New approaches to identification and characterization of tioconazole in raw material and in pharmaceutical dosage forms

Tioconazole(TCZ), a broad-spectrum antifungal agent, has significant activity against Candida albicans and other Candida species, and therefore, it is indicated for the topical treatment of superficial mycoses.The main goal of this work is to report an exhaustive identification and characterization procedure to improve and facilitate the online quality control and continuous process monitoring of TCZ in bulk material and loaded in two different dosage forms: ovules and nail lacquer. The methodologies were based on thermal(differential scanning calorimetry(DSC), melting point, and thermogravimetry(TG)),spectroscopic(ultraviolet(UV), Raman, near infrared(NIR), infrared spectroscopy coupled to attenuated total reflectance(FTIR-ATR), and nuclear magnetic resonance(NMR)), microscopic and X-ray diffraction(XRD). The TCZ bulk powder showed a high crystallinity, as observed by XRD, with a particles size distribution(3–95 mm) resolved by microscopic measurements. TCZ melting point(82.8 °C) and a degradation peak centered at 297.8 °C were obtained by DSC and DTG, respectively. An unambiguous structure elucidation of TCZ was obtained by mono-and two-dimensional1 H and13 C NMR spectral data analysis. The FTIR-ATR, Raman and NIR spectra of both the raw material and the commercial products were analyzed and their characteristic bands were tabulated. The best methods for TCZ identification in ovules were DSC, TG, XRD, NIR and Raman, while NIR and FTIR-ATR were the most appropriate techniques to analyze it in the nail lacquer. DSC, TG, DRX, Raman, FTIR-ATR and NIR spectroscopy are effective techniques to be used in online process analysis, because they do not require sample preparation, and they are considerably sensitive to analyze complex samples.

Improving Flow Property of Nifedipine Loaded Solid-Lipid Nanoparticles by Means of Silica for Oral Solid Dosage Form

In this study, a new formulation of silica nanocomposite containing nifedipine (NI) loaded freeze-dried solid-lipid nanoparticles (NI-SLNs) and silica have been developed with improved flowability of powders, which can lead to the formulation of a widely acceptable oral dosage form. The stable NI-SLNs were prepared using two phospholipids, hydrogenated soybean phosphatidylcholine and dipalmitoylphosphatidylglycerol mixed with 2.5% w/v trehalose as a cryoprotectant followed by lyophilization. We employed various grades of two types of silica, such as fumed and precipitated. Silica improved the poor flow property of NI-SLNs to good category as per USP-29. In addition, most of the silica nanocomposites showed the satisfactory results in their physicochemical properties such as particle size, polydispersity index, zeta potential, and recovered potency by around 100 nm, 0.3, -50 mV, and 80%, respectively. Furthermore, it was found that NI-SLNs were easily released form nanocomposites within 30 min, therefore, suggesting an improvement of drug dissolutions. Among them, precipitated silica cooperated fairly in improving the powder characteristics as well as the physicochemical, morphological, and pharmaceutical properties.

Design and Development of an <i>in Vitro</i>Assay for Evaluation of Solid Vaginal Dosage Forms

Vaginal dosage forms are seen as a viable option for empowering women to protect themselves from the risk of HIV transmission. Because of limited research in the field, there is a lack of suitable dissolution methods established for determination of drug release from vaginal formulations inside the vaginal tract. The main aim of this study was to develop a simple, reliable and reproducible in vitro release method for evaluation of solid vaginal dosage forms (VDFs) which was hoped to exhibit a close in vitro-in vivo correlation. Dapivirine, a drug being developed as a microbicide and a well established marketed anti fungal drug, Clotrimazole were used as model drugs. Two doses (0.5 mg and 1.25 mg) of Dapivirine were prepared as novel rapidly disintegrating, bioadhesive tablets. Clotrimazole 100 mg, prepared in house as conventional release tablets and commercially available Canesten (Clotrimazole tablet 100 mg) were used. The in vitro drug release testing of these tablets was carried out using a designed system which consisted of modified USP dissolution Apparatus II in conjunction with Enhancer cell (as sample holder) in 150 ml capacity flasks instead of the standard 900 ml flasks. The suitability of the system was investigated for variable parameters such as formulation types, drug concentration, stirring speeds, media volume and comparison of in house product with marketed product. The method was successfully optimized at a volume of 100 ml and a low speed of 25 rpm at pH 4 and was found sensitive enough to distinguish between formulations and evaluate products of different strengths. A linear drug release profile (R2 = 0.99) was obtained in case of Dapivirine, indicating that drug release is controlled by diffusion. The developed dissolution system has a potential to exhibit a good in vitro-in vivo correlation in addition to carrying out routine dissolution tests for solid VDFs.

