Pharmacokinetics of nifedipine sustained-release tablets in healthy Chinese volunteers

Aim To establish a LC-MS method for determining the concentration of nifedipine in human plasma and to evaluate the pharmacokinetic characteristics of nifedipine sustained-release tablets. Methods A XB-C18 （5 μm, 4.6 mm ×150 mm） column and a mobile phase of methanol： 0.01 mol·L^-1ammonium acetate （60：40, V/V） were used to separate nifedipine, the detections was accuracy under atmosperic pressure electronic spray ionization （AP-ESI） mode and ion mass spectrum （m/z） of 314.9 [M＋H]^＋ for nifedipine, and 320.8 [M＋H]^＋ for lorazepam （Internal Standard, IS）. Results The linear range of nifedipine was 0.3 - 80 ng·mL^-1 （ r = 0.9997）, and the limit of quantitation （LOQ） was 0.3 ng·mL^-1. The nifedipine pharmacokinetic parameters after a single dose of 20 mg nifedipine sustained-release tablets test （T） or reference （R） were as the followings, t1/2 （6.73 ± 2.00） h and （7.04 ± 2.18） h, Tmax （4.28 ± 0.70） h and （4.48 ± 0.70） h, Cmax（39.66 ± 10.58） ng·mL^-1 and （40.19 ± 10.97） ng·mL^-1, AUC0-36 （391.63 ± 108.55） ng·mL^-1·h and （387.57 ± 121.51） ng·mL^-1·h, and AUC0-∞ （408.28 ± 121.16） ng·mL^-1·h and （406.15 ± 133.13） ng·mL^-1·h. The relative bioavailability of nifedipine sustained-release tablets （test） was （103.02 ± 13.93） %. Conclusion LC-MS method for the determination of concentrations of nifedipine in human plasma was sensitive and accurate, and could be used in nifedipine bioavailability and pharmacokinetic studies.

Preparation and <i>in Vitro</i>Drug Release Evaluation of Once-Daily Metformin Hydrochloride Sustained-Release Tablets

The objective of this study was to develop once-daily metformin hydrochloride sustained-release tablets (MHSRT) and evaluate their in vitro release behavior. MHSRT were prepared by the film coating method. The in vitro drug release rate of MHSRT and the commercial tablets Fortamet? made in the United States of America in water was fitted with zero order kinetic equation, and Ritger-Peppas kinetic equation in 0.1 M HCl and pH 6.8-phosphate buffer, respectively. The similarity factor f2 values of MHSRT in three different dissolution medium were 82, 80 and 74, respectively in comparison with imported Fortamet?, which were all greater than 50. The results of storage-stability showed that MHSRT were stable for at least 6 months under stress condition (40℃ ± 2℃, RH 75% ± 5%). Therefore, in this study, MHSRT were successfully prepared using optimized formulation technologies that meet mass produce. The in vitro release behavior of MHSRT was almost similar to that of imported Fortamet?.

Pharmacokinetic Study on Lovastatin Sustained-release Tablet and Sustained-release Capsule in Begal Dogs

This study pharmacokinetically examined the lovastatin sustained-release tablet and sustained-release capsule in Beagle dogs. An reversed-phase HPLC method was established for the determination of lovastatin in Beagle dog plasma. Pharmacokinetic findings were compared among three preparation(lovastatin sustained-release tablet,T p; sustained-release capsule,T J and conventional capsule). Our results showed that the pharmacokinetic parameters in 6 dogs after single-dose oral administration of three perparations were calculated. T max, C max and MRT revealed significant difference (P<0.05). Relative bioavailability was 111.5±16.9 % (T P) and 110.4%±9.6 % (T J). The pharmacokinetic parameters in the 6 dogs after multiple-dose oral administration of three perparations, T max, C max MRT and DF had significant difference (P<0.05); C av , C min and AUC 0-24 h displayed no significant difference (P>0.05). It is concluded that the lovastatin sustained-release tablet and sustained-release capsule are able to maintain a sustained-release for 24 h.

