Continuous flow technology vs. the batch-by-batch approach to produce pharmaceutical compounds

Introduction: For the manufacture of small molecule drugs, many pharmaceutical innovator companies have recently invested in continuous processing, which can offer significant technical and economic advantages over traditional batch methodology. This Expert Review will describe the reasons for this interest as well as many considerations and challenges that exist today concerning continuous manufacturing.

Areas covered: Continuous processing is defined and many reasons for its adoption are described. The current state of continuous drug substance manufacturing within the pharmaceutical industry is summarized. Current key challenges to implementation of continuous manufacturing are highlighted, and an outlook provided regarding the prospects for continuous within the industry.

Expert commentary: Continuous processing at Lilly has been a journey that started with the need for increased safety and capability. Over twelve years the original small, dedicated group has grown to more than 100 Lilly employees in discovery, development, quality, manufacturing, and regulatory designing in continuous drug substance processing. Recently we have focused on linked continuous unit operations for the purpose of all-at-once pharmaceutical manufacturing, but the technical and business drivers that existed in the very beginning for stand-alone continuous unit operations in hybrid processes have persisted, which merits investment in both approaches.     

前馈控制技术研究进展及其在中药质控中的应用展望

前馈控制是化工领域广泛使用的过程控制方法,主要用于减少控制目标的波动,也在化学药品生产过程质量控制中得到应用。中药生产过程的前馈控制方法是指在理解物料性质、工艺参数与产品质量之间关系的基础上,建立工艺参数优化模型,根据物料性质计算合适的工艺参数,从而减少原料质量波动对产品质量的影响。主要介绍前馈控制技术的研究进展,并展望其在中药生产领域的应用前景。     

炮制技术流派——樟树帮药文化探究

樟树帮是我国传统四大地方炮制流派之一,其药业繁荣在我国历史上留下了浓墨重彩的一笔,至今仍产生深远影响。本文探讨了樟树帮技术流派形成的历史背景,分析了道教文化对其药文化的影响,并对樟树帮药事、药业、药俗和药膳构成的药文化进行了剖析,系统地对樟树帮药文化形成的历史沿革、发展脉络及主要内容进行探究,樟树帮药事分为识药之绝、抖择之优、切制之精,炮炙之秘和成方之独,樟树帮药业分为药摊、药店、药墟、药市和药码头,樟树帮药俗分为接仙桥、百草园和洗药池等。以期为樟树帮药文化的发展历史研究,以及传承我国传统中药炮制技术与中医药文化提供参考。     

探讨中药处方分析运用在中药药学服务中的效果

目的:探讨中药处方分析运用在中药药学服务中的临床效果。方法:选取2018年3月-2018年6月-门诊中药房接受存在处方问题的164张中药处方作为研究对象。对所有处方进行中药处方分析,明确处方中存在的问题,并统计被干预处方的来源科室,最终与来源科室沟通纠正处方中存在的问题。结果:164例中药处方分析结果显示超量是主要的处方问题(占54.88%),其次为配伍禁忌(26.83%),二者均明显高于其他处方问题发生率(P<0.05);而问题处方来源主要集中在消化与肾病科、儿科、名中医科以及肿瘤与风湿科;164张问题处方经分析以及与来源科室沟通、修正后均满足中医药合理用药要求。结论:临床中药处方中超量、配伍禁忌等问题现象较为普遍,经中药处方分析可及时发现处方中存在的问题,对提高中医药应用的合理性与安全性、有效性具有重要的临床意义。     

创新药学无机化学教学充电云端学习满格

为开展好新型冠状病毒疫情期间药学专业无机化学课程的“云”端直播教学工作,无机化学教学团队依据课程及药学专业特点,将疫情时政、生活与医药学应用及最新前沿等内容,从多角度、全方位把这些“思政”元素隐性渗透融入到药学无机化学教学之中。同时,还首创了学生居家“云”端实验教学设计,“充电”学生居家“云”端学习,达到了特殊时期立德育人的教学目的。     

