Structure based release kinetics analysis of doxazosin mesylate sustained-release tablets using micro-computed tomography

The structures of solid dosage forms determine their release behaviors and are critical attributes for the design and evaluation of the solid dosage forms.Here,the 3D structures of doxazosin mesylate sustained-release tablets were parallelly assessed by micro-computed tomography(micro-CT).There were no significant differences observed in the release profiles between the RLD and the generic formulation in the conventional dissolution,but the generic preparation released slightly faster in media with ethanol during an alcohol-induced dose-dumping test.With their 3D structures obtained via micro-CT determination,the unique release behaviors of both RLD and the generic were investigated to reveal the effects of internal fine structure on the release kinetics.The structural parameters for both preparations were similar in conventional dissolution test,while the dissolutions in ethanol media showed some distinctions between RLD and generic preparations due to their static and dynamic structures.Furthermore,the findings revealed that the presence of ethanol accelerated dissolution and induced changes in internal structure of both RLD and generic preparations.Moreover,structure parameters like volume and area of outer contour,remaining solid volume and cavity volumewere not equivalent between the two formulations in 40%ethanol.In conclusion,the structure data obtained from this study provided valuable insights into the diverse release behaviors observed in various modified-release formulations in drug development and quality control.

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.

Formulation Development, in Vitro Evaluation and Stability Study of Aceclofenac Tablet

The objective of the study was to develop film coated tablets of aceclofenac using wet granulation technique. Possible drug-excipient interaction was evaluated by HPLC （high performance liquid chromatography） and FTIR （fourier infrared spectroscopy）. The tablets prepared were assessed for their physicochemical, in vitro dissolution at pH 1.2, 4.5, 6.8 and 7.5 and stability characteristics. Comparison with a commercial aceclofenac product was made in vitro and in vitro studies. There was no interaction between aceclofenac and used excipients. Furthermore, the physicochemical properties of the tablets were satisfactory. The dissolution profile of one of the formulated aceclofenac tablets （D07） was statistically similar （p 〈 0.05） to that of the commercial aceclofenac brand in all the dissolution media. The formulated products ware stable and showed no changes in physical appearance, drug content, or dissolution pattern after storage at 40 ℃/75% RH for 6 months. The results indicate that it is feasible to achieve a stable aceclofenac tablet formulation by using wet granulation technique.

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.

醋氯芬酸缓释片治疗骨关节炎有效性和安全性评价

目的比较醋氯芬酸缓释片和阳性对照药醋氯芬酸片治疗骨关节炎(Osteoarthritis,OA)疗效和安全性。方法采用随机、双盲双模拟、平行对照方法,选择疾病活动期患者40例,试验组19例,对照组21例,实验药醋氯芬酸缓释片200 mg,每天一次;对照药醋氯芬酸片100 mg,每天二次。4周为一疗程。结果治疗4周后,醋氯芬酸缓释片总有效率为84.21%;醋氯芬酸总有效率为85.27%;两组间疗效比较差异无显著性(P>0.05)。4周疗程后,两药均能显著改善骨关节炎患者的症状和体征(P<0.O5)。不良反应发生率试验组为10.53%,对照组为15.79%,两组间不良反应发生率统计学分析无明显差异(P>0.05)。不良反应均以轻度消化道症状为主,无需特殊处理。结论醋氯芬酸缓释片治疗骨关节炎的疗效和安全性与醋氯芬酸片类似,但用药方便。

醋氯芬酸缓释片在犬体内药代动力学及其相对生物利用度研究

目的 :建立了测定犬血浆中醋氯芬酸浓度的HPLC方法 ,研究醋氯芬酸缓释片在犬体内药代动力学及其相对生物利用度。方法 :样品采用正己烷提取 ,HPLC UV法测定 ,紫外检测波长为 2 76nm。流动相 :甲醇 三蒸水 冰醋酸 (77∶2 3∶0 3)组成。流速 1 5ml/min。色谱柱为C18,10 μm ,柱长 30 0mm× 4 6mmI.D .。 结果 :血浆中杂质不干扰样品峰 ,方法的回收率大于 90 % ,最低检测浓度醋氯芬酸为 1 6 5 μg/ml;线性范围为 1 6 5～ 10 0μg/ml。犬单剂量ig 2 0 0mg醋氯芬酸缓释片后 ,估算的末端相半衰期为 6 0 3± 1 95h ,峰时间和峰浓度分别为 5 0± 2 7h和 6 1 36± 2 0 75 μg/ml,MRT为 9 79± 1 71h。其t1/ 2 、tmax、MRT显著大于普通片 (P <0 0 5 ) ,峰浓度显著低于普通片 (P <0 0 5 )。结论 :本文建立的HPLC UV法适合用于醋氯芬酸的临床研究 ;缓释片具有缓释特征 。

