Smaller particles make for a better mouthfeel in an ODT; larger particles give a gritty sensation as the tablets disintegrate. For products A and B, in-vitro dissolution testing could be a potential indicator of the product performance in vivo, rather than the disintegration test. Hence, development of new technologies and new disintegrants are still in progress. This material may not be published, broadcast, rewritten, or redistributed withoutpermission. 3099067 Palm Springs, CA, DRUG DEVELOPMENT & DELIVERY Mathias Bayru is Catalent Pharma Solutions Group Product Manager for Drug Delivery Solutions. Samples were withdrawn at standardized intervals and the amount released was quantified using HPLC-UV determination. Existing compendial dissolution methods may be adequate for testing the quality of many ODT formulations. It is not only patients at either end of the age spectrum the very old and the very young who suffer from an inability to swallow, or dysphagia, either, with a recent study indicating that 70% of younger people aged 16-34 who were surveyed reporting that they had difficulties swallowing tablets and capsules. Not only does it offer the potential for a faster onset of action, but by removing that first-pass metabolism of the liver, side-effect profiles can be greatly improved. ODTs has become a common term for dosage forms based on their disintegration patterns, with a multitude of technologies and a wide array of formulation strategies. Regardless of the type of API that is being delivered, the fact that ODTs offer a route to pre-gastric absorption instead of parenteral delivery can offer some significant benefits to patients. Here, the techniques currently available for the dissolution testing of ODTs have been reviewed. Orally disintegrating tablets, fast-diss . : Issue Theme: Orally disintegrating tablets, fast-dissolving, buccal and sublingual formulations, comoglu@pharmacy.ankara.edu.tr tcomoglu@yahoo.com, Medicine, Dentistry, Nursing & Allied Health. The results of the investigation before and after the disintegration are shown in Figure 1. The USP disintegration tester[47] with 700 ml of buffer solution adjusted to pH 6.8 to mimic salivary pH was used. European Directorate for the Quality of Medicines, Council of Europe. Current technologies employed for ODT manufacturing have been thoroughly reviewed elsewhere. As an example, the monoamine oxidase B drug selegeline, used in Parkinsons disease and depression, may cause patients to suffer side-effects. Did you know that with a free Taylor & Francis Online account you can gain access to the following benefits? Montville, NJ 07045 The ingredients are all dissolved or suspended in water, accurately dosed into blister trays, and then frozen in liquid nitrogen freeze tunnels before being placed in freeze dryers. Tel: (973) 299-1200 In many instances, individual quality test methods developed by manufacturers are not reported in publicly available sources, although a number of alternative methods have been published and these are summarized in Table 3. These techniques are lyophilization, tablet moulding, sublimation, spray drying, flash heat process and films. November 1-3 During this time, he has gained expertise in freeze-drying and is a named inventor on several patents related to formulation of lyophilized dosage forms. October 18-19 This has allowed ODTs containing 15 mg of the oil to be created, and an oil-soluble API could be dissolved in this before the tablet is formed. Several process techniques can be involved in production of ODTs. Therefore, if the drug enters the bloodstream directly, these metabolites are not formed and the side-effects they cause cannot occur. ODTs have become a standard dosage form for a number of medicines, where the fast onset of action or ease of dosing are important. As can be seen in the graph in Figure 5, the AUC for the ODT, taken both with and without water, is essentially the same as a standard 10-mg formulation. Recent developments have made it possible to formulate a number of different types of medicine as ODTs that at first sight, one might think would not be compatible with this type of oral dosage form. As an ODT is designed to reside in the mouth for only a number of seconds; it cannot avoid the taste buds. The drug release was complete for both products A and B within the tested time. The composition of saliva produced at varying rates of secretion by the same person with special reference to calcium and phosphorus, A New Method of Characterizing the Buccal Dissolution of Drugs, The composition of unstimulated whole saliva of healthy dental students. No solvent is needed for this coating process. He earned his BSc in Pharmaceutical Science from the University of Greenwich, London and his Masters in Industrial Pharmaceutical Science from the University of Manchester, UK. [3] Thus, the results of the disintegration test allow a given product to be categorized as an ODT formulation. Cited by lists all citing articles based on Crossref citations.Articles with the Crossref icon will open in a new tab. These result from some of the active metabolites generated by liver enzymes, including methamphetamine. While liquid formulations can provide successful