Cyclodextrin-Modified Film Dosage Forms for Oral Candidiasis Treatment

Oral candidiasis is a common disease in patients with dry mouth. In this study, film dosage forms (FD) incorporating miconazole nitrate, an antifungal agent, were prepared with water-soluble polysaccharide and cyclodextrin (CD). The dissolution profiles of the drug from the FDs were investigated in limited dissolution medium. Soft films were obtained from sodium alginate containing 0.5% α-CD, β-CD, or γ-CD. Most FDs were easy to handle, though the film tearing resistance was lower than that of CD-free FDs. Addition of CD to the FD accelerated the drug dissolution rate. Interestingly, this phenomenon was also observed in FDs prepared with pullulan. In contrast, acceleration of the drug dissolution rate was not observed when CD polymer was added to the base solution. The initial drug dissolution rate was controllable by the amount of CD added to the FD. Therefore, FDs prepared with these materials are useful to treat oral candidiasis in patients with dry mouth syndrome.

Preparation and Characteristics of Film Dosage Form Natural Polysaccharides

We investigated preparation of film dosage form (FD) from natural polysaccharides using the casting method without organic solvents, heating or pH control. Ferulic acid (FA) and catechin were employed as model compounds incorporated in the FD, and the release profile of each compound from the form was investigated in the limited medium. Film formation was affected by the addition of the model compound to the polysaccharide solution. Rigid FD was obtained with 2% low-molecular-weight alginate (L-ALG;thickness, 65 μm), and it hardened after the addition of 0.5% polygalacturonic acid, although the thickness of the film did not change. The FDs immediately released the model compound, and the forms dissolved in phosphate-buffered saline. FD modification did not affect the FA release rate except in the early stage. FD would be a useful dosage form, especially for preventing or treating localized problems in the oral cavity.

Development of Film Dosage Forms Containing Miconazole for the Treatment of Oral Candidiasis

Film dosage forms (FDs) containing miconazole (MCZ) for the treatment of oral candidiasis were prepared using water-soluble polysaccharides, and the dissolution profiles of MCZ from the FDs were investigated. In addition, the forms were modified by the addition of a surface active agent to accelerate the drug dissolution rate. Circular films incorporating MCZ were obtained using each polysaccharide. Most FDs were easy to handle and resistant to tearing. No diffraction peaks were observed in the X-ray diffractograms of FDs. FDs prepared with sodium alginate or pullulan immediately swelled and disintegrated in aqueous medium, whereas MCZ incorporated in the FD gradually dissolved. A marked acceleration in the MCZ dissolution rate was observed when FD was prepared with polysaccharide containing a surfactant. These results confirmed that modified FDs are useful for treating localized conditions in the oral cavity, such as oral candidiasis, and that FDs can simplify the administration of drugs to patients.

