CN1473562A - Mouth cavity quick dissolving quick disintegrating freeze-dried tablet and its preparing method - Google Patents

Mouth cavity quick dissolving quick disintegrating freeze-dried tablet and its preparing method Download PDF

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CN1473562A
CN1473562A CNA031302688A CN03130268A CN1473562A CN 1473562 A CN1473562 A CN 1473562A CN A031302688 A CNA031302688 A CN A031302688A CN 03130268 A CN03130268 A CN 03130268A CN 1473562 A CN1473562 A CN 1473562A
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children
lyophilized
freeze
rapidly disintegrating
amount
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辉 刘
刘辉
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辉 刘
刘辉
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Abstract

The oral cavity quick dissolving and quick disintegrating freeze dried tablet for children includes at least one medicinal active component and at least one medicinal stuffing, adhesive and other supplementary material. It is loose and porous tablet in network structure and prepared through common freeze drying process. The said medicinal active component may be different children's medicines, such as antibiotic, antipyretic, analgesic, cough stopping and phlegm eliminating medicine, cold medicine, etc. Bitter or excitant medicine may be coated and water insoluble medicine is prepared intofine powder of 50 micron below size for stable dispersion in liquid. The present invention has fast disintegration, no jamming in throat, simple preparation process and low cost.

Description

儿用口腔速溶、速崩冻干片及其制备方法 Children with instant oral, rapidly disintegrating tablets, and lyophilized preparation

技术领域 FIELD

本发明涉及一种药物剂型,特别是涉及一种儿用口腔速溶、速崩冻干片及其制备方法。 The present invention relates to a pharmaceutical dosage form, more particularly to a child with an oral fast-dissolving, fast disintegrating tablets lyophilized preparation method thereof.

上世纪70年代末,英国Weyth公司首先将注射用冻干剂的技术(即所谓“zidys”技术)应用在制造口服药物制剂上,开始研制口服冻干药物片剂。 In the late 1970s, the British company Weyth first injection technology lyophilized agent (the so-called "zidys" technology) used in the manufacture of oral pharmaceutical formulations, started to develop oral freeze-dried pharmaceutical tablets. 到了80年代,舍勒公司开始参与口服冻干药物片剂的高效、低耗的工业化生产。 By the 1980s, the company became involved in Scheler oral freeze-dried pharmaceutical tablets of efficiency, low consumption of industrial production. 英国专利GB-A-1548022和GB-A-2111423公开了一种口腔中迅速崩解的口服固体药物剂型及制备方法,该剂型为载有药物的开放的网状结构基质,该开放的基质为对药物呈惰性的水溶性或遇水可分散的载体材料,从含药物和载体材料的溶液或混悬液中冻干升华除去溶剂,制备固体剂型。 British Patent GB-A-1548022 and GB-A-2111423 discloses an oral solid pharmaceutical dosage form and a method of preparing rapidly disintegrating in the oral cavity, the dosage form is a pharmaceutical containing the open mesh structure of the matrix, the matrix is ​​an open drug inert water soluble or water dispersible carrier material, the solvent removed by sublimation lyophilization to prepare a solid dosage form containing the drug and support material from a solution or suspension. 美国专利US539540、5120549、US5558880、US4546684、5330763、US6063802和中国专利CN1085081、CN1290525、CN1171741也分别公开了一种口腔中迅速崩解的口服固体药物剂型及制备方法。 U.S. Patent No. US539540,5120549, US5558880, US4546684,5330763, US6063802 and Chinese patent CN1085081, CN1290525, CN1171741 also discloses in an oral solid pharmaceutical dosage form and a method for preparing an orally rapidly disintegrating.

