An analytical approach for determination of amoxicillin and potassium clavulanate in pharmaceutical dosage form review

Modern medicines for human use are required to comply with specific standards and regulation set forth by the concerned authorities. The efficacy and safety ofmedicinal products can only be assured by analytical monitoring of its quality. Pharmaceutical analysis is an art and science of determining the concentration of drugconstituents present in marketed formulation. It is considered as an application of procedures necessary to determine and estimate the identity, strength, quality andpurity of drug. Therefore, the quality control laboratory is considered as the backbone of the pharmaceutical industries with ever-increasing need for the developmentof analytical techniques for drug formulation. In the present review a successful attempt was made to focus various analytical methods available to estimation of amoxicillin sodium and potassium clavulanate in bulk as well as in pharmaceutical dosage form.INTRODUCTIONPharmaceutical industries are coming up with new products, which are virtually a combination of different drugs rather than a single drug alone. Because there is a generalized fact that a combination of drugs have a wider range to treat ailments as compared to the single drug component, therefore industries launches its multicomponent formulations to meet the demand of the market. Pharmaceutical analysis, a branch of pharmacy plays the key role in quality control of pharmaceuticals, through rigid check of raw materials, in process quality of product and finished product[1]. Quality of drugs can only be maintained by developing analytical methods with high degree of accuracy and precision and should satisfy all othervalidation parameters[2-4]. Validation of analytical methods is an important and mandatory aspect of their development or utilization and is widely required on support of industrialproduct development and regulation so methods developed and utilized for analytical monitoring of products must be validated[5-8]. Regardless of the various pharmacopeias and reported methods available, development of procedures that is simple, rapid, precise, and economical and gives a clear separation of drugs is barely needed to maintain the quality of pharmaceuticals. It may be a difficult task, but can be achieved by giving a sincere effort[9].Amoxicillin is a member of the penicillin family[10]. The penicillin nucleus consists of a thiazolidine ring connected to a ß-lactam ring to which is attached a side-chain. The side-chain determines most of the pharmacological and antibacterial properties of the penicillin in question[11]. In the case of amoxicillin the benzyl ring in the side chain extends the range of antimicrobial activity into the Gram-negative bacteria. Amoxicillin kills bacteria by interferingwith the synthesis of the bacterial cell wall. As a result the bacterial cell wall is weakened, the cell swells and then ruptures. Amoxicillin is readily hydrolysed by the staphylococcal penicillinase[12,13].Clavulanic acid, produced by the fermentation of Streptomyces clavuligerus, is a beta-lactam structurally related to the penicillins[14]. Clavulanic acid competitively and irreversibly inhibits a wide variety of beta-lactamases, commonly found in microorganisms resistant to penicillinsand cephalosporins[15]. By inactivating beta-lactamase (the bacterial resistance protein), spectrum of activity of amoxicillin is extended by administration with the ß-lactamase inhibitor clavulanic acid, thus clavulanic acid is used in conjunction with amoxicillin for the treatment of bronchitis and urinary tract, skin, and soft tissue infections caused by betalactamase producing organisms.

供人类使用的现代药物需符合主管当局制定的特定标准与法规。药品的有效性与安全性唯有通过对其质量开展分析监测方可得到保障。药物分析（Pharmaceutical analysis）是测定市售制剂中药物成分浓度的技艺与科学，其被视作用于确定、评估药物的身份、效价、质量与纯度的必要应用流程。因此，质量控制实验室被视为制药工业的支柱，而药物制剂分析技术的开发需求与日俱增。本综述旨在系统性梳理可用于测定原料药及药物制剂中阿莫西林钠与克拉维酸钾的各类分析方法。

引言：制药工业近年来不断推出新产品，这类产品大多为不同药物的复方组合，而非单一药物制剂。普遍认知中，复方药物相较于单一药物成分，拥有更广泛的病症治疗谱，因此工业界推出多组分制剂以契合市场需求。药物分析作为药学的分支学科，通过对原料药、生产过程中间体质量以及成品的严格检测，在药品质量控制中发挥核心作用[1]。药品质量的维持，有赖于开发具备高精度与高准确度的分析方法，并满足所有相关验证参数要求[2-4]。分析方法验证是方法开发与应用过程中不可或缺的重要环节，在工业产品开发与监管支撑中被广泛要求，因此用于产品分析监测的方法必须经过验证[5-8]。尽管现有各类药典与已报道的分析方法，但开发简便、快速、精准、经济且可实现药物清晰分离的分析程序，仍是保障药品质量的迫切需求。这一目标虽具挑战性，但通过潜心钻研可得以实现[9]。

阿莫西林（Amoxicillin）属于青霉素类家族成员[10]。青霉素母核由噻唑烷环与β-内酰胺（beta-lactam）环相连构成，该环上连有侧链，侧链决定了目标青霉素的绝大多数药理与抗菌特性[11]。就阿莫西林而言，其侧链上的苯环将抗菌活性范围拓展至革兰氏阴性菌（Gram-negative bacteria）。阿莫西林通过干扰细菌细胞壁的合成杀灭细菌，致使细菌细胞壁被削弱、细胞膨胀最终破裂。阿莫西林易被葡萄球菌青霉素酶水解[12,13]。

克拉维酸（Clavulanic acid）由棒状链霉菌（Streptomyces clavuligerus）发酵制备，其结构与青霉素类药物同源，属于β-内酰胺类化合物[14]。克拉维酸可竞争性且不可逆地抑制多种β-内酰胺酶（beta-lactamase），这类酶广泛存在于对青霉素与头孢菌素类药物耐药的微生物中[15]。通过灭活β-内酰胺酶（细菌耐药性蛋白），与β-内酰胺酶抑制剂克拉维酸联用可拓展阿莫西林的抗菌谱，因此克拉维酸常与阿莫西林联合使用，用于治疗由产β-内酰胺酶的微生物引发的支气管炎、尿路感染、皮肤及软组织感染。