舌下给药正确方法
正确的服药方法
正确的服药方法
.口服药时宜取站位，躺着服药，会使药片在胃和食管内溶解，疗效下降，对食管有害。
滴眼药水应取半躺位，点1～2滴后，轻闭双眼5分钟，使药物充分吸收。
不要捏鼻子喂药，否则易使药物呛入气管或支气管，轻则咳嗽，重则发生吸入性肺炎或窒息。
温水送下不要干吞药片，这样易使药物黏附食管壁，使黏膜损伤，导致炎症或出血。
服药时饮水量应有200毫升，服药后不宜立即卧床，以免引起药物性食管溃疡。
不宜用酒类送药，因酒中的乙醇与多种药物相互反应，升高毒性反应。
不用饮料送药果汁因含酸性物质可使药物提前分解或糖衣融化，不利吸收，相互作用使药效下降，尤其是抗感冒药。
不用茶水或牛奶服药，茶叶中含咖啡因、茶碱、鞣酸等，牛奶中含蛋白质、脂肪酸，可使药品周围形成薄膜包裹降低吸收，牛奶中的钙磷酸盐与药物反应形成难溶性物质沉淀。
药中不要加糖尤其是红糖中药中的蛋白质、鞣酸等可与红糖中的铁、钙反应使药效下降。
是否与食物同服要按医嘱因为食物可以增加或减少某种药物的吸收。
是否能同服多药要按医嘱慢性病患者往往同服数种药物，但有些药会出现相互影响。
不要将药掰开糖衣片、肠溶片、缓释片、控释片不能掰开服用，胶囊拆散服用则失去了保护功能，味苦、刺激性药物可致恶心呕吐或被胃酸溶解药效下降。
舌下含服有些药需舌下含服，此时应将药品放在齿颊之间或舌下，不要。
怎么进行舍下含药方法
如对您有帮助，可购买打赏，谢谢生活常识分享怎么进行舍下含药方法导语：舍下含药是常见的急救方式之一。
那么你知道日常生活中，关于舍下含药有哪些注意事项呢？疾病的急性发作常使患者措手不及，特别是心脏病、结石等症，让人不知如何是好。
如果你在到医院前能采取适当地自我治疗，既能减轻疾病的痛苦，又可收到良好地疗效。
某些时候，舌下含药的方法是最适宜用来救治急症病人的。
舌下含药就是将药片放在舌下含化，通过口腔粘膜吸收进入血液循环而发挥作用，从口腔粘膜吸收到发挥药效仅需30秒至几分钟的时候，比口服给药快10-20倍。
1.心绞痛硝酸甘油是一种治疗心绞痛的药物，具有吸收快、疗效高的特点，当心绞痛发作时，应将硝酸甘油片置于舌下含化，1分钟即发挥作用。
若用门牙将药片嚼碎后，用舌尖舔，见效更为迅速。
2.胆绞痛急性胆囊炎、胆结石、胆道蛔虫症均可引起剧烈的胆绞痛。
在急性发作时停用其它镇痛药，舌下含服速效救心丸4-6粒，2-10分钟能迅速起到止痛作用。
经临床观察，其产生作用的时间和效果与阿托品等解痉止痛药相似，但起效时间明显快于其它药物。
3.胆道蛔虫症胆道蛔虫症引起腹痛发作时，舌下含化0.5mg硝酸甘油片，症状很快缓解。
其作用机理为硝酸甘油可使胆道口肌肉紧张度下降，有利于蛔虫退出胆道而使疼痛缓解。
4.肾绞痛肾结石、输尿管结石都可引起剧烈的腰腹部绞痛，即肾绞痛。
近年来发现硝苯吡啶具有缓解疼痛的作用，治疗肾绞痛效果较好。
当肾绞痛发作时，速取1-2粒(5-10毫克)硝苯吡啶，嚼碎后置于舌下，约5分钟后绞痛就可得到明显缓解。
5.慢性肛裂用含0.2%的硝酸甘油软膏涂抹病患部，每天两次，疗程为8周。
止痛效果明显而持久。
常用实验动物的给药途径和方法
常用实验动物的给药途径和方法在动物实验中，为了观察药物对机体功能、代谢及形态的变化，常需将药物注入动物体内。
由于实验目的、动物种类、药物剂型不同，给药途径和方法也多种多样。
一经口给药法(一)灌胃法此法给药剂量准确，是借灌胃器将药物直接灌到动物胃内的一种常用给药方法。
1、白鼠灌胃法：抓起小鼠，以左手拇指、食指固定头部，小指、无名指和掌心夹注尾巴，使腹部朝上，颈部拉直，右手持灌胃器，将灌胃针从鼠的口角插入口腔，从舌背沿上腭插入食道。
灌胃量0.2～0.5ml/10g。
胃管可用适宜口径的硬质塑料管或磨去针头的8号注射针头弯成适当的弧度制成。
注意，操作时不要用力猛插，以免插破食道或误插入器官造成动物死亡。
2、白鼠灌胃法：左手戴上棉手套，用左手拇指和食指将大鼠头部固定，将大鼠灌胃器沿腭后壁慢慢插入食道。
灌胃针插入时应无阻力，如有阻力或动物挣扎则应退针或将针拔出，重新再插。
灌胃器由注射器和特殊的灌胃针构成。
灌胃量10～20ml/kg3 兔、犬等:灌胃一般要借助于开口器、灌胃管进行。
先将动物固定，再将开口器固定于上下门齿之间，然后将灌胃管(常用导尿管代替)从开口器的小孔插入动物口中，沿咽后壁而进入食道。
插入后应检查灌胃管是否确实插入食道。
可将灌胃管外开口放入盛水的烧杯中，若无气泡产生，表明灌胃管被正确插入胃中，未误入气管。
此时将注射器与灌胃管相连，注入药液。
4、猪的胃内灌注法：给猪下鼻饲管较困难，因猪的鼻翼与上唇联合形成吻突，鼻腔内上下鼻夹与鼻中隔通道极窄，只能通过F10－12号的导尿管，F14号以上的导尿管不能插入，故一般均给猪采用经口入胃的灌胃方法。
具体方法是，预先做好一矩形小木块，中间有一洞，让小猪咬住，将其固定，然后再由此洞下胃管。
此种操作较为简便。
5、鸟类：包括鸽、鸡等，经口灌胃给药，可由助手将其身体用毛巾裹住固定好。
实验者用左手将动物向后拉，使其颈部倾斜，用左拇指和食指将动物嘴撬开，其他三只手指固定好动物头部，右手取带有灌胃针头的注射器，将灌胃针头由动物舌后插入食管。
2021年药学单选题与答案解析(54)
2021年药学单选题与答案解析54一、单选题(共60题)1.咖啡因复合盐安钠咖的常用组成药物是A：咖啡因和葡萄糖盐B：咖啡因和羟乙基淀粉40C：咖啡因和氯化钠D：咖啡因和苯甲酸钠E：咖啡因和乙醇【答案】：D【解析】：2.关于片剂的质量要求叙述错误的是A：含量均匀度应符合规定B：外观色泽均匀，完整美观C：含量准确，片重差异小D：硬度适宜，普通口服片剂的崩解时限或溶出度应符合规定E：在规定贮藏期内不得变质【答案】：A【解析】：3.药物不良反应因果关系的确定程度，哪项是错误的A：很肯定B：肯定C：怀疑D：很可能E：可能【答案】：A【解析】：4.对变异型心绞痛最为有效的药物是A：硝苯地平B：普萘洛尔C：硝酸甘油D：吲哚洛尔E：硝酸异山梨酯【答案】：A【解析】：5.氨茶碱的平喘作用原理不包括A：降低细胞内钙B：阻断腺苷受体C：抑制磷酸二酯酶D：抑制过敏性介质释放E：抑制前列腺素合成酶【答案】：E【解析】：氨茶碱松弛支气管平滑肌作用与下列因素有关。
①抑制磷酸二酯酶，使cAMP的含量增加，引起气管舒张；②抑制过敏性介质释放、降低细胞内钙，减轻炎性反应；③阻断腺苷受体，对腺苷或腺苷受体激动剂引起的哮喘有明显作用。
6.肾对葡萄糖的重吸收发生在A：远球小管B：髓袢C：各段肾小管D：近球小管E：集合管【答案】：D【解析】：7.在下列药品质量标准检查项目中。
是颗粒剂与栓剂共有的检项为A：融变时限B：重量差异C：药物溶出速度和吸收试验D：干燥失重E：颗粒细度【答案】：B【解析】：8.以下关于给药方法的描述，错误的是()A：舌下给药无首过消除现象B：气体、易挥发的药物应鼻腔给药C：急救时常用注射给药D：口服是常用的给药方法E：舌下给药吸收速度较口服慢【答案】：B【解析】：9.儿茶素属于A：鞣质B：氨基酸C：有机酸D：多糖E：蛋白质【答案】：A【解析】：10.欲杀灭芽胞，不宜采用A：高压蒸汽灭菌法B：间歇灭菌法C：流通蒸汽灭菌法D：焚烧法E：干烤法【答案】：C【解析】：流通蒸汽灭菌法可杀死细菌的繁殖体，但不能杀灭芽胞。
舌下取血栓、舌下取栓、针刀取栓常用操作
中医刺血疗法所谓刺血疗法即用三棱针在恕张的浅表静脉血管刺出血的一种方法。
也叫放血疗法。
本法不太严格刺什么穴，所谓的穴位在本法中只是指大概的位置而已。
本法对一切以痛为主的病症有特效。
临床中对头痛，麦粒肿，红眼病，颈椎病，肩周炎，中风偏瘫，风湿关节炎，心脏病，高血压，肝炎，肝硬化，扁桃腺炎，阑尾炎等效果显著。
本法取得疗效的关键是刺血量要大。
而取得血量的前提是：肉不是你自己的，认准了要放心刺。
一般刺血后再拨罐。
如恕张的血管，则血后任其流出，自然停止为止。
刺血手法一、认定血位后，腕劲快速点刺，一秒钟要求刺6---9次。
二、对恕张的脉络要求一针见血，一般都会喷涌而出，要有所准备，不要给污血浅到刺血后的反应一、 80%的病人刺血后即感到轻松舒服，20%的病人反而感到疼痛加重。
凡痛感加重的人治愈的速度要比马上感到减轻的人要快得多。
二、经5---10次刺血无感觉的不宜再刺血。
刺血的时间一、对炎症，急性疼痛病人可一天一次，减轻症状后3---5天刺血一次。
二、慢性病人隔天一次，见效后5---7天一次，可以拨罐的部位刺后拨罐15---20分钟。
刺血的禁忌一、大出血的病人及容易皮下出血者。
二、严重的心脏病。
三、性病，皮肤病，皮肤溃烂者。
四、孕妇或经期，白血病禁刺。
五、病人过饥过饱，惊吓后，精神过度紧张者不刺。
六、对肝病的病人不但刺血要小心，〔其它任何疗法要求一样〕不要将血碰到自己，千万不要将血碰到伤口上，否则即会传染。
对任何疗治“晕针”的救治一、即刻用手掌将病人的大椎穴擦热。
二、用拇指掐人中，合谷同按掐。
三、再按内关，涌泉，太冲，有条件者必需叫病人马上饮一杯温糖开水或葡萄糖水。
四、立即叫病人卧下，〔头低脚高〕从出血看病法一、凡出的血很淡为炎症，初病。
凡风湿病，肝病，血中夹水，血出如墨，则为久病，於血阻络。
二、凡白天刺血痛减，而晚上又加重者为於血，必须再刺一次，直至减轻临床经验教材中的刺血经验都是非常有效的，必须认真研读运用。
口腔给药的用药教育
口腔给药的用药教育根据口腔粘膜解剖与生理特点，我们将口腔粘膜给药途径分为：颊粘膜途径、舌下粘膜途径和局部给药。
其中颊粘膜途径和舌下粘膜途径为全身给药途径。
口腔内给药剂型有舌下含片、粉(喷)雾剂、含片、含漱液及其片剂等。
各种剂型的给药方式有所不同，患者错误的给药方法可影响药效，引起严重不良反应，甚至威胁生命。
药师必须通过指导患者掌握具体剂型的正确使用方法、剂量及注意事项。
1.舌下含服：先使口腔内有唾液，将舌下片或颊含片嚼碎后置于舌的下方或颊部，闭嘴长时间保留唾液。
注意事项：⑴舌表面有舌苔和角化层难吸收，应舌下含药,更不得用水吞服。
⑵口腔干燥唾液少时，可先饮少许水，易使药片溶解、吸收。
⑶含药后至少5分钟内不要有饮水、吸烟、进食等吞咽动作。
⑷注意交代舌下含服时间，如有的药品说明书或医嘱“必要时服”、“即刻服”，指疾病发作时马上舌下含服，防止习惯性地每天三次用药。
⑸心绞痛含服时，须采用半卧位。
平卧位可增加回心血量，加重心肌负担，增加心肌耗氧量作用减弱。
