Preparation and Characterization of Orally Fast-Disintegrating Mini-Tablets Containing Diphenhydramine Hydrochloride and Aspartic or Glutamic Acid as an Umami Amino Acid

The aim of this study was to prepare diphenhydramine hydrochloride (DPH)-loaded orally fast-disintegrating mini-tablets (OFDMTs) containing either L-aspartic acid (Asp) or L-glutamic acid (Glu) as bitterness-suppressant, to characterize the prepared tablets and to evaluate their bitterness under conditions mimicking those of the oral cavity. The preparation of five formulation batches of the OFDMTs involved mixing DPH, with or without two different concentrations of Asp or Glu, and a premix containing a disintegrating agent. When all ingredients were well mixed, the mixture was directly compacted to form small (4 mm diameter) DPH-loaded OFDMTs. There were only small differences between the tablets with respect to mass, diameter, width and hardness. The disintegration times of the five formulation batches of DPH-loaded OFDMTs were measured using the OD-mate, a disintegration test apparatus in which conditions resemble those of the oral cavity. The disintegration times were all within 10 s of exposure to a medium representing the inside of the oral cavity. Rapid release profiles were observed for DPH, Asp and Glu in these dissolution tests. The taste sensor outputs of samples taken at different times (5 - 30 s) from the dissolution test solutions of the four DPH-loaded OFDMTs containing Asp or Glu were significantly inhibited compared with those of control DPH-loaded OFDMT. These results suggest that the inclusion of Asp or Glu in DPH-loaded OFDMTs is sufficient to mask bitterness in the oral cavity for the first 30 s after the tablet is placed in the mouth. It is anticipated that swallowing will have taken place within 30 s.

High Resolution Determination of Ondansetron in Human Plasma by HPLC and Pharmacokinetics of Orally Disintegrating Tablets

Ahn To develop a high resolution HPLC method for the determination of ondansetron in human plasma and to study the pharmacokinetics of ondansetron in orally disintegrating tablets. Methods HPLC determination involved liquid-liquid extraction, separation on a CN column and ultraviolet detection at 310 ran with granisetron as an internal standard. Pharmacokinetics and bioequivalence of ondansetron in orally disintegrating tablets by direct compression and conventional 8 mg tablets were evaluated and compared in 20 healthy human male volunteers after a single oral dose in a randomized cross-over study. Results The limit of quantification was 0.25 ng· mL^-1. The recovery was about 85 % or over for ondan setron and about 90% for internal standard. Linearity was good within the concentration range of 0.5 - 50 ng·mL^-1 with r^2 ranging from 0.997 1 to 0.999 9. Intra- and inter-assay coefficients of variation ranged from 1.78% to 2.38% and 3.88% -5.19%, respectively. Accuracies for spiked concentrations of 2.0, 10.0, and 30.0 ng·mL^-1 were 104.7% ±4.4%, 102.2% ± 1.1%, and99.51% ±2.34%, respectively. Pharmacokinetic parameters of AUCo-t, AUCo-∞ , Cmax, Tmax, and T1/2 were 230.2 ± 78.0 ng·h·L^-1 , 265.2± 101.5 ng·h·mL^-1, 35.67 ± 8.94 ng·mL^-l, 1.51 ±0.79 h, and 5.00± 1.41 h for orally disintegrating tablets, respectively. The analysis of variance did not show any significant difference between orally disintegrating tablets and conventional tablets, and 90% confidence intervals fell within the acceptable range for bioequivalence. Conclusion High resolution HPLC method has been set up and applied in pharmacokinetic evaluation of ondansetron in orally disintegrating tablets.

