NSAIDs As Microspheres

Mathew T. Sam; Devi S. Gayathri; V.V. Prasanth; B. Vinod

摘要

Nonsteriodal anti-inflammatory drugs (NSAIDs) are amongst the most commonly prescribed medications in the world. Almost all the NSAIDs available in the market have severe side effects. As awareness of the GI side effects associated with NSAIDs increases, safety becomes a primary requisite in treatment. A trend in NSAID development has been to improve therapeutic efficacy and reduce the severity of GI side effects through altering dosage forms by modifying release of the formulations to optimize drug delivery. One such approach is using polymeric microspheres as carriers of drugs. A brief review of the NSAIDs which are incorporated into microspheres, the polymers used, various methods of preparation, in vitro and in vivo evaluation are given in this review with more importance to methods adopted. Introduction Non steroidal anti-inflammatory drugs (NSAIDs)The use of Nonsteriodal anti-inflammatory drugs (NSAIDs) began over 100 years ago with the introduction of salicylic acid for the treatment of rheumatic diseases. Now NSAIDs are amongst the most commonly prescribed medications in the world owing to their efficacy as anti-inflammatory, anti-thrombotic, anti-pyretic, and analgesic agents. During the past 30 years, there has been a substantial increase in the number of clinically available NSAIDs. They annually account for 70 million prescriptions and 30 billion over-the-counter (OTC) medications sold in the United States alone. (1) Despite the diversity of their chemical structures, these NSAIDs all share the same therapeutic properties alleviating swelling, redness and pain of inflammation, reducing fever and curing headache. However, numerous reported adverse drug reactions, case-control, and post-marketing surveillance studies have revealed that NSAIDs are associated with extensive side effects, the most prevalent being GI disturbances (2).Side effects also include interfering with the birth process and damaging the kidney. Indeed epidemiological studies have characterized the degree of gastric damage caused by different compounds. An estimated 34-46% of the patients on NSAID therapy would have some form of GI side effects. In USA alone some 100000 patients on NSAIDs are hospitalized each year because of perforations, ulcers, or bleeding in the stomach and about 15000 of these die in intensive care (3). Koch M et al studied the average risk for GI ulceration and reported that gastric ulcers were 3.6% and 6.8% with up to2 weeks and more than 4 weeks use of NSAIDs, and duodenal ulcers the average risks were 3.0% and 4.0% with <2 weeks and >4 weeks use of NSAIDs respectively. (4)These adverse effects are dose-dependent, and in many cases severe enough to pose the risk of ulcer perforation, upper gastrointestinal bleeding, and death, limiting the use of NSAID therapy. NSAIDs exert their clinical effects by inhibiting cyclooxygenase (COX), thereby blocking the synthesis of prostaglandins. Cyclooxygenase exists in at least two different isoforms COX-1 and COX-2. COX- 1 is expressed constitutively and is present in most cells under physiological conditions, whereas COX-2 is induced in response to inflammatory stimuli. A major change in the use of NSAIDs occurred with the discovery of COX-2 inhibitors. In the beginning it was thought that COX- 2 inhibitors eliminate the side effects of COX-1. But the latest findings from clinical trials and other sources reported that their side effect profile is almost similar to that of older NSAIDs. These COX-2 inhibitors are contraindicated in kidney dysfunction and congestive heart failure where the extent of effect is severe than in the case of some COX-1 inhibitors (5). More reports on safety have to come for the complete acceptance of COX- 2 inhibitors. Therefore older COX-1 NSAIDs are still in use. More over many of the COX- 2 inhibitors available now are having higher elimination half-life. There fore there is no much potential in formulating them into controlled release dosage forms. Hence

机译：非甾体抗炎药（NSAIDs）是世界上最常用的处方药。市场上几乎所有的NSAID都有严重的副作用。随着对与NSAIDs相关的GI副作用的认识的提高，安全性成为治疗的主要要求。 NSAID发展的趋势是通过改变剂型通过改变制剂的释放以优化药物递送来改善治疗功效并降低胃肠道副作用的严重性。一种这样的方法是使用聚合物微球作为药物载体。本文简要介绍了掺入微球的NSAID，使用的聚合物，各种制备方法，体外和体内评估，其中对采用的方法更为重视。简介非甾体类抗炎药（NSAIDs）的使用非甾体类抗炎药（NSAIDs）始于100多年前，当时引入了水杨酸用于治疗风湿病。现在，由于它们作为抗炎药，抗血栓药，抗退热药和镇痛药的功效，NSAID已成为世界上最常用的处方药。在过去的30年中，可临床使用的NSAID的数量已大大增加。仅在美国，它们每年就销售7000万张处方药和300亿种非处方药。（1）尽管它们的化学结构各不相同，但这些NSAID都具有相同的治疗特性，可减轻肿胀，发红和发炎的疼痛，减少发烧并治愈头痛。然而，大量报道的药物不良反应，病例对照和上市后监测研究表明，非甾体抗炎药与广泛的副作用有关，最普遍的是胃肠道疾病（2）。副作用还包括干扰生育过程和损害。肾脏。确实，流行病学研究已经表征了由不同化合物引起的胃损害程度。估计有34-46％的接受NSAID治疗的患者会有某种形式的GI副作用。仅在美国，每年就因穿孔，溃疡或胃出血而住院治疗的非甾体抗炎药患者约为100000例，其中约15000例因重症监护而死亡（3）。 Koch M等人研究了胃肠道溃疡的平均风险，并报告使用NSAID长达2周和4周以上的胃溃疡分别为3.6％和6.8％，而十二指肠溃疡的平均风险分别为3.0％和4.0％，<2使用非甾体抗炎药的时间分别为2周和4周以上。（4）这些不良反应是剂量依赖性的，并且在许多情况下严重到足以引起溃疡穿孔，上消化道出血和死亡的风险，从而限制了NSAID疗法的使用。 NSAID通过抑制环氧合酶（COX）发挥其临床作用，从而阻止前列腺素的合成。环氧合酶存在于至少两种不同的亚型COX-1和COX-2中。 COX-1组成型表达，并在生理条件下存在于大多数细胞中，而COX-2是响应炎症刺激而诱导的。 NSAIDs的使用发生了重大变化，这是因为发现了COX-2抑制剂。起初，人们认为COX-2抑制剂可消除COX-1的副作用。但是，临床试验和其他来源的最新发现表明，它们的副作用几乎与较老的NSAID相似。这些COX-2抑制剂禁忌肾功能不全和充血性心力衰竭，其作用范围比某些COX-1抑制剂严重（5）。为了完全接受COX-2抑制剂，还必须有更多的安全性报告。因此，较旧的COX-1 NSAID仍在使用。现在，许多可用的COX-2抑制剂具有更高的消除半衰期。因此，将它们配制成控释剂型没有太大的潜力。因此

NSAIDs As Microspheres

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