站立含服易出现体位性低血压。
⑹舌下含药可治疗各种内脏绞痛、支气管哮喘、高血压危象、贲门失弛缓症等疾病。
2.口腔粉（喷）雾剂：使用张大嘴向口腔内的两侧颊部喷药。
而喉部粉（喷）雾剂则张大嘴并尽可能向口腔后部喷药。
每次揿喷射阀2～3次即可。
注意事项：⑴口腔粉（喷）雾剂药效优于舌下含服。
⑵用药后30分钟内不要有饮水、进食等影响药物充分接触的吞咽动作。
⑶粉（喷）雾剂用途广泛，应该注意不同的粉（喷）雾剂的使用部位。
⑷一日3次，清洁口腔后使用，早晚刷牙后各1次，午饭后1次。
3.含漱液：按药品说明书的要求溶解或稀释后含漱1～5分钟。
注意事项：⑴含漱液通常称之为“漱口水”,多为消毒防腐药，含漱时不宜咽下或吞下。
幼儿或恶心、呕吐者暂时不宜含漱。
⑵一日漱口3次，清洁口腔后使用即早晚刷牙后各1次，午饭后1次。
⑶含漱后不宜马上饮水和进食、刷牙，欲使用其它口腔内给药剂型或口服药品，应至少间隔1小时，防止含漱液浓度被稀释而影响疗效。
精选-合理用药宣教
合理用药知识的宣教一、口服给药方法指导1.一般药物在饭后服，胃动力药、易于被消化酶破坏及妨碍食物吸收的药物，则在两餐之间或餐前服，如吗丁啉。
2.胶囊及糖衣片应整片吞服，不能有任何破损，否则可刺激胃肠道或在不适当的酸碱度下被破坏，影响药效。
需要减少剂量的药片可锉开（不能粉碎）按量服用。
3.舌下含服药物要放在舌下，不要吞咽或咬破，也不要饮水，以免影响药效，如硝酸甘油。
4.口含片放在颊粘膜与牙龈之间，让其慢慢融化，如溶菌酶、草珊瑚含片。
5.乳剂可用水稀释，混悬剂用药前要摇匀。
6.有呕吐时，暂停服药，并报告医护人员。
7.铁剂不能接触牙齿；水剂需用量杯核准剂量，量小的油剂必须用滴管，可先在杯内加入少量的冷开水，以免药液附着在杯上，影响服下的剂量。
二、家庭用药指导病人带药回家或自己在市场药店购药，须注意以下事项。
1.药物保管：①根据药物不同性质，妥善保存。
如容易氧化和遇光变质的药物，应装在有色密盖瓶中，放阴凉或用黑纸遮盖，如维生素C、氨茶碱等，一般置阴凉干燥、小儿不易拿到的地方。
②生物制品如乙肝疫苗、胎盘球蛋白、胰岛素等，应放在冰箱内保存。
③不同品种的药不能混放，如内服药与外用药应分放。
2.药物有变色、混浊、发霉、潮解及失效过期（超过药物标签上的有效期），均不可使用。
3.家庭保健药箱可配备少量常用药，其品种可按家庭成员情况、季节以及供应条件适当增减以治疗小伤小病。
常备药物：①外用药：碘酒、酒精、创可贴、金霉素眼膏等。
②内服药：感冒药，小儿退热灵、SMZ 、去痛片，储存量以3天左右的成人剂量为准。
③器具类：体温表、消毒的棉签、纱布、胶布等。
三、答疑解惑1、怎样理解药品说明书上的“慎用”、“忌用”和“禁用”？绝大多数的药品说明书上都印有“慎用”、“忌用”和“禁用”的事项，这三个词语虽只有一字之差，但嘱咐的轻重程度却大不相同。
“慎用”提醒服药的人服用本药时要小心谨慎。
就是在服用之后，要细心地观察有无不良反应出现，如有就必须立即停止服用；如没有就可继续使用。
舌下给药
International Journal of Pharmaceutics 457(2013)168–176Contents lists available at ScienceDirectInternational Journal ofPharmaceuticsj o u r n a l h o m e p a g e :w w w.e l s e v i e r.c o m /l o c a t e /i j p h a rmElectrospun drug loaded membranes for sublingual administration of sumatriptan and naproxenPetr Vrbata a ,Pavel Berka a ,Denisa Stránskáb ,Pavel Doleˇz al a ,∗,Marie Musilováa ,Lucie ˇCiˇz inskáa a Department of Pharmaceutical Technology,Faculty of Pharmacy in Hradec Králové,Charles University in Prague,Czech RepublicbElmarco Ltd.Co.,Liberec,Czech Republica r t i c l e i n f o Article history:Received 17July 2013Received in revised form 27August 2013Accepted 28August 2013Available online 16September 2013Keywords:Electrospinning Nanofibre Migraine Sublingual Sumatriptan Naproxena b s t r a c tSublingual administration of active pharmaceutical substances is in principle favourable for rapid onset of drug action,ready accessibility and avoidance of first pass metabolism.This administration could prove very useful in the treatment of migraines,thus two frequently used drugs were selected for our study.Sumatriptan succinate,naproxen,and its salt as well as combinations of these were incorporated into nanofibrous membranes via the electrospinning process.DSC measurements proved that the resulted membranes contained non-crystalline drug forms.SEM imaging approved good homogeneity of diameter and shape of the membrane nanofibres.The nanofibrous membranes always showed the rapid and mutually independent release of the tested drugs.The drugs exhibited very high differences in sublingual permeation rates in vitro ,but the rates of both substances were increased several times using nanofibrous membranes as the drug carrier in comparison to drug solutions.The released drugs subsequently permeated through sublingual mucosa preferentially as non-ionized moieties.The prepared nanofibrous membranes proved very flexible and mechanically resistant.With their drug load capacity of up to 40%of membrane mass,they could be very advantageous for the formulation of sublingual drug delivery systems.©2013Elsevier B.V.All rights reserved.1.IntroductionMigraine is a chronic relapsing brain disorder that affects about 12%of the Western population.It occurs as a unilateral headache,often accompanied by other symptoms,including nau-sea,vomiting,photophobia,and phonophobia,lasting from 4to 72h (Arulmozhi et al.,2005).In 15%of cases,a migraine headache is preceded by the aura,a transient neurological dysfunction,which is usually characterized by visual and/or sensory symptoms.Migraine has a very strong social impact,influencing quality of life and work productivity (Ramdan and Buchanan,2006).Sumatriptan is the most frequently used member of triptans commonly prescribed for the treatment of migraine headaches (with or without aura).Suma-triptan could be also administered together with NSAID naproxen sodium,which brings higher benefits to diminish symptoms of migraine than usage of either of the drugs separately.Abbreviations:SUS,sumatriptan succinate;NAPS,naproxen sodium;NAP,naproxen.