72 Bioinfo Publications IJMCR International Journal of Medical and Clinical Research ISSN: 0976-5530 & E-ISSN: 0976-5549, Volume 2, Issue 2, 2011, pp-72-77 Available online at http://www.bioinfo.in/contents.php?id=39 IN VITRO DISSOLUTION AND PILOT PHARMACOKINETIC STUDIES OF ACETYLSALICYLIC ACID FROM AN ORALLY DISINTEGRATING TABLET FORMULATION OF LOW-DOSE ASPIRIN YOUSIF ROJEAB 1,* , SHANE MARTIN B. 2 , ROBIN WHITE 3 , SUSAN MONTENERY 3 , MARY MCWILLIAMS 3 , MARJORIE WALKER 3 AND DAVID KISOR 1 1 Department of Pharmaceutical and Biomedical Sciences, 2 Department of Pharmacy Practice, College of Pharmacy, Ohio Northern University, Ada, Ohio, 45810, USA 3 Department of Nursing, Ohio Northern University, Ada, Ohio, 45810, USA * Corresponding Author: E-mail: y-rojeab@onu.edu, Tel: +1-419-772-3957, Fax: +1-419-772-1917 Received: November 21, 2011; Accepted: December 01, 2011 Abstract- Purpose: Low-dose aspirin (acetylsalicylic acid; ASA) is in routine use today in preventing myocardial infarction and cardiovascular events. Fasprin® (ASA, 81 mg) is a new orally disintegrating tablet formulation of low-dose ASA (ODA) that was designed as a fast-acting, quick-dissolving solid dosage form. The purpose of this work was to (1) evaluate, comparatively, the in vitro dissolution, and (2) evaluate the absorption kinetics of ASA in healthy adults following oral administration of the ODA product. Methods: USP type II dissolution apparatus was implemented in the dissolution studies. For the pharmacokinetic studies, a single ODA dose was administered and blood samples were collected and analyzed for ASA content using a validated HPLC method. Absorption-related pharmacokinetic parameters were estimated using WinNonlin®. Results: Dissolution rate and extent of ASA from the ODA formulation were either higher than or similar to those from leading aspirin-containing products. Noncompartmental pharmacokinetic analysis of ASA plasma profiles from the ODA product revealed a lag-time of at least three minutes. The maximum concentration (Cmax) of ASA was 0.61 µg/mL and the time of Cmax (tmax) ranged from 15 - 75 minutes. The elimination rate constant of ASA was 0.0245 min -1 , corresponding to a terminal t½ of 28.3 minutes. Conclusion: The ODA product demonstrated favorable dissolution compared to some leading ASA-containing products. It also provided systemic concentration of ASA at a relatively early time. While the overall absorption kinetics of the ODA product was generally comparable to those from other low-dose ASA-containing products, a direct product comparison is warranted. Keywords- low-dose aspirin, Fasprin ® , ASA, dissolution, pharmacokinetics, absorption Introduction In 1988, the United States Food and Drug Administration moved forward on approving the use of aspirin (acetylsalicylic acid; ASA) for reduction of the risk of a second or subsequent myocardial infarction, and prevention of an initial incidence of myocardial infarction (Bayer HealthCare LLC 2008; Food and Drug Administration 2008). This along with the approval of ASA as an agent to prevent transient ischemic attacks and stroke in men moved aspirin beyond its anti- inflammatory indication. Since that time, ASA has been shown time and time again to be effective in preventing myocardial infarction in a number of patient populations. A decade later, the results of studies further supported the effectiveness of ASA, this time in prevention of cardiovascular events in patients at risk [1]. In 2005, the benefits of ASA use in women with respect to lowering the risk of stroke were documented [2]. To this day, ASA is recommended by the American Heart Association and the U.S. Preventive Services Task Force for patients at moderate risk for cardiovascular events (American Heart Association 2008; United States Department of Health and Human Services). The mechanism of action of ASA involved permanent inhibition of cyclooxygenase1 - dependent platelet aggregation [3]. Specifically, ASA irreversibly acetylates the cyclooxygenase1 enzyme at a serine side chain [4, 5]. This acetylation of the enzyme inhibits the synthesis of thromboxane A2, a key mediator in platelet activation, from arachidonic acid [5]. Owing to its irreversible effect on platelets aggregation, small doses of ASA administered chronically should be as effective as much larger doses [6]. In addition to its protective indications within the cardiovascular system, use of daily ASA for about 5 years has been shown to be effective in primary prevention of colorectal cancer in randomized controlled trials, with a latency of about 10 years [7]. While doses