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.

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.

HPLC测定某妇科泡腾片中苦参碱的含量

目的:建立以高效液相色谱法(HPLC)测定某妇科泡腾片中苦参碱含量的方法。方法:超声提取该妇科泡腾片中苦参碱。以氨基键合硅胶作为色谱柱的填充剂,流动相分别为无水乙醇-3%磷酸溶液-乙腈,其比例为10∶10∶80,流速调节为1.0 mL/min,检测波长为220 nm。结果:苦参碱在0.014~0.084 mg/mL浓度范围内呈良好的线性关系A=8638885.18C+2100.68(r=0.9998,n=6),平均回收率为98.16%,RSD=1.56%。结论:采用HPLC法能够快速并且准确的测出苦参碱的含量,同时能够排除其他生物碱的干扰,适合用于测定苦参碱的含量。

普瑞巴林联合盐酸羟考酮缓释片、复方苦参注射液治疗神经病理性癌症疼痛患者临床观察

目的评价普瑞巴林与盐酸羟考酮缓释片联合复方苦参注射液在治疗癌性神经病理性疼痛(malignant neuropathic pain,MNP)的疗效及不良反应。方法选取2019年3月—2021年4月66例疼痛评分大于等于4分的MNP患者,根据随机数字排列表方法将其随机分为:A组:盐酸羟考酮缓释片30 mg,q12 h口服,B组:盐酸羟考酮缓释片30 mg,q12 h口服,联合普瑞巴林口服,至最大剂量300 mg/d。C组:盐酸羟考酮缓释片30 mg,q12 h口服,联合普瑞巴林口服,至最大剂量300 mg/d,并配合给予复方苦参注射液20 mL,qd,iv。观察3组患者疼痛控制情况,不良反应情况、生活质量及睡眠改善情况。结果C组疼痛控制比A组明显改善(χ^(2)=7.333,P=0.007),C组的生活质量比A组明显改善(t=13.803,P=0.0001),睡眠质量改善明显(t=8.340,P=0.0001),在不良事件中,C组的不良事件明显少于A组(χ^(2)=7.333,P=0.007)。结论C组疗效优于A组,睡眠质量和生活质量皆有明显改善,且不良事件发生更少。普瑞巴林联合盐酸羟考酮缓释片及复方苦参注射液治疗控制疼痛效果较好,优于单用阿片类药物。

HPLC法同时测定复方石韦片中2种生物碱类成分的含量

目的建立高效液相色谱法(HPLC)测定复方石韦片中2种生物碱类成分(苦参碱和槐果碱)含量的方法。方法采用Agilent TC-C_(18)色谱柱(250 mm×4.6 mm,5μm),以乙腈-0.1%磷酸溶液(20∶80)(用三乙胺调节至p H8.0)为流动相,流速1.0 ml/min,检测波长210 nm,柱温30℃,进样量10μl。结果苦参碱、槐果碱质量浓度分别在0.01994~1.99430 mg/ml(r=0.9999)、0.010059~1.005900mg/ml(r=1)范围内与峰面积呈良好的线性关系,平均加样回收率分别为95.9%(RSD=2.9%)、103.3%(RSD=2.8%),15批样品苦参碱、槐果碱含量分别在7.75~10.40 mg/g、2.34~3.18 mg/g范围内。结论HPLC法测定复方石韦片中苦参碱、槐果碱含量简便、准确、快捷,可为复方石韦片的质量控制提供参考。

苦参碱联合阿德福韦酯治疗乙型病毒性肝炎的效果及对患者血清sST2、CEA及ALT水平的影响

目的观察苦参碱联合阿德福韦酯治疗乙型病毒性肝炎的效果,并探讨其对患者血浆可溶性生长刺激表达基因2蛋白(sST2)、癌胚抗原(CEA)及谷丙转氨酶(ALT)水平的影响。方法选取2019年1月至2021年1月于陕西航天医院就诊的60例乙型病毒性肝炎患者纳入研究,按照随机数表法分为对照组和观察组各30例。对照组患者采用阿德福韦酯治疗,观察组患者采用苦参碱联合阿德福韦酯治疗,疗程3个月。比较两组患者的治疗效果、治疗前后的sST2、CEA、ALT水平、乙肝病毒(HBV)DNA转阴情况和并发症发生情况。结果观察组患者的治疗总有效率为93.33%,明显高于对照组的70.00%,差异具有统计学意义(P<0.05);两组患者治疗后的sST2、CEA和ALT明显低于其治疗前,且观察组患者治疗后的sST2、CEA和ALT水平分别为(0.32±0.03)μg/mL、(0.94±0.02)μg/L、(72.36±10.04)U/L,明显低于对照组的(0.62±0.04)μg/mL、(1.12±0.03)μg/L、(93.57±10.13)U/L,差异均具有统计学意义(P<0.05);观察组治疗后的HBV DNA转阴率为26.67%,明显低于对照组的53.33%,差异具有统计学意义(P<0.05);治疗期间,两组患者的并发症发生率比较差异无统计学意义(P>0.05)。结论苦参碱联合阿德福韦酯治疗乙型病毒性肝炎能有效降低患者的血清sST2、CEA及ALT水平,提高治疗效果。