∗Corresponding author.Tel.:+420495067438.E-mail address:dolezal@faf.cuni.cz (P.Doleˇz al).Actual dosage forms of sumatriptan are pills (50and 100mg),subcutaneous injection (4and 6mg),and nasal spray (10and 20mg).Succinate salt is well soluble in water,but its bioavailabil-ity (BA)after oral administration is only about 14%.Nasal spray administration of a sumatriptan base has a BA of about 16%(Imitrex,2013).Low BA following oral administration,relatively short half-life,and a requirement for the fast onset of action instigated the research for a new route of administration of this drug.A sublingual route of administration could be very advantageous in the given case.Although a relatively small surface area and dif-ficulties with the dosage form (permanently washed by saliva,and involuntary swallowing of liquids greater than 200L)have limited this site for drug administration so far,it possesses many advanta-geous characteristics.Very thin mucosa (100–200m),good blood supply,perfect accessibility,non-invasiveness of administration,and potential ease of removal encouraged research efforts in this area.The fast onset of systemic drug action is also very important,and the avoidance of the first-pass metabolism is in many cases essential (Hearnden et al.,2012;Bayrak et al.,2011;Patel et al.,2011a,b ).Moreover,this way of administration is also suitable for small children,elderly people,and other patients with swallowing or digestion problems (Patel et al.,2011b ).0378-5173/$–see front matter ©2013Elsevier B.V.All rights reserved./10.1016/j.ijpharm.2013.08.085P.Vrbata et al./International Journal of Pharmaceutics457(2013)168–176169Currently,there are several sublingual preparations,mostly based on fast dissolving(disintegrating)tablets,films,wafers,and sublingual sprays commercially available,and new dosage forms are being tested(Patel et al.,2011a;Hearnden et al.,2012).A relatively new and very promising technology for the for-mulation of sublingual drug delivery systems is based on the use of electrospun drug loaded nanofibrous membranes(Nagy et al., 2010;Yu et al.,2010a,b;Stranska et al.,2012).Electrospinning is a unique technique for the preparation of ultra-finefibres with the diameter size going down to nanometres.Although the principle of this procedure has been known for almost a century,it became a topic of great interest in the early1990s,when Reneker and co-workers demonstrated the possibility of electrospinning a wide range of polymers(Reneker and Chun,1996;Frenot and Chronakis, 2003).Nowadays,most of linear synthetic and also natural polymeric compounds can be easily electrospun into nanofibres(Frenot and Chronakis,2003;Agarwal et al.,2013).A very important moment for further development was the invention of a large-scale produc-tion device the Nanospider TM which makes it easier to scale up production for commercial processing(Jirsak et al.,2005).Never-theless,scaling up production of every individual product is always challenging,especially in pharmaceutical industry.Nanofibres,or rather nanofibrous membranes,have already found their application in many disciplines.Thanks to their unique properties,namely high surface area to volume ratio,high nanoporosity,high mechanical strength,and structural similarity to an extracellular matrix,they attract a lot of attention within tech-nical disciplines,but also in biomedicine and pharmacotherapy and new dosage formulation types(Agarwal et al.,2013;Leung and Ko, 2011;Nagy et al.,2012).In the biomedicalfield,nanofibresfind usage in the forma-tion of tissue engineering scaffolds(Cao et al.,2009;Leung and Ko,2011),wound dressing(Zhang et al.,2009;Leung and Ko, 2011;Sell et al.,2009),vascular grafts(Zhang et al.,2009;Sell et al.,2009),and drug delivery systems(Leung and Ko,2011; Chakraborty et al.,2009;Meinel et al.,2012).Many kinds of drugs have already been incorporated into the nanofibrous mats and then successfully released from them without a significant loss of their activity.Among low molecular drugs antibiotics(Kenawy et al.,2002;Kim et al.,2004),non-steroidal anti-inflammatory drugs(NSAID)(Taepaiboon et al.,2006;Kenawy et al.,2007; Huang et al.,2012),vitamins(Taepaiboon et al.,2007;Madhaiyana et al.,2013),chemotherapeutics(Xu et al.,2009),and many oth-ers have already been described.Higher molecular compounds, mostly protein based,were also shown to be effectively released from nanofibres(Maretschek et al.,2008;Han et al.,2012).In our work,we focused on the limits of sublingual administra-tion of sumatriptan and naproxen,in the context of permeability of sublingual mucosa in vitro,then on the examination of suitable polymers for co-formulation of both the drug-loaded electrospun membranes and estimation of formulation parameters for release profiles potentially suitable for anti-migraine action.2.Materials and methods2.1.MaterialsSumatriptan succinate(SUS)was kindly donated by Teva Czech Industries s.r.o.