Dissolution Testing of Orally Disintegrating Tablets

1 6 DissolutionTechnologies| MAY 2003 IntroductionOrally Disintegrating Tablets contain a widevariety of pharmaceutical actives coveringmany therapeutic categories, and can beparticularly good applications for pediatric andgeriatric time for disintegration oforally Disintegrating Tablets is generally consideredto be less than one minute [1-4], although patientscan experience actual oral disintegration timesthat typically range from 5-30 seconds. Orally disin-tegrating Tablets are characterized by highporosity, low density, and low , an in-situ suspension is created inthe oral cavity as the tablet disintegrates and issubsequently swallowed.

2 Recently, the Orally Disin-tegrating Tablets terminology has been approvedby the Nomenclature and Labeling committee atUSP (reference Nomeclature Notes, page 8).Although fast Disintegrating and patientpreferred, Orally Disintegrating Tablets are typi-cally not meant to have fastertherapeutic onset. In fact,demonstration of bioequiva-lence is sufficient for productregistration, therefore dissolu-tion profiles which match thatof a reference listed drug areoften sought. Nonetheless, orallydisintegrating Tablets havegained acceptance and marketshare, and have achievedreputable status amongstproduct life cycle managementstrategies.

3 Patented Orally disin-tegrating Tablets technologiesinclude OraSolv , DuraSolv ,Zydis , FlashTab , Wowtab , andothers. Products representativeof these technologies are shownin Table development of Dissolution methods fororally Disintegrating Tablets is comparable to theapproach taken for conventional Tablets , and ispractically identical when the Orally disintegratingtablet does not utilize taste referencelisted drug may have Dissolution conditions in aUSP monograph, and is a good place to start withscouting runs for a bioequivalent ODT. Other mediasuch as N hydrochloric acid, and pH and should be evaluated for Orally disintegratingtablets much in the same way as their ordinarytablet counterparts.

4 Experience has shown that theUSP 2 paddle apparatus is the most suitable andcommon choice for Orally Disintegrating Tablets ,with a paddle speed of 50 rpm commonly , the Dissolution of Orally disintegratingtablets is very fast when using USP monographconditions, hence slower paddle speeds may beutilized to obtain a profile. Large tabletsDissolution Testing of Orally Disintegrating TabletsJames KlanckeSr. Director, Analytical Development, CIMA LABS INC, Brooklyn Park, MNAbstractOrally Disintegrating Tablets (ODT ) are solid dosage forms that disintegrate in the oral cavity leaving aneasy-to-swallow disintegration times are generally less than one minute.

5 For Orally disinte-grating Tablets , taste-masking of bitter or objectional-tasting drug substances is taste-maskingaspect plays a significant role in Dissolution method development, specifications, and USP 2paddle apparatus is the most suitable and common choice for Orally Disintegrating Tablets . Discriminating,robust Dissolution methods are extremely useful for monitoring process optimization and changes duringscale-up of taste-masked bulk drug and tablet Commercial Orally Disintegrating Tablet ProductsProductODT Company/PartnerAlavert Loratadine ODTCIMA/Wyeth Consumer HealthBenadryl Fastmelt Yamanouchi/PfizerClaritin RediTabs Scherer/Schering-PloughTe m p ra FirsTabsCIMA/Mead JohnsonExcedrin QuickTabs Ethypharm/BMSM axalt Scherer/MerckNuLev CIMA/Schwarz PharmaRemeron SolTabs CIMA/OrganonTriaminic SoftChews CIMA/Novartis Consumer HealthZofran ODT Scherer/Glaxo SmithKlineZomig ZMT and

6 RapimeltCIMA/Astra ZenecaZyprexa Zydis Scherer/Eli Lillyemail correspondence: or exceeding one gram and containing rela-tively dense particles may produce a mound in the dissolu-tion vessel, which can be prevented by using higher two situations expand the suitable range to 25 75 USP 1 basket apparatus may have certain appli-cations for Orally Disintegrating Tablets , but is used lessfrequently due to the physical properties of these , tablet fragments or disintegrated tablet massesmay become trapped on the inside top of the basket at thespindle where little or no effective stirring occurs, yieldingirreproducible Dissolution Drives Dissolution Taste-masking of bitter or objectional-tasting drugsubstances is critical for any Orally -adminstered dosageform, including suspensions and chewable Tablets .

7 Lesscommonly, active pharmaceutical ingredients to be incor-porated are tasteless and do not require aspect greatly influences Dissolution methoddevelopment, specifications, and Testing . Several factorsinfluence Dissolution profiles of Orally Disintegrating tabletsthat contain taste-masked actives. Drug particle coatingscan vary in thickness, and certain polymer coatings have pH-dependent solubility such as methacrylates which influencedissolution profiles. Surface wettability of these particles isdependent on composition and may also be dependent onthe process by which they were are multiple approaches to taste-masking andcoating which have applicability to Orally disintegratingtablets and must be understood by method developmentpersonnel.

8 A drug solution or suspension can be applied to asubstrate followed by polymer coating, or the drug particlesmay be coated directly. Alternatively, granulation of the drugwith certain excipients followed by polymer coating canachieve taste-masking. Certain taste-mask coatings are pH-independent, while others are coatingscan dissolve, swell, or become permeable during the disso-lution test depending on the selected media. Coating forcontrolled-release, where taste-masking is a given, can alsobe used and incorporated into fast-dissolve dosage formssince compression forces are low and the controlled-releaseparticles remain intact.

9 If the drug is tasteless or very lowdose, direct blend of bulk drug substance into fast-dissolvematrix is straightforward, and the Dissolution profile is influ-enced primarily by properties of the drug disintegration time of Orally Disintegrating Tablets in adissolution vessel is generally less than thirty seconds andtherefore not an important factor in the resulting dissolu-tion profile in terms of discrimination isbased on taste-masked coating and the active ingredientitself. Since Orally Disintegrating Tablets are of low density,floating particles may be observed even after completetablet disintegration has taken disintegrationtime of an ODT is obvious to patients and product develop-ment specialists, so in-vivo and in-vitro times are oftencompared during the development fast disin-tegration makes it very important to observe how the tabletfragments and particles are behaving during the dissolutiontest compared to conventional Tablets , which typicallydisplay much less breakup at the bottom of the vessel earlyin the with all solid oral dosage forms.

10 Dissolution serves as acontrol same is true for taste-masked bulk consistency can be assured, and dissolutiondata on the taste-masked drug is frequently predictive ofdissolution of the tableted USP 2 paddle appa-ratus at 50-100 rpm is suitable for Dissolution Testing oftaste-masked drug as media used for the taste-masked drug should match that of the finished product tomaximize the value of the are certain cases whereit may be advantageous to use increased paddle speed fortaste-masked drug in order to better match the Orally disin-tegrating Tablets profile. Dissolution as a stability test fortaste-masked drug is indicative of performance of coatingover time and is a meaningful test in stability (for bulk warehousing) specifications shouldmatch the release of taste-masked bulk drug is an important testmethod for both product development and quality Q-type specifications are not applicable since it is notrepresentative of finished dosage unit (but rather is ahomogenous sample).