Brief Introduction to Application of Dosage of Chinese Herbs

Accurate application of dosage of Chinese herbs based on differentiation of symptoms and signs is an important link for a better therapeutic result with less adverse effects. Some of the experiences are briefly introduced in the following aspects. ……

浅议仲景方之煎服法

东汉张仲景作《伤寒杂病论》,其条文论述精当,理、法、方、药具备,开后世中医辨证论治之先河。针对疾病和患病个体,辨证施治,立法选方而作仲景方,精简不杂、立意明确、疗效突出。并详细叙述了相应方剂的剂型、煎药溶媒、煎煮方法、给药方式、服药频次、服药时间、药后调理方法等,对疾病的治疗效果及预后调护亦发挥了重要作用。文章对仲景方的煎服法进行归纳及总结。

311例化妆品皮肤不良反应临床特征分析

目的探究不同剂型化妆品皮肤不良反应患者的临床特征,为化妆品皮肤不良反应监管和防治提供资料。方法回顾性分析2020年1月至2023年7月我院化妆品皮肤不良反应患者的一般情况、临床资料、化妆品产品剂型等信息,汇总数据并进行统计分析。结果311例患者中,发病以女性(88.75%)为主,年龄主要集中在21-50岁(71.38%),临床特征以面部受累、瘙痒、红斑为主,临床类型以化妆品接触性皮炎最常见。共涉及7种产品剂型,膏霜乳皮肤不良反应(膏霜乳组)患者最多,占48.87%,其次为液体皮肤不良反应(液体组)患者占29.90%,贴、膜、含基材皮肤不良反应(贴膜组)患者占17.36%。以普通护肤类化妆品为主,占总化妆品类别的72.99%。特殊化妆品中以染发类最多(占总化妆品类别的8.04%)且剂型多数为膏霜乳(23/25)。结论不同剂型化妆品皮肤不良反应患者有一定的临床特征,可为化妆品皮肤不良反应监管和防治提供参考。

某院2022年丙戊酸钠血药浓度监测结果分析

目的分析某院丙戊酸钠(VPA)血药浓度监测结果及其影响因素,为临床合理用药提供参考。方法回顾性收集2022年1月~12月在常熟市第二人民医院行VPA血药浓度监测的241例患者资料,采用卡方检验或Fisher精确检验分析年龄、药物剂型及联合用药对VPA血药浓度的影响。结果241例患者共行438例次VPA治疗药物监测,血药浓度达标率为58.7%。监测多次的患者中,调整剂量后的监测结果达标率较调整前均有提高。单因素分析显示,剂型和联合用药是影响VPA血药浓度的相关因素(P<0.05)。结论临床使用丙戊酸钠时应注重血药浓度监测,并及时根据监测结果及临床症状调整给药剂量,以提高抗癫痫治疗效果,降低不良反应发生率。

《鼓励研发申报儿童药品清单》口服药品有效成分在某儿童专科医院住院患儿中药物剂型可接受性情况调查

目的 分析《鼓励研发申报儿童药品清单》中的口服药物成分在某三甲儿童专科医院不同年龄段患儿中的实际应用及该院目前配备剂型适宜性的情况。方法 从4批《鼓励研发申报儿童药品清单》中的口服液体制剂的有效成分中,选取某三级儿童专科医院目前有该活性成分的口服药物,分析2023年11月9日至2023年12月8日住院患儿使用这些药物的调剂频次及用药时的年龄。基于我国《儿童用药(化学药品)药学开发指导原则(试行)》提出的不同年龄段儿科人群用药可接受的剂型选择,针对不同年龄组(新生儿、婴幼儿、学龄前儿童、学龄儿童、青少年),评估各药物的剂型适宜性。结果 在2023年11月9日至2023年12月8日时间段内,该院住院患儿使用过含4批《鼓励研发申报儿童药品清单》中的口服液体制剂的有效成分的口服药物共14种。在14种药物(片剂或胶囊剂)的4542次调剂记录中,新生儿和婴幼儿均为剂型“不适宜”,分别为132次和1111次;此2个年龄段使用频次最高的药物为左甲状腺素钠片、螺内酯片、熊去氧胆酸胶囊。对于学龄前儿童,适宜程度为“适用但存在问题”的胶囊剂共992次,其余为可“适用但不优选”的片剂1327次;对于学龄儿童,均为“适用”;对于青少年,均为“最优选”。“不适宜”或“适用但存在问题”的用药次数占总次数的49.2%。对各药物的剂型适宜性得分计算加权平均,剂型适宜性最低的药物分别为左甲状腺素钠片、熊去氧胆酸胶囊、他克莫司胶囊。结论 《鼓励研发申报儿童药品清单》中的口服液体制剂对应的片剂或胶囊剂在该院新生儿和婴幼儿中均有一定的应用,且剂型适宜性较低。医疗机构应当进一步加强儿童用药遴选与配备。对于新生儿及婴幼儿,需要加急研发他们常用药物的剂型以及分剂量调配的相关规范。