(Opava,CZ).Naproxen(NAP),naproxen sodium(NAPS)and chitosan(CHI,Mw60,000–120,000)were pur-chased from Sigma–Aldrich(Prague,CZ),polyacrylic acid(PAA,Mw 450,000),poly--caprolacton(PCL,Mw100,000)were purchased from Scientific Polymer Products(New York,USA),polyvinylalco-hol(PVA,type Z220,viscosity of4wt%water solution at20◦C 11.5–15mPa s)from Nippon Gohsei(Düsseldorf,GE).Acetic acid, formic acid,phosphoric acid,and potassium dihydrogen phosphate were supplied by Penta Chemicals(Prague,CZ).The aqueous solutions were prepared with purified water.All the chemicals were used as received without further purification.2.2.Methods2.2.1.Formulation of drug loaded electrospun membranesThe nanofibrous mats were produced by electrospinning from polymer solutions using Nanospider TM technology(Jirsak et al., 2005).Chitosan was dissolved in a mixture of acetic acid and water2:1in a concentration of2.25%;PVA was dissolved in a water:phosphoric acid mixture(99.3:0.7)in a concentration of11%; PAA was dissolved in a0.1M sodium chloride solution in a con-centration of6%with the addition of-cyclodextrin1.2%(as a cross-linking agent);PCL was dissolved in a mixture of acetic acid: formic acid(2:1)in a concentration of12%.The active substances were added in concentrations ranging from5%to30%related to the mass of the polymer in the solution for electrospinning.All the chemicals were stirred until homogenous solutions were obtained,and then poured into the container of an elec-trospinning device.Spinning electrode was in a shape of wire, electrospinning is nozzle free.After the application of a high volt-age,nanofibres were formed and then collected on a spunbond textile covering the collector plate.Speed of spunbond movement through the device determines nanofibrous layer thickness(g/m2). In the case of water-soluble polymers(PVA,PAA)cross-linking was performed.After electrospinning process the membranes were thermally treated in a drying oven at130◦C for15min in the case of PVA and at140◦C for20min in the case of PAA.2.2.2.CharacterizationThe morphology of prepared nanofibrous membranes was eval-uated by scanning electron microscopy–NOVA NanoSem230(FEI, USA)with maximal resolution up to1.3nm at30kV and magnifi-cation up to1,000,000times.The differential scanning calorimetry(DSC)analyses were car-ried out using a200F3MAJA calorimeter(NETZSCH,Germany). Samples were heated at speed5◦C/min from20◦C to200◦C.The nitrogen gasflow rate was set at40mL/min.2.2.3.Drug release evaluationDrug release measurements were conducted in a water bath under a constant temperature(36.5±0.5◦C)and permanent stir-ring(magnetic bar;200rpm).Pieces of membrane5cm×4cm (20cm2)were precisely weighed and then placed inside vials.The vials werefilled with20mL of a pre-tempered phosphate buffered solution of pH7.4(PBS)as an acceptor phase,and placed inside the water bath.The samples of the acceptor phase(0.6mL)were with-drawn in pre-determined time intervals(5,10,15,and30min,1,2, 4,8,and24h)and the pertinent volume was replaced with a fresh buffer.2.2.4.In vitro permeation experimentsIn vitro drug permeation experiments were performed using a porcine sublingual mucosa.The basic principles were derived from analogical experiments used in transdermal permeations,previ-ously described in detail(Patel et al.,2011a).Pieces of mucosa were obtained from the lower side of fresh porcine tongues(supplied from a local slaughterhouse) by surgically removing the muscle and connective tissues.After preparation,large pieces of obtained mucosa were stored in a 0.9%sodium chloride solution with the addition of sodium azide (0.002%).The processed sublingual membranes were about0.4mm170P.Vrbata et al./International Journal of Pharmaceutics457(2013)168–176Fig.1.Diffusion and permeation