Preparation and evaluation of sustained-release azithromycin tablets in vitro and in vivo

The objective of this study was to prepare azithromycin(AZI)sustained-release products in order to allow for a high dose to be administered,reduce gastrointestinal side-effects and increase the compliance of patients.AZI sustained-release tablets with different release performance(F-I:T_(100%)=3 h and F-II:T_(100%)=8 h in pH 6.0 phosphate buffer)were successfully prepared by wet granulation.The in vitro release rate and drug release mechanism were studied.The release rate of F-Iwas affected by dissolutionmedia with different pH,but not for F-II.HixsoneCrowellmodel was the best regression fitting model for F-I and F-II.Additionally,F-I and F-II both belonged to non-Fick diffusion.Oral pharmacokinetics of the two tablets and one AZI dispersible tablet as reference were studied in six healthy beagle dogs after oral administration.Compared with the reference,the C_(max) of F-I and F-II were decreased,and the T_(max) were prolonged,in that case which meet the requirement of sustained-release tablets.The relative bioavailability of F-I and F-II were 79.12%and 64.09%.T-test ofAUC_(0-144),and AUC_(0-∞) for F-I and F-II indicated there was no significant difference between F-I and F-II.These mean that the extended release rate did not induce different pharmacokinetics in vivo.

Clinical observation of Baitou Weng Decoction combined with mesalazine sustained-release tablets in treating heat-toxic and smoldering ulcerative colitis

Objective:To observe the clinical efficacy of Baitou Weng Decoction combined with mesalazine sustained-release tablets in the treatment of ulcerative colitis with febrile heat and its effect on immune function and serum inflammatory factors.Methods: A total of 84 patients with ulcerative colitis were randomly divided into control group and treatment group, with 42 cases in each group. The control group was given mesalazine sustained-release tablets orally, while the treatment group was given Baitou Weng Decoction and mesalazine sustained-release tablets orally. The treatment period was 30 days and the patients were followed up for 3 months. After treatment, the clinical efficacy, quality of life, immune function and serum inflammatory factors of the two groups were observed.Results: The effective rate of treatment group (90.47%) was higher than that of control group (73.81%) (P<0.05);compared with before treatment, the scores of inflammatory bowel disease quality of life questionnaire scale in both groups were significantly improved (P<0.05), and the difference between the two groups was significant (P<0.05);after treatment, the plasma CD4+/CD8+ ratio and NK+ levels in both groups were significantly higher than those before treatment (P<0.05), and the treatment group was changed. The serum levels of tumor necrosis factor-α, interleukin-17 and interleukin-23 were significantly decreased in both groups after treatment (P<0.05), and the improvement was more significant in the treatment group (P<0.05). No significant adverse reactions were observed in the treatment group.Conclusions: Modified Baitou Weng Decoction combined with mesalazine in the treatment of heat-toxic and incandescent ulcerative colitis can significantly improve the clinical efficacy, improve the quality of life of patients, effectively regulate the expression level of serum inflammatory factors in ulcerative colitis patients, promote the recovery of patients' immune function, and have high drug safety.

Clinical observation on treatment of cancer pain with TCM oriented drugs combined with oxycodone sustained-release tablets and nimesulide sustained-release tablets

Objective： To study the effect of the transdermal preparation of traditional Chinese medicine in treating cancer pain. Methods： From October 2016 to January 2018, 126 patients with cancer pain were enrolled and divided into 4 groups, 39 patients in group A （directed TCM permeation）, 26 patients in group B （oxycodone sustained-release tablets）, 32 patients in group C （Chinese medicine directed drug penetration ＋ oxycodone sustained-release tablets）, and 29 patients group D （Chinese medicine directed drug penetration ＋ oxycodone sustained-release tablets ＋ nimesulide sustained release tablets）, according to KPS scores. Results： Transdermal preparations of traditional Chinese medicine can significantly alleviate cancer pain. For the treatment of moderate to severe cancer pain, the Chinese medicine transdermal preparation can reduce the dosage of oxycodone sustained-release tablets. At the same time, the patient＇s KPS and NRS scores were significantly reduced. Moreover, the transdermal preparation of traditional Chinese medicine has a better therapeutic effect on visceral pain. Conclusion： The traditional Chinese medicine tra_nsdermal preparation combined with western medicine for the treatment of cancer pain may be a new method for the treatment of cancer pain.