但是,利用上述专利公开的冻干方法制备出的口腔中迅速崩解的口服固体药物剂型,特别是儿用规格的口腔速溶、速崩冻干片剂常常达不到理想的效果,其原因有以下几种:(1)冻干前所配制的含药及载体物质的溶液或混悬液中的含固量,即溶液或混悬液中所含可溶或不溶的总固体物量,直接影响到冻干固体剂型的孔隙网状结构的状况及该剂型的机械强度。 However, an oral preparation using lyophilization method disclosed in the above patent in oral solid rapidly disintegrating pharmaceutical dosage forms, particularly children with specifications instant oral, rapidly disintegrating tablets are often lyophilized to reach the desired effect, the reason the following: (1) the drug-containing solids and carrier substance solution or suspension in the formulation before freeze-drying, i.e. a solution or suspension in amount of solid soluble or insoluble, directly affect contained Availability of the pore network structure lyophilized solid dosage form and mechanical strength of the dosage form. 如果含固物过多,不仅不易分配到塑膜制的凹陷模型中,所得产物孔隙网状结构少,达不到理想的速崩速溶效果。 If a solid composition containing too much, not only difficult to assign model recess made in plastic film, the resulting product is small pore network structure, it is not ideal rapidly disintegrating instant effect. 如果含固量少,则产品过于疏松,孔隙过大,虽然在口腔内崩溶速度快,但产品不仅外观差,机械强度也小,易破碎,甚至难以从模型中取出服用。 If a small amount of solids, the product is too loose, the porosity is too large, although the dissolution rate in the buccal cavity disintegrating fast, but the product is not only poor appearance, mechanical strength is small, easily broken, difficult to remove even taken from the model. 上述已有的的专利技术对待分配液的含量固没有提及或不明确。 The above-described prior art patents assigned treatment solution had a solid content of not explicitly mentioned or not. 另外,上述已有的专利技术虽对载体中某些物质(如作为填充剂的主要物质——甘露醇、明胶等)做了量的规定,但是没有考虑到药用活性物质本身,特别是一次服用量大的药物,其本身也是网状结构的骨架材料这一情况,给制备理想的冻干药物剂型带来困难。 Further, although the above-described prior art patents on certain carrier materials (e.g., as the main filler material - mannitol, gelatin, etc.) made of a predetermined amount, but did not take into account the pharmaceutically active substance itself, in particular a taking a large amount of the drug, which itself is the framework material of the mesh structure, the lyophilized drug to produce the desired dosage difficult.

(2)口腔速溶、速崩冻干片因为是多孔隙的网状结构形式,其机械强度差,抗破碎性差,为了解决这个缺点,上述已有的专利技术大都加大了作为载体物质之一的明胶的用量,有的明胶含量占20%以上,有的已接近40%。 (2) instant oral, rapidly disintegrating tablets because lyophilized porous reticulated structure, which poor mechanical strength, poor resistance to crushing, in order to solve this drawback, the aforementioned prior art patents largely increased as one carrier substance the amount of gelatin, the gelatin content of some 20% or more, and some have been close to 40%. 但是,明胶用量不适当,特别是用量过多,将会产生两个问题:一是若组份中的明胶用量多,室温下待分配液呈凝胶状(而不是混悬液或溶液),难以分配至多元凹陷模型中。 However, the amount of gelatin inappropriate, especially excessive amount, results in two problems: First, if the concentration of gelatin in the multi-component, the liquid to be dispensed as a gel (not a suspension or solution) at room temperature, polyhydric difficult to dispense to the recess in the model. 二是明胶在常温下(和37℃的人体温度下)很难溶于水,更何况在口腔中唾液较少的情况下难溶解。 Second, hard gelatin dissolved in water at room temperature (and lower the body temperature 37 ℃), not to mention the case of difficult to dissolve in the mouth saliva less. 这样制备出的口腔速溶、速崩冻干片在口腔中难以迅速崩解分散,如果用于儿童则容易产生“卡喉”的危险。 Such instant oral prepared, lyophilized rapidly disintegrating tablets disintegrate rapidly dispersed in the oral cavity is difficult, if it is dangerous to children is "card throat" of.