cell.in thickness.They were cut into pieces(2cm×2cm)andfixed between a donor and an acceptor compartment of diffusion cells (Fig.1).The actual area exposed for permeation was2cm2.The PBS(pH7.4)was used as an acceptor phase.Permeation was con-ducted in a water bath–temperature(36.5±0.5◦C)and stirring with magnetic bar.In vitro permeation of SUS,NAP and NAPS was evaluated using the donor solutions(PBS,pH6.8,0.5mL)with selected concentra-tions(1%,3%,6%for SUS;1%,2%,3%,10%for NAPS)and the tested nanofibrous membranes.Samples(0.6mL)of the acceptor phase were withdrawn in pre-determined time intervals(15,30min,1, 2,4,6,and8h)and replaced with a fresh buffer.The samples were briefly stored in a refrigerator until HPLC determination of investi-gated substances was performed.All drug release measurements were performed in triplicate,and in the case of in vitro sublin-gual permeation experiments,four replicates were performed.The values presented below are calculated as the means with their standard errors of the means(SEM).The stability pre-tests of the drugs were carried out in arti-ficial saliva(pH6.8)and an isotonic phosphate buffer(pH7.4). Low stability of the drugs in one of these mediums would be very limiting for potential use.The obtained results showed no signifi-cant decrease in the concentration of the drugs during a24h period.2.2.5.HPLC analysisDrug concentrations in the samples of the acceptor phase were determined using HPLC set Agilent Technologies1200(USA) equipped with an auto sampler ALS1329A,UV/VIS detector VWD G1414B,and an isocratic pump G1310A.2.2.5.1.Sumatriptan.The mobile phase was a mixture of ammo-nium phosphate(0.05M)and acetonitrile(84:16,v/v),pH was adjusted to3.0with the addition of0.1M phosphoric acid.Theflow rate was set at1.5mL/min.The method of Nozal et al.(2002)was modified to avoid interference from skin residues at the retention time of sumatriptan at227.4nm;the detection wavelength was set at282.7nm(Femenıa-Font et al.,2005).Separation was carried out at30◦C with the use of250mm×4.6mm,a reverse-phase column packed with5m C18silica particles(Zorbax Eclipse XDB C18). 2.2.5.2.Naproxen.The mobile phase was a mixture of potassium dihydrogen phosphate(0.01M;pH adjusted to2.5with the addi-tion of0.1M phosphoric acid)and acetonitrile(55:45,v/v).Theflow rate was set at1.5mL/min.Separation was carried out at25◦C,on a150mm×4.6mm,reverse-phase column packed with5m C18 silica particles(Zorbax Eclipse XDB C18).The detection wavelength was set at230nm.2.2.6.Data treatmentThe primary data from HPLC assay of the samples were further corrected for sampling and replacement of the pure acceptor phase. The amounts of the drug passed through the1cm2of sublingual mucosa were obtained.The cumulative amount of the drug vs.time dependence was used to calculate the pertinent slope values of the linear part of the concerned dependence with linear regression. The values obtained were understood as the individualflux values J[g/cm2/h]of the pseudosteady state permeation.Theflux values means and standard error of the means(SEM)(number of replicates n=4)were calculated.3.Results and discussionIn this paper,we focused on membranes ensuring longer con-tact time of the drug with absorption mucosa using a non-soluble (removable)membrane.Membrane prevents the leaking of a drug to an oral cavity and swallowing the drug,whilst masking the unpleasant taste.3.1.Scanning electron microscopyThe prepared nanomembranes were analyzed by scanning elec-tron microscope for averagefibre diameter and uniformity of the membranefibres.This characterization confirmed that the diam-eters of all the membrane nanofibres were within the nanometre scale and of good shape and diameter uniformity(Fig.2).It can be concluded that incorporation of the drugs into the nanofibrous membranes brought no free particles of the drugs,neither on the surface of nanofibres,nor particles larger than nanofibre diam-eter embedded within the mass of thefibres.It is important as evidence of well-tuned electrospinning parameters that make it possible to obtainfibres without loss of the drug,and with good shape homogeneity.Very similar images were also obtained for all other prepared membranes.3.2.Differential scanning calorimetry(DSC)The physical state of the carrier polymers and the incorporated drugs was investigated by DSC measurements.The DSC