CN108078962A - A kind of instant film of donepezil hydrochloride orally and preparation method thereof - Google Patents
A kind of instant film of donepezil hydrochloride orally and preparation method thereof Download PDFInfo
- Publication number
- CN108078962A CN108078962A CN201810104327.1A CN201810104327A CN108078962A CN 108078962 A CN108078962 A CN 108078962A CN 201810104327 A CN201810104327 A CN 201810104327A CN 108078962 A CN108078962 A CN 108078962A
- Authority
- CN
- China
- Prior art keywords
- donepezil hydrochloride
- instant film
- film
- preparation
- hydrochloride orally
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
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- XWAIAVWHZJNZQQ-UHFFFAOYSA-N donepezil hydrochloride Chemical compound [H+].[Cl-].O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 XWAIAVWHZJNZQQ-UHFFFAOYSA-N 0.000 title claims abstract description 41
- 229960003135 donepezil hydrochloride Drugs 0.000 title claims abstract description 41
- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- 239000000463 material Substances 0.000 claims abstract description 15
- 239000000945 filler Substances 0.000 claims abstract description 10
- 239000004014 plasticizer Substances 0.000 claims abstract description 9
- 235000019640 taste Nutrition 0.000 claims abstract description 7
- 239000006068 taste-masking agent Substances 0.000 claims abstract description 5
- 238000001035 drying Methods 0.000 claims abstract 2
- 238000003756 stirring Methods 0.000 claims description 21
- 239000004376 Sucralose Substances 0.000 claims description 16
- 235000019408 sucralose Nutrition 0.000 claims description 16
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 claims description 16
- 239000004378 Glycyrrhizin Substances 0.000 claims description 15
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 claims description 15
- 229960004949 glycyrrhizic acid Drugs 0.000 claims description 15
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 claims description 15
- 235000019410 glycyrrhizin Nutrition 0.000 claims description 15
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 claims description 15
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 14
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
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- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 claims description 2
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 2
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- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 claims description 2
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- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 2
- 235000010449 maltitol Nutrition 0.000 claims description 2
- 239000000845 maltitol Substances 0.000 claims description 2
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 claims description 2
- 229940035436 maltitol Drugs 0.000 claims description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 2
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- OHHNJQXIOPOJSC-UHFFFAOYSA-N stevioside Natural products CC1(CCCC2(C)C3(C)CCC4(CC3(CCC12C)CC4=C)OC5OC(CO)C(O)C(O)C5OC6OC(CO)C(O)C(O)C6O)C(=O)OC7OC(CO)C(O)C(O)C7O OHHNJQXIOPOJSC-UHFFFAOYSA-N 0.000 claims description 2
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- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 2
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 2
- ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 claims 2
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- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 claims 1
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- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 1
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims 1
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
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Abstract
本发明属于药物制剂领域，涉及一种技术工艺简单的盐酸多奈哌齐口腔速溶膜剂及其制备方法。本发明提供的一种口味良好的口腔速溶膜剂，其各组分按照重量百分比计，包含盐酸多奈哌齐1‑40％、成膜材料20‑80％、增塑剂1‑20％、掩味剂1‑20％、填充剂10‑30％、其他辅料0‑5％。制备方法简单，可以通过直接将各种成分在适当溶剂中溶解分散均匀后涂布于背衬材料上，烘干制得。所制得的膜剂外观均匀平滑、物理机械性能良好、溶解迅速、口味良好，且携带方便，可提高阿尔兹海默病患者用药的顺应性。The invention belongs to the field of pharmaceutical preparations, and relates to an oral instant film of donepezil hydrochloride with simple technical process and a preparation method thereof. The oral cavity instant film with good taste provided by the present invention, each component thereof comprises 1-40% of donepezil hydrochloride, 20-80% of a film-forming material, 1-20% of a plasticizer, and a taste-masking agent in terms of percentage by weight. 1‑20%, filler 10‑30%, other excipients 0‑5%. The preparation method is simple, and can be prepared by directly dissolving and dispersing various components in an appropriate solvent, coating them on the backing material, and drying them. The prepared film has uniform and smooth appearance, good physical and mechanical properties, rapid dissolution, good taste, and is easy to carry, which can improve the drug compliance of patients with Alzheimer's disease.