醋氯芬酸缓释片治疗类风湿关节炎有效性和安全性评价

目的:比较醋氯芬酸缓释片和阳性对照药醋氯芬酸片治疗活动期类风湿关节炎(RA)疗效和安全性。方法:采用随机、双盲双模拟、平行对照方法,选择疾病活动期RA患者45例(试验组22例,对照组23例);试验药醋氯芬酸缓释片200 mg,每天一次;对照药醋氯芬酸片100 mg,每天2次;4周为一疗程。结果:治疗4周后,试验组总有效率为63.6%,对照组总有效率69.6%(P>0.05)。两药均能显著改善RA患者的症状和体征(P<0.05)。不良反应发生率试验组为13.0%,对照组为12.0%,两组间不良反应发生率差异无统计学意义(P>0.05)。结论:醋氯芬酸缓释片治疗RA的疗效和安全性与醋氯芬酸片类似,但用药方便。

醋氯芬酸肠溶片在健康男性志愿者体内的药代动力学及生物等效性研究

目的 :研究国产醋氯芬酸肠溶片在健康志愿者体内的药代动力学参数和生物等效性。方法 :2 0名健康男性志愿者随机交叉口服国产醋氯芬酸肠溶片 1 0 0mg和进口醋氯芬酸片 1 0 0mg,采用HPLC法测定给药后不同时间点的血浆醋氯芬酸浓度。用3p97程序计算其药代动力学参数 ,评价两种制剂的生物等效性和生物利用度。AUC0 - 2 4 ,AUC0 -inf和Cmax经方差分析和双单侧t检验。结果 :试验药和参比药的醋氯芬酸Cmax分别为 2 0±5mg·L- 1 和 2 0±6mg·L- 1 ;Tmax分别为 2 .7± 0 .5h和 2 .0±0 .5h;AUC0 - 2 4 分别为 5 5±2 6mg·h- 1 ·L- 1 和 5 2± 2 1mg·h- 1 ·L- 1 。试验药与参比药AUC0 - 2 4 之比和Cmax之比的 90 %可信区间分别为 92 .2 %～ 1 2 0 .7%和 91 .8%～ 1 1 8.9%。试验药的人体相对生物利用度为 1 1 2 %± 42 %。结论 :两种制剂的主要药代动力学参数均无显著性差异 ,具有生物等效性。试验药的生物利用度符合要求。

醋氯芬酸缓释片的研制及释药性质

为了减轻醋氯芬酸对胃肠道的刺激作用和副作用，减少服药次数，利用其几乎不溶于水的特性，制成亲水性凝胶骨架片。通过测定制剂的体外溶出度评价了该缓释片的处方，结果表明该制剂的体外溶出行为符合Ｈｉｇｕｃｈｉ方程，处方Ｒ４具有较好的缓释效果。

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.

星点设计-效应面法优化醋氯芬酸双层渗透泵控释片处方

目的优化醋氯芬酸双层渗透泵控释片处方。方法以片芯药层中混悬剂聚氧乙烯、促渗剂、包衣液中增塑剂聚乙二醇的用量和包衣膜增重为考察因素,以2、6、12h累积释放量和2～12h累积释放曲线的线性程度作为优化指标,应用星点设计-效应面法筛选最佳处方,并对优化处方进行验证。结果最优处方组成:混悬剂为197mg,促渗剂为38mg,致孔剂为3.8g,包衣增量质量分数为7.9%。其释放曲线在2-12h零级释放特征显著,12h累计释放量90%,实测值与预测值无明显差异。结论采用星点设计-效应面法得到了醋氯芬酸双层渗透泵控释片的处方优化模型,实现了处方优化。