为了解决上述技术问题,本发明采用的技术方案是:本发明儿用口腔速溶、速崩冻干片包括:至少一种药物活性成份和至少一种药学适用的填充剂、粘合剂及其他辅料;采用通用冷冻干燥方法制备成疏松且具孔隙网状结构的冻干片剂。 To solve the above technical problem, the technical solution of the present invention is that: children instant oral use of the present invention, a lyophilized rapidly disintegrating tablets comprising: at least one pharmaceutically active ingredient and at least one pharmaceutically acceptable fillers, binders and other excipients ; using a common method to prepare a freeze-dried lyophilized tablets and having a loose pore network structure.

所述的药用活性物质是指可用于儿童的不同药效的药物,包括抗生素或其他抗菌药、解热止疼药、止咳祛痰药、抗感冒药及其他适于儿童的用药。 The pharmaceutically active substance refers to the efficacy of different drugs can be used for children, comprising an antibiotic or other antibacterial drugs, antipyretic analgesic agents, antitussive expectorants, anti-cold drugs and other drugs suitable for children. 药物没有严重的苦味或严重的刺激气味时,可以直接应用。 When the drug is no serious or severe irritation bitter smell, it can be applied directly. 对于苦味重或刺激性气味重者,可采用掩味的包衣粉末,但水不溶性药物需要细粉,颗粒<50μm,以便稳定的分散在液体中。 For bitter taste or severe irritating smell, taste-masking coating powder employed, but water-insoluble drugs requires fine particles <50μm, in order to stabilize the dispersion in liquids.

根据本发明制备适于儿用的冻干片,除含药用活性物质外,须加入药学适用的填充剂。 The lyophilized preparation of the present invention is suitable for children sheet used, in addition to containing pharmaceutically active substance, the pharmaceutically acceptable filler to be added. 填充剂是药物的载体,并形成多孔网状结构的骨架材料。 Filler is a drug carrier, and the material forming the skeleton of the porous structure. 本发明中的填充剂是指药学适用的水溶性或水不溶性但遇水可分散的、对药物惰性且冻干成形性良好的物质,优选甘露醇、乳糖、葡萄糖、蔗糖、山梨醇、木糖醇、水溶性糊精、水溶性预胶化淀粉、麦芽糖、甘氨酸等,特别优选甘露醇、木糖醇、甘氨酸、乳糖。 The present invention refers to a filler pharmaceutically acceptable water soluble or water insoluble but dispersible in water, and lyophilized to pharmaceutically inert molding material having good, preferably mannitol, lactose, dextrose, sucrose, sorbitol, xylose alcohols, water soluble dextrin, water soluble pre-gelatinized starch, maltose, glycine and the like, particularly preferably mannitol, xylitol, glycine, lactose. 上述填充剂既可单独应用,也可用其混合物。 The filler can be used alone, or as a mixture thereof.

根据本发明,填充剂的用量对于所制备的儿用口腔速溶、速崩冻干片有重要的作用,影响到冻干片的孔隙率和网状结构状况,直接关系到冻干片在口腔中溶解或崩解的状况。 According to the present invention, the amount of filler used for children prepared instant oral, rapidly disintegrating freeze-dried sheet has an important role, affecting the porosity of the freeze-dried network structure and status of the sheet, related to the lyophilized directly in the mouth piece dissolution or disintegration of the condition. 填充剂用量多,则冻干片孔隙少,网状结构差,冻干片过于紧密,在口腔中溶解或崩解则缓慢;如果填充剂用量少,则制备的冻干片孔隙多,片剂过于疏松,在口腔中虽溶解或崩解分散快,但外观差,机械强度差,特别容易破碎。 Amount of filler is large, the freeze-dried sheet less porosity, mesh structure difference, lyophilized sheet too close, then slowly dissolve or disintegrate in the oral cavity; If the extender used is small, the freeze-dried sheet prepared in pores of the sheet agent is too loose, although dissolve or disintegrate quickly in the oral cavity dispersion, but poor appearance, poor mechanical strength, particularly easily broken. 根据本发明,填充剂的用量取决于下面两个因素:①设计冻干片中药物活性成份的含量。 According to the present invention, the amount of filler depends on two factors: the content of the pharmaceutically active ingredient lyophilized tablets ① design. 无论是水溶性活性成份还是水不溶性活性成份,经冻干后均形成固体物,构成多孔隙网状结构冻干片的一部分。 Whether it is water-soluble active ingredient or water-insoluble active ingredient, are each formed by solid after lyophilization, form part of the porous network structure of the freeze-dried sheet. 因此,当冻干片的总重量确定后,药物活性成份计量大者,填充剂用量减少;如药物活性成份量小,则应增加填充剂的量。 Thus, when the total weight of the freeze-dried sheet is determined, the pharmaceutically active ingredient is greater measurement, the amount of filler is reduced; pharmaceutically active ingredients such as small amounts, increase the amount of the filler.