Predicting oral disintegrating tablet formulations by neural network techniques

Oral disintegrating tablets(ODTs) are a novel dosage form that can be dissolved on thetongue within 3 min or less especially for geriatric and pediatric patients. Current ODT for-mulation studies usually rely on the personal experience of pharmaceutical experts andtrial-and-error in the laboratory, which is inefficient and time-consuming. The aim of cur-rent research was to establish the prediction model of ODT formulations with direct com-pression process by artificial neural network(ANN) and deep neural network(DNN) tech-niques. 145 formulation data were extracted from Web of Science. All datasets were dividedinto three parts: training set(105 data), validation set(20) and testing set(20). ANN andDNN were compared for the prediction of the disintegrating time. The accuracy of the ANNmodel have reached 85.60%, 80.00% and 75.00% on the training set, validation set and testingset respectively, whereas that of the DNN model were 85.60%, 85.00% and 80.00%, respec-tively. Compared with the ANN, DNN showed the better prediction for ODT formulations.It is the first time that deep neural network with the improved dataset selection algorithmis applied to formulation prediction on small data. The proposed predictive approach couldevaluate the critical parameters about quality control of formulation, and guide researchand process development. The implementation of this prediction model could effectivelyreduce drug product development timeline and material usage, and proactively facilitatethe development of a robust drug product.

Comparative Observation on the Effects of Radix Tripterygium Hypoglaucum Tablet and Tripterygium Glycosides Tablet in Treating Erosive Oral Lichen Planus

Objective: To compare the therapeutic effects of Radix Tripterygium hypoglaucum tablet (THT) and Tripterygium glycosides tablet (TGT) in treating erosive oral lichen planus(EOLP).Methods: The patients were randomized into two groups, and they were treated with THT (n=47) or TGT (n=47), respectively. The therapeutic effects were evaluated after 3 months treatment.Results: For the patients of grade 1, the total efficacy in TGT group was 85.71%, compared with 52.38% in THT group, the efficacy was statistically greater in the group receiving TGT (P=0.043). However, for the patients of grade 2, the difference was not statistically significant (P=0.173).Conclusion: TGT is more effective in treating EOLP than THT for grade 1 patients. However, TGT is not suitable for patients of child bearing age.

Early effects of Lansoprazole orally disintegrating tablets on intragastric pH in CYP2C19 extensive metabolizers

AIM: To compare rabeprazole (RPZ; 10 mg) with Lansoprazole orally disintegrating tablets (LPZ; 30 mg OD) in terms of antisecretory activity and blood drug concentration after a single dose. METHODS: Eight H pylori-negative cytochrome P450 (CYP) 2C19 extensive metabolizers were assigned to receive a single oral dose of RPZ 10 mg or LPZ 30 mg OD. Twelve hour intragastric pH monitoring was perform- ed on the day of treatment. Blood samples were also collected after the administration of each drug. RESULTS: LPZ 30 mg OD induced a significantly earlier rise in blood drug concentration than RPZ 10 mg; consequently, LPZ 30 mg OD induced a significantly earlier rise in median pH in the third and fourth hours of the study. CONCLUSION: In H pylori-negative CYP2C19 extensive metabolizers, LPZ 30 mg OD induced a significantly faster inhibition of gastric acid secretion than RPZ 10 mg.

The Effect of Food Thickeners on the Bitterness and Dissolution of Amlodipine Besilate Loaded Oral Disintegration Tablets: Assessment of Potential Suitability for Patients with Dysphagia

The purpose of this research was to evaluate the effect of starch- and xanthan gum-based food thickeners on the bitterness and dissolution of amlodipine besilate (AMPB) loaded orally disintegrating tablets (ODT) for potential use with patients with dysphagia. A conventional dissolution test simulating the oral cavity was performed and the taste sensor output of the dissolved sample was evaluated over a 60-seconds period. When four types of AMPB loaded ODTs were tested alone, at 60 seconds, branded product (A) was the least bitter, followed by generic product (B)/generic product (C) which were equal, and finally generic product (D) which was the most bitter. Inhibition of bitterness of AMPB loaded ODTs mixed thickeners, 1.0 (w/v) % xanthan gum-based food thickener solution was significantly strong. The 7.1 (w/v) % and 4.7 (w/v) % starch-based food thickeners solution also effective in bitterness inhibition compared to the 2.4 (w/v) % starch-based food thickener solution. The dissolution test under pH 1.2 in related to 7.1 (w/v) % and 4.7 (w/v) % starch-based thickener contained each of AMPB loaded ODTs were associated with an almost complete amlodipine (AMP) dissolution (almost 90% at 10 minutes), whereas the 1.0, 2.0, 3.0 (w/v) % xanthan gum-based food thickener solution containing AMPB loaded ODTs did not show complete AMP dissolution and there were large variations in the initial dissolution stage. This suggests that a mixture of xanthan gum-based thickener and AMPB loaded ODT poses a risk of reduction of bioavailability. In conclusion, a mixture of 4.7 (w/v) % or 7.1 (w/v) % starch-based thickener with ODTs provides complete release of AMP and superior bitterness inhibition, so is the best choice for administration to patients with dysphagia.

