HPLC测定奥美沙坦酯氢氯噻嗪片含量和有关物质

目的:建立高效液相色谱法(HPLC)测定奥美沙坦酯氢氯噻嗪片含量和有关物质的测定方法。方法:采用HPLC,色谱柱:C1(84.6mm×250mm,Kromasil);流动相A:0.02mol/L磷酸二氢钠溶液(用磷酸调节pH至3.0),流动相B:甲醇-乙腈(100∶900),梯度洗脱。结果:奥美沙坦酯和氢氯噻嗪均能与其他杂质较好分离;奥美沙坦酯浓度在0.002026~0.04052mg/mL(r=0.999)范围内线性良好,氢氯噻嗪在0.001265~0.02530mg/mL范围内线性良好(r=1.000)。结论:本方法灵敏、准确,可作为奥美沙坦酯氢氯噻嗪片含量和有关物质的测定方法。     

新Vierordt法测定复方奥美沙坦酯片中两组分溶出度

目的:探讨复方奥美沙坦酯片中奥美沙坦酯和氢氯噻嗪两组分溶出度测定新方法。方法:采用新Vierordt法,不经提取分离直接测定复方奥美沙坦酯片中两组分含量和溶出度。测定波长为:λ1=256.8 nm,2λ=271.4 nm。结果:奥美沙坦酯和氢氯噻嗪的线性范围分别为2~12 mg/L(r=0.9999)和1.25~7.5 mg/L(r=0.9999),其平均回收率分别为(99.75±0.93)%和(100.31±0.125)%。本法与HPLC法测定结果无显著差异(P>0.05)。结论:本法操作简便、快速,可消除两组分的相互干扰,具较大灵活性和实用性。     

HPLC法测定复方奥美沙坦氢氯噻嗪片的含量

目的:建立奥美沙坦氢氯噻嗪片中奥美沙坦酯与氢氯噻嗪的测定方法。方法:采用高效液相色谱法,色谱柱为ODS-C18柱(250 mm×4．6 mm,5μm);流动相为0．03 mol·L-1磷酸二氢钾溶液(用磷酸调至pH3．6)-乙腈(50:50),流速为1．0 mL·min-1;检测波长为271 nm。结果:奥美沙坦酯在7．89～71．03μg·mL-1范围内,峰面积与浓度呈良好的线性关系,r=0．999 9,平均回收率为99．7％(n=9);氢氯噻嗪在5．02～45．22μg·mL-1范围内,峰面积与浓度呈良好的线性关系,r=0．999 9,平均回收率为99．9％(n=9)。结论:该方法可同时用于奥美沙坦氢氯噻嗪片中奥美沙坦酯与氢氯噻嗪的质量控制。     

复方替米沙坦片的制备及其稳定性研究

目的:制备复方替米沙坦片并对其稳定性进行考察.方法:制备替米沙坦分散体以提高替米沙坦的水溶性,选用利于氢氯噻嗪稳定的辅料,采用双层压片工艺制备了复方替米沙坦片,对处方工艺进行筛选与优化,采用高效液相色谱法测定其含量,并通过加速试验考察片剂稳定性.结果:以优选处方工艺制备的样品质量稳定,高效液相色谱法测定该片替米沙坦和氢氯噻嗪含量的平均回收率分别为99.85%(RSD=0.79%)和99.37%(RSD=0.40%).结论:该处方工艺合理,所得产品质量稳定.     