②设计的冻干片大小。 ② design freeze-dried sheet size. 当药物活性成份规格确定后,设计的片重大,为达到所制冻干片具有的适当的网状结构,则所用凹陷模型体积也相应增大,分配进入的溶液或混悬液溶积相应增加,则填充剂用量增加;反之,应减少用量。 When the pharmaceutically active ingredient is determined specification, major design sheet, prepared freeze-dried to achieve a suitable sheet having a network structure, the volume of the model with a recess correspondingly increased partition into the solvent solution or suspension volume corresponding increase , the amount of filler increases; conversely, should reduce the dosage.

根据本发明制备儿用口腔速溶、速崩冻干片配制的药物溶液或混悬液,所用溶剂为水和低碳醇类,但特别优选水和浓度低于30%的乙醇水溶液,其总含固量(重量/体积)应在5-40%之间,优选7.5-35%,特别优选10-25%。 Prepared according to the present invention by children instant oral, rapidly disintegrating tablets formulated lyophilized drug solution or suspension, the solvent is water and lower alcohols, and particularly preferred water concentrations below 30% aqueous ethanol containing total the solid content (w / v) should be between 5-40%, preferably 7.5-35%, particularly preferably 10-25%.

根据本发明制备儿用口腔速溶、速崩冻干片,还必须加入粘合剂,粘合剂的主要作用是在制成的冻干剂中粘连药物活性成份、填充剂和其他辅料,保证冻干片有适当的机械强度,抗破碎性。 Prepared according to the present invention by children instant oral, lyophilized rapidly disintegrating tablets, a binder must also be added, mainly as an adhesive agent is made of lyophilized pharmaceutically active ingredient adhesions, fillers and other excipients, to ensure that freezing dry film with a suitable mechanical strength, crush resistance. 本发明适用的粘合剂有天然胶类物质,如明胶、果胶、金合欢胶、黄芪胶、瓜尔胶、阿拉伯胶、桃胶、黄原胶等;合成聚合物类物质,如聚乙烯吡咯烷酮、卡波姆、羧甲基纤维素钠、羟丙基纤维素、羟丙基甲基纤维素、聚氧化乙烯、聚乙烯醇及藻酸盐等。 The present invention is applicable with a natural rubber adhesive substances, such as gelatin, pectin, acacia, tragacanth, guar gum, acacia gum, peach gum, xanthan gum and the like; synthetic polymeric substances, such as polyethylene pyrrolidone, carbomer, sodium carboxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyethylene oxide, polyvinyl alcohol, alginates and the like. 优选明胶、聚乙烯吡咯烷酮、卡波姆。 Preferably gelatin, polyvinyl pyrrolidone, carbopol. 根据本发明,可使用一种粘合剂,也可以使用两种或两种以上粘合剂混合物。 According to the present invention, an adhesive may be used, an adhesive may be a mixture of two or more.

