An In Vitro Analysis of Disintegration Times of Different Formulations of Olanzapine Orodispersible Tablet: A Preliminary Report

Abstract

BackgroundOrodispersible tablets (ODTs) are tablet or wafer forms of medication that disintegrate in the mouth, aided only by saliva. ODTs rely on different fast dissolve/disintegration manufacturing technologies.ObjectivesDisintegration time differences for several olanzapine ODT forms were investigated. Risperdal M-Tab® was included as a non-olanzapine ODT comparator.Research Design and MethodsEleven olanzapine ODT examples and orodispersible risperidone strengths were evaluated in vitro for formulation composition, manufacturing method, disintegration and dissolution characteristics, and formulation differences in comparison with freeze dried Zydis® ODT. Automated dissolution test equipment captured ODT dissolution rates by measuring real-time release of active ingredient. A high-speed video camera was used to capture tablet disintegration times in warm simulated saliva.Main Outcome MeasureThe main outcome measure was the disintegration and dissolution characteristics of the ODT formulations.ResultsThe ODT manufacturing method was associated with time to disintegrate; the fastest were freeze dried tablets, followed by soft compressed tablets and then hard/dense tablets. Olanzapine Zydis® was the only ODT that completely disintegrated in less than 4 s for all strengths (5, 10, 15, and 20 mg), followed by 5-mg Prolanz FAST® (12 s) and then risperidone ODT 4 mg (40 s). Reasons for slow dissolution of the olanzapine generics may include low product potency, excipient binding, excipient solubility, active ingredient particle size and incomplete disintegration.ConclusionsDifferences in the formulation and manufacturing process of olanzapine ODTs appear to have a strong influence on the disintegration time of the active compound; differences that may potentially impact their use in clinical practice.Electronic supplementary materialThe online version of this article (doi:10.1007/s40268-013-0030-8) contains supplementary material, which is available to authorized users.

Evaluation and Comparison of Three Types of Spray Dried Coprocessed Excipient Avicel® for Direct Compression

“…One gram of the sample was dried in hot air oven (60°C, 4 h) and dissolved in 900 mL of artificial saliva by stirring (600 rounds per minute) in mechanical stirrer for 24 hours. Artificial saliva was prepared according to the formula as observed in the study Hobbs et al [ 17 ]. The following procedure coincided with the first evaluation method.…”

Investigation of biopharmaceutical drug properties suitable for orally disintegrating tablets

“…An orally disintegrating tablet (ODT) improves patient compliance because it can be taken without water, does not cause dysphagia, and can prevent patients from spitting out their medication [1,2]. Many pharmaceutical companies are working on the development of ODTs.…”

Orally disintegrating olanzapine review: effectiveness, patient preference, adherence, and other properties

“…ODO may also have benefits over SOT in terms of nursing burden and patient preferences, and this should be taken into consideration when making treatment decisions. While other rapidly dissolving generic formulations of olanzapine are available in various countries around the world, given the ostensibly important role of physical characteristics in determining patient preference and adherence, the recent comparative dissolution study of Hobbs et al26 suggests that the majority of findings (other than bioequivalence) reviewed here may not necessarily be extrapolated to these other formulations.…”

“…In a recent in vitro study by Hobbs et al, differences in disintegration and dissolution time of the active ingredient (along with a number of other parameters) of twelve types of mouth-disintegrating olanzapine tablets (including ODO), along with Risperdal M-Tab ® as a comparator, were investigated using automated dissolution test equipment. 26 While this study is the subject of a manuscript in preparation and will not be described here in detail, ODO disintegrated and dissolved (ie, released active ingredient) more rapidly in a solution of synthetic saliva than any of the generic tablets. Some of the generic tablets were also found to leave a coarse insoluble residue from the excipients used.…”