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.

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.

Study of Sustained Release Phenylpropanolamine Hydrochloride Hydrophilic Matrix Tablets Containing Hydroxypropylmethylcellulose K100M and Carbopol 971P

选用HPMC K100M和卡波普971P为骨架材料，粉末直接压片法制备骨架片，考察释放度，反相高效液相色谱法检测盐酸苯丙醇胺（PPA·HCl）的浓度。释药曲线均符合Higuchi方程（R＞0．98，P＜0．01）。运用正交设计法，以美国市场的PPA·HCl缓释片Acutrim^R为对照，相似因子f2值为指标，筛选获得了最优处方。其工艺重现性合格。研制片在0．1mol·L^-1 HCl,H2O(pH6.5)，磷酸盐缓冲液（PBS）pH5.0,6.8和7.4的介质中，以及在0.1mol·L^-1HCl中释放2h，转移至PBS6．8中释放10h，相对于对照品的f2值为63－74，表明在各介质中两制剂的释药曲线相似。释药影响因素的考察结果表明：在本实验考察的范围内，骨架片在水中的释药速率与HPMC K100M和卡波普971P的用量呈负相关。HPMC K100M和卡波普971P的比例（保持聚合物总用量相同），硬脂酸镁量和骨架片硬度对释药速率无显著性影响。

Huoxue Rongluo Tablet reduces matrix metalloproteinase-9 expression in infarcted brain tissue

Huoxue Rongluo Tablet was made of tall gastrodis tuber, dahurian angelica root, honeysuckle stem, grassleaf sweetflag rhizome, common flowering quince fruit, figwort root, red peony root and peach seed at a ratio of 3：2：6：2：3：3：3：3. Huoxue Rongluo Tablet is a well-established and common pre- scription for the treatment of cerebral infarction. In this study, a rat model of cerebral ischemia was established and the animals were intragastrically administered Huoxue Rongluo Tablet. This treat- ment reduced infarct volume, decreased matrix metalloproteinase-9 expression, and improved neurological function. Moreover, the effects of Huoxue Rongluo Tablet were better than those of buflomedil pyridoxal phosphate. These results indicate that Huoxue Rongluo Tablet is effective in treating cerebral infarction by regulating matrix metalloproteinase-9 protein expression.

Design and evaluation of an extended-release matrix tablet formulation; the combination of hypromellose acetate succinate and hydroxypropylcellulose

The purpose of this study was to develop an extended-release(ER) matrix tablet that shows robust dissolution properties able to account for the variability of pH and mechanical stress in the GI tract using a combination of enteric polymer and hydrophilic polymer. Hypromellose acetate succinate(HPMCAS) and hydroxypropylcellulose(HPC) were selected as ER polymers for the ER matrix tablet(HPMCAS/HPC ER matrix tablet). Oxycodone hydrochloride was employed as a model drug. Dissolution properties of the HPMCAS/HPC ER matrix tablets were evaluated and were not affected by the pH of the test medium or paddle rotating speed.In a USP apparatus 3(bio-relevant dissolution method), dissolution profiles of the HPMCAS/HPC ER matrix tablets containing oxycodone hydrochloride were similar to that of the reference product(OxyC ontin). Moreover, in vivo performance after oral administration of the HPMCAS/HPC ER matrix tablets to humans was simulated by GastroP lus based on dissolution profiles from the USP apparatus 3. The plasma concentration-time profile simulated was similar to that of the reference product. These results suggest that the combination of HPMCAS and HPC shows a robust dissolution profile against pH and paddle rotating speed and indicates the appropriate extended-release profile in humans.

Effect of formulation variables on in vitro release of a water-soluble drug from chitosanesodium alginate matrix tablets

The objective of this study is to investigate the feasibility of using chitosanesodium alginate(CSeSA)based matrix tablets for extended-release of highly water-soluble drugs by changing formulation variables.Using trimetazidine hydrochloride(TH)as a water-soluble model drug,influence of dissolution medium,the amount of CSeSA,the CS:SA ratio,the type of SA,the type and amount of diluents,on in vitro drug release from CSeSA based matrix tablets were studied.Drug release kinetics and release mechanisms were elucidated.In vitro release experiments were conducted in simulated gastric fluid(SGF)followed by simulated intestinal fluid(SIF).Drug release rate decreased with the increase of CSeSA amount.CS:SA ratio had only slight effect on drug release and no influence of SA type on drug release was found.On the other hand,a large amount of water-soluble diluents could modify drug release profiles.It was found that drug release kinetics showed the best fit to Higuchi equation with Fickian diffusion as the main release mechanism.In conclusion,this study demonstrated that it is possible to design extended-release tablets of watersoluble drugs using CSeSA as the matrix by optimizing formulation components,and provide better understanding about drug release from CSeSA matrix tablets.