替米沙坦氢氯噻嗪片的溶出度研究

目的考察替米沙坦氢氯噻嗪片中替米沙坦和氢氯噻嗪在四种不同介质中的溶出行为。方法参照日本《医疗用药品品质情报集》中的溶出度试验条件,并根据替米沙坦氢氯噻嗪片处方成分的理化性质对溶出介质进行选择,分别考察了替米沙坦氢氯噻嗪片在p H 1.2的人工胃液(含0.5%十二烷基硫酸钠溶液)、p H 4.0醋酸盐缓冲液(含0.5%十二烷基硫酸钠溶液)、p H 6.8磷酸盐缓冲液(含0.25%十二烷基硫酸钠溶液)及水(含0.25%十二烷基硫酸钠溶液)中的体外溶出行为,采用高效液相色谱法测定替米沙坦氢氯噻嗪片中替米沙坦和氢氯噻嗪的溶出度,并通过相似因子(f2)法对两种成分的溶出度曲线进行相似性比较。结果替米沙坦和氢氯噻嗪的线性范围分别为20⁵0μg·L-1和650μg·L-1和6²0μg·L-1;在以上四种介质中,以替米沙坦为参比,替米沙坦氢氯噻嗪片中氢氯噻嗪的f2大于50。结论该方法简便、准确,重复性好,可用于该片剂的溶出度测定;替米沙坦氢氯噻嗪片中替米沙坦和氢氯噻嗪具有相似的溶出特点。     

高效液相色谱法测定复方缬沙坦片溶出度

采用反相高效液相色谱法,同时测定复方制剂中缬沙坦和氢氯噻嗪的溶出度,方法准确,简便. 1     

氢氯噻嗪分散片的制备及质量控制

目的:研究处方中各组分对氢氯噻嗪分散片的影响及其制备工艺。方法:以崩解时限为指标,采用正交设计试验,对氢氯噻嗪分散片处方进行筛选并考察了溶出度及稳定性。结果:按优化处方制备的氢氯噻嗪分散片,可在1 min内完全崩解,稳定性好。结论:氢氯噻嗪分散片其体外溶出度明显优于普通片。     

流化床颗粒包衣法制备替米沙坦氢氯噻嗪片

目的 采用流化床颗粒包衣法制备替米沙坦氢氯噻嗪片,并对其稳定性进行考察。方法 采用流化床一步造粒工艺制备替米沙坦颗粒,然后将替米沙坦颗粒进行不同包衣增重后与氢氯噻嗪以及合适的辅料混合,用普通旋转压片机进行压片制备替米沙坦氢氯噻片,并利用正交试验设计,优化替米沙坦氢氯噻嗪片处方;用HPLC进行含量和杂质检测,通过加速试验和长期试验考察片剂稳定性和溶出度。结果 该方法制备的替米沙坦氢氯噻嗪片质量稳定。羧甲基淀粉钠外加用量20.4 mg、氢氧化钠用量8.5 mg溶出指标最为理想,最终优化的处方与原研制剂溶出特征一致。结论 以流化床颗粒包衣法制备的替米沙坦氢氯噻嗪片质量稳定,工艺较双层片简单,具有可行性。     

脉君安胶囊中氢氯噻嗪的溶出度研究

摘要 目的 建立脉君安胶囊中氢氯噻嗪的溶出度测定方法。方法采用小杯法,以盐酸溶液为溶出介质、转速50 r•min－1测定溶出度,采用高效液相色谱法测定有效成分氢氯噻嗪的溶出量。结果氢氯噻嗪在2.48～12.40 mg•L－1浓度内线性关系良好（r＝0.999 9）,平均回收率为99.1%。结论该方法简便、准确、重复性好,可用于该药的溶出度测定。     