选用明胶作为粘合剂,如果用量过多,在温室状态下,配制的、待分配的药物溶液或混悬液易呈凝胶状,很难定量分至凹陷模型中。 Selection of gelatin as the binder, if too large an amount, the state in the greenhouse, the formulated, the drug to be dispensed easily gelatinous solution or suspension, it is difficult to quantify recess model. 如果明胶在所制冻干片的重量中超过10%,则此冻干片放入口腔中难以在10秒内溶解或崩解,用于儿童则易产生“卡喉”的危险。 If the weight of the lyophilized gelatin sheet prepared in more than 10%, then the freeze-dried sheet into the oral cavity is difficult to dissolve or disintegrate within 10 seconds, it is easy to produce dangerous for children "card throat" of. 根据本发明,选用明胶作为粘合剂,其用量为冻干片重量的0.2-15%,优选0.5-10%。 According to the present invention, use gelatin as a binder in an amount of from 0.2 to 15% by weight of the freeze-dried sheet, preferably 0.5 to 10%.

根据本发明,制备儿用口腔速溶、速崩冻干片除药物活性物质、填充剂、粘合剂外,还应加入药学适用的其他物质,包括表面活性剂、助悬剂、矫味剂、甜味剂、色素、防腐剂等。 According to the present invention, prepared by children instant oral, rapidly disintegrating tablets in addition to lyophilized pharmaceutical active substances, fillers, binders, pharmaceutically acceptable should be added to other substances, including surfactants, suspending agents, flavoring agents, sweeteners, colors, preservatives and so on.

根据本发明制备的儿用口腔速溶、速崩冻干片,不溶于配液溶剂的药物活性物质及各种药学适用的填充剂及其他辅料均为粉末,其粒度应<50μm。 According to the present invention is prepared in a child instant oral, lyophilized rapidly disintegrating tablets, a liquid insoluble in the solvent with the pharmaceutically active substance and a variety of other pharmaceutically acceptable excipients and fillers are powders having a particle size should be <50μm.

本发明的儿用口腔冻干片的制备方法包括:步骤1.配制溶液及混悬液:按照处方量称取药物活性成分、填充剂、粘合剂及其他辅料溶于或分散于所选溶剂中,制备成溶液及稳定的混悬液。 Children according to the present invention a lyophilized preparation of oral tablets comprising the steps of: 1. Preparation of solutions and suspensions: weighed amounts as prescribed pharmaceutical active ingredients, filler, binder and other adjuvants dissolved or dispersed in a solvent selected to prepare a solution and suspension stability.

步骤2.冻结:将上述溶液或混悬液按要求分配到多元凹陷模型中,然后放入冷冻机内在摄氏-20--30℃温度下迅速冻结成型。 Step 2. Freeze: The above solution or suspension polyhydric recess assigned to the model as required, and then into the internal degrees Celsius freezer at a temperature of -20--30 ℃ rapidly frozen molded.

步骤3.升华干燥:将冻结后的装药模型于冷冻干燥设备中,在高真空低温条件下(温度低于摄氏-40℃,压力0.1-1.0毫巴)升华,除去水分并适当干燥除去残余水分,所需时间根据模型中液体量一般3-8小时。 Step 3. sublimation drying: Charge model will freeze in a freeze drying apparatus, under high vacuum conditions of low temperature (below -40 Celsius ℃, 0.1-1.0 mbar pressure) sublimation, and properly dried to remove water residue was removed water, the time required for the model liquid amount is generally 3-8 hours.

步骤4.压模包装:将冻干后的产品模型板上覆盖一层铝箔。 Step 4. stamper Packaging: The product after lyophilization model plate covered with aluminum foil.

本发明的有益效果是:儿用口腔速崩、速溶冻干片崩溶速度快,在口腔中10秒之内即可快速溶解或崩解分散,可有效地防止儿童服药“卡喉”现象;制备方法简单实用,制造成本低。 Advantageous effect of the invention is: with children orally rapidly disintegrating, dissolving instant freeze-dried sheet fast disintegrating speed to quickly dissolve or disintegrate within 10 seconds of the dispersion in the oral cavity, which can effectively prevent children from taking "card throat" phenomenon; preparation method is simple and practical, low manufacturing cost.