Description
技术领域technical field
本发明涉及药物制剂领域，具体涉及一种盐酸多奈哌齐口腔速溶膜剂及其制备方法。The invention relates to the field of pharmaceutical preparations, in particular to a donepezil hydrochloride oral instant film and a preparation method thereof.
背景技术Background technique
阿尔茨海默病是一种起病隐匿的进行性发展的神经系统退行性疾病，俗称老年痴呆。阿尔茨海默病发现于上世纪，常起病于老年或老年前期，多缓慢发病，逐渐进展，临床主要表现为记忆障碍、失语、失用、失认、视空间技能损害、执行功能障碍以及人格和行为改变等全面性痴呆，病因迄今未明，目前临床治疗依然面临极大挑战。一般认为，年龄每增加5年，患病率将增加1倍。在如今老龄化日渐严重的情况下，阿尔兹海默病已成为严重的社会公共卫生问题，成为影响人类健康的重大疾患，为社会和家庭带来了沉重的负担。Alzheimer's disease is a neurodegenerative disease with insidious onset and progressive development, commonly known as senile dementia. Alzheimer's disease was discovered in the last century. It often starts in old age or early old age. It usually develops slowly and progresses gradually. The etiology of generalized dementia such as personality and behavioral changes is still unknown, and clinical treatment is still facing great challenges. It is generally believed that the prevalence rate will double for every 5 years of age increase. In today's increasingly serious aging situation, Alzheimer's disease has become a serious social public health problem, a major disease affecting human health, and a heavy burden for society and families.
盐酸多奈哌齐是目前用于治疗阿尔兹海默病的首选药物，能够可逆性地抑制胆碱性神经内神经突触间隙内乙酰胆碱的水解，增加感受器对乙酰胆碱的使用量，提高阿尔兹海默病患者脑部的胆碱能神经功能，对中枢乙酰胆碱酯酶具有更高的选择性，无明显的肝毒性。与同类药物相比，具有作用时间长、药效高、安全性高、药物不良反应小等特点。Donepezil hydrochloride is currently the drug of choice for the treatment of Alzheimer's disease. It can reversibly inhibit the hydrolysis of acetylcholine in the synaptic cleft of cholinergic nerves, increase the use of acetylcholine by receptors, and improve the efficacy of Alzheimer's disease patients. The cholinergic nerve function of the brain has higher selectivity to central acetylcholinesterase, and has no obvious liver toxicity. Compared with similar drugs, it has the characteristics of long action time, high efficacy, high safety, and small adverse drug reactions.
口腔膜剂是一种新兴的药物递送系统，能在口腔中迅速溶解，释放药物，适用于不同人群，尤其为吞咽困难的老人和儿童提供了便捷。口腔膜剂采用水溶性聚合物作为成膜材料，在口腔中遇唾液后很快溶解并释放药物。与需要特殊包装的市售口服快速崩解片相比，口腔膜剂不易碎并且易于携带，故而在临床上受到医者和患者偏爱。口腔速溶膜剂的剂型特点决定了其在口腔中迅速溶解，所以对于较苦的药物亦需关注掩味。Oral film is an emerging drug delivery system, which can quickly dissolve in the mouth and release drugs. It is suitable for different groups of people, especially for the elderly and children who have difficulty swallowing. Oral films use water-soluble polymers as film-forming materials, which dissolve and release drugs quickly after meeting saliva in the oral cavity. Compared with commercially available oral rapidly disintegrating tablets that require special packaging, oral films are not fragile and easy to carry, so they are preferred by doctors and patients clinically. The characteristics of the dosage form of oral instant film determine that it dissolves quickly in the mouth, so it is also necessary to pay attention to taste masking for bitter drugs.
发明内容Contents of the invention
本发明的目的之一是提供一种制备方法简单、口味良好、释药速度快、可迅速起效的盐酸多奈哌齐口腔速溶膜剂，提高阿尔兹海默病患者用药的顺应性。One of the objects of the present invention is to provide an oral instant film of donepezil hydrochloride with simple preparation method, good taste, fast drug release and rapid onset of action, so as to improve the drug compliance of patients with Alzheimer's disease.