Evaluation of the quality of olanzapine orally disintegrated tablets by multiple dissolution curves

Objective: To investigate the dissolution behavior similarity between Self-made praeparatum and reference praeparatum in different pH menstruum,using the Olanzapine Orally Disintegrating Tablets listed in abroad as the reference praeparatum. Methods: The dissolution curve of olanzapine in Self-made praeparatum and reference praeparatum was measured,the similarity of the dissolution curve was evalued by F2 similar factor. Results: The single-point dissolution of both Self-made praeparatum and reference praeparatum within 15 min was more than 85%. Conclusion: Self-made praeparatum and reference praeparatum were similar in dissolution behavior.

当归芍药散与布洛芬口崩片治疗原发性痛经气滞血瘀证的疗效比较

目的 比较当归芍药散与布洛芬口崩片治疗原发性痛经气滞血瘀证的临床疗效。方法 前瞻性选取2020年1月—2023年12月琼海市中医院收治的原发性痛经气滞血瘀证患者144例作为研究对象,采用随机数字表法分为西药治疗组和中药治疗组,各72例。西药治疗组患者接受布洛芬口崩片治疗,中药治疗组患者接受当归芍药散治疗。2组患者均连续治疗3个月经周期。比较2组临床疗效,治疗前后痛经程度评分、血清学指标[前列腺素F_(2)α(PGF_(2)α)、前列腺素E_(2)(PGE_(2))]。结果 中药治疗组患者治疗总有效率为93.06%,高于西药治疗组的77.78%(χ^(2)=6.746,P=0.009)。治疗3个月经周期后,2组患者痛经程度评分低于治疗前,且中药治疗组低于西药治疗组(P<0.01);2组患者血清PGF_(2)α水平低于治疗前,血清PGE_(2)水平高于治疗前,且中药治疗组低/高于西药治疗组(P<0.05或P<0.01)。结论 采用布洛芬口崩片及当归芍药散治疗原发性痛经气滞血瘀证均能通过降低PGF_(2)α、提高PGE_(2)水平而减轻痛经程度,但当归芍药散的效果更佳。

大黄三味片治疗抗精神病药药物性便秘临床观察

目的探讨大黄三味片治疗抗精神病药药物性便秘的有效性和安全性。方法收集2020年7月至2022年12月沈阳市精神科卫生中心精神科病房符合抗精神病药药物性便秘诊断标准的120例患者,按照随机数字法分为治疗组和对照组,每组60例,治疗组予大黄三味片治疗,对照组予乳果糖口服溶液。观察两组患者治疗前后便秘症状积分,排便时间,腹痛评分(VAS),大便性状改善时间、停药7 d内排便次数及生活质量评分。结果两组治疗有效率对比无统计学差异(P>0.05);治疗组大便性状改善时间短于对照组、停药7 d的排便次数多于对照组(均P<0.05);治疗后,治疗组便秘症状评分、腹痛评分、排便时间低于对照组,生活质量评分高于对照组(均P<0.05)。结论大黄三味片治疗抗精神病药药物性便秘临床疗效确切,有效减轻患者痛苦,停药后疗效持久,两组患者均未见不良反应,安全有效。

医院药房口服单剂量调配模式的探索与实践

目的:缩短口服单剂量调配时间,提高工作效率。方法:分析既往单剂量分包模式的不足,从设备、软件、流程等方面改进,包括设计智能棋盘式摆药盘、优化合并备用药槽及使用三备用药槽。比较口服单剂量调配模式改进前后的工作效率。结果:使用智能棋盘式摆药盘后,每条口服医嘱的调配时间从之前的(5.4±0.16)s缩短至(3.5±0.27)s,药师调配速度显著提高(P<0.05)。与改进前的全自动摆药模式相较,改进后平均每包调配时间缩短了24.72%~56.39%,平均每包调配时长显著短于改进前(P<0.05)。与人工摆药模式相较,改进前的全自动摆药模式调配药师从3名缩减至2名,每日人均调配医嘱条数提高至2848.90±153.21,显著高于人工摆药模式(P<0.05),工作效率提升了114.82%;改进后的全自动摆药模式每日人均调配医嘱条数提高至3671.90±56.48,显著高于人工摆药模式(P<0.05),效率提升了176.87%。结论:通过对我院既往单剂量调配模式的改进,工作效率显著提高。

