Study of processing parameters influencing the properties of Diltiazem hydrochloride microspheres

Diltiazem hydrochloride-ethylcellulose microspheres were prepared by the water-in-oil emulsion-solvent evaporation technique. Small and spherical microspheres having a mean microsphere diameter in the range of 40-300 µm and entrapment efficiency of ~60-90% were obtained. Scanning electron micrographs of drug-loaded microspheres showed the presence of uniformly distributed small pores and absence of drug crystals on their surface, indicating simultaneous precipitation of drug and the polymer from the solvent during solvent evaporation. Differential scanning calorimetric analysis confirmed the absence of any drug-polymer interaction. The in vitro release profile could be altered significantly by changing various processing parameters to give a controlled release of drug from the microspheres. The stability studies of the drug-loaded microspheres showed that the drug was stable at storage temperatures, 5-55°C, for 12 weeks.     

Diltiazem for Reducing Heart Rate in Orthotopic Heart Transplant Patients During Coronary Computed Tomography Angiography

ObjectiveThis study sought to evaluate the effectiveness of diltiazem at achieving a targeted heart rate (HR) of ≤75 bpm in orthotopic heart transplant patients during coronary computed tomography (CT) angiography.MethodsBaseline heart rates were compared to heart rates after diltiazem administration in 25 adult orthotopic heart transplant subjects being monitored by electrocardiogram (ECG) gaiting on a multidetector CT scanner.ResultsThe mean baseline HR of the group was 84.28 ± 11.305 bpm. After diltiazem administration, the mean heart rate of the group at the time of the coronary CT angiography study was 75.32 ± 9.49 bpm. Heart rates decreased in 23 subjects (92%) and the targeted heart rate of ≤75 bpm was observed in 13 subjects (52%).ConclusionDiltiazem administration was associated with a decrease in heart rate, yet reaching the targeted heart rate was limited. Further study regarding diltiazem dosing and its impact is warranted.     

Comparison of Observational and Controlled Clinical Trials of Diltiazem in the Treatment of Chronic Anal Fissure

Diltiazem has been extensively studied in the treatment of chronic anal fissures, but efficacy in clinical practice is not fully established. The aim of the present study was to evaluate the safety and efficacy of topical application diltiazem in observational studies as well as in controlled clinical trials in the treatment of chronic anal fissures. A systematic literature search was carried out from 1966 to 31 December, 2007 on PubMed, Medline, Embase and Cochrane database, using the appropriate search words. We found six observational studies with 392 patients and five controlled clinical trials with 289 patients in which topical diltiazem treatment was given. Efficacy was found to be very high in observational studies (56.88%), whereas it was found to be modest in controlled clinical trials (29.41%). In observational studies, most of the patients reported complete healing of fissures within 6–12 weeks, whereas in controlled trials healing was reported within 8 weeks, with tolerable adverse effects of diltiazem. On the basis of the above studies, it can be concluded that topical application of diltiazem is useful in the treatment of chronic anal fissure, but to fully establish its efficacy, larger prospective double-blind study is required in the near future.     

Antireproductive effect of calcium channel blockers on male rats

Introduction  Drugs have been shown to adversely affect male fertility and recently anti-hypertensive drugs were added to the list. The anti-fertility effects of nifedipine and similar calcium channel blockers are well-illustrated in in vitro experiments but not in vivo. Purpose  The present study was designed to experimentally elucidate the sub-chronic effect of nifedipine, verapamil and diltiazem on sperm functions and reproductive hormone levels in vivo. Methods  Male rats (150–200 g) were divided into four groups of ten rats each. Group 1 (control) received distilled water; Group 2 received nifedipine 0.57 mg/kg BW; Group 3 were given verapamil 3.40 mg/kg BW and Group 4 were given diltiazem 2.57 mg/kg BW. Each drug-treated group had its own recovery group from which treatment was discontinued for 30 days before the animals were sacrificed. Blood samples were collected for hormonal assay of FSH, LH and testosterone. Semen evaluation was done and the testes, seminal vesicle, epididymis and prostate were removed, and weighed immediately. Results  Nifedipine, verapamil and diltiazem significantly decreased (P < 0.05) sperm count and motility in drug treated groups. The weight of the epididymis was significantly reduced (P < 0.05) in the drug treated rats. Semen parameters and other associated changes were restored after 30 days of drug withdrawal. Conclusion  Calcium channel blockers appear to have a reversible anti-fertility effect on male rats which does not occur through inhibition of the pituitary-gonadal axis.     