Enhancement of solubility and therapeutic potential of poorly soluble lovastatin by SMEDDS formulation adsorbed on directly compressed spray dried magnesium aluminometasilicate liquid loadable tablets: A study in diet induced hyperlipidemic rabbits

The aim of present study was to formulate and evaluate a self-microemulsifying drug delivery systems(SMEDDS)containing lovastatin and to further explore the ability of porous Neusilin■ US2 tablet as a solid carrier for SMEDDS.SMEDDS formulations of varying proportions of peceol,cremophor RH 40 and transcutol-P were selected and subjected to invitro evaluation,including dispersibility studies,droplet size,zeta potential measurement and release studies.The results indicated that the drug release profile of lovastatin from SMEDDS formulations was statistically significantly higher(p-value<0.05)than the plain lovastatin powder.Thermodynamic stability studies also confirmed the stability of the prepared SMEDDS formulations.The optimized formulation,which consists of 12% of peceol,44% of cremophor RH 40,and 44% of transcutol-P was loaded into directly compressed liquid loadable tablet of Neusilin■ US2 by simple adsorption method.In order to determine the ability of Neusilin®US2 as a suitable carrier pharmacodynamics study were also carried out in healthy diet induced hyperlipidemic rabbits.Animals were administered with both liquid SMEDDS and solid SMEDDS as well.From the results obtained,Neusilin■ was found to be a suitable carrier for SMEDDS and was equally effective in reducing the elevated lipid profile.In conclusion,liquid loadable tablet(LLT)is predicted to be a promising technique to deliver a liquid formulation in solid state.

Simultaneous Analysis of Indapamide and Related Impurities in Sustained-Release Tablets by a Single-Run HPLC-PDA Method

The contents of indapamide and related impurities in generic indapamide sustained-release tablets were simultaneously detected by a single-run high performance liquid chromatography equipped with photodiode array detector(HPLC-PDA)method for the quality control in this paper.The results showed the method had a good selectivity and was validated through linearity,limits of detection and quantification,recovery,and precision.The linear ranges of indapamide,2-methyl-1-nitroso-2,3-dihydro-1H-indole(impurity A,ImA),4-chloro-N-(2-methyl-1H-indol-1-yl)-3-sulphamoyl-benzamide(impurity B,ImB)and 4-chloro-3-sulfamoylbenzoic acid(impurity 1,Im1)were 0.028-1.80μg/mL(R=0.99995),0.060-1.20μg/mL(R=0.9996),0.0324-1.20μg/mL(R=0.99985)and 0.060-1.20μg/mL(R=0.9997)with detection limits of 0.0093,0.012,0.012 and 0.006μg/mL,respectively.ImA and Im1 were not detectable in the generic drug.The content of indapamide was 96.7%of the labeled amount with a relative standard deviation(RSD)of 1.30%,and the percentage of ImB relative to the labeled amounts of indapamide was 0.106%with an RSD of 1.82%.The content of other unspecified impurities all met the reference quality standards.The results provided references for the quality control and the quality standard study of generic indapamide sustained-release tablets.

Qualitative and quantitative analysis of HPLC fingerprint of Wuji gastric floating sustained-release tablets

A qualitative and quantitative test method of fingerprint of Wuji gastric floating sustained-release tablets was established. High performance liquid chromatography （HPLC） was adopted, using Agilent ZORBAX SB-C18 column （250 mm×4.6 mm, 5 μm） as the chromatographic column, and acetonitrile-0.05 mol/L potassium dihydrogen phosphate solution as the mobile phase in a gradient elution with the flow rate of 1.0 mL/min. Sample solution （10 μL） was injected and was tested at the wavelength of 225 nm for 75 min at the column temperature of 30 ℃, Fingerprint similarity software （2004A version） was used to conduct data analysis. A total of 11 batches of Wuji gastric floating sustained-release tablets were tested and analyzed with HPLC fingerprint. Seventeen common peaks were found and the similarity of the 11 batches of agents was greater than 0.9, indicating that the production process of the agent is stable and feasible. The method is operable and could effectively control the quality of Wuji gastric floating sustained-release tablets.

