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.

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.

Development of curcumin floating tablets based on low density foam powder

The floating drug delivery system (FDDS) has become increasingly attractive system for gastroretentive dosage forms because it can prolong gastric retention time and improve drug bioavailability (1)Using low density material of polypropylene foam powder is one of the interesting approaches for FDDS development. This floating system has initial low density so it can float immediately without lag time.

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.

Film coated floating tablets using sublimable substances

During the past few decades floating drug delivery systems(FDDSs)have been developed to prolong gastric retention time and obtain sufficient drug bioavailability[1].To avoid unpredictable time to float due to variable pH of the gastric fluid in each subject and food in the stomach[2],sublimation technique is the new interesting approach to prepare noneffervescent FDDSs[3].The objective of the present study was to develop the low-density film coated floating tablets using sublimable substances.

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.

Pulsatile core-in-cup valsartan tablet formulations:In vitro evaluation

The aim of the present study was to design and evaluate single pulse and floating double pulse valsartan core-in-cup tablets.Core tablets were prepared by direct compression of a homogenous mixture of valsartan,Avicel PH-101,Croscarmellose sodium(CCNa),magnesium stearate&Aerosil.Weight variation,Hardness and Disintegration time were measured for the core tablets.Core-in-cup tablets were formulated using different polymers as a plug layer,including sodium alginate(SA),sodium carboxymethylcellulose(NaCMC)and hydroxypropyl methyl cellulose(HPMC).The floating behavior,water uptake and drug release from the prepared formulations were evaluated.Differential Scanning Calorimetry(DSC)was also performed to detect the possible drug excipient interaction.Stability study of the selected formula was performed at 25
C&60%RH and at 40
C&75%RH for 3 months.Finally,the existence of the selected formula in the stomach after oral administration to human volunteers was verified via x-ray radiography.The results showed that the release lag time of the tablets increased when the quantity of the plug layer increased thus decreasing the drug release.Plug layer polymers showed a lag time with rank order:SA<NaCMC<HPMC.Selected formulations are F5&F6.F5(having SA as the plug polymer)released valsartan after a lag time of 2 h while F6 released the drug in two successive pulses with a reasonable lag time in between due to its floating behavior.Formulations were stable for at least 3 months under standard long-term and accelerated storage conditions.In conclusion,pulsatile single pulse and floating double pulse stable valsartan core-incup tablets were successfully formulated which provided a desirable lag time followed by a rapid drug release.

吴茱萸碱胃漂浮片制备及其对家兔胃黏膜损伤的保护作用

目的制备吴茱萸碱胃漂浮片,并考察其对家兔胃黏膜损伤的保护作用。方法粉末压片法制备胃漂浮片。以HPMC K15M用量、十六醇用量、碳酸氢钠用量为影响因素,2、6、12 h内累积释放度的综合评分为评价指标,Box-Behnken响应面法优化处方。30只家兔随机分为正常组、模型组、吴茱萸碱胃漂浮片低剂量组(20 mg/kg)、吴茱萸碱胃漂浮片高剂量组(40 mg/kg)、西咪替丁组(20 mg/kg),灌胃给药13 d,第14天灌胃给予无水乙醇制备胃黏膜损伤模型,计算胃黏膜损伤指数、溃疡抑制率,观察胃组织病理变化。结果最佳处方为HPMC K15M用量25.5%,十六醇用量7.0%,碳酸氢钠用量13.6%,平均浮动滞后时间为76 s,漂浮时间为12 h,12 h内累积释放度大于90%,综合评分为1.6分。吴茱萸碱胃漂浮片高剂量组胃黏膜损伤指数为2.08±0.40,溃疡抑制率为58.56%,接近西咪替丁。结论吴茱萸碱胃漂浮片体外缓释作用明显,并且对家兔胃黏膜损伤具有保护作用。

Statistical design and evaluation of a propranolol HCl gastric floating tablet

The purpose of this research was to apply statistical design for the preparation of a gastric floating tablet(GFT)of propranolol HCl and to investigate the effect of formulation variables on drug release and the buoyancy properties of the delivery system.The contents of polyethylene oxide(PEO)WSR coagulant and sodium bicarbonate were used as independent variables in central composite design of the best formulation.Main effects and interaction terms of the formulation variables were evaluated quantitatively using a mathematical model approach showing that both independent variables have significant effects on floating lag time,%drug release at 1 h(D_(1h))and time required to release 90%of the drug(t_(90)).The desired function was used to optimize the response variables,each with a different target,and the observed responses were in good agreement with the experimental values.FTIR and DSC studies of the statistically optimized formulation revealed there was no chemical interaction between drug and polymer.The statistically optimized formulation released drug according to first order kinetics with a non-Fickian diffusion mechanism.Evaluation of the optimized formulation in vivo in human volunteers showed that the GFT was buoyant in gastric fluid and that its gastric residence time was enhanced in the fed but not the fasted state.