Development and <i>in Vitro-in Vivo</i>Evaluation of Controlled Release Matrix Tablets of Desvenlafaxine

The objective of this investigation was to prepare extended release tablet containing matrix granules of Desvenlafaxine succinate monohydrate and to study its in vitro release and in vivo absorption. The design of dosage form was performed by choosing hydrophilic hydroxypropyl methyl cellulose (HPMC K100M), sodium carboxyl methyl cellulose (Blanose), microcrystalline cellulose (MCC) and lactose monohydrate polymers as matrix builders and polyvinyl pyrolidine (Kollidon K30) as granulating polymers. Granules were prepared by composing drug with HPMC K100M, sodium CMC, MCC and lactose monohydrate by spray drying method. Optimized formulation of Desvenlafaxine succinate monohydrate was formed by using 20% HPMC K100M, 26.6% MCC, 6.6% of sodium CMC (Blanose), 13.3% of lactose monohydrate and 5% ratio of Kollidon K30 as binder. Tablets were compressed with free flowing optimized granules of uniform drug content. This extended the release period up to 24 h in vitro study. Similarity factor and mean dissolution time were also reported to compare various dissolution profiles. The network formed by HPMC, MCC and Blanose had been coupled satisfactorily with the controlled resistance. Biopharmaceutical study of this optimized dosage form in rabbit model showed 24 h prolonged drug release in vivo. A close correlation (R2 = 0.9833) was established between the in vitro release and the in vivo absorption of drug. The results suggested that wet granulation with spray dried technique, is a suitable method to formulate sustained release Desvenlafaxine succinate monohydrate and it can Perform therapeutically better than conventional immediate release dosage form.

Evaluation of gum mastic(Pistacia lentiscus) as a microencapsulating and matrix forming material for sustained drug release

In this study, a natural gum mastic was evaluated as a microencapsulating and matrixforming material for sustained drug release. Mastic was characterized for its physicochemical properties. Microparticles were prepared by oil-in-oil solvent evaporation method. Matrix tablets were prepared by wet and melt granulation techniques. Diclofenac sodium(DFS) and diltiazem hydrochloride(DLTZ) were used as model drugs. Mastic produced discrete and spherical microspheres with DLTZ and microcapsules with DFS. Particle size and drug loading of microparticles was in the range of 22–62 μm and 50–87%, respectively. Increase in mastic:drug ratio increased microparticle size, improved drug loading and decreased the drug release rate. Microparticles with gum: drug ratio of 2:1 could sustain DLTZ release up to 12 h and released 57% DFS in 12 h. Mastic produced tablets with acceptable pharmacotechnical properties. A 30% w/w of mastic in tablet could sustain DLTZ release for 5 h from wet granulation,and DFS release for 8 h and 11 h from wet and melt granulation, respectively. Results revealed that a natural gum mastic can be used successfully to formulate matrix tablets and microparticles for sustained drug release.

Formulation development of nifedipine controlled-release coated tablets

Due to frequent administration of oral nifedipine tablet, controlled or sustained release of the drug will improve patient compliance, stable blood level and side effect decrement [1,2].Various extended release nifedipine products have been commercially available. In this study, extended release tablets of this drug were formulated using sodium alginate,hydroxypropylmethylcellulose (HPMC) as controlled release matrix materials.

Evaluation of Tablets Containing a Probiotic Strain for an Oral Administration

The scientific concept of probiotics has been widely accepted throughout the last decades; consequently, its industrial production and commercialization have been increased. This is only the beginning since a recent global probiotic market analysis estimated an annual growth, boosted mainly by a rising request from the Asian and European consumer in the next 5 years. So the pharmaceutical industry needs to develop new dosage forms containing probiotic microorganisms in order to offer consumers a variety of products. Different kinds of matrix tablets with Lactobacillus coryniformis CECT 5711 were designed to protect this strain from the technological process and harsh gastrointestinal conditions up until their arrival in the gut, as well as environmental conditions during their storage. With this aim, various retarding polymers were combined so as to get controlled release tablets. All formulations were evaluated in terms of technological processability, bacterial viability and stability. Finally, an optimal formulation with Methocel K-15 M EP, Eudragit L-100 and alginate sodium, which contain Lactobacillus coryniformis CECT 5711, was selected due to the fact that it assured an excellent survival of the microorganisms after their exposition to all conditions mentioned above, besides it will be able to improve human＇s health.