一测多评法同时测定红曲茯苓片中洛伐他汀和洛伐他汀酸含量

目的:建立适于红曲茯苓片质量控制的洛伐他汀和洛伐他汀酸的一测多评含量测定方法。方法:采用高效液相色谱法,以洛伐他汀为对照,建立与其开环产物洛伐他汀酸的校正因子关系,同时对产品中洛伐他汀和洛伐他汀酸两种成分同时进行定量检测的一测多评方法。结果:阴性样品无干扰,样品检测方法的专属性良好,洛伐他汀和洛伐他汀酸在相应的线性范围内线性关系良好,R^(2)>0.9999,精密度和重复性RSD值均小于3%,加标回收率为在98.43%~103.18%之间。洛伐他汀对洛伐他汀酸的相对校正因子为0.9000;一测多评法测定三批红曲茯苓片中洛伐他汀酸的平均含量为0.3563 mg/g,外标法测定洛伐他汀酸的平均含量为0.3668 mg/g;洛伐他汀的平均含量为1.1113 mg/g,表明所构建的一测多评法可用于红曲茯苓片的多成分质量评价研究。结论:本研究建立的产品中洛伐他汀定量方法稳定准确,专属性强,为以红曲为原料的红曲茯苓片的质量控制和深度开发提供了科学依据。

洛伐烟酸双层缓释片的制备及释放度考察

目的分别采用进口与国产羟丙基甲基纤维素 (HPMC)作为骨架材料制备洛伐烟酸缓释双层片 ,并比较国内外HPMC的缓释作用。方法用紫外分光光度法测定该制剂缓释层中烟酸的释放度 ,并用相似因子法和Chow′s法对溶出试验数据进行统计分析。结果使用国产HPMC制得的缓释片及进口HPMC制得的缓释片与国外市售片Niaspan的释放行为完全相似 ,相似因子分别为F2 =87 6和F2 =89 2 (5 0≤F2 ≤ 10 0 )。结论缓释片处方设计合理 ,工艺简单 。

HPLC测定洛伐他汀烟酸缓释片中两组分含量

目的建立洛伐他汀烟酸缓释片中2个组分(洛伐他汀、烟酸)含量的高效液相色谱法。方法采用Hypersil C18色谱柱(4.6 mm×250 mm,5μm),以0.005 mol·L-1己烷磺酸钠溶液-乙腈(35:65)为流动相,检测波长为239 nm。结果烟酸和洛伐他汀的浓度分别在49.8～249和2～10 mg·L-1有良好的线性关系(r=0.999 6),样品的回收率分别为99.93%(n=6,RSD= 0.73%)和101.3%(n=6,RSD=1.61%)。结论本法简便、快速,重现性好,灵敏度高,适用于洛伐他汀烟酸缓释片的质量控制。

洛汀烟酸缓释片中洛伐他汀溶出度的测定

目的建立了洛汀烟酸缓释片中洛伐他汀溶出度测定方法。方法采用转蓝法,以2%十二烷基硫酸钠溶液1 000 m l（内含1.38 g磷酸二氢钠,并用1 mol·L^-1氢氧化钠溶液调pH至7.0）为溶出介质,转速为75 r·min^-1,采用HPLC法检测。结果洛伐他汀在2.5-25 mg·L^-1范围内峰面积与浓度呈良好的线性关系,r=0.9998,平均回收率为97.39%,RSD=1.68%（n=9）,与国外同品种AdvicorTM中洛伐他汀溶出度一致。结论方法准确可靠,可用于洛汀烟酸缓释片的质量控制。

洛伐他汀烟酸缓释片研制

目的制备洛伐他汀烟酸缓释片,解析释药机理,并考察烟酸缓释层组成对药物释放的影响。方法通过压制双层片制备洛伐他汀烟酸缓释片。通过释药速率常数(k)将各因素对烟酸和洛伐他汀的释放效果进行评价。结果HPMC用量或黏度增大,k减慢;PVPK30用量增大,k加快;在一定范围内压片压力波动对烟酸和洛伐他汀的释药行为无明显影响。结论缓释片中药物主要是通过溶蚀机制释放。