thermo-grams of chosen samples are shown in Figs.3–5.The thermogram of crystalline naproxen exhibits a strong endothermic peak at 157.1◦C,while no melting peak was present on thermograms of nanofibrous mats containing5%or30%of incorporated naproxen. This result proves that naproxen in the tested nanofibrous mats is present in an amorphous state,or more likely,homogeneously dispersed in the polymer matrix offilaments.Moreover,no glass transition peak of carrier polymer was found.Thisfinding is also important,because polymer crystallinity plays an important role in interactions with water,and therefore also drug release(Natu et al.,2010).Similar results were concluded from measurements with suma-triptan succinate.The crystalline form of sumatriptan succinate provided an endothermic peak at169.7◦C,no melting peak or glass transition peak were found on the other thermograms.3.3.Release of the drugs from nanofibrous membranesRelease characteristics of the investigated drugs were tested and evaluated by the complete immersion of the mats in the release medium.P.Vrbata et al./International Journal of Pharmaceutics457(2013)168–176171Fig.2.SEM images of the prepared membranes.A:Chitosan–blank;B:chitosan–containing SUS(5%);C:chitosan–containing NAP(5%);D:PVA–blank;E:PVA–containing SUS(5%);F:PVA–containing NAP(5%).Several different polymers with expected fast drug release were chosen.The polymer selection was further influenced by the intended purpose of their use in the sublingual dosage form. Bioadhesivity and biocompatibility of polymers were therefore important.The amounts of the incorporated drugs ranged from5%to30%of mass of the polymer in an electrospinning solution.The influence of drug concentrations in the nanofibres on the release profiles of the drugs was also evaluated,and is discussed later.The release of SUS from three different hydrophilic polymers–PVA,CHI,and PAA was tested.In all of the cases,burst release of the drug was observed with more than90%of the total releasable amount of the drug being dissolved in an acceptor phase within thefirst10min of the experiments(Fig.6).The amount of the drug released then remained at the same level for up to a further 24h.The release of NAP from three hydrophilic(CHI,PVA,PAA) and one hydrophobic polymer(PCL)was tested.All of the poly-mers provided burst release of naproxen.Similarly to sumatriptan, more than90%of the releasable drug was dissolved in the acceptor phase within10min(Fig.7).Interestingly,the membranes made of hydrophobic PCL also showed a very fast release of NAP.All of the membranes under investigation showed suitable drug release for formulation of a sublingual dosage form for whose requirement of fast drug release is of great importance(Hearnden et al.,2012).Under the given conditions,the release profiles of NAP and NAPS from electrospun mats did not show any evident differences, although the solubility and rate of dissolution of the crystalline form of the given substances in the acceptor mediumusedFig.3.DSC profiles of A:sumatriptan succinate(crystalline powder);B:PVA+sumatriptan suc.20%(nanofibrous membrane);C:PVA(nanofibrous membrane without drug); D:PVA(powder).172P.Vrbata et al./International Journal of Pharmaceutics 457(2013)168–176Fig.4.DSC profiles of A:naproxen (crystalline powder);B:PVA +naproxen 30%(nanofibrous membrane);C:PVA +naproxen 5%(nanofibrous membrane);D:PVA (nanofibrous membrane without drug);E:PVA (powder).Fig.5.DSC profiles of A:naproxen (crystalline powder);B:chitosan +naproxen 5%(nanofibrous membrane);C:chitosan (nanofibrous membrane without drug);D:chitosan (powder).Fig.6.The release profiles of sumatriptan succ.from nanofibrous membranes containing 5%of the drug made of polyvinylalcohol (PVA),chitosan (CHI),and poly-acrylacrylate (PAA)(n =3;mean ±SEM).Fig.7.The release profiles of naproxen from nanofibrous membranes containing 5%of the drug made of polyvinylalcohol (PVA),chitosan (CHI),polyacrylacrylate (PAA),and poly--caprolacton (PCL)(n =3;mean ±SEM).P.Vrbata et al./International Journal of Pharmaceutics457(2013)168–176173Fig.8.A:Release of sumatriptan succinate from PVA nanofibrous membranes containing5%,10%,or20%of the drug incorporated.B:Release of naproxen from PVA nanofibrous membranes containing5%,10%,or30%of the drug incorporated.differs greatly.It seems to be an indirect evidence of the fact that drug incorporation into nanofibres by the electrospinning process has brought dramatic changes in solubility properties,and that an initial difference of the drug solubilities is levelled in direction to higher solubility.In most cases,40–80%of the theoretically calculated amount of the drugs loaded in nanofibrous membranes were released,varying with the polymer used.Differences between the amounts of drugs incorporated and released were probably caused by different sol-ubility of the polymeric nanofibrous membranes in the acceptor phase.Srikar et al.