苦参碱固体脂质纳米粒的制备及其体外透皮研究

目的制备苦参碱固体脂质纳米粒(matrine solid lipid nanoparticles,MA-SLN),并考察其药剂学性质与体外透皮给药行为。方法采用微乳-低温固化法制备MA-SLN,以粒径、ζ电位和包封率为评价指标,通过正交试验筛选最佳处方和工艺;扫描电子显微镜(SEM)和透射电子显微镜(TEM)观察MA-SLN的形态;差示扫描量热法(DSC)和X射线衍射扫描(XRD)分析苦参碱在MA-SLN中的包埋状态;体外透皮实验考察药物的透皮及释放行为。结果最佳处方工艺制得的MA-SLN包封率可达(56.12±0.82)%,激光粒度仪(DLS)检测MA-SLN的平均粒径为(196.31±6.26)nm,电位为(-37.18±2.36)mV。SEM和TEM显示MA-SLN呈规整的均匀球状或类球状结构;DSC和XRD检测可确定苦参碱可完全包裹在SLN内,苦参碱与SLN骨架材料相容性良好;体外透皮实验显示,9 h时累积透过量(ΔM)达到500μg/cm~2,且可持续释放至24 h,表明MA-SLN能够显著提高苦参碱的透皮吸收效率并具有较好的缓释行为。结论采用微乳-低温固化法制备MA-SLN,其工艺简单、周期短、可控性高,易于产业化推广;且制成的MA-SLN性能优良、透皮吸收率高与缓释行为显著,可为透皮给药制剂提供一种较好的给药模型,为苦参碱进一步开发应用奠定基础。     

实验教学案例在药物分析理论教学中的应用

基于药物分析的学科特点,探讨实验教学案例在药物分析理论教学中的实践与应用,其内容涉及实验案例的建设与选择、理论教学中引入实验案例的教学效果、教学过程中存在问题的讨论等方面。通过实验教学案例与理论知识的有效结合,使得学生更易于进入教学过程中所呈现的具体情境,帮助学生对所设问题进行思考、分析和解决,从而有效培养了学生独立检验药品的实践能力。     

基于“药辅合一”制备艾天羊肌肉关节通络膏Ⅱ并评价药效

目的 发挥“药辅合一”的优势,将艾天羊肌肉关节通络膏（ATY乳膏）油相的中链脂肪酸更换为薄荷油,优化处方工艺,得到ATY乳膏Ⅱ,并对2种通络膏进行药效学比较研究。方法 以油/水相质量比、促透剂、添加剂量和药液与基质质量比为考察因素,采用Box-Behnken响应面法优化ATY乳膏Ⅱ制备工艺。通过热板实验,研究比较2种通络膏对小鼠痛阈值的影响;通过小鼠耳肿胀实验,研究比较2种通络膏抗炎的作用;通过醋酸扭体实验,观察2种通络膏对化学刺激引起的疼痛的影响。结果 ATY乳膏Ⅱ的优化工艺处方为油/水相质量比35∶65,促透剂添加剂量8%,药液与基质质量比1∶10。药效实验中,改进后的ATY乳膏Ⅱ组与模型组比较,可显著提高小鼠痛阈值（P<0.01）,抑制二甲苯致小鼠耳肿胀的程度（P<0.01）,对化学刺激引起的疼痛具有一定的镇痛作用（P<0.01）;且上述作用ATY乳膏Ⅱ优于ATY乳膏。结论 改进后的ATY乳膏Ⅱ的工艺简单、可行,稳定性良好,且具有活血化瘀、抗炎镇痛作用。     

Characterization of the Percutaneous Absorption of Ketoprofen Using the Franz Skin Finite Dose Model

Objectives: Ketoprofen is an analgesic, anti-inflammatory agent commonly used in the management of chronic musculoskeletal pain. The aim of this study is to characterize the percutaneous absorption of 2 ketoprofen formulations (ketoprofen 10% in Pluronic Lecithin Organogel (PLO) and ketoprofen 10% in Lipoderm, referred to as phospholipid base), when applied to the human cadaver trunk skin, in vitro, using the Franz skin finite dose model. PLO and phospholipid base are vehicles used to facilitate the delivery of drugs into and through the skin following topical applications.

Methods: The percutaneous absorption of ketoprofen was evaluated using human cadaver trunk skin from 3 donors. The skin was cut into small sections and cultured within Franz diffusion cells. A variable finite dose of each formulation was then applied to 3 replicate skin sections per donor and receptor solutions were collected at predetermined time points (0, 4, 8, 12, 24, 32, and 48 hr). After the last receptor sample was collected, skin surfaces were washed and split into epidermis and dermis. Collected samples were analyzed using HPLC.

Results: Both PLO and phospholipid base were capable of facilitating the absorption of ketoprofen across human cadaver trunk skin. However, ketoprofen, when in phospholipid base, showed higher mean total absorption (p = 0.022) and faster rate of absorption (p < 0.05 at 2, 6, 10, and 18 hr) than when in PLO.

Conclusion: Chronic musculoskeletal pain can be a major burden for most patients, affecting their lifestyle and reducing overall quality of life. When compared to PLO, phospholipid base has the ability to potentially deliver higher concentrations of ketoprofen to underlying soft tissues and at a more rapid rate. With more ketoprofen at the site of injury, the analgesic and anti-inflammatory effects will likely be enhanced, potentially reducing pain and improving quality of life.