曲安奈德给药途径及相应剂型的研究进展

曲安奈德作为一种临床应用广泛的糖皮质激素药物,可以通过眼部、鼻腔、关节腔、皮肤等多途径给药,用于治疗关节炎、黄斑水肿、鼻炎、荨麻疹等多种局部疾病。曲安奈德作为一种在水中溶解度极低的药物,剂型与给药途径、给药部位息息相关。曲安奈德经注射(包括关节腔注射、玻璃体注射、脉络膜上腔注射、肌内注射)给药的剂型主要为混悬剂,代表性药物包括Kenalog-40■、Zilretta■、Triesence■、Xipere■等;鼻腔黏膜给药的剂型多为喷雾剂,代表性药物为Nasacort■;口腔黏膜给药的剂型多为贴剂、软膏剂和乳膏剂,代表性药物为Oracort■;经皮给药的剂型多为软膏剂、乳膏剂和洗剂,代表性药物包括Trianex■、Teva-Triacomb■等。现阶段有关曲安奈德各种给药途径的剂型研究主要围绕递送载体的构建、增加助溶剂或借助新型递送工具等展开。

基于超高效液相色谱—串联质谱同时测定大鼠血浆中杜仲制剂的药代动力学研究

目的 建立用于血浆中杜仲各成分含量测定的超高效液相色谱—串联质谱的方法,并进行杜仲及其制剂各成分的药代动力学研究。方法 SD大鼠口服不同的杜仲制剂后,于不同的时间点收集血浆样品,以0.1%甲酸水溶液(A)-0.1%甲酸乙腈(B)为流动相,梯度洗脱,采用安捷伦SB C_(18)色谱柱(2.1 mm×50 mm, 1.8μm)进行分离;在多反应监测模式下,负离子模式测定;通过Phoenix Winnonlin 8.1软件计算药代动力学参数。结果 原儿茶酸、京尼平苷酸、松脂醇二葡萄糖苷、无梗五加苷、松脂醇葡萄糖苷、京尼平苷、绿原酸、咖啡酸分别在3.2-2000,3.3-2044,0.6-2028, 0.6-1770,0.3-2036,0.6-2004,0.5-1596,0.7-1090 ng/mL范围内,线性良好;专属性、准确度、精密度、稳定性、回收率和基质效应均符合生物样本检定要求。采用非房室模型分析,8个成分在AUC_(0-∞)、t_(1/2z)、T_(max)、C_(max)、V_(z)/F、Cl_(z)/F、MRT_(0-∞)方面均不相同。结论 该方法灵敏度高、专属性强、准确性好,可用于杜仲成分在大鼠体内的药代动力学研究。不同杜仲制剂在大鼠体内的释药速度、起效快慢及作用强度均不相同,在临床应用上具有指导意义。

三七总皂苷及其制剂治疗糖尿病视网膜病变的研究进展

糖尿病视网膜病变(DR)是糖尿病常见的并发症,也是导致糖尿病患者失明的主要原因,严重影响糖尿病患者的生活质量。目前,临床上治疗DR的主要手段包括手术治疗、激光治疗以及药物治疗。其中,药物治疗能够对病情发展的多个环节进行干预,并减少激光治疗和手术治疗引起的相关并发症。然而,由于眼部结构的特殊性,导致药物的生物利用度较低,迫切需要寻求和开发疗效好、毒副作用低的药物以及合适剂型。中药具有历史悠久、来源广泛、多靶点协同作用等优点,在治疗DR方面具有独特优势。三七总皂苷是从中药三七中提取的主要有效活性成分群,目前已被证实具有治疗DR的作用。文章对三七总皂苷治疗DR的机制及其临床应用于DR的剂型进行分析与归纳,对三七总皂苷的药物剂型开发前景提出展望。