步骤2.配制混悬液:按照处方量称取各组分,然后在85%的纯水中加入明胶在约60℃温度下搅拌溶解,再加入甘露醇搅拌溶解,将溶液冷却到室温,然后加入阿莫西林及其他组份的细粉,搅拌均匀后,加入另外15%的纯水至250ml,搅拌均匀制成稳定的混悬液。 Step 2. A suspension formulation: Weigh the components according to prescribed amounts, and then added with stirring to dissolve the gelatin at a temperature of about 60 deg.] C in 85% purified water, further mannitol was added and dissolved under stirring, the solution was cooled to room temperature, and then Add amoxicillin and other components of the powder, stir, an additional 15% of the water to 250ml, stir to prepare a stable suspension.

步骤3.冷冻干燥:将上述混悬液分配到特制PVC塑膜凹陷模型中,每一个凹陷模型0.5ml混悬液,放入冷冻机中在-30℃温度下迅速冻结,在温度-40℃、真空度1.0毫巴的条件下冷冻干燥,冻干周期为2.5小时。 3. lyophilization step of: specially assigned to the above suspension PVC Plastic model recesses, each recess model 0.5ml suspension, rapidly frozen into the freezer at a temperature of -30 deg.] C, at a temperature of -40 ℃ , under a vacuum of 1.0 mbar freeze drying, lyophilization cycle was 2.5 hours.

步骤4.压覆盖膜:从冻干机中取出含冻干片的模型板,用热压方法覆盖一层铝塑膜后密封,即得成品。 Step 4. caul film: Model plate removed from the sheet containing the lyophilized lyophilizer, hot press with a layer of plastic film sealed rear cover, that is finished.

儿用对乙酰氨基酚冻干片,其配方为(100片):包衣对乙酰氨基酚粉末 9.4g(折纯对乙酰氨基酚8.0g)甘露醇 4.0g甘氨酸 3.0g明胶 0.4g糖精钠 1gPVPK300.2g柠檬香精 0.3g尼泊金甲酯 0.085g尼泊金丙酯 0.045g纯水加至 80ml儿用对乙酰氨基酚冻干片的制备方法与实施方式1儿用阿莫西林冻干片的制备方法基本相同,不同之处仅在于:在步骤2.配制混悬液之前,用乙基纤维素、乙醇溶液将对乙酰氨基酚粉末进行包衣掩味处理,包衣对乙酰氨基酚折纯含乙酰氨基酚8.0g。 Children with acetaminophen lyophilized sheet, the formula is (100): coating powder 9.4 g of acetaminophen (paracetamol pure discount 8.0g) 4.0g Glycine 3.0g 0.4g Sodium Saccharin gelatin mannitol 1gPVPK300 lemon flavor .2g 0.3g methyl paraben 0.085g propyl paraben 0.045g Purified water to 80ml children with acetaminophen for preparing a lyophilized sheet of embodiment 1 child amoxicillin lyophilized sheet substantially the same production method, except that only: before step 2 for suspension, with ethyl cellulose, an ethanol solution paracetamol powder is taste-masking coating process, coated acetaminophen pure discount containing acetaminophen 8.0g.

Claims (10)

