CMR college of Pharmacy, Department of Pharmaceutical Analysis, Kandlakoya (V), Medchal Road, Hyderabad 501 401, India.
Sri Ramachandra Institute of Higher Education and Research (Deemed to be University), Sri Ramachandra Faculty of pharmacy, Department of Pharmaceutical Chemistry, No.1 Ramachandra Nagar, Porur, Chennai 600 116, India.
J AOAC Int. 2022 Mar 15;105(2):370-378. doi: 10.1093/jaoacint/qsab157.
Garenoxacin mesylate is a novel des-fluoro(6) quinolone, approved and marketed for human use in Japan under the name Geninax.
In this current work, a simple and stability-indicating method for the assay and dissolution of garenoxacin in garenoxacin tablets 200 mg was performed. New method developed for the particle size measurement of Garenoxacin mesylate Active Pharmaceutical Ingredient using Malvern 2000.
A quality by design (QbD)-based stability-indicating assay method was developed using 0.1% (v/v) formic acid in water and methanol (70:30). Using a photodiode array detector the peak purity of the garenoxacin peak for all degradation samples was studied. The biopharmaceutical classification system (BCS) solubility of garenoxacin mesylate active pharmaceutical ingredient (API) was studied by a modified shake flask method. A dissolution test method was developed using 0.1 N hydrochloric acid as the medium, United State Pharmacopoeia apparatus-II (paddle), revolution per minute (rpm) 50, temperature 37 ± 0.5°C and time 30 min. Liquid paraffin was used as the dispersant in the particle size measurement of garenoxacin mesylate API using the Malvern Mastersizer-wet method.
The QbD-based RP-HPLC method was stability-indicating, simple, precise, and accurate. The assay method was linear over 12.5 to 75 µg/mL at the detection wavelength of 280 nm. A UV-based method was developed and validated for the dissolution of garenoxacin 200 mg tablets and the method was found to be linear over 2.9 to 34.2 µg/mL at 280 nm. Based on data, the dissolution tolerance for garenoxacin 200 mg tablets was proposed as Q not less than 80% at time 30 min (% drug released with respect to label claim (Q). The effect of garenoxacin mesylate API particle size in the tablet dosage form was studied using particles of 92 µm and 220 µm [90% of the total particles are smaller than this size (D90)] and it was found that there was no impact on the in vitro dissolution profile.
The reported stability-indicating assay and dissolution test methods can be used in regular QC testing of garenoxacin 200 mg tablets. The Malvern particle size wet dispersion measurement method developed and validated for garenoxacin mesylate API is simple and robust.
A QbD based RP-HPLC method (using Design Expert Software version 11) was developed and studied peak purity of Garenoxacin peak using Photo Diode Array detector (for all degradation samples, control sample and standard solution) and the same method is validated following USP and ICH guidelines. LC-MS compatible volatile buffer solution is used in the preparation of the mobile phase for the novel stability-indicating RP-HPLC assay method.
甲磺酸加替沙星是一种新型的去氟（6）喹诺酮类药物，在日本以 Geninax 的名称获得批准并上市用于人体。
本研究旨在建立一种简单且具有稳定性指示的方法，用于测定加替沙星片 200mg 中的加替沙星含量和溶出度。使用 Malvern 2000 建立了甲磺酸加替沙星活性药物成分（API）粒度测量的新方法。
采用基于质量源于设计（QbD）的稳定性指示含量测定方法，以水和甲醇（70:30）中的 0.1%（v/v）甲酸作为流动相。使用光电二极管阵列检测器研究了所有降解样品中加替沙星峰的峰纯度。采用改良的振摇瓶法研究了甲磺酸加替沙星 API 的生物药剂学分类系统（BCS）溶解度。采用 0.1N 盐酸作为介质，美国药典装置 II（桨），转速 50rpm，温度 37±0.5°C，时间 30min，建立并验证了溶出度试验方法。使用液态石蜡作为分散剂，采用 Malvern Mastersizer-wet 法对甲磺酸加替沙星 API 的粒度进行测量。
基于 QbD 的反相高效液相色谱法具有稳定性指示、简单、精确和准确的特点。在 280nm 检测波长下，检测限为 12.5至 75μg/mL，定量限为 20μg/mL，该方法呈线性。建立并验证了用于测定加替沙星 200mg 片溶出度的紫外法，在 280nm 处，线性范围为 2.9 至 34.2μg/mL。根据数据，提出了加替沙星 200mg 片的溶出度容忍度 Q 不低于 80%，即在 30min 时（相对于标签声称的释放量（Q）的药物释放量）。研究了片剂中不同甲磺酸加替沙星 API 粒径（92μm 和 220μm[90%的总颗粒粒径小于该粒径（D90）]）对体外溶出度的影响，结果表明对溶出度无影响。
所报道的稳定性指示含量测定和溶出度试验方法可用于加替沙星 200mg 片的常规 QC 检测。为甲磺酸加替沙星 API 开发和验证的简单、稳健的 Malvern 粒径湿分散测量方法。
采用 Design Expert Software version 11 开发了基于 QbD 的反相高效液相色谱法，并使用光电二极管阵列检测器研究了加替沙星峰的峰纯度（所有降解样品、对照样品和标准溶液），该方法按照 USP 和 ICH 指南进行了验证。新型稳定性指示反相高效液相色谱测定方法中，使用挥发性缓冲溶液作为流动相的组成部分。
