Abstract：
BACKGROUND: Patient adherence to therapy and compliance is always a challenge for care providers in the management of chronic disorders with multiple medications.
OBJECTIVE: Our study focused on formulating concurrently prescribed ARB (Angiotensin Receptor Blocker), i.e., losartan potassium, and a cholesterol-lowering statin derivative, i.e., rosuvastatin calcium, in a fixed-dose combination tablet.
METHODS: The drugs were selected based on the presence of synergism and variation in solubility characteristics. Trial batches with fixed concentrations of both active pharmaceutical ingredients (APIs) and varying quantities of different excipients were prepared by dry granulation technique and subjected to different quality control tests for tablets. Batch F5 was selected on the basis of in-process quality control data for the development of a drug release protocol. Experimental conditions were optimized. Based on the sink condition, phosphate buffer (pH 6.8) was selected as the dissolution medium. Simultaneous determination of both APIs in samples collected at predetermined time intervals was carried out using the RP-HPLC technique with acetonitrile, methanol, and water (20:25:55 v/v/v) as mobile phase.
RESULTS: Complete dissolution of both APIs in the FDC tablet was achieved in 45 min in 900 mL of the selected medium. The in vitro drug release protocol was validated for accuracy and precision without interference with sample analysis.
CONCLUSIONS: In this study, a validated, accurate, and robust dissolution testing method was developed for the newly formulated FDC tablet.
OBJECTIVE: Our study focused on formulating concurrently prescribed ARB (Angiotensin Receptor Blocker), i.e., losartan potassium, and a cholesterol-lowering statin derivative, i.e., rosuvastatin calcium, in a fixed-dose combination tablet.
METHODS: The drugs were selected based on the presence of synergism and variation in solubility characteristics. Trial batches with fixed concentrations of both active pharmaceutical ingredients (APIs) and varying quantities of different excipients were prepared by dry granulation technique and subjected to different quality control tests for tablets. Batch F5 was selected on the basis of in-process quality control data for the development of a drug release protocol. Experimental conditions were optimized. Based on the sink condition, phosphate buffer (pH 6.8) was selected as the dissolution medium. Simultaneous determination of both APIs in samples collected at predetermined time intervals was carried out using the RP-HPLC technique with acetonitrile, methanol, and water (20:25:55 v/v/v) as mobile phase.
RESULTS: Complete dissolution of both APIs in the FDC tablet was achieved in 45 min in 900 mL of the selected medium. The in vitro drug release protocol was validated for accuracy and precision without interference with sample analysis.
CONCLUSIONS: In this study, a validated, accurate, and robust dissolution testing method was developed for the newly formulated FDC tablet.
摘要：
背景：患者对治疗的依从性和依从性始终是护理提供者使用多种药物治疗慢性疾病的挑战。
目的：我们的研究重点是同时制定处方ARB（血管紧张素受体阻滞剂），即，氯沙坦钾，和降低胆固醇的他汀类药物衍生物，即，瑞舒伐他汀钙,在固定剂量组合片剂中。
方法：基于协同作用的存在和溶解度特征的变化来选择药物。通过干法制粒技术制备具有固定浓度的两种活性药物成分(API)和不同量的不同赋形剂的试验批次,并对片剂进行不同的质量控制测试。基于过程中的质量控制数据选择批次F5,用于开发药物释放方案。优化了实验条件。根据水槽情况，选择磷酸盐缓冲液(pH6.8)作为溶出介质。使用RP-HPLC技术用乙腈同时测定以预定时间间隔收集的样品中的两种API，甲醇,和水（20:25:55v/v/v）作为流动相。
结果:两种API在FDC片剂中的完全溶解在900mL的所选培养基中在45分钟内实现。在不干扰样品分析的情况下，对体外药物释放方案的准确性和精密度进行了验证。
结论：在这项研究中，一个经过验证的，准确,并为新配制的FDC片剂开发了稳健的溶出度测试方法。
目的：我们的研究重点是同时制定处方ARB（血管紧张素受体阻滞剂），即，氯沙坦钾，和降低胆固醇的他汀类药物衍生物，即，瑞舒伐他汀钙,在固定剂量组合片剂中。
方法：基于协同作用的存在和溶解度特征的变化来选择药物。通过干法制粒技术制备具有固定浓度的两种活性药物成分(API)和不同量的不同赋形剂的试验批次,并对片剂进行不同的质量控制测试。基于过程中的质量控制数据选择批次F5,用于开发药物释放方案。优化了实验条件。根据水槽情况，选择磷酸盐缓冲液(pH6.8)作为溶出介质。使用RP-HPLC技术用乙腈同时测定以预定时间间隔收集的样品中的两种API，甲醇,和水（20:25:55v/v/v）作为流动相。
结果:两种API在FDC片剂中的完全溶解在900mL的所选培养基中在45分钟内实现。在不干扰样品分析的情况下，对体外药物释放方案的准确性和精密度进行了验证。
结论：在这项研究中，一个经过验证的，准确,并为新配制的FDC片剂开发了稳健的溶出度测试方法。