本发明的特点是以简单方法制备盐酸多奈哌齐口腔速溶膜剂，通过甘草甜素、三氯蔗糖、薄荷醇等进行掩味，解决了盐酸多奈哌齐在口腔中苦味和麻痹的不良口感；成膜材料选用水溶性好的高分子材料，保证了药膜在口腔中能够快速溶解并释放药物。The feature of the present invention is to prepare donepezil hydrochloride oral instant film in a simple way, mask the taste by glycyrrhizin, sucralose, menthol, etc., and solve the bad mouthfeel of donepezil hydrochloride bitterness and numbness in the oral cavity; the film-forming material is selected The polymer material with good water solubility ensures that the drug film can quickly dissolve and release the drug in the oral cavity.
本发明提供的一种口味良好的口腔速溶膜剂，其各组分按照重量百分比计，包含盐酸多奈哌齐1-40％、成膜材料20-80％、增塑剂1-20％、掩味剂1-20％、填充剂10-30％、遮光剂和其他辅料0-5％。The present invention provides a good-tasting oral fast-dissolving film, the components of which include 1-40% of donepezil hydrochloride, 20-80% of film-forming material, 1-20% of plasticizer, and taste-masking agent in terms of weight percentage. 1-20%, filler 10-30%, opacifier and other auxiliary materials 0-5%.
成膜材料应具有溶解快、良好的成膜性和脱模性的特点，此外还应具有无毒、无刺激、性质稳定、不与药物发生作用等特点。本发明中所用成膜材料选自Kollicoat、聚氧乙烯、聚乙烯醇、羟丙甲基纤维素、普鲁兰糖、海藻酸钠、明胶、黄原胶、羟乙基纤维素、羧甲基纤维中的一种或多种。增塑剂改善膜剂性能，增加韧性，降低脆性。增塑剂选自聚乙二醇、乙二醇、丙二醇、邻苯二甲酸酯类、甘油、蓖麻油、乙酰单甘油酸酯、甘油三醋酸酯中的一种或多种。填充剂可增加膜剂重量和体积，降低成型收缩率，调节树脂粘度，减小表面粗糙度。本发明采用适量填充剂改善膜剂性能和外观，使制备过程顺利进行。填充剂选自甘露糖醇、山梨醇、赤藓糖醇、木糖醇、麦芽糖醇、糊精、海藻糖中的一种或多种。掩味剂选自三氯蔗糖、甘露醇、阿斯巴甜、甜菊糖、甘草甜素、糖精钠、薄荷醇、香精中的一种或多种，优选三氯蔗糖和甘草甜素组合使用。三氯蔗糖是迄今为止人类开发出来的较完美、竞争力很强的新一代甜味剂，其甜度为蔗糖的600倍，是一种甜味爆发比较快的甜味剂。但单独以三氯蔗糖作为掩味手段，很难掩盖后期的苦味。甘草甜素甜度为蔗糖的200倍，其甜味不同于蔗糖，入口后稍经片刻才有甜味感，保持时间长，有特殊风味和增香效果。将这二者联合使用能较好的掩盖盐酸多奈哌齐的苦味和麻痹感。其他成分如着色剂选自氧化铁红、氧化铁黄，遮光剂为二氧化钛。The film-forming material should have the characteristics of fast dissolution, good film-forming properties and mold release properties. In addition, it should also have the characteristics of non-toxic, non-irritating, stable properties, and no interaction with drugs. The film-forming material used in the present invention is selected from Kollicoat, polyoxyethylene, polyvinyl alcohol, hydroxypropyl methylcellulose, pullulan, sodium alginate, gelatin, xanthan gum, hydroxyethyl cellulose, carboxymethyl One or more of the fibers. Plasticizers improve film properties, increase toughness and reduce brittleness. The plasticizer is selected from one or more of polyethylene glycol, ethylene glycol, propylene glycol, phthalates, glycerin, castor oil, acetyl monoglyceride, and glycerol triacetate. The filler can increase the weight and volume of the film, reduce the molding shrinkage, adjust the viscosity of the resin, and reduce the surface roughness. The invention adopts an appropriate amount of filler to improve the performance and appearance of the film, so that the preparation process goes smoothly. The filler is selected from one or more of mannitol, sorbitol, erythritol, xylitol, maltitol, dextrin, and trehalose. The taste-masking agent is selected from one or more of sucralose, mannitol, aspartame, stevioside, glycyrrhizin, sodium