培哚普利与硫氮唑酮联合治疗阵发性心房颤动

为探讨培哚普利 +硫氮唑酮对控制阵发心房颤动 (简称房颤 )发作和左心房扩张的疗效 ,将阵发性房颤分为硫氮唑酮组 (Ⅰ组 )和培哚普利 +硫氮唑酮组 (Ⅱ组 ) ,二组根据左房内径大小分为左房正常组 (Ⅰa=33例、Ⅱa =33例 ) ,左房扩大组 (Ⅰb =34例、Ⅱb =31例 )。Ⅰ组给予硫氮唑酮 30mg 2次 /日或 3次 /日 ;Ⅱ组给予硫氮唑酮 30mg 2次 /日 +培哚普利 4mg 1次 /日。所有患者均治疗 3年。结果 :①各组房颤年发作次数治疗后均有显著减少 (P <0 .0 5 )。②Ⅰb、Ⅱa、Ⅱb组治疗后的房颤持续时间显著缩短 (P <0 .0 5 )。③房颤的年发作次数治疗后 1,2 ,3年间 ,Ⅰa、Ⅱa组显著高于Ⅰb、Ⅱb组 (P <0 .0 5 )。④随治疗时间的延长 ,Ⅱ组左房扩张的增幅明显低于Ⅰ组 (P <0 .0 5 )。结论 :硫氮唑酮和培哚普利 +硫氮唑酮治疗阵发性房颤均可减少房颤的发作 ,但后者优于前者 ,培哚普利 +硫氮唑酮治疗可明显减慢左房的扩张速度。     

地尔硫卓在颅内动脉狭窄支架置入术中的应用

目的：对比分析地尔硫卓和尼莫通在颅内动脉狭窄支架置入术中、术后预防和治疗血管痉挛以及对血压调控的疗效。方法：选择2013年3月至2014年12月间经全脑血管造影后明确颅内动脉狭窄的缺血性脑血管病,需进行支架置入术治疗的患者84例,按照随机分配的原则分为地尔硫卓组和尼莫通组,术中及术后24 h给予上述两种药物微量泵入,术中若出现血管痉挛,地尔硫卓组给予微导管注射地尔硫卓缓解痉挛,而尼莫通组则加大尼莫通泵入量,若术中出现血压升高,地尔硫卓组给予静脉注射地尔硫卓,尼莫通组给予加大尼莫通泵入量。记录两组药物对于血管痉挛的预防效果,以及出现血管痉挛后的治疗效果及痉挛缓解的时间,出现血压升高后,两组的降压效果及血压下降的时间,以及药物的不良反应。术前始至术后24 h给予持续心电、血压、血氧监测。结果：两组患者在预防血管痉挛方面差异无统计学意义,但在术中出现血管痉挛及血压升高时,地尔硫卓组在解除血管痉挛及降压效果及时间方面优于尼莫通组。结论：地尔硫卓可用于颅内动脉狭窄支架置入术中及术后预防血管痉挛。地尔硫卓在术中解除血管痉挛及迅速控制血压方面疗效优于尼莫通组。     

Thermodynamics of clayedrug complex dispersions: Isothermal titration calorimetry and high-performance liquid chromatography

An understanding of the thermodynamics of the complexation process utilized in sustaining drug release in clay matrices is of great importance.Several characterisation techniques as well as isothermal calorimetry were utilized in investigating the adsorption process of a model cationic drug(diltiazem hydrochloride,DIL)onto a pharmaceutical clay system(magnesium aluminium silicate,MAS).X-ray powder diffraction(XRPD),attenuated total reflectance Fourier transform infrared spectroscopy(ATRFTIR)and optical microscopy confirmed the successful formation of the DIL-MAS complexes.Drug quantification from the complexes demonstrated variable behaviour in the differing media used with DIL degrading to desacetyl diltiazem hydrochloride(DC-DIL)in the 2 M HCl media.Here also,the authors report for the first time two binding processes that occurred for DIL and MAS.A competitor binding model was thus proposed and the thermodynamics obtained suggested their binding processes to be enthalpy driven and entropically unfavourable.This information is of great importance for a formulator as care and consideration should be given with appropriate media selection as well as the nature of binding in complexes.     