尼可地尔胃漂浮型缓释片的研制

开发一种基于粉末直压工艺制备尼可地尔胃漂浮型缓释片。以HPMC K100M与Kollidon SR为骨架通道,以累计释放度、起漂时滞与总漂浮时长为评价指标,成功制备出尼可地尔胃漂浮型缓释片。该缓释片体外释放时间可达24 h,起漂时滞为3 min,总漂浮时长超过12 h。对制备的尼可地尔胃漂浮型缓释片进行质量评价,片重差异、硬度以及脆碎度均符合药典要求,片重差异为3.5%,硬度均在10~12 kg,脆碎度减失差重为0.34%。

Utilization of biodiesel waste in the development of botanical-based floating tablet formulation against early stages of mosquitoes

The current paper has elaborated the efficient utilization of liquid biodiesel waste in combination with dillapiole and citronella essential oil as active ingredients.Sawdust,cellulose and hydrophobic silica were used as inert ingredients,which make the tablet to float over the water surface.ATR-FTIR analysis of tablet confirmed the compatibility with citronella oil,dillapiole,liquid biodiesel waste in tablet composition after compression.Physico-chemical analysis studies show that tablet parameters are in standard limits.SEM analysis shows some porous structures in tablet composition which confirms the floating nature of the tablets.The specific ratio(2:2:1)of citronella oil,dillapiole and liquid biodiesel waste showed maximum mortality,i.e.95%after 24 h.After application,the tablet is nontoxic towards the aquatic organisms and water quality remains unaf-fected.The better performance of the tablets has been evaluated in terms of characterization studies,viz.ATR-FTIR and SEM studies and bioefficacy trials which confirmed the presence of active ingredients responsible for insecticidal activity.

PVP、PVA 为辅料的胃漂浮缓释片研究Ⅱ地尔硫胃漂浮缓释片

以 PVP、PVA 为辅料制备了一种能漂浮在胃液上的地尔硫草(简称 D)漂浮片(HBS),测定了该片的体内外释药情况。D 能在人工胃液中缓慢持久地释放,药物系通过凝胶层扩散溶出,释药过程接近零级。家犬口服给药试验表明 D-HBS 片较 D 普通胶丸维持平稳而持久的血药浓度,其生物利用度也大致相同。

泡腾技术在药物制剂中的研究进展

泡腾技术作为加快制剂崩解,促进药物溶出的技术,常用于速释制剂中,随着相关技术与理论研究深入,泡腾技术越来越广泛应用于缓控释制剂和脉冲释药系统中,调节释药制剂行为。作者主要介绍了泡腾技术在泡腾片、胃漂浮制剂、渗透泵片和脉冲释药系统中研究应用,以及泡腾制剂共性关键技术研究进展,有利于泡腾制剂研究与开发。

尼莫地平胃内滞留漂浮型缓释片的研究

将尼莫地平先制成速释型固体分散体，再压制成胃内滞留漂浮型缓释片（ＮＭＦＳＲＴ）。均匀设计法优选处方，并考察处方因素对尼莫地平释放的影响，在人体内对ＮＭＦＳＲＴ进行了初步评价。结果表明优选处方于体外漂浮达１０ｈ，０１５～６ｈ释放符合零级动力学。ＨＰＭＣ量越大，药物释放越慢，ＰＥＧ６０００量越大，释放越快。饮食后ＮＭＦＳＲＴ于胃内滞留时间约５ｈ，空腹时约３ｈ；对照非漂浮片饭后服滞留时间为３ｈ，空腹２ｈ排空。体内相对生物利用度为３９１４６％，ＭＲＴ较普通片延长一倍多。

氯氮平胃内漂浮片的研制

采用羟丙甲纤维素、十六醇等材料 ,湿法制颗粒压片 ,制备了氯氮平胃内漂浮片并进行了体外漂浮性与体外释放度的研究。与普通氯氮平片比较 ,本品体外漂浮性良好 ,具有很好的缓释效果 ,其体外释放行为符合 Higuchi方程。

辅料因素对胃漂浮片的制备及漂浮能力的影响

目的以较难压缩成型且压缩后表观密度较大的三七粉为模型药物，研究影响中药胃漂浮片漂浮能力的关键因素。方法利用粉体压缩特性分析仪，建立常用辅料应力缓和曲线数据库，比较三七粉的应力缓和曲线与常用辅料曲线的相似度；将质量比不同的十六醇与三七粉混合制粒，比较在相同条件下的压缩功和对应压块的表观密度，筛选出十六醇的最佳用量；通过正交实验设计，比较各种辅料因素对漂浮能力的影响。结果三七粉应力缓和曲线与玉米淀粉最相似；十六醇与三七粉的质量比为1：20时为最优制粒比例；胃漂浮片中羟丙甲基纤维素（HPMC）用量占总质量的30％以上时，较易形成凝胶骨架；低黏度HPMC、起泡剂中含有NaHCO3有利于漂浮片的溶蚀；制备了5min内起漂、续漂时间在8～24h间的胃漂浮片。结论选择合适的凝胶骨架剂、起泡剂，平衡片剂的硬度与密度的矛盾，是成功制备胃漂浮片的关键因素；本研究对中药胃漂浮片制备中辅料的筛选具有一定的借鉴意义。