Kołodziejczyk Michał Krzysztof, Kołodziejska Justyna, Zgoda Marian Mikołaj
Zakład Technologii Postaci Leku, Katedra Farmacji Stosowanej, Uniwersytet Medyczny w Łodzi.
Polim Med. 2012;42(2):121-32.
Diclofenac and its sodium salt is one of the best-known and popular therapeutic agents from the group of NSAIDs used in medicine in many various pharmaceutical forms. Therapeutic products containing diclofenac sodium salt in doses of 100 mg and 75 mg with a qualitatively and quantitatively diversified share of excipients and a variable dosage form of the drug (solid capsules, tablets with modified release) were subjected to technological and pharmaceutical analysis. The effect of solid formulation components of polymer character making the core and the coating of the pharmaceutical form of therapeutic products on the disintegration time and pharmaceutical availability in pharmacopoeial receptor fluids was estimated.
Market therapeutic products with diclofenac sodium in doses of 75 mg and 100 mg, technological analysis of the drug dosage form was conducted, disintegration time of solid oral dosage forms of the drug with diclofenac sodium salt was examined and research on pharmaceutical availability of diclofenac sodium salt from tested therapeutic products was conducted using the acid phase and the buffer phase according to the FP standards for delayed release enteral dosage forms. The experimental data was supplemented with the statistical analysis.
There are three formulations in the form of solid capsules and one formulation in the form of a coated tablet. All therapeutic products bear features of a dosage form of modified release of diclofenac sodium salt, frequently of a delayed release formula in the duodenum or the small intestine with regard to the limitation of typical undesirable effects after taking NSAIDs. Considerable diversity between solid capsules and the tablet with modified release during disintegration or hydration and swelling has been observed. In the environment of a receptor fluid--purified water (pH = 7) the capsule Dicloberl retard disintegrates at the fastest rate in 5,49 minutes, and then in the order: DicloDuo 75 mg--8,13 minutes and Olfen 100 SR--11,27 minutes. The hydration degree of gelatin walls of capsules depends on the pH of the receptor fluid. The availability of diclofenac sodium salt in given receptor fluids confirms the fact of significant connection of clinical effectiveness of the tested pharmaceutical forms with the activity of hydrogen ions (pH) of the environment in which there are therapeutic products, and excipients used for making the pharmaceutical phase.
Tested therapeutic products with diclofenac sodium salt are differentiated by the type of a dosage form. Dicloberl retard contains the minimally indispensable number of simple, commonly used excipients. The research on the disintegration time may only be related to the products Dicloberl retard, Olfen 100 SR and DicloDuo 75 mg treating it as the time of deformation and disintegration of a capsule. In all three types of receptor fluids, the capsule Dicloberl retard has the fastest disintegration rate. The "acid phase" demonstrated stability of the products with a slight dissolution of diclofenac sodium salt on the level 1,3-4,18% of the Q release coefficient. In the environment of artificial intestinal juice, Dicloberl retard is more effective releasing larger amounts of diclofenac sodium salt during 4 hours of exposition (differences from 10% to 14% of the Q release coefficient).
双氯芬酸及其钠盐是医学上使用的非甾体抗炎药（NSAIDs）组中最知名且常用的治疗药物之一。对含有100毫克和75毫克双氯芬酸钠盐、辅料在质量和数量上具有多样化且药物剂型可变（硬胶囊、缓释片）的治疗产品进行了工艺和药学分析。评估了构成治疗产品药物剂型核心和包衣的聚合物性质的固体制剂成分对崩解时间和在药典受体液中的药物可用性的影响。
对市场上75毫克和100毫克剂量的双氯芬酸钠治疗产品进行药物剂型的工艺分析，检测含双氯芬酸钠盐的药物固体口服剂型的崩解时间，并根据延迟释放肠内剂型的FP标准，使用酸相和缓冲相进行测试治疗产品中双氯芬酸钠盐的药物可用性研究。实验数据辅以统计分析。
有三种硬胶囊形式的制剂和一种包衣片形式的制剂。所有治疗产品都具有双氯芬酸钠盐缓释剂型的特征，就服用NSAIDs后典型不良反应的局限性而言，通常是十二指肠或小肠中的延迟释放配方。在崩解、水化和溶胀过程中，观察到硬胶囊和缓释片之间存在相当大的差异。在受体液——纯化水（pH = 7）环境中，胶囊Dicloberl retard崩解速度最快，为5.49分钟，然后依次为：DicloDuo 75毫克——8.13分钟和Olfen 100 SR——11.27分钟。胶囊明胶壁的水化程度取决于受体液的pH值。双氯芬酸钠盐在给定受体液中的可用性证实了测试药物剂型的临床有效性与治疗产品所在环境的氢离子活性（pH）以及用于制备药物相的辅料之间存在显著关联这一事实。
测试的含双氯芬酸钠盐治疗产品在剂型类型上存在差异。Dicloberl retard含有最少数量的简单常用辅料。崩解时间的研究可能仅与将Dicloberl retard、Olfen 100 SR和DicloDuo 75毫克视为胶囊变形和崩解时间的产品相关。在所有三种类型的受体液中，胶囊Dicloberl retard的崩解速度最快。“酸相”显示产品具有稳定性，双氯芬酸钠盐的轻微溶解水平为释放系数Q的1.3 - 4.18%。在人工肠液环境中，Dicloberl retard在4小时暴露期间释放大量双氯芬酸钠盐更有效（与释放系数Q的差异为10%至14%）。