奥美沙坦酯联合氨氯地平与奥美沙坦酯联合氢氯噻嗪治疗原发性高血压的对比

目的比较奥美沙坦酯联合氨氯地平与奥美沙坦酯联合氢氯噻嗪在治疗原发性高血压中的降压疗效。方法 80例原发性高血压患者随机分为奥美沙坦-氨氯地平组和奥美沙坦-氢氯噻嗪组,每组40例。奥美沙坦-氨氯地平组给予奥美沙坦酯20 mg和氨氯地平5 mg,口服,qd;奥美沙坦-氢氯噻嗪组给予奥美沙坦酯20 mg和氢氯噻嗪12.5 mg,口服,qd;疗程均为8周。观察患者24 h动态血压变化情况、血压昼夜波动节律,检测治疗前后实验室指标并记录不良反应发生情况。结果两组患者治疗后白昼、夜间平均收缩压和舒张压均降低(P<0.05),两组降低幅度无显著差异(P>0.05)。奥美沙坦-氨氯地平组治疗后白昼、夜间收缩压和舒张压变异均低于奥美沙坦-氢氯噻嗪组(P<0.05)。奥美沙坦-氨氯地平组血压昼夜节律异常逆转率为79%(11/14),高于奥美沙坦-氢氯噻嗪组(25%,4/16,P<0.05)。两组实验室指标均无明显变化。两组均无明显不良反应发生。结论奥美沙坦酯联合氨氯地平与奥美沙坦酯联合氢氯噻嗪治疗原发性高血压的降压效果相当,但前者在降低血压变异性、改善高血压患者血压昼夜节律变化方面效果更佳,具有平稳降压的作用。     

奥美沙坦氢氯噻嗪片在中国健康志愿者体中的药代动力学

目的:研究单次、多次口服奥美沙坦氢氯噻嗪片在中国健康受试者体内的药代动力学。方法:本研究为随机、开放、单次和多次口服给药的单中心试验。12位健康受试者单次和多次口服1片奥美沙坦氢氯噻嗪片(每片含奥美沙坦20 mg,氢氯噻嗪12.5 mg),采用HPLC-MS-MS法测定奥美沙坦和氢氯噻嗪的血浆药物浓度,利用DAS2.0和SPSS 13.0计算药动学参数和进行统计学分析。结果:单次和多次口服给药后奥美沙坦的药动学参数如下:Cmax分别为(489±122)μg/L和(531±125)μg/L,AUC0→t分别为(3468±869)μg.L-1.h和(3557±1209)μg.L-1.h,tmax分别为(2.6±0.5)h和(2.3±0.8)h,t1/2分别为(7.3±4.0)h和(8.3±3.6)h;单次和多次口服给药后氢氯噻嗪的药动学参数如下:Cmax分别为(122±34)μg/L和(182±39)μg/L,AUC0→t分别为(764±211)μg.L-1.h和(1079±361)μg.L-1.h,Cmax分别为(2.2±0.7)h和(1.6±0.6)h,t1/2分别为(6.8±2.3)h和(7.1±1.6)h。结论:奥美沙坦氢氯噻嗪片主要药动学参数单剂量和多剂量给药差异无统计学意义,奥美沙坦和氢氯噻嗪在人体内均无明显蓄积。     

十一酸睾酮自微乳化制剂的处方研究

目的制备十一酸睾酮（TU）自微乳化制剂。方法通过伪三元相图绘制和自乳化效率的评价筛选TU自微乳化制剂处方,用HPLC测定药物的含量,考察制剂经高温和光照的影响因素试验后的质量。结果以辛癸酸甘油酯为油相、Cremophor EL／Tween85（1：4）为混合乳化剂、油相与乳化剂重量比1：1作为TU自乳化制剂介质的处方,在不同介质能迅速形成自微乳液。经高温10d放置,TU自乳化制剂的质量未发生变化,光照10d后药物含量略有下降。结论制备了不舍助乳化剂的TU自微乳化制剂,适合于进一步制成软胶囊。     

