Review Article NUTRACEUTICAL FORMULATIONS CONTAINING GLUCOSAMINE AND CHONDROITIN SULPHATE IN THE TREATMENT OF OSTEOARTHRITIS: EMPHASIS ON CLINICAL EFFICACY AND FORMULATION CHALLENGES AHMED M. AGIBA Research and Development Department, SIGMA Pharmaceutical Industries, Egypt Email: ahmed.agiba@gmail.com Received: 27 Nov 2016, Revised and Accepted: 23 Jan 2017 ABSTRACT Osteoarthritis (OA) is essentially a debilitating disease symptomatized by a gradual loss of articular joint cartilage, causing painful impairment among the population of different ages, particularly patients over the age of 50 y. Nutraceuticals; namely glucosamine and chondroitin have been widely used in the treatment of OA. The chondroprotective properties of the aforementioned agents have been reported, allowing the repair and recovery of the articular surface in OA. The purpose of this review article is to report the current evidence for the use of glucosamine and chondroitin sulphate in the treatment of knee OA with emphasis on their indications for clinical use, effectiveness and safety. It also highlights the role of some advanced formulation technologies in optimizing the delivery of those drugs. Keywords: Osteoarthritis, Glucosamine, Chondroitin, Clinical use, Formulation technologies © 2016 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) DOI: http://dx.doi.org/10.22159/ijcpr.2017v9i2.17380 INTRODUCTION Osteoarthritis (OA), also known as degenerative joint disease, degenerative arthritis or osteoarthrosis, is the most common musculoskeletal disease affecting the whole synovial joint [1]. It is believed that cartilage is not the sole organ being affected by OA, but also ligaments, synovia and bone, which undergo metabolic and structural modifications as the disease progresses. OA is the prominent form of arthritis; its prevalence increases dramatically with age [2], and can lead to significant pain, reduced range of motion and increased disability [3]. As a result, it is considered a disabling arthritic condition that causes activity limitation and reduced quality of life among the population over the age of fifty. It has been estimated that each year, more than 75% of individuals over the age of 65 present with OA in one or more joints [4]. In addition, some studies have shown that 12.1% of American individuals over the age of 25 y show clinical symptoms of OA [5]. OA is characterised by a gradual loss of articular cartilage in synovial joints, causing articular cartilage destruction with subsequent loss of joint space. Clinical manifestations of this disease are joint pain and damage, stiffness, effusion, instability, and ultimately, deformity. Genetic and nutritional factors mainly contribute to the etiology of OA, in addition to other biological, biochemical and mechanical factors [5, 6]. It is believed that the primary OA is characterized by mechanical, repetitive overloading of the articular cartilage, which leads to a vicious circle of inflammation, degradation and loss of joint cartilage. This inflammation is mainly attributed to the secretion of interleukin-1 (1L-1) and a monocyte-derived cytotoxin (i.e. tumor necrosis factor TNFα), which increase metalloproteinases and nitric oxide synthase production, which are the main catabolic agents in joint cartilage lesions [6-8]. A demand for OA treatment is gradually increasing each year due to the rise in its prevalence caused by the dramatic increase in average life expectancy among the population, with a higher degree of degenerative joint arthritis [9]. The pathogenic complexity of OA creates a challenge for diagnosis and management of this disease, which mainly relies on symptomatic treatment and improvement of patients’ functional abilities. Treatment mainly includes a combination of pharmacological and non-pharmacological methods (physiotherapy, occupational therapy, weight loss and exercise). In addition, alternative therapies, such as; homeopathy, acupuncture, phytotherapeutic medications; and surgical methods are also utilized [10]. The pharmacological therapy is directed towards the prevention of pain and improvement of function among patients with OA. The first choice medications in the pharmacological treatment of OA-related pain include analgesics (acetaminophen and paracetamol) and non-steroidal anti- inflammatory drugs (NSAIDs) [11, 12]. However, some studies have indicated that NSAIDs are only used to treat symptoms without correction of the degenerative disorder of the connective tissue. Furthermore, the long-term use of NSAIDs causes potential adverse effects on the gastrointestinal and cardiovascular systems, which are mainly popular among elderly patients [13]. Therefore it can be deduced that medical treatments available for OA are moderately effective and are mostly directed at short-term pain relief, In addition, side effects of these treatments can be quite significant. The need for the development of new drug treatments for OA that could systemically relieve pain and potentially modify structural damage has emerged. Nutraceuticals such as glucosaminoglycans (GAGs) have recently been introduced as biological alternatives for drug treatment since there is a substantial interest in the chondroprotective effects of GAGs such as glucosamine sulphate and chondroitin sulphate. Both of these drugs have been approved as agents that modify the natural history of OA [14]. Glucosamine sulphate and chondroitin sulphate are natural nutraceutical compounds which are known as cartilage precursors. They are not only considered as symptomatic drugs for OA, but they also have a disease-modifying potential, hence, they have gained worldwide popularity over the last decades [15]. This review article focuses on those two compounds for the treatment of OA. Preparations, dosages, bioavailability and pharmacokinetics of glucosamine Glucosamine, 2-amino-2-deoxy-D-glucose (C6H14NoO5), is a monosaccharide with a molecular weight (197.2 Da). It is naturally produced in the body and acts as a precursor for the biosynthesis of glycosylated lipids and proteins. Functionally, glucosamine is a prominent precursor for GAGs or mucopolysaccharides and is structurally belonging to glycoproteins and proteoglycans. Glucosamine helps in the maintenance of healthy joint function, primarily targeting people suffering from OA. Although glucosamine has not been approved yet by FDA as a drug of choice in the treatment of OA, it is prescribed as a first-line drug in OA treatment in Europe [16]. International Journal of Current Pharmaceutical Research ISSN- 0975-7066 Vol 9, Issue 2, 2017