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.

针刺联合西药治疗寒凝血瘀型子宫内膜异位症的临床疗效观察

【目的】观察针刺联合西药治疗子宫内膜异位症(EMs)的临床疗效。【方法】将82例寒凝血瘀型子宫内膜异位症患者随机分为观察组和对照组,每组各41例,对照组给予米非司酮和桂枝茯苓胶囊口服,观察组在对照组治疗的基础上,给予针刺治疗。2组患者均治疗3个月经周期。治疗3个月后,评价2组临床疗效,观察2组患者治疗前后疼痛视觉模拟量表(VAS)评分和焦虑自评量表(SAS)的变化情况,以及中医证候积分的情况。比较2组患者治疗前后血清血管内皮生长因子(VEGF)、基质金属蛋白酶-9(MMP-9)和前列腺素E2(PGE2)水平的变化情况。【结果】(1)观察组总有效率为92.68%(38/41),对照组为75.61%(31/41)。观察组疗效优于对照组,差异有统计学意义(P<0.05)。(2)治疗后,2组患者VAS评分和SAS评分均明显改善,且观察组在改善VAS评分和SAS评分方面明显优于对照组,差异均有统计学意义(P<0.05)。(3)治疗后,2组患者中医证候积分均明显改善,且观察组在改善中医证候积分方面明显优于对照组,差异有统计学意义(P<0.05)。(4)治疗后,2组患者血清VEGF、MMP-9和PGE2水平明显改善,且观察组在改善血清VEGF、MMP-9和PGE2水平方面明显优于对照组,差异均有统计学意义(P<0.05)。【结论】针刺联合西药治疗子宫内膜异位症,可明显改善患者的疼痛症状,缓解患者的焦虑状况,减轻患者的临床症状,并调节患者VEGF、MMP-9和PGE2水平,临床疗效显著。

X射线荧光光谱仪粉末压片法分析炉前硅锰合金的应用研究

本文介绍了X射线荧光光谱仪粉末压片法分析炉前硅锰合金在试验应用过程中样品不均匀性、基体效应、样品变化等因素影响,以及如何控制、减少影响、提高分析结果的准确性的研究。最终达到精密度试验和正确度试验结果均满足化学分析重复限性和再现性要求以及炼钢对硅锰物料的分析检测要求。

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.

富血小板血浆联合氨糖美辛肠溶片治疗早中期膝骨关节炎患者的效果

目的:观察富血小板血浆(PRP)联合氨糖美辛肠溶片治疗早中期膝骨关节炎(KOA)患者的效果。方法:回顾性分析2022年1月至2023年1月该院收治的96例早中期KOA患者的临床资料,根据治疗方案不同将其分为对照组和研究组各48例。对照组予以氨糖美辛肠溶片治疗,研究组在对照组基础上联合PRP治疗。比较两组临床疗效,治疗前后关节功能[膝关节功能评分表(Lysholm)、骨关节炎指数量表(WOMAC)]评分、关节滑液炎性因子[白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)]水平、关节滑液基质代谢相关指标[基质金属蛋白酶-3(MMP-3)、基质金属蛋白酶-13(MMP-13)、透明质酸(HA)]水平、血清微小RNA-140(miR-140)和微小RNA-365(miR-365)水平。结果:研究组治疗总有效率为91.67%(44/48),高于对照组的72.92%(35/48),差异有统计学意义(P<0.05);治疗后,研究组Lysholm评分高于对照组,WOMAC评分低于对照组,差异均有统计学意义(P<0.05);治疗后,研究组关节滑液IL-6、IL-1β、TNF-α、MMP-3、MMP-13水平均低于对照组,HA水平高于对照组,差异有统计学意义(P<0.05);治疗后,研究组血清miR-140水平高于对照组,miR-365水平低于对照组,差异均有统计学意义(P<0.05)。结论:PRP联合氨糖美辛肠溶片治疗早中期KOA患者可提高治疗总有效率和miR-140水平,改善关节功能评分和关节滑液基质代谢相关指标水平,降低关节滑液炎性因子和miR-365水平,效果优于单纯氨糖美辛肠溶片治疗。