dosing options in some cases, the ODT can work in all of these situations. FDA, United States Food and Drug Administration; USP, United States Pharmacopeia. (a) Product A before disintegration. The use of the basket apparatus (USP 1) for dissolution testing of ODTs is also described. And, importantly, the two are bioequivalent. Superdisintegrants, such as crosscarmellose sodium, starch glycolate and crospovidone, are responsible for rapid dissolution in the mouth. The test is only to ensure the complete disintegration of the unit, which is acceptable for dosage forms where dissolution is limited by disintegration. Table 1 contains all the ODTs with the recommended testing methods described in the USP[4] and the FDA database. Prior to the dissolution test, three individual units of the samples were allowed to disintegrate in a 100-mesh basket placed in a 30-ml beaker containing 10 ml of the buffer solution adjusted to pH 6.8 for 60 s. The sample suspension in the beaker was then transferred directly to the dissolution vessel and the testing was carried at 50 rev/min for 1 h using the paddle apparatus (USP 2). However, these dosage forms require more than 1 min to disintegrate in the oral cavity[6] or do not disintegrate at all. For both formulations, disintegration was complete in 60 s. In the case of product A, the disintegrated particles were retained in the 100-mesh basket. This is less than half the size of the smallest particles that can be coated using more traditional coating processes. The loss of bodyweight is indicative of disease severity, and those mice infected with influenza but who were unvaccinated lost significant amounts of weight. Moreover, the presence of a large volume of medium and the mechanical agitation does not accurately reflect the disintegration environment in vivo. By closing this message, you are consenting to our use of cookies. To view this issue and all back issues online, please visit www.drug-dev.com. By avoiding the need for injection, there would be none of the pain, and potential for injection site reactions, that can engender reluctance to immunization among patients and parents. Based on experimental results, it appears that it may be feasible to rely on the dissolution test without a need for disintegration studies for selected ODTs on the market. Chewable Oral Drug Products: What's New with In Vitro Drug Release? Register a free Taylor & Francis Online account today to boost your research and gain these benefits: Orally disintegrating tablets, fast-dissolving, buccal and sublingual formulations, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey, Faculty of Pharmacy, Ankara University, Ankara, Turkey, Pharmaceutical Development and Technology. (d) Product B after a disintegration time of 60 s. Summary of experimental conditions to test the performance of orally disintegrating tablets. 219 Changebridge Road Sublingual formulations exert similar characteristics to orally disintegrating formulations such as the short residence time in the mouth, rapid disintegration and dissolution, both being crucial for drug absorption following administration of sublingual tablets. Cyclodextrins are sugar-based, ring-shaped macromolecules with holes in the middle that can trap smaller molecules inside if they are the right size. For full access to this pdf, sign in to an existing account, or purchase an annual subscription. Orally Disintegrating Tablet and Film Technologies 6th Edition. Recent market studies indicate that more than half of the patient population prefers orally disintegrating dosage forms and most consumers would ask their doctors for ODTs (70%), purchase ODTs (70%). From the industrial point of view, development of different orally disintegrating formulations (tablet, films etc.) The difference between the release profiles of the two can be seen in Figure 2. Subsequently, a non-compendial disintegration method was used. The results of the in-vitro dissolution test for products A and B are given in Figure 2. When the vibrator is activated, the contents begin to accelerate rapidly, and the polymer is deposited around the API. All Rights Reserved. Furthermore, for systemic effect, sublingual route provides faster absorption when compared to buccal route. The decision and requirement of such tests are based solely on product characteristics. Absorption enhancers and bioadhesives can be included in the ODT formulation to promote absorption. Dissolution Methods, Comparative pharmacokinetics and safety of lansoprazole oral capsules and orally disintegrating tablets in healthy subjects, Saliva as an analytical tool in toxicology, Studies on the chemistry of mixed human saliva III. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide, This PDF is available to Subscribers Only. Eur.) If the taste of the active ingredient, or the sensation it generates on the tongue, is not too unpleasant, the simple strategy of including flavor ingredients and sweeteners in the formulation can be sufficient to make it acceptable to patients. In both cases; the hepatic first-pass effect as well as gastric degradation is avoided; therefore, the efficacy is enhanced. Over the past three decades, orally disintegrating tablets (ODTs) as well as films, which require less than a minute to dissolve in the mouth, have gained more attention as an alternative to conventional sublingual, buccal formulations and lozenges. For product B, after the disintegration test, gel formation was observed due to the presence of gelatin in the matrix. The peptide drug calcitonin has been successfully formulated in this way, and vaccine ODTs could be particularly important in the future. A number of technologies are available to create ODTs. The temperature of the test medium was maintained at 37C. When a drug is absorbed within the mouth, it enters the bloodstream directly, thus avoiding the first-pass metabolism by the liver, where side-effect-causing metabolites may be formed. It can be easier to give a medication to a child using an ODT and of course, in the animal health arena, it can be a significant challenge to get pets or livestock to swallow tablets. Although a general product performance test is desirable for orally disintegrating tablets (ODTs), the complexity of the release controlling mechanisms and short time-frame of release make such tests difficult to establish. It is inferred from the results that for the test ODT formulations, prior disintegration has no influence on the release behaviour. They offer significant advantages to both patients and consumers of OTC medications, and although their advantage over conventional tablets is perhaps more obvious when thinking of the young and old, there are many people outside of these groups who have difficulty swallowing tablets and capsules and would welcome an ODT alternative dose form. Compendial and non-compendial apparatus for disintegration testing of orally disintegrating tablets. For conventional oral solid dosage forms (COSDFs), disintegration is often considered to be the prerequisite for subsequent dissolution. The United States Pharmacopeial Convention. technologies and commercialization of these products bring numerous marketing advantages such as expanded product lines, improved life-cycle management and extended patent life. The dissolution conditions were 500 ml of buffer solution adjusted to pH 6.8 for products A and B, and additionally pH 1.2 for product B. In many cases, a single point dissolution is required for ODTs; exceptions include where a controlled release behaviour is intended. Intrabuccaly rapidly disintegrating tablet. ODTs are designed to disperse quickly within the oral cavity, removing the need to swallow a solid tablet or capsule. A summary of the investigation and the test results are given in Table 4. In order to increase the precision of the disintegration method, modification of conventional methods of testing is needed. [49] Suitability of the USP 2 at 100 rev/min has also been reported. [53] As far as the dissolution testing is concerned, it is fair to assume that the application of the Quality by Design concept to link dissolution testing to the clinical quality attributes during the product development phase and to the manufacturing would reduce extensive product quality tests on the end product.[54,55]. This is particularly important for biologic products, such as vaccines, that are destined for developing countries, where access to refrigeration cannot be relied upon, and in pandemic situations, where speed of distribution is key to success. [37,38] Tablet hardness and porosity are directly linked to the disintegration time. Mr. Bayru has more than 12 years of experience in the pharmaceutical industry, and prior to joining Catalents marketing team, held roles as Marketing Manager for several CDMOs and Senior Scientist for Big Pharma companies. This article reviews the current status of dissolution testing of ODTs to establish the product quality standards. These points can be summarized[25,26] as follows: (1) do not require water to swallow and should dissolve or disintegrate in the mouth within a few seconds; (2) allow high drug loading and compatible with taste-masking and other excipients; (3) have a pleasant mouth feel and leave minimal or no residue in the mouth after oral administration; (4) avoid local irritations in particular if used for longterm treatment; (5) exhibit low sensitivity to humidity and temperature; (6) be adaptable and amenable to existing processing and packing machinery; and (7) have sufficient strength towithstand the rigors of the manufacturing process and post-manufacturing handling. Disintegration time monitored by a CCD camera, ODT placed in glass cylinder with a 10 mesh. One way this can be achieved is via the Zydis Ultra formulation. defines them as uncoated tablets intended to be placed in the mouth where they disperse rapidly before being swallowed. For ODTs, a disintegration test would only be used in lieu of dissolution if a relationship between the two performance methods for the product is established. In place of a fluidized bed coating method, in the Zydis Ultra process, API particles are mixed with micronized polymer agglomerates in a vessel that has an acoustic vibrator. Due to the nature of the dosage form and the existing standardized equipment, conventional methods of dissolution testing[48] could be extended to ODTs.
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