Ratnaparkhi et al Journal of Drug Delivery & Therapeutics; 2013, 3(4), 229-236 229 © 2011, JDDT. All Rights Reserved ISSN: 2250-1177 CODEN (USA): JDDTAO Available online at http://jddtonline.info RESEARCH ARTICLE FORMULATION AND EVALUATION OF CHRONOTHERAPEUTIC DRUG DELIVERY SYSTEM OF MELOXICAM * Ratnaparkhi Mukesh P., Khade Ravindra B., Chaudhari Shilpa P. Marathawada Mitra Mandals College of Pharmacy, University of Pune, Pune, India- 411 033 * Corresponding Author’s Tel +919960865355, E mail ID: mukeshparkhi@yahoo.co.in INTRODUCTION Oral controlled release drug delivery systems offer a number of advantages over the conventional immediate release delivery preparations. These systems are designed to deliver the drugs at a controlled and predetermined rate thus maintaining their therapeutically effective concentration in systemic circulation for prolonged period. On the other hand, for certain therapies a pulsatile drug release pattern, where the drug is released after well- defined lag time, exhibits significant advantages. It is well documented that most of the body functions display circadian rhythms, e.g. heart rate, stroke volume, blood pressure, blood flow, body temperature, gastric-pH. 1 Moreover, in a number of organs their functions vary with the time of the day. It is increasingly recognized that there are rhythmic and temporal patterns in the manifestation of many disease states. The symptoms for a number of diseases, such as bronchial asthma, myocardial infarction, angina pectoris, hypertension, rheumatic diseases etc. follow a circadian rhythm. 2 Circadian rhythms are self-sustaining, endogenous oscillations that occur with a periodicity of about 24 Hours. 3 Interestingly, the term circadian is derived from the Latin circa which means “about” and dies which can be defined as “a day”. Normally, circadian rhythms are synchronized according to internal biologic clocks related to the sleep-wake cycle. Our circadian rhythm is based on sleep-activity cycle and is influenced by our genetic makeup and thereby affects our body’s function throughout day and night (24-hour period). Circadian rhythm regulates many body functions in humans like metabolism, physiology, behaviour, sleep pattern, hormone production 4 as many conditions show circadian pattern, advantage could be taken by timing and adjusting the administration of drugs according to the circadian rhythm of the disease. Oral pulsatile administration could be useful for the treatment of certain diseases, such as asthma, gastric ulcer, hypertension, ischemic heart disease, arthritis, etc., which exhibit circadian rhythms. A pulsatile release profile is characterized by a lag time followed by rapid and complete drug release. Most pulsatile systems are reservoir systems and usually covered with a barrier. This barrier can be dissolved, eroded or removed at a predetermined period of time after which the drug is dissolved and rapidly released. Meloxicam is an nonsteroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic properties. Prostaglandins are substances that contribute to inflammation of joints. Meloxicam inhibits prostaglandin synthetase (cylooxygenase 1 and 2) and leads to a decrease of the synthesis of prostaglandins, therefore, inflammation is reduced. 5 Pulsatile drug delivery system is a controlled drug delivery system where drug is released after a pre- programmed lag time. Various approaches have been used to design a pulsatile release formulation, erodible devices provided with hydrophilic polymer coating are widely used and such a system when exposed to dissolution medium undergo swelling, dissolution and/or erosion. Lag time in such a system can be controlled by using various hydrophilic polymers such as HPMC, polyethylene oxide, sodium alginate, sodium CMC. The concentration and viscosity of these polymers play a significant role in controlling the lag time and release pattern. 6 A Capsular system in which the body part coated with impermeable polymer and hydrophilic matrix plug sealing the drug formulation is used to prepare pulsatile drug delivery system. Upon contact with aqueous fluids a rapid dissolution would occur and plug undergoes a gradual swelling and finally expluded from the body thus allowing the drug to release. The lag time in such formulation controlled by the time needed for the plug removal and its duration depends on the physical, chemical nature, size and position of the plug. 7 ABSTRACT The objective of this work is to formulate a pulsatile drug delivery system using Meloxicam drug. The drug delivery system was designed to deliver the drug in such a way that it could be most useful to the patient of rheumatoid arthritis. A core in cup (three component tablet) is prepared where in core tablet, an impermeable material surrounding the tablet except the top and soluble hydrophilic polymer layer at the top is designed. The core tablet contains Meloxicam, ethyl cellulose is used as impermeable membrane and polyethylene oxide used as soluble hydrophilic polymer layer. The release profile of press coated tablet exhibited a lag time followed by burst release, in which outer shell ruptured into two halves. The effect of the core, the polymer characteristics and quantity at the top cover layer, on the lag time and drug release was investigated. The prepared tablets were evaluated for uniformity of weight, hardness, friability, wetting time, in-vitro disintegration time, stability study and drug release study. Fourier transform infrared spectroscopy study showed compatibility between Meloxicam and coating material. Keywords: Pulsatile Release Tablet, Press-coated tablet, Rheumatoid arthritis.