复方奥美沙坦酯片的人体药动学研究

目的研究健康受试者口服复方奥美沙坦酯片的药物动力学特征。方法30名健康受试者随机分成3组,分别空腹服用复方奥美沙坦酯片1片、2片与3片,定时取血,采用高效液相色谱法测定人血浆中氢氯噻嗪与奥美沙坦浓度并利用DAS药动学软件计算药动学参数。结果氢氯噻嗪低中高剂量给药后的主要药动学参数分别是：t1/2为（9．68±3．37）h、（10．11±4．96）h、（11．02±4．77）h,Cmax为（69．7±19．8）μg·L^-1、（158．5±62-4）μg·L^-1、（209．4±85．7）μg·L^-1,AUC0→ι为（737．8±110．6）μg·L^-1．h、（1397．2±252．0）μg·L^-1．h、（2200．3±517．6）μg·L^-1．h;奥美沙坦低中高剂量给药后的主要药动学参数分别是：t1/2为（6．25±1．98）h、（7．99±2．43）h、（7．03±2．86）h,Cmax为（635．1±237．7）μg·L^-1、（1336．8±452．0）μg·L^-1、（1774．7±792．2）μg·L^-1,AUC0→ι为（4438．4±1058．1）μg·L^-1．h、（8239．6±1909．7）μg·L^-1．h、（13150．3±3627．5）μg·L^-1．h。结论复方奥美沙坦酯片2组分在健康受试者体内为线性动力学过程。     

高效液相色谱法测定奥美沙坦酯片的含量

目的：建立高效液相色谱法测定奥美沙坦酯片的含量。方法：采用C18色谱柱,乙腈-10mmol/L磷酸二氢钾缓冲液（0.2%三乙胺,用磷酸调节pH至3.0）（45：55）为流动相,检测波长为256nm。结果：奥美沙坦酯浓度在10.8～86.4μg/ml范围内线性关系良好（r=0.9999）,平均回收率为：100.75%（RSD=0.61%）。结论：该方法简单、准确,适用于奥美沙坦酯片的含量测定。     

Spectrophotometric Estimation of Olmesartan Medoxomil and Hydrochlorothiazide in Tablet

A simultaneous determination of olmesartan medoxomil and hydrochlorothiazide by absorption ratio spectrophotometric method has been developed in combined tablet dosage form. The method is based on measurements of absorbance at isoabsoptive point. The Beer''s law obeys in the range of 10–30 μg/ml for both olmesartan medoxomil and hydrochlorothiazide respectively. The proposed method was validated by performing recovery study and statistically.     

Olmesartan medoxomil/amlodipine/hydrochlorothiazide: fixed-dose combination in hypertension

The antihypertensive agents olmesartan medoxomil, amlodipine and hydrochlorothiazide (HCTZ) are now available as a fixed-dose combination tablet (olmesartan medoxomil/amlodipine/HCTZ). In a 12-week, randomized, double-blind, multicentre trial (TRINITY) in adults with moderate to severe hypertension, olmesartan medoxomil?+?amlodipine?+?HCTZ triple combination therapy produced significantly greater least squares mean reductions from baseline in seated diastolic blood pressure (BP) [primary endpoint] and seated systolic BP than olmesartan medoxomil/amlodipine, olmesartan medoxomil/HCTZ or amlodipine?+?HCTZ. Furthermore, significantly more patients achieved BP goals and targets with the triple combination regimen than with any of the dual combination regimens at week 12, with olmesartan medoxomil?+?amlodipine?+?HCTZ also demonstrating benefit over the dual regimens in terms of ambulatory BP control. According to subgroup analyses of the TRINITY trial, olmesartan medoxomil?+?amlodipine?+?HCTZ was more effective in reducing BP and achieving BP goals than each of the dual therapies, irrespective of hypertension severity, age, sex, race or diabetes mellitus status. Data from a number of smaller clinical studies indicated that olmesartan medoxomil?+?amlodipine?+?HCTZ triple combination therapy provides antihypertensive efficacy in patients whose BP is not adequately controlled with olmesartan medoxomil?+?amlodipine. Olmesartan medoxomil?+?amlodipine?+?HCTZ was generally well tolerated in the TRINITY study, with adverse events usually being mild or moderate in severity.     

奥美沙坦酯氢氯噻嗪片治疗原发性高血压患者的临床有效性及安全性分析

目的 观察原发性高血压患者应用奥美沙坦酯氢氯噻嗪片治疗的效果及安全性.方法 80例原发性高血压患者,依据用药方案不同分为对照组和观察组,每组40例.对照组患者应用氯沙坦钾片进行治疗,观察组患者应用奥美沙坦酯氢氯噻嗪片进行治疗.对比两组患者的舒张压(DBP)、收缩压(SBP)、临床疗效、血清超敏C反应蛋白(hs-CRP)...     