反相高效液相色谱法检测脂必妥片中洛伐他汀的含量

对脂必妥片样品进行预处理，得到的混合物用薄层色谱、反相高效液相色谱法进行定性、定量分析，建立检测其含量的方法。当色谱条件为色谱柱：Kromasil（C18 250mm×4．6mm，5μm）；流动相体积比：乙腈：水为85：15，；流速：1．0ml·min^-1；检测波长：420nm；柱温：30℃；测定结果表明被测峰和其它峰可完全分离，在每毫升10．21～200．03μg内具有良好的线性关系，r=0．9997，测得其中洛伐他汀含量为0．25％，回收率：97．73％，RSD：0．56％。这种方法准确、可靠，可用于含洛伐他汀药品的质量控制。

洛伐他汀片溶出度测定的研究

目的:建立洛伐他汀片溶出度检测的新方法。方法:桨法,以0.5％十二烷基硫酸钠的磷酸二氢钠溶液为溶剂,采用紫外分光光度法测定,检测波长238nm。结果:线性范围2～14μg·ml^(-1),r=1.0000,回收率99.8％,RSD=0.2％。结论:方法简便,结果准确,可作为该品种溶出度测定的检测方法。

洛伐他汀缓释片的质量控制研究

目的研究洛伐他汀缓释片的质量控制方法。方法采用紫外分光光度法测定含量;根据《中国药典》缓释、控释制剂指导原则选择适宜的体外释放条件。结果洛伐他汀在177～1062μg/ml浓度范围内线性关系良好;洛伐他汀缓释片含量在95%～105%范围内;其在pH=70的十二烷基硫酸钠溶液中可持续释药24h,释放规律符合零级动力学和Higuchi方程。结论本方法方便、准确、重现性好,可用于洛伐他汀缓释片的质量控制。

烟酸/洛伐他汀复方缓释片及其3种Ⅱ期临床试验方案的比较

目的通过对烟酸(维生素PP,周围血管扩张药)/洛伐他汀(调血脂药)复方缓释片的3种临床试验方案的讨论,提高II期临床试验的质量水平。方法根据国内外临床试验,拟定出3种临床试验方案。结果用烟酸/洛伐他汀复方缓释整体剂量滴定法在II期临床试验中较为合理。结论在进行烟酸/洛伐他汀复方缓释整体剂量滴定法的II期临床试验中,控制其病例脱落率较为重要。

洛汀烟酸缓释片烟酸释放度的测定

目的建立洛汀烟酸缓释片中烟酸的释放度测定方法。方法以1000mL水为溶出介质,转速为100r/min,考察释放曲线;释放度测定采用紫外法。结果烟酸的释放符合一级释药方程,并与国外上市的同品种Advicor的烟酸释放度一致。结论洛汀烟酸缓释片符合2000年版《中国药典(二部)》附录ⅪⅩD中关于缓释制剂的相关规定。

左旋氨氯地平联合饱和剂量他汀类药物治疗老年早期高血压的疗效及依从性研究

目的研究左旋氨氯地平联合饱和剂量他汀类药物治疗老年早期高血压的疗效及依从性,为临床治疗提供参考依据。方法采用随机数表法将本院2011年1月至2013年12月收治的符合老年早期高血压纳入与排除标准的124例患者分为观察组和对照组。对照组61例患者单纯口服左旋氨氯地平治疗,观察组63例患者在对照组基础上联合饱和剂量洛伐他汀片治疗。治疗3个月后,对比分析两组疗效、患者治疗依从性及不良反应发生情况。结果治疗3个月后,观察组患者血压、脉压差、血脂水平明显优于对照组,差异具有显著性(P<0.05);观察组显效43例,有效16例,无效4例,总有效率为93.7%,明显优于对照组(73.8%),差异具有显著性(P<0.05);观察组患者不良反应发生率为4.8%,明显低于对照组(13.1%),差异具有显著性(P<0.05);观察组患者治疗依从性明显高于对照组,差异具有显著性(P<0.05)。结论左旋氨氯地平联合饱和剂量他汀类药物能有效降低患者血脂、血压、脉压差及不良反应发生率,提高患者治疗依从性,是老年早期高血压患者的理想辅助药物。