivery technologies that can be leveraged on improving drug therapy from ODTs have yet to be fully realized. The target population has expanded to those who want convenient dosing anywhere, anytime, without water.

50 (4), 375382 (1998). The result is a fast-disintegrating tablet that has adequate hardness for packaging in bottles and easy handling. The inclusion of bioadhesives and absorption enhancers can promote absorption. 27. 35. Stage 3 Lyophilization The process works by removing water using an excess of alcohol (solvent extraction). Gregory, "Solid Shaped Particles," US Patent 4,758,598 (1988).

5 (1), 3437 (2005). Table I lists several ODT products that are marketed in the United States. The Zydis technology requires specific characteristics for drug candidates and matrix-forming materials. 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). S.V. 42. P. Kearney and S.K. (CRC Press, New York, NY, 2005), pp. Fix, "Advances in Quick-Dissolving Tablets Technology Employing WOWTAB," paper presented at the IIR Conference on Drug Delivery Systems, Washington DC, Oct. 1998. The effervescent excipient (known as effervescence couple) is prepared by coating the organic acid crystals using a stoichiometrically lesser amount of base material. Biologic medicines are rarely orally available, not least because they cannot withstand the harsh acidic and enzyme-rich conditions in the gastrointestinal tract. 14. Drug coatings also can be used to mask bitter drugs and to protect the drug from stomach acidinduced metabolism. 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. Prescription ODT products initially were developed to overcome the difficulty in swallowing conventional tablets with water among pediatric, geriatric, and psychiatric patients with dysphagia. For example, ODT formulations of selegiline, apomorphine, and buspirone have significantly different pharmacokinetic profiles compared with the same dose administered in a conventional dosage form (1719). The principal ODT manufacturing processes include conventional, freeze-dried, and floss-based tableting technology (4, 16, 20). Drug Carr. One strategy involves the use of cyclodextrins. It is also dependent on the dose, lipophilicity and molecular weight of the drug molecule. It also dilutes the dose, and the high molecular weight can lead to absorption problems. Quick-dissolve tablets can offer several biopharmaceutical advantages such as improved efficiency over conventional dosage forms.

Technol. Using otherwise standard ODT formulation technology, freeze dried ODTs, each containing 75mg of olive oil, were successfully made. The convenience of the dosing, and the lack of requirement for cold chain storage, could permit faster distribution in pandemic and emergency situations, and would permit administration by less qualified healthcare professionals. All of these are well established and widely accepted ingredients in pharmaceutical formulations. Submitted: June 17, 2005. ODT products have been developed for numerous indications ranging from migraines (for which a rapid onset of action is important) to mental illness (for which patient compliance is important for treating chronic indications such as depression and schizophrenia) (3). 311336. A Publication of 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. 15. 28. The trays are stored in a freezer until a sufficient quantity has been prepared to fill the freeze dryer, and then they are transferred into the dryer. The lyophilization based manufacturing process and its low temperatures reduces the potential for heat damage to the biologics. Furthermore, if the drug is absorbed within the oral cavity rather than being digested, it avoids the first pass of the liver. Zydis ODT technology was first developed by RP Scherer (now part of Catalent) in the 1980s, and the first products reached patients in the early 1990s. The WOWTAB manufacturing technique is one successful method that features conventional tablet characteristics for ease of handling, packaging, and fast disintegration (20). more delivered to your inbox. Orally disintegrating tablets (ODTs) have better patient acceptance and compliance and may offer improved biopharmaceutical properties, improved efficacy, and better safety compared with conventional oral dosage forms.

Sitemap 17