Central Composite Design for Validation of HPTLC Method for Simultaneous Estimation of Olmesartan Medoxomil,Amlodipine Besylate and Hydrochlorothiazide in Tablets

High performance thin layer chromatographic method for simultaneous estimation of olmesartan medoxomil, amlodipine besylate and hydrochlorothiazide was developed and validated as per ICH guidelines. Moreover, robustness testing was performed applying a central composite design with k factor having 2^k factorial runs, 2k axial experiments and two center points. High performance thin layer chromatographic separation was performed on aluminium plates precoated with silica gel 60F₂₅₄ and toluene:chloroform:methanol:acetonitrile:formic acid (2:7:1.8:0.8:0.2% v/v) as optimized mobile phase. The detection wavelength for simultaneous estimation of three drugs was 232nm. The R_f values for olmesartan medoxomil, amlodipine besylate and hydrochlorthiazide were 0.78, 0.20 and 0.45, respectively. Percent recoveries in terms of accuracy for the marketed formulation was found to be 101.3-104.4, 100.7-104 and 101.5-103.9 for, olmesartan medoxomil, amlodipine besylate and hydrochlorthiazide, respectively. The pooled %relative standard deviation values for repeatability studies and intermediate precision studies was found to be less than 2% for olmesartan medoxomil, amlodipine besylate and hydrochlorthiazide, respectively. All the three factors evaluated in the robustness testing by central composite design were found to have an insignificant effect on the retention factor. However, methanol content in total mobile phase as a factor appeared to have significant effect on robustness, compared to band size and developing distance and hence it is important to be carefully controlled. In summary, a novel, simple, accurate and reproducible high performance thin layer chromatographic method was developed, which would be of use in quality control of these tablets.     

Blood pressure reduction with olmesartan in mild-to-moderate essential hypertension: a planned interim analysis of an open label sub-study in German patients

OBJECTIVE: To present the baseline characteristics and open-label treatment phase results for German patients in OLMEBEST, a European, multinational, partially randomized, partially double-blind study in patients with mild-to-moderate essential hypertension. RESEARCH DESIGN AND METHODS: After a 2-week placebo run-in, patients received olmesartan 20 mg for 8 weeks. Controlled patients (mean sitting diastolic blood pressure [sDBP] < 90 mmHg) continued on olmesartan 20 mg/day for a further 4 weeks. Non-controlled patients (sDBP > 90 mmHg) were randomized to olmesartan 40 mg/day or olmesartan 20 mg/day plus 12.5 mg hydrochlorothiazide for 4 weeks. Of 823 patients included, 558 continued olmesartan 20 mg treatment and 228 patients were randomized to olmesartan 40 mg/day or combination therapy. Efficacy variables included the change from baseline in mean sitting DBP and systolic blood pressure [sSBP] at Week 8 (and Week 12 for controlled patients), and the proportion of controlled patients and responders (mean sDBP < 90 mmHg or improvement of > 10 mmHg from baseline at Week 8). RESULTS: After 8 weeks of olmesartan medoxomil 20 mg, mean reduction from baseline in sDBP was 11.8 mmHg and in sSBP was 17.1 mmHg. In controlled patients continuing open-label olmesartan medoxomil 20 mg, mean reduction from baseline at 12 weeks in sDBP was 14.9 mmHg and in sSBP was 20.1 mmHg. At Week 8, the response rate was 76% and the control rate was 70%. Olmesartan medoxomil 20 mg/day was well tolerated; 30.9% of patients experienced an adverse event, and the majority of these events were judged by the investigators to be mild. CONCLUSION: Olmesartan medoxomil monotherapy at the recommended dosage of 20 mg once daily is effective and well tolerated in patients with mild-to-moderate hypertension.