地尔硫(艹卓)与西地兰-D对心房颤动心室率的控制及其对房室传导的影响

目的:比较地尔硫革(Diltiazem)及西地兰-D对心房颤动(房颤)心室率控制的安全性和有效率以及对传导系统的影响。方法:对43例房颤患者随机地接受0.4mg西地兰-D(n-22)或0.25mg/kg地尔硫(?)(n=21)。120 min时无效者重复同剂量地尔硫(?)或0.2 mg西地兰-D。记录用药前后5、10、20、30、60 min的心室率及血压。无效者观察120 min及第2次用药者180 min的心室率及血压。19例窦性心律患者随机分为西地兰-D(n=10)和地尔硫(?)(n=9)组行希氏束电图检查测量PA、AH、HV间期而评估西地兰-D及地尔硫(?)对传导系统的影响。记录药物注射前及注射后的5、10、20、30 min的希氏束电图。结果:地尔硫(?)及西地兰-D组中180min内能有效控制心室率分别为20及15例(95.2％:68.2％,P<0.05)。地尔硫(?)及西地兰-D均延长AH间期,但对PA、HV问期无影响。结论:地尔硫(?)及西地兰-D均能减慢房颤心室率,但地尔硫(?)的有效率、心室率下降幅度优于西地兰-D。地尔硫(?)对心室率快的房颤伴充血性心力衰竭患者是一种较为合适的药物,在密切监护下应是安全的。两药均不影响HV、PA间期而通过延长AH间期减慢心室率。     

地尔硫注射液治疗老年心力衰竭伴快速房性心律失常的疗效和安全性研究

目的观察老年中度和重度心力衰竭伴快速房性心律失常(包括心房颤动和心房扑动)患者静脉注射地尔硫控制心室率的有效性和安全性。方法选取NYHAⅢ、Ⅳ级的中、重度心力衰竭伴快速房性心律失常的老年患者,给予地尔硫静脉注射,观察有效率及血压、症状和体征变化。结果85例患者入选,80例(94.1%)患者有效,心室率由用药前的(149.5±18.2)次/分下降至用药结束时的(95.3±17.5)次/分,下降幅度36.2%,平均起效时间(6.3±3.9)分钟,用药前后心室率下降有显著意义(P<0.001)。所有患者血压均有下降但多在正常范围,有5例出现低血压,1例出现Ⅰ度房室传导阻滞伴窦性心动过缓,无1例出现心功能恶化。结论静脉注射地尔硫能迅速有效地控制中重度心力衰竭伴快速房性心律失常的老年患者的快速心室率,而且安全性高。     

地尔硫(艹卓)对缺氧所致血管内皮细胞线粒体膜电位变化的保护作用

目的 观察地尔硫(艹卓)对人大血管内皮细胞缺氧损伤时线粒体膜电位的影响.方法 将培养的血管内皮细胞分为对照组、单纯缺氧组和加入地尔硫卓后再缺氧组,应用激光共聚焦显微镜扫描,并测定标记的血管内皮细胞每秒钟线粒体膜电位值,观察缺氧前后人大动脉血管内皮细胞线粒体膜电位变化.结果 与对照组相比,单纯缺氧组的线粒体膜电位水平显著降低(P＜0.01);加入地尔硫(艹卓)后再进行缺氧组与单纯缺氧组相比,内皮细胞线粒体膜电位水平有显著升高(P＜0.01),与对照组相比内皮细胞线粒体膜电位水平变化不明显(P＞0.05).结论 缺氧引起血管内皮细胞线粒体膜电位降低;地尔硫(艹卓)可抑制缺氧损伤所致的线粒体膜电位的降低,从而具有稳定线粒体膜电位、保护血管内皮细胞的作用.