雌激素的2种给药途径对高龄女性冻融胚胎移植临床结局的影响

目的 探讨经皮雌二醇凝胶和口服戊酸雌二醇片对高龄女性冻融胚胎移植(FET)临床结局的影响。方法回顾性分析2021年1月至2022年7月于江西省妇幼保健院辅助生殖中心进行FET治疗的391例高龄(≥38岁)女性患者的临床资料,将在内膜准备中经皮外用雌二醇凝胶的患者归为经皮组(n=192),口服戊酸雌二醇片的患者归为口服组(n=199),比较2组的临床特征。结果 2组患者年龄、体重指数、窦卵泡计数、抗缪勒管激素比较差异无统计学意义(P>0.05)、且其治疗情况(转化日内膜厚度、凝血功能、肝功能)及临床结局(HCG阳性率、生化流产率、临床妊娠率、多胎率、种植率、流产率、活产率)比较,其差异亦无统计学意义(P>0.05)。结论 在高龄女性FET助孕过程中经皮雌二醇凝胶与口服戊酸雌二醇片给药具有相似的临床结局和较好的安全性。

盐酸左西替利嗪冻干口崩片的制备

目的:设计盐酸左西替利嗪冻干口崩片的制备工艺并评价成品质量。方法:采用冷冻干燥法制备盐酸左西替利嗪冻干口崩片,以成品外观、崩解时限、口感口味等为指标对口崩片质量进行单因素考察,并通过正交试验优化处方。结果:口崩片最优处方:盐酸左西替利嗪-β-环糊精包合物每片11.25 mg、甘氨酸每片10 mg、普鲁兰多糖每片8 mg、三氯蔗糖每片0.5 mg、白桃香精每片1.5μL;最终制备得到外观优美、崩解迅速、口味良好的盐酸左西替利嗪冻干口崩片。结论:盐酸左西替利嗪冻干口崩片制备工艺稳定可靠,可用于大规模生产。

盐酸米诺环素软膏与甲硝唑片联合治疗对牙周炎患者口腔环境的影响及安全性

目的分析盐酸米诺环素软膏与甲硝唑片联合治疗对牙周炎患者口腔环境的影响及安全性。方法方便选取2021年8月—2023年10月经漳浦县中医院确诊为牙周炎的患者84例作为研究对象,结合随机数表法将其分为两组,每组42例。对照组予以甲硝唑片单药治疗,观察组予以盐酸米诺环素软膏及甲硝唑片联合治疗,对比两组用药疗效、口腔环境、龈沟液炎症情况以及用药安全性。结果观察组用药总有效率(95.24%)高于对照组(80.95%),差异有统计学意义(χ^(2)=4.086,P<0.05)。治疗后,观察组龈沟出血指数、菌斑指数均低于对照组,差异有统计学意义(P均<0.05)。治疗后,观察组各项龈沟液炎症指标检测值均低于对照组,差异有统计学意义(P均<0.05)。两组用药不良反应发生率对比,差异无统计学意义(P>0.05)。结论盐酸米诺环素软膏及甲硝唑片联合治疗可提升对牙周炎的治疗效果,更有效清除龈沟液炎症,改善患者的口腔健康环境,且用药相对安全可靠。

Comparative efficacy and safety of Chinese patent medicines of iron deficiency anemia during pregnancy:A network meta-analysis