saccharin, menthol, essence, preferably in combination with sucralose and glycyrrhizin. Sucralose is a relatively perfect and highly competitive new-generation sweetener developed by humans so far. Its sweetness is 600 times that of sucrose, and it is a sweetener with a relatively fast burst of sweetness. However, using sucralose alone as a taste-masking means is difficult to cover up the later bitterness. The sweetness of glycyrrhizin is 200 times that of sucrose. Its sweetness is different from that of sucrose. It takes a short time after the entrance to have a sweet taste. It lasts for a long time and has a special flavor and aroma-enhancing effect. The combined use of the two can better mask the bitter taste and numbness of donepezil hydrochloride. Other components such as the coloring agent are selected from iron oxide red and iron oxide yellow, and the opacifying agent is titanium dioxide.
本发明还提供盐酸多奈哌齐口腔速溶膜剂的制备方法，包括如下步骤：The present invention also provides a preparation method of donepezil hydrochloride oral fast-dissolving film, comprising the steps of:
称取成膜材料、增塑剂在30-80℃水浴中搅拌溶解，加入盐酸多奈哌齐、掩味剂、填充剂和遮光剂等在相同条件下继续搅拌，使其分散，待搅拌均匀后超声脱气，将其均匀涂布背衬材料上，30-60℃加热干燥，切割成一定大小的膜片，即得盐酸多奈哌齐口腔速溶膜剂。Weigh the film-forming material and plasticizer, stir and dissolve in a water bath at 30-80°C, add donepezil hydrochloride, taste-masking agent, filler and opacifier, and continue stirring under the same conditions to disperse them. Gas, evenly coated on the backing material, heated and dried at 30-60°C, cut into membranes of a certain size, and then the donepezil hydrochloride oral fast-dissolving film was obtained.
所述的盐酸多奈哌齐口腔速溶膜剂，其特征是，外观均匀平滑；韧性高，耐折次数多；机械性能好，有较好的抗拉强度和百分伸长率；溶解速度快，在37℃水中的崩解时间小于30s，一般小于20s，能在口腔中迅速溶解分散，释放药物。The oral instant film of donepezil hydrochloride is characterized in that the appearance is uniform and smooth; the toughness is high, and the number of folding times is high; the mechanical properties are good, and the tensile strength and percent elongation are good; The disintegration time in ℃ water is less than 30s, generally less than 20s, and it can quickly dissolve and disperse in the oral cavity to release the drug.
具体实施方式Detailed ways
下面对本发明进行进一步的阐述。The present invention is further elaborated below.
实施例1Example 1
具体制备过程：称取Kollicoat IR、甘油在60℃水浴中搅拌溶解，加入盐酸多奈哌齐、三氯蔗糖、甘草甜素、薄荷醇、二氧化钛继续搅拌，使其充分溶解分散，分散均匀后超声30min脱气，均匀涂布于玻璃板上，60℃干燥，切割成2×1.5cm2大小膜片，得盐酸多奈哌齐口腔速溶膜剂。Specific preparation process: Weigh Kollicoat IR and glycerin, stir and dissolve in a water bath at 60°C, add donepezil hydrochloride, sucralose, glycyrrhizin, menthol, and titanium dioxide and continue stirring to fully dissolve and disperse, disperse evenly, and degas by ultrasonication for 30 minutes , uniformly coated on a glass plate, dried at 60°C, and cut into 2×1.5cm 2 size membranes to obtain donepezil hydrochloride oral fast-dissolving film.