1.一种儿用口腔速溶、速崩冻干片,包括:至少一种药物活性成份和至少一种药学适用的填充剂、粘合剂及其他辅料;所述药物活性成份是抗生素或其他抗菌药物、解热镇痛药、止咳祛痰药、抗感冒药及其他药物活性成分;其特征在于:所述的粘合剂用量为冻干片重量的0.2-15%,优选量为0.5-10%;冻干前配制的含药及各种辅料的溶液(药物溶液)或混悬液,其含固量(重量/体积)为5-40%,优选含固量7.5-35%,特别优选含固量10-25%。 A child with the instant oral, rapidly disintegrating tablets lyophilization, comprising: at least one pharmaceutically active ingredient and at least one pharmaceutically acceptable fillers, binders and other excipients; the pharmaceutically active ingredient is an antibiotic or other antimicrobial drugs, anti-inflammatory drugs, antitussive expectorants, anti-cold drugs and other pharmaceutical active ingredients; wherein: said adhesive in an amount of 0.2 to 15% by weight of the freeze-dried sheet, preferably in an amount of 0.5 to 10 %; formulation before lyophilization solution containing various excipients and drug (drug solution) or suspensions, solid content thereof (weight / volume) 5-40%, preferably 7.5-35% solid content, particularly preferably 10-25% solids.
2.根据权利要求1所述的儿用口腔速溶、速崩冻干片,其特征在于:所述的药学适用的填充剂是指对药物活性成份呈惰性的、在制备冻干固体剂型中成型性良好的填充剂,优选甘露醇、山梨醇、木糖醇、乳糖、葡萄糖、麦芽糖、甘氨酸可溶性糊精或可溶性予胶化淀粉。 The children of claim 1 of the instant oral, rapidly disintegrating freeze-dried sheet, wherein: the pharmaceutically acceptable filler is a pharmaceutically active ingredient refers to inert molded in a lyophilized preparation of solid dosage forms good filler, preferably mannitol, sorbitol, xylitol, lactose, glucose, maltose, glycine, dextrin or soluble to soluble gelatinized starch.
3.根据权利要求1所述的儿用口腔速溶、速崩冻干片,其特征在于:所述的药学适用的粘合剂是指药学适用的天然胶类,如明胶、黄原胶、瓜尔胶、桃胶、果胶、黄芪胶、金合欢胶,和药学适用的有机聚合物类,如羧甲基纤维素钠、聚乙烯、吡咯烷酮、卡波姆、羟丙基纤维素、羟丙基甲基纤维素、聚氧化乙烯、聚乙烯醇以及藻酸盐类,优选明胶PVP、卡波姆。 The children of claim 1 of the instant oral, rapidly disintegrating freeze-dried sheet, wherein: the pharmaceutically acceptable binder is meant pharmaceutically acceptable natural gums, such as gelatin, xanthan gum, guar guar gum, peach gum, pectin, tragacanth, acacia, and a pharmaceutically suitable organic polymers, such as sodium carboxymethyl cellulose, polyvinyl, pyrrolidone, carbomer, hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyethylene oxide, polyvinyl alcohol, and alginates, gelatin preferably PVP, carbomer.
4.根据权利要求1所述的儿用口腔速溶、速崩冻干片,其特征在于:所述其他药学适用的辅料是指药学适用的表面活性剂、助悬剂、色素、防腐剂、矫味剂和甜味剂,其品种和用量不做特殊规定。 The children according to claim 1 instant oral, lyophilized rapidly disintegrating tablets, characterized in that: said other pharmaceutically acceptable excipient refers to a pharmaceutically acceptable surfactant, suspending agents, dyes, preservatives, flavoring and sweetening agents, the species and amount no special provisions.
5.根据权利要求1所述的儿用口腔速溶、速崩冻干片,其特征在于:所述的药物活性成分及辅料中不溶于配液溶剂的成分的状态均为粒度约50μm的细粉。 The children of claim 1 of the instant oral, rapidly disintegrating freeze-dried sheet, wherein: said pharmaceutically active ingredient and excipients insoluble fine powder component with the liquid solvent are of a particle size of about 50μm .