苦参碱缓释片、胶囊、注射液的药代动力学及生物利用度比较研究

目的:比较苦参碱缓释片、苦参碱普通胶囊和苦参碱注射液的药代动力学及生物利用度。方法:对杂种犬进行单剂量及多剂量试验,采用反相液相色谱法测定血药浓度,对苦参碱的三种剂型进行药物动力学及生物利用度研究。结果:苦参碱普通胶囊tmax为(85±12)min,cmax为(6.360±0.215)μg/ml,缓释片的tmax为300min,cmax为(5.088±0.490)μg/ml,注射剂的tmax为10min,cmax为(6.500±0.404)μg/ml。缓释片相对于普通胶囊之相对生物利用度为(153.7±9.4)%,相对于注射剂的绝对生物利用度为(73.5±14.2)%。体内外相关性显著(r=0.9812,P<0.01)。结论:苦参碱缓释片释药迟缓,达峰时间长,血药浓度变化平缓,达到设计要求。

氧化苦参碱生物黏附缓释片在Beagle犬体内的药动学

目的:考察氧化苦参碱生物黏附缓释片在Beagle犬体内的药动学过程。方法:建立LC-MS法同时测定Beagle犬血浆中的氧化苦参碱及其代谢产物苦参碱。采用BAPP 2.3程序估算犬服用市售普通胶囊(参比制剂)和氧化苦参碱生物黏附缓释片(受试制剂)后的药动学参数。结果:氧化苦参碱血药浓度-时间曲线符合双室模型特征。受试制剂的生物利用度为110.9,且cmax降低、tmax延长,具有缓释效果。服用受试制剂后测得苦参碱的量为服用参比制剂后测得量的90.5%。结论:氧化苦参碱生物黏附缓释片与市售普通胶囊相比,生物利用度等效,具有明显的缓释效果。

氧化苦参碱缓释片在犬体内的代谢及其相对生物利用度

目的研究氧化苦参碱缓释片在Beagle犬体内的代谢及其相对生物利用度。方法采用单剂量双周期自身交叉设计,分别给犬单剂量灌胃氧化苦参碱缓释片或胶囊,用LC-MS测定给药后的血浆中氧化苦参碱和其代谢物苦参碱浓度。结果氧化苦参碱缓释片中氧化苦参碱、代谢物苦参碱的相对生物利用度分别为(73.9±2.1)%和(122.0±11.7)%。结论以氧化苦参碱或代谢物苦参碱为统计指标,氧化苦参碱缓释片和胶囊在吸收程度上生物不等效。

均匀设计法制备苦参碱渗透泵型控释片

目的制备苦参碱渗透泵型控释片,同时建立一种新的设计初级渗透泵处方的方法。方法利用均匀设计法得到释放速率与各处方因素间的定量关系,通过回归方程预测合适的处方。结果回归方程的显著性和精度较好,以其为依据制备了苦参碱控释片。结论对于初级渗透泵的处方设计,均匀设计法是可行的方法。

复方石韦片中生物碱的分离测定

目的:建立了复方石韦片中槐果碱和苦参碱的分离测定方法。方法:采用高效毛细管电泳法进行测定。运行电压27kV;运行缓冲液为0.2 mol·L^(-1) Tris-40 mmol·L^(-1)磷酸二氢钠-5％异丙醇,磷酸调pH 5.75;进样方式:真空进样;进样时间:5s;检测波长:205nm。结果:槐果碱和苦参碱的线性范围分别为0.5～5.76μg·mL^(-1)和0.66～13.2μg·mL^(-1),相关系数分别为0.9991和0.999 3,平均回收率分别为99.5％和99.3%,RSD分别小于4％和2％(n=3)。结论;本法简便、快速、重现性好。

高效液相色谱法同时测定苦参片中苦参碱和氧化苦参碱的含量

目的建立苦参片中氧化苦参碱和苦参碱的含量测定方法。方法采用高效液相色谱法，使用Thermo色谱柱，以乙腈-磷酸盐缓冲液（取磷酸二氢钾1．36g，加1ml三乙胺，加水至1000ml，用磷酸调节pH5．5）（3：97）为流动相，流速为1．0mE／min，检测波长为220nm。结果氧化苦参碱在0．0055～0．088mg／ml之间与峰面积积分值呈良好的线性关系（r=0．9998），平均加样回收率99．41％，RSD为1．28％；苦参碱在0．106～0．170mg／ml之间与峰面积积分值呈良好的线性关系（r=0．9999），平均加样回收率99．35％，RSD=1．25％。结论该法灵敏、准确、专属性强，重现性好，可作为苦参片的质量控制方法。

苦参碱缓释片的制备及释放度研究

目的:制备苦参碱缓释片,研究体外释放特性。方法:筛选缓释片处方,优化制备工艺,建立苦参碱缓释片释放度HPLC测定方法,测定苦参碱缓释片的累积释放度,并进行释放机制的研究。结果:所制备的苦参碱缓释片体外释放符合Higuchi方程。结论:苦参碱缓释片体外释药性能良好,符合设计要求,易于工业化生产。

苦参碱缓释片的研制及体外释放特性研究

目的 为延长苦参碱的作用时间 ,将其制成缓释片 ,并对该缓释片的体外释放特性进行研究。方法 利用亲水性凝胶骨架将苦参碱制成缓释片 ,并进行体外累积释放度测定。结果 该缓释片的释药曲线基本符合Higuchi方程 ,具有缓释片的体外溶出特征。硬度和溶出介质的pH对释药行为影响不大 ,而转速及辅料用量有一定影响。结论 苦参碱缓释片释药缓慢、平稳 ,达到了设计要求 ,有利于降低不良反应发生率。