BACKGROUND Iron deficiency anemia(IDA)is a prevalent nutritional disorder during pregnancy.Clinical studies indicate that incorporating Chinese patent medicines(CPMs)with oral iron(OI)in treating IDA in pregnancy can reduce adverse effects and improve clinical outcomes.Nonetheless,the comparative efficacy of different CPMs remains unclear.AIM To assess the safety and effectiveness of different CPMs for treating IDA during pregnancy using network meta-analysis.METHODS We conducted a search for randomized controlled trials(RCTs)that combined CPM and OI for IDA treatment in pregnancy,spanning from 2013 to the present.Data analysis was performed using Rev Man 5.3 and Stata 14.0 on literature that satisfied the quality criteria.RESULTS The analysis included 45 RCTs,encompassing 4422 pregnant patients with IDA.Six CPMs were examined,including Shengxuebao Mixture,Shengxuening Tablets(SXN),Yiqi Weixue CPMs(YQWX),Jianpi Shengxue CPMs(JPSX),Yiqi Buxue Tablets,and Compound Hongyi Buxue Oral Liquid(FFHY).Findings indicated that FFHY+OI significantly improved the clinical effective rate.SXN+OI was most effective in boosting red blood cells counts and hemoglobin levels.YQWX+OI showed superior results in improving serum ferritin,and SXN+OI was most effective in increasing serum iron levels.JPSX+OI was optimal in reducing adverse pregnancy outcomes,while YQBX+OI effectively minimized adverse events.A cluster analysis suggested that SXN+OI could be the potentially optimal therapeutic regimen for IDA in pregnancy.CONCLUSION This study demonstrates that the combination of OI with CPMs offers better outcomes than OI alone.Based on clinical efficacy and other measured outcomes,SXN+OI emerges as the most effective treatment modality for improving the health of pregnant patients with IDA.

阿卡波糖片与克林霉素联合口腔干预对2型糖尿病牙周病患者血糖水平的影响

目的探究阿卡波糖片与克林霉素联合口腔干预对2型糖尿病牙周病患者血糖水平的影响。方法选取福建省泉州市第一医院于2023年3—11月收治的98例2型糖尿病牙周病患者为研究对象,采用密闭信封法分为对照组和研究组,各49例。两组均常规口服盐酸二甲双胍片并行口腔干预,对照组在常规治疗基础上联用克林霉素治疗,研究组在常规治疗基础上联用阿卡波糖片治疗。于干预前及干预2个月后,对比两组患者空腹血糖(Fasting Plasma Glucose,FPG)、餐后2 h血糖(2 h Postprandial Blood Glucose,2 hPG)水平,及两组菌斑指数(Plaque Index,PLI)、牙龈指数(Gingival Index,GI)、临床附着丧失(Clinical Attachment Loss,CAL)水平。结果干预2个月后,研究组FPG为(5.46±0.27)mmol/L,2 hPG为(7.83±0.92)mmol/L,均低于对照组,差异有统计学意义(t=3.466、9.654,P均<0.05)。研究组PLI、GI、CAL水平均低于对照组,差异有统计学意义(P均<0.05)。结论2型糖尿病牙周病患者实施阿卡波糖片联合口腔干预能够降低患者血糖水平,并改善牙周指标。

盐酸米诺环素软膏配合甲硝唑口腔粘贴片对牙周炎患者的治疗效果

目的:分析盐酸米诺环素软膏配合甲硝唑口腔粘贴片对牙周炎患者的治疗效果。方法:选取2021年10月至2023年9月郑州市口腔医院收治的178例牙周炎患者,按照随机分组原则分为对照组和观察组,各89例。对照组采用甲硝唑口腔粘贴片治疗,观察组在对照组的治疗方案上采用盐酸米诺环素软膏治疗。比较两组患者牙周指数及牙周袋深度(PD)、龈沟液炎症因子、临床疗效。结果:观察组患者临床总有效率高于对照组,差异具有统计学意义(P<0.05)。治疗后,观察组患者牙龈指数(GI)、菌斑指数(PLI)、龈沟出血指数(SBI)、PD均低于对照组,差异具有统计学意义(P<0.05)。治疗后,观察组患者龈沟液白细胞介素(IL)-6、IL-1β、基质金属蛋白酶(MMP)-8水平低于对照组,差异具有统计学意义(P<0.05)。结论:盐酸米诺环素软膏配合甲硝唑口腔粘贴片治疗牙周炎,可明显减轻牙龈炎症反应,改善牙周病理状态。