(2008)assumed that substances(dyes in their study) might only be released from the available surface layers of the poly-mer,including surfaces of nanopores,whereas the drug inside the polymer bulk will not be released at all.The results of our experi-ments corroborate this assumption,because in no experiment was complete release of the incorporated drugs from membranes insol-uble in the acceptor phase achieved.This assumption also correlates with otherfindings that higher percentages(not only amounts)of the drugs were released from the nanofibrous mats containing higher levels of the drug per mass of polymer(Fig.8).When a higher level of a drug is incorporated,a higher proportion of the drug is likely to be deposited next to the fibre surfaces,and is therefore available for release.The membranes highly soluble in acceptor phase allowed almost complete release of the drugs theoretically incorporated into the membranes.Further reduction in the amount of the drugs released was probably caused by cross-linking of polymer chains.Cross-linking agents could bind incorporated drugs to the polymeric chains,ren-dering the drug un-releasable,and thus reducing the total amount of drug available.Theoretically,the bonding of drug molecule to polymer chains can form new,barely soluble molecules.The reduc-tion was most apparent in the case of PAA,where the released drug in some cases represented only about30%of the incorporated amount,while the amount of drug released from non-cross-linked nanofibrous mats reached almost the entire incorporated drug.In the case of simultaneous release of two different drugs,when both of the drugs were incorporated either in one single nanofi-brous layer or in multilayered electrospun membrane separately, the release of one drug did not influence the release of the other (Fig.9).In the experiments dealing with maximal drug load capacity, the maximal level of drug incorporated in nanofibrous membranes using this electrospinning method was found to be around40% of the membrane mass.With further increase in a drug concen-tration the electrospinning process was disturbed and structural defects multiplied(detected by SEM)or the process was completely disrupted.3.4.Permeation of the drugsPermeation of both the drugs through a porcine sublingual mucosal membrane was tested using drug solutions atfirst,because sublingual permeability of neither SUS nor NAP had already been sufficiently explored.Sumatriptan succinate is a hydrophilic substance.Although its molecular weight is relatively low,it exerted slow and incomplete permeation through the sublingual mucosa.For instance,usage of saturated solutions(30mg/0.5mL,pH7.4)as donors yielded only about0.1mg of SUS totally found in the acceptor phase(20mL) within8h,e.g.only0.33%of the drug loaded in a donor compart-ment.Because of very slow permeation(pH7.4donor),the influence of ionization of SUS(the p K a values are4.21,5.67,9.63,>12)on permeation rate was explored.Permeation was evaluated using donor solutions of pH values3.9,7.4,12.0.The highest concentra-tions in the acceptor phase and highest pseudosteady statefluxes were obtained at pH12.0,where sumatriptan occurs mostly in the unionized form as a sumatriptan base.The lowest permeation rate was found with donors of pH3.9,where the sumatriptan succi-nate molecule is fully ionized(Fig.10and Table1).It is in good agreement with the theory of passive permeation through most biological membranes.Results of a similar character wereobtainedFig.9.Simultaneous release of naproxen sodium and sumatriptan succinate from chitosan nanofibrous membranes(n=3;mean±SEM).174P.Vrbata et al./International Journal of Pharmaceutics 457(2013)168–176Fig.10.Permeation of sumatriptan through a porcine sublingual membrane using donor solutions (6%,0.5mL)of three different pH (3.9,7.4and12.0).Fig.11.Permeation of sumatriptan through a porcine sublingual membrane.Donors:PVA nanofibrous membrane 2mg,solution 1%(sol 5mg),solution 6%(sol 30mg).in a study with nicotine,where the differences of permeation rates at various pH values (expressed as cumulative amounts)were even more significant (Chen et al.,1999).The nanofibrous PVA membranes containing 20%of SUS were placed on the sublingual mucosa as the donor samples,and con-centrations of the permeated drug in acceptor compartments were measured.The results showed (Fig.11)that permeation from the nanofibrous donor was much faster compared to the solution con-taining 5mg of the drug in 0.5mL of donor (e.g.1%),although the amount of the drug in the solution was more than 2times higher than in the nanofibrous membranes.Moreover,within the initial 2h period,SUS permeation from nanofibres was even faster thanTable 1The sublingual permeation flux values.Sample (SUS)Flux (g/cm 2/h)Sample (NAPS)Flux (g/cm 2/h)Nano PVA –2mg 4.39±0.56Nano PCL 5mg 180.59±14.05Sol pH 7.4–5mg 2.71±1.00Sol 5mg 77.30±16.56Sol pH 12–30mg 13.47±3.47Sol 10mg 185.95±19.40Sol pH 7.4–30mg 10.32±2.72Sol 16mg 521.26±14.03Sol pH 3.9–30mg6.43±2.47Sol 50mg2277.31±41.71Fig.12.Amounts of sumatriptan permeated.Donors:PVA nanofibrous membrane 2mg,solution 1%(sol 5mg),solution 6%(sol 30mg,pH 12).from the saturated solution.This finding can be explained by a much higher concentration of the drug presented at the very large interface of nanofibre/mucosa.It is possible to imagine an exposed mucosal layer that is fully saturated with the drug released from the nanofibres,and an immediate replacement of permeated-off drug from nanofibrous storage.This situation is quite different in com-parison with the drug solution donor sample.Nanofibres probably served as a reservoir for surface facilitated drug release supplying the carrier/mucosa interface with a higher efficiency than was the case with solutions.As results in Fig.12show the transmucosal drug permeation was increased about 5times when the drug is loaded in nanofibrous membranes,compared to the highly concentrated solutions used as a donor.The increase in released and subsequently permeated drug amounts in percentages of initially loaded amounts is substantial from a practical point of view.We consider the necessary permeated dose of SUS should reach at least 4mg (or rather 6mg)of the drug.It represents an equivalent of a subcutaneously administered dose of SUS with a bioavailability of about 96%(Imitrex,2013).Thus,if the permeated amount of SUS from the nanofibrous donor was about 4%of the loaded dose,then about 100mg of SUS would have to be administered (on 20cm 2,which is the estimated area size of the sublingual mucosa available for administration,and also the size of the intended membrane formulation).This require-ment could be technologically realizable.For instance,to obtain 100mg of API for delivery the nanomembrane weight would have to be about 250or 300mg of nanofibres made of one or more poly-mers.The membrane would have to be produced of a high drug load and a high mass per area (g/m 2).The membranes could be lay-ered and then pressed to fix them.This reservoir would be covered by an impermeable layer on one side.We also take into account a possible addition of an adhesive at the edges of a final preparation to ensure a good and long term contact at a place of absorption.Further improvement could be achieved by the use of a suma-triptan base for the formulation of drug loaded nanofibrous membranes,because this form of the drug is more permeable across the sublingual membrane,as illustrated in Fig.10.Penetration enhancers are another applicable possibility to improve the per-meation rate.They can be directly incorporated into electrospun membranes,and released simultaneously with a drug affecting its permeation.。
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舌下给药正确方法
舌下给药是除动、静脉注射使药物直接进入血液循环快速起效的另一快速给药方法之一。
如心绞痛突然发作或发生高血压危象时，患者可立即舌下含服速效救心丸、硝酸甘油、硝苯吡啶等。
一般来说，只要用药方法正确，仅需要30——60s即可发挥药效，2——5分钟内控制症状，但无论是基础护理教科书，还是内、外科学均没有规范的舌下给药操作方法介绍，医护人员自己的理解和经验指导病人将药片放在舌下，不嚼碎吞服，让其自行溶解吸收。
根据多年临床经验，总结舌下给药的正确给药方法如下：取半卧位或坐位，仰起头部，下颌抬起，张口用舌尖舔上牙床，将药物碾碎或掰开，分别放置在舌下的舌系带两侧凹窝内。
然后舌尖放下，舔在下牙龈内侧，张口深呼吸10—50次即可。
如果口腔干燥，可含（禁吞咽）少许白开水，以利药物的溶解吸收。
如果唾液分泌过多，药片容易浸到舌上，难以控制吞咽动作，可指导病人进行深呼吸。
因张口深呼吸，使会厌关闭食道，吞咽动作停止，同时深呼吸可加速淋巴循环，促进药物自舌下黏膜吸收。
摘自《现代护理报》2013年10月刊。