Inventi Rapid: Pharmacokinetics & Pharmacodynamics Vol. 2013, Issue 2 [ISSN 2278-4101] 2013 pkd 97, CCC: $10 © Inventi Journals (P) Ltd Published on Web 12/04/2013, www.inventi.in RESEARCH ARTICLE INTRODUCTION Piroxicam (PIRO) is a nonsteroidal anti-inflammatory drug (NSAID) of the oxicam family that has been recognized for its value as a chemopreventative, anti-tumor agent, acute and chronic musculoskeletal and joint disorders such as ankylosing spondylitis, osteoarthritis, rheumatoid arthritis, dysmenorrhoea and sometimes for pain associated with it. [1] Oxicams derive their anti inflammatory effect from inhibition of cyclooxygenase (COX) activity and subsequent repression of prostaglandin synthesis. Two forms of COX are currently recognized. Cyclooxygenase-1 is found in the stomach, gastrointestinal tract, platelets and kidney. It is this form that is responsible for most of the side effects associated with NSAIDs. [2] Cyclooxygenase-2 (COX-2) predominates at areas of inflammation, immune reaction, and increased cellular activity. Although the precise anti-tumor mechanisms of PIRO and other NSAIDs are unknown, some have suggested that they may be secondary to the aforementioned COX and PG inhibition. [3] For poorly soluble, highly permeable (class II) drugs (like piroxicam), the rate of oral absorption is often controlled by the dissolution rate in the gastrointestinal (GI) tract. [2] Therefore, together with permeability, the solubility and dissolution behaviour of a drug are key determinants of its oral bioavailability. This undesired property, may also increase the amount of GI damage, due to long contact of drug with the mucous of G. [4] The pharmacokinetics of PIRO have been evaluated in humans, monkeys, rats, rabbits, and dogs. PIRO is almost completely absorbed following oral (p.o.) administration with a long apparent terminal half-life (t 1/2 ) in all species evaluated. Once absorbed, it undergoes enterohepatic recirculation and extensive metabolism in the dog, rabbit, and humans, with only a small amount of the drug being excreted unchanged, Neither hepatic disorders nor 1 Tatyasaheb Kore College of Pharmacy, Warananagar, Kolhapur, M. S., India. E-mail: santosh14july@rediffmail.com *Corresponding author 2 Bharti Vidyappeth’s College of Pharmacy, Kolhapur, M.S., India. disruption of the cytochrome P-450 system alter the elimination rate of PIRO. However, as part of the metabolism of PIRO in humans, a glucuronide conjugate is formed. Rabbits are limited in their ability to form glucuronide conjugates. The potential usefulness of this drug in rabbits, the long t 1/2 , the presence of a glucuronide conjugate, and the likelihood of adverse effects make it important to determine the pharmacokinetics and bioavailability (F) of PIRO in rabbit. The purpose of this study was to determine these factors after both a single intravenous (i.v.) and p.o. administration. [3] The studies described in this work were designed to evaluate a new sublingual tablet system using low doses of piroxicam. In this system, water-soluble carrier particles are covered with piroxicam and a bioadhesive material during dry mixing. In principle, the tablet quickly disintegrates into the ordered units consisting of carrier, piroxicam and bioadhesive component. These units initially adhere to the mucosa. The water-soluble carrier particles gradually dissolve and piroxicam dissolves along with them. With this approach, optimal exposure of active substance to the dissolving fluid is combined with bioadhesive retention of the drug in the oral cavity. [5] The main objective of this report is to investigate single dose pharmacokinetics after administration of mucoadhesive fast disintegrating piroxicam tablet and marketed formulation in rabbit and observed the improved systemic exposure of the parent drug, especially regarding absorption rate. MATERIALS AND METHODS Reagents and Samples All the Analytical grade materials were used. Piroxicam reference standard was collected from Asoj Soft Caps. Pvt. Ltd., India. Mucoadhesive fast disintegrating tablets were formulated using mannitol, sodium croscramellose (SCC), microcrystalline cellulose (MCC), dicalcium phosphate (DCP), magesium stearate and mango flavor as an excipient. Acetonitrile (HPLC grade), Distilled water (HPLC grade) were used as analytical grade solvent for analysis purpose. [6, 7] All the excipients and solvents were purchased from Loba Cheme, Mumbai. Single Dose Pharmacokinetics of Mucoadehsive Fast Disintegrating Sublingual Tablet of Piroxicam in Rabbits Kate V K 1 , Payghan S A 1* , Shinde A J 2 Abstract: Oromucosal delivery, especially that utilising the buccal and sublingual mucosa as the absorption site, is a promising drug delivery route which promotes rapid absorption and high bioavailability, with subseqent almost immediate onset of pharmacological effect. These advantages are the result of the highly vascularised oral mucosa through which drugs enter the systemic circulation directly, thus bypassing the gastrointestinal tract and the first pass effect in the liver. MFD tablet of piroxicam (PX) are subjected to in-vivo pharmacokinetic evaluation to evaluate whether these systems improve oral bioavailability of the piroxicam. All the pharmacokinetic parameters of absorption, namely Ka, Cmax, Tmax, percent absorbed to various times and AUC indicated rapid absorption and higher bioavailability of piroxicam when administered as MFD Tablet. The absorption rate constant (Ka) was found to be increased compare with marketed formulation. Both Ka and AUC were markedly increased by MFD tablet. Thus, the results of pharmacokinetic studies indicated rapid and higher oral absorption of piroxicam when administered as MFD tablet. 1