盐酸苯海拉明微丸型口腔崩解片的制备工艺研究

采用挤出滚圆及包衣制备缓释微丸,湿法制粒法制备辅料颗粒,将缓释微丸、辅料颗粒及外加物料混合压片制备了盐酸苯海拉明口腔崩解片。结果表明:盐酸苯海拉明与微晶纤维素以质量比1∶1混合后挤出滚圆,并采用乙基纤维素乙醇溶液包衣制备缓释微丸,然后再与其他辅料混合压片制备口腔崩解片,其溶出曲线与原研制剂不同介质中体外溶出相似。采用缓释微丸压片的方法制备口腔崩解片可以减缓药物溶出速度,达到与原研制剂不同介质中溶出曲线相似目的,该技术可为其他溶出类似口腔崩解片的研究开发提供参考。

咀嚼片适口性及可咀嚼性的体外口腔模拟评估

目的 评估咀嚼片的适口性及可咀嚼性,为各类咀嚼片的质量评价提供参考。方法 以自制盐酸氨基葡萄糖咀嚼片为模型药,并进行质量检测。通过质构仪及流变仪建立咀嚼片体外模拟体系,对咀嚼片进行口腔模拟实验。采用质构仪测定咀嚼片咀嚼所需的力及模拟静态崩解过程,采用流变仪测定咀嚼片咀嚼过程中的黏弹性、触变性及变形性。结果 自制盐酸氨基葡萄糖咀嚼片的崩解时限、主成分含量、溶出等结果均符合限度要求。质构仪体外模拟结果显示,自制咀嚼片无论轴向或径向咀嚼均易被嚼碎,咀嚼所需的力在牙齿咀嚼力承受范围内;咀嚼片不经咀嚼仅含服于口腔中也可在适宜时间内崩解完成。流变仪体外模拟结果显示,咀嚼片在口腔中通过舌头不断搅动,表现出以弹性为主、黏性为辅的行为,且咀嚼片的黏度会随着舌头的搅动或牙齿咀嚼而逐渐下降;牙齿咀嚼时,咀嚼片内部应力降低,发生塑性变形被压碎,被嚼碎后形状不可恢复,易于咀嚼吞咽。结论 通过质构仪及流变仪联合运用模拟口腔咀嚼过程可对自制盐酸氨基葡萄糖咀嚼片的适口性及可咀嚼性进行评估,该模型可为各类咀嚼片的评价提供参考。

临床药师参与1例心力衰竭、心肌梗死合并房颤患者的药物治疗

目的梳理复杂治疗方案后的抗栓方案,重整抗栓药物和疗程,纠正不合理用药,促进合理用药。方法临床药师介入1例心力衰竭、多次因心肌梗死植入多枚支架,合并房颤,行射频消融和左心耳封堵患者的药物治疗,重整抗栓药物方案,并全程监控治疗药物,就不合理用药提出警示。结果患者明显好转,住院及出院随访期间未发生不良事件。结论临床药师的参与有助于精细化管理患者的药物治疗方案,并及时纠正不合理用药,更好的为患者服务。

复方益心酮口崩片的质量控制研究

目的 建立复方益心酮口崩片主要有效成分山楂叶提取物指标性成分牡荆素葡萄糖苷(pectin glucoside,PG)、牡荆素鼠李糖苷(pectin rhamnoside,PR)的含量测定方法。方法 采用高效液相色谱(high-performance liquid chromatography,HPLC)法,对山楂叶提取物PG、PR进行含量测定,色谱柱使用Diamonsil C18,四氢呋喃-乙腈-甲醇-醋酸-水(38∶3∶3∶4∶152)为流动相,检测波长为330 nm,柱温为30℃,进样量为20μl。结果 PG在0.40~8.00μg/ml浓度范围内线性关系良好(r=0.999),PR在1.50~30.00μg/ml浓度范围内线性关系良好(r=0.999);精密度、重复性、稳定性试验,相对标准偏差(relative standard deviation,RSD)均小于2.00%;PG平均回收率为99.40%,RSD为1.21%(n=6),PR平均回收率为99.61%,RSD为0.52%(n=6)。结论 本研究所建立的HPLC法专属性强,重现性良好,结果准确,可用于复方益心酮口崩片的质量控制。