塞来昔布制剂新剂型研究进展

塞来昔布是常用的治疗急慢性骨关节炎和类风湿性关节炎的药物,但因其溶解度低,使其临床应用受到限制,为了解决塞来昔布的溶解度差、生物利用度低的问题,综述了近三年来塞来昔布新剂型新技术的研究现状,并对各种剂型和技术做出了评价。未来塞来昔布的研究方向是开发高溶解度、低毒性、稳定性好的新型制剂,从而提高其溶解度降低用药剂量,减少不良反应。

《本草图经》药物剂型分析及对现代制剂的启示

目的:通过分析宋代药物剂型的应用状况,探究我国药物制剂的发展历程。方法:对北宋本草著作《本草图经》中相关中药剂型数据进行统计与分析。结果:《本草图经》中明确记载的药物剂型,主要有散剂、丸剂、膏剂、丹剂这传统的四大剂型,其中散剂最多(总计142种),丸剂其次(总计94种)。剂型的统计还呈现出一些规律:(1)植物药中,草类以丸剂为主,散剂次之;木类以膏剂为主;果部、菜部和米部以散剂为主;本经外草类与本经外木蔓类以散剂为主,其中均出现了贴剂的记载。(2)矿物药中,因其药物特殊性,主要以丹剂为主。(3)动物药中禽兽部和鱼虫部,主要以散剂为主,丸剂次之。(4)部分药物可适用于多种剂型,共有35种药适用于2种以上剂型,3种药适用于3种以上剂型。结论:《本草图经》药物剂型不仅反映了宋代以前中药传统剂型的应用状况,对现代药物制剂的古为今用、临床运用等具有较好的启示。

以中药促进《兽医药理学》课程的改革

《兽医药理学》作为动物医学专业的一门重要专业基础课,因其学时有限,内容多而散,导致学生学习兴趣不大,进而影响教学效果。中药具有辨证施治、多靶点干预的独特优势,目前本科生对其兴趣较大。故可在《兽医药理学》课程中引入中药,使学生产生浓厚的学习兴趣,以期改善教学效果。通过加强兽医中药药理学研究、促进兽医中药剂型的创新、强化实践教学环节、加大兽医中药实验课的比例等方面,引入兽医中药,有助于促进《兽医药理学》课程的改革。

变容与平衡:西药东渐背景下近代中国汤剂改良之争

近代大量西药入华,对中国传统医药市场产生持续冲击,中药的不足之处日显。部分中医药界人士顺应时代潮流,向西方学习,力图革新中药。汤剂与中医诊疗观念联系紧密,其革新过程不仅受到医界关注,还多次成为中西医论争的焦点。由于近代中国现实政治与客观研究能力的不足,汤剂改良未能实现科学化发展,但关于其改良过程的争论,亦展现了近代中西医在制药方面的平衡与近代中医药界对于西医学知识的收受与变容。

膏方制备及对改善患者服药依从性的探讨

膏方是将药材反复煎煮后,去掉药渣,将药液浓缩,再添加胶类、糖类等药料反复熬制的一种中药剂型,结合患者的疾病特点及体质特点,“因人处方、因人制宜”,保持鲜明的个性化治疗特点。膏方在制备上需要更加规范的准备及制作过程,以便保证质量与功效,且在辅料、细料的选择上也有自己的特色。它的制备过程包括审方、调配、浸泡、煎煮、浓缩、收膏、凉膏等。文章从膏方制备过程中的注意事项及膏方改善患者服药依从性等方面进行探讨,为膏方的制备提供详细参考,对推动膏方的普及与发展具有一定的研究意义。