6.根据权利要求1所述的儿用口腔速溶、速崩冻干片,其特征在于:儿用阿莫西林冻干片,其配方为(500片):阿莫西林 25g(以无水物计算)甘露醇 32g明胶 2g聚乙二醇6000 3g桔子香精 0.5g阿司巴甜 2.5g尼泊金甲酯 0.21g尼泊金乙酯 0.11g纯水加至 250ml The children of the instant oral claim 1, lyophilized rapidly disintegrating tablets, characterized in that: children with amoxicillin lyophilized sheet, the formula is (500): amoxicillin 25g (on an anhydrous calculated) gelatin 2g mannitol 32g polyethylene glycol 6000 3g orange flavor 0.5g aspartame 2.5g methyl paraben, ethyl paraben 0.21g 0.11g Purified water to 250ml
7.根据权利要求1所述的儿用口腔速溶、速崩冻干片,其特征在于:儿用止咳祛痰冻干片,其配方为(100片):氢溴酸右美沙芬 0.5g愈创木酚甘油醚 10g甘露醇 6.5g桃胶 0.5g交联索甲基纤维素钠 0.32g聚乙二醇6000 0.8g阿司巴坦 0.8g菠萝香精 0.8g尼泊金甲酯 0.085g尼泊金丙酯 0.045g纯水加至 250ml The children according to claim 1 instant oral, lyophilized rapidly disintegrating tablets, characterized in that: children with cough expectorant lyophilized sheet, the formula is (100): dextromethorphan hydrobromide 0.5g more guaiacol glyceryl ether peach gum 0.5g 6.5g mannitol 10g crosslinked sodium carboxymethylcellulose cable 0.32g 0.8g polyethylene glycol 6000 0.8g tazobactam pineapple essence Aspirin 0.8g methyl paraben 0.085g paraben propylparaben 0.045g Purified water to 250ml
8.根据权利要求1所述的儿用口腔速溶、速崩冻干片,其特征在于:儿用对乙酰氨基酚冻干片,其配方为(100片):包衣对乙酰氨基酚粉末 9.4g(折纯对乙酰氨基酚8.0g)甘露醇 4.0g甘氨酸 3.0g明胶 0.4g糖精钠 1gPVPK300.2g柠檬香精 0.3g尼泊金甲酯 0.085g尼泊金丙酯 0.045g纯水加至 80ml The children of the instant oral claim 1, lyophilized rapidly disintegrating tablets, characterized in that: children with acetaminophen lyophilized sheet, the formula is (100): Coated acetaminophen powder 9.4 G (pure discount acetaminophen 8.0 g) glycine mannitol 4.0g 3.0g 0.4g Sodium Saccharin 1gPVPK300.2g lemon flavor gelatin 0.3g methyl paraben 0.085g propyl paraben 0.045g Purified water to 80ml
9.根据权利要求1所述的儿用口腔速溶、速崩冻干片的制备方法,包括:步骤1.配制溶液及混悬液、步骤2.冻结、步骤3.升华干燥和步骤4.压模包装;其特征在于:所述的步骤2为:将根据步骤1配制的溶液或混悬液按要求分配到多元凹陷模型中,然后放入冷冻机内在摄氏-20℃--30℃度温度下迅速冻结成型;所述的步骤3为:将冻结后的装药模型于冷冻干燥设备中,在高真空低温条件下(温度低于摄氏-40℃,压力0.1-1.0毫巴)升华,除去水分并适当干燥除去残余水分,所需时间根据模型中液体量一般3-8小时。 9. The children according to claim 1 instant oral, rapidly disintegrating tablets lyophilized preparation, comprising the steps of: 1. Preparation of solutions and suspensions, Step 2. freezing, primary drying and the step 3. Step 4. Pressure mold packing; wherein: said step 2: dispensing required according to the multivariate model recess prepared in step a solution or suspension, and then placed in a freezer inner Celsius degrees temperature -20 ℃ --30 ℃ forming a rapidly freezing; step 3 according to: charge model is freeze dried in a freeze apparatus, under high vacuum conditions of low temperature (below -40 Celsius ℃, 0.1-1.0 mbar pressure) sublimation removed water and properly dried to remove residual water, the time required for the model liquid amount is generally 3-8 hours.
10.根据权利要求9所述的儿用口腔速溶、速崩冻干片的制备方法,其特征在于:冻干前配制的溶液或混悬液,所用溶剂为水和低碳醇类水溶液(<30%浓度),其含固量在5-40%(重量/体积),优选含固量在7.5-35%,特别优选含固量在10-25%。 10. The children according to claim 9 instant oral use, a lyophilized preparation of fast-disintegrating tablets, characterized in that: the formulation prior to lyophilization solution or suspension, the solvent is water and an aqueous solution of lower alcohol used (< 30% concentration), its solid content of 5-40% (w / v), preferably in an amount of 7.5-35% solids, especially preferably in an amount of 10-25% solids.
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