醋氯芬酸缓释片治疗骨关节炎的临床研究

目的:比较醋氯芬酸缓释片和阳性对照药醋氯芬酸片治疗骨关节炎的疗效和安全性。方法:共有42例骨关节炎患者参加本实验。试验组21例,口服醋氯芬酸缓释片200mg,每日1次;对照组21例,口服醋氯芬酸片100mg,每日2次。疗程4周,采用随机、双盲、双模拟、平行对照的试验方法。结果:治疗2周后:试验组总有效率52.38%,对照组总有效率42.86%(P>0.05)。治疗4周后:试验组总有效率80.95%,对照组总有效率61.90%(P>0.05)。4周疗程后,两药均能显著改善骨关节炎患者的症状和体征(P<0.05)。试验组不良反应发生率为14.29%,对照组为9.52%,统计学分析显示两组间不良反应发生率无明显差异(P>0.05)。不良反应均以轻度消化道症状为主,无需特殊处理。结论:醋氯芬酸缓释片治疗骨关节炎的疗效和安全性与普通片相近,但服用更方便。

高效液相色谱法测定醋氯芬酸缓释片的含量

目的 :建立了高效液相色谱法测定醋氯芬酸缓释片的含量。方法 :采用ZorbaxSB C18色谱柱 ,以乙腈 四氢呋喃 冰醋酸(2 5∶2 5∶5 0 ,用 1.0mol/L的NaOH调pH 3.5 )为流动相 ,流速为 1.0ml/min ,以对羟基联苯为内标物 ,检测波长为 2 75nm。结果 :醋氯芬酸在 10 .2～ 5 0 .1μg/ml范围内呈良好线性 (r=0 .9993) ,平均回收率为 10 0 .3% ,RSD为 0 .45 %。 结论 :本法可用于该片剂的测定 ,操作简便 ,结果准确。

单剂量口服醋氯芬酸肠溶片的人体药代动力学研究

目的研究醋氯芬酸肠溶片的人体药代动力学。方法12名健康男性志愿者口服国产醋氯芬酸肠溶片100mg,采用HPLC法测定给药后不同时间点的血浆醋氯芬酸浓度。用DAS程序计算其药代动力学参数。结果健康志愿者单剂量口服醋氯芬酸肠溶片后,血浆的醋氯芬酸Cmax为(9.13±3.73)mg/L;Tmax为(2.27±0.88)h;t1/2(ke)为(2.54±1.35)h;CL为(1.96±0.79)L/h;Vd为(6.50±3.16)L;AUC为(54.40±20.22)mg·h/L。结论单剂量口服国产醋氯芬酸肠溶片,其人体药代动力学符合一级吸收的一室模型。

醋氯芬酸分散片致严重多形红斑1例

1例63岁女性患者因类风湿性关节炎关节疼痛,给予醋氯芬酸分散片口服治疗(100 mg,bid)。第2天四肢、躯干起红斑丘疹,伴瘙痒,当日停服该药,次日红斑丘疹逐渐蔓延至全身,部分皮损融合成斑片状,给予抗过敏等对症治疗,症状逐渐缓解。8天后出院时躯干四肢红斑较前明显变淡,未见新发皮损出现。

醋氯芬酸缓释片治疗膝关节骨性关节炎临床疗效和安全性研究

目的评价醋氯芬酸缓释片治疗膝骨关节炎临床疗效和安全性。方法将80例膝骨关节炎患者随机分为试验组和对照组,各40例。试验组给予醋氯芬酸缓释片和维固力模拟片,对照组给予维固力胶片和醋氯芬酸缓释模拟片,两组疗程均为12周。观察比较骨关节炎指数评估量表(WOMAC),视觉模拟量表(VAS)评分及不良反应发生情况。结果治疗后以及随访3、6个月,两组患者的WOMAC评分均优于治疗前,且试验组的WOMAC评分优于对照组(P<0.05);两组患者的VAS评分均低于治疗前,且试验组明显低于对照组(P<0.05);而两组患者的不良反应比较,差异不显著(P>0.05)。结论醋氯芬酸缓释片治疗膝骨关节炎疗效优于维固力片,安全性较高,可作为临床上治疗膝骨关节炎的选择药物。