实施例2Example 2
具体制备过程：称取Kollicoat IR、甘油在60℃水浴中搅拌溶解，加入盐酸多奈哌齐、三氯蔗糖、甘草甜素、薄荷醇、二氧化钛继续搅拌，使其充分溶解分散，分散均匀后超声30min脱气，均匀涂布于玻璃板上，60℃干燥，切割成2×1.5cm2大小膜片，得盐酸多奈哌齐口腔速溶膜剂。Specific preparation process: Weigh Kollicoat IR and glycerin, stir and dissolve in a water bath at 60°C, add donepezil hydrochloride, sucralose, glycyrrhizin, menthol, and titanium dioxide and continue stirring to fully dissolve and disperse, disperse evenly, and degas by ultrasonication for 30 minutes , evenly coated on a glass plate, dried at 60°C, and cut into 2×1.5cm2 size membranes to obtain donepezil hydrochloride oral instant film.
实施例3Example 3
具体制备过程：称取成膜材料HPMC E5、甘油在60℃水浴中搅拌溶解，加入盐酸多奈哌齐、三氯蔗糖、甘草甜素、薄荷醇、二氧化钛继续搅拌，使其充分溶解分散，分散均匀后超声30min脱气，均匀涂布于玻璃板上，60℃干燥，切割成2×1.5cm2大小膜片，得盐酸多奈哌齐口腔速溶膜剂。Specific preparation process: Weigh the film-forming material HPMC E5 and glycerin, stir and dissolve in a water bath at 60°C, add donepezil hydrochloride, sucralose, glycyrrhizin, menthol, and titanium dioxide and continue stirring to fully dissolve and disperse, and disperse evenly before ultrasonication Degas for 30 minutes, spread evenly on a glass plate, dry at 60°C, and cut into 2×1.5cm2 size membranes to obtain donepezil hydrochloride oral fast-dissolving film.
实施例4Example 4
具体制备过程：称取成膜材料HPMC E5、甘油在60℃水浴中搅拌溶解，加入盐酸多奈哌齐、三氯蔗糖、甘草甜素、薄荷醇、二氧化钛继续搅拌，使其充分溶解分散，分散均匀后超声30min脱气，均匀涂布于玻璃板上，60℃干燥，切割成2×1.5cm2大小膜片，得盐酸多奈哌齐口腔速溶膜剂。Specific preparation process: Weigh the film-forming material HPMC E5 and glycerin, stir and dissolve in a water bath at 60°C, add donepezil hydrochloride, sucralose, glycyrrhizin, menthol, and titanium dioxide and continue stirring to fully dissolve and disperse, and disperse evenly before ultrasonication Degas for 30 minutes, spread evenly on a glass plate, dry at 60°C, and cut into 2×1.5cm2 size membranes to obtain donepezil hydrochloride oral fast-dissolving film.
实施例5Example 5
具体制备过程：称取Kollicoat IR、1，2-丙二醇在60℃水浴中搅拌溶解，加入盐酸多奈哌齐、三氯蔗糖、甘草甜素、薄荷醇、二氧化钛继续搅拌，使其充分溶解分散，分散均匀后超声30min脱气，均匀涂布于玻璃板上，60℃干燥，切割成2×1.5cm2大小膜片，得盐酸多奈哌齐口腔速溶膜剂。Specific preparation process: Weigh Kollicoat IR and 1,2-propanediol, stir and dissolve in a water bath at 60°C, add donepezil hydrochloride, sucralose, glycyrrhizin, menthol, and titanium dioxide and continue stirring to fully dissolve and disperse, and disperse evenly Ultrasound for 30 minutes to degas, spread evenly on a glass plate, dry at 60°C, cut into 2×1.5cm2 size membranes, and obtain donepezil hydrochloride oral fast-dissolving film.
实施例6Example 6
具体制备过程：称取Kollicoat IR、PEG-400在60℃水浴中搅拌溶解，加入盐酸多奈哌齐、三氯蔗糖、甘草甜素、薄荷醇、二氧化钛继续搅拌，使其充分溶解分散，分散均匀后超声30min脱气，均匀涂布于玻璃板上，60℃干燥，切割成2×1.5cm2大小膜片，得盐酸多奈哌齐口腔速溶膜剂。Specific preparation process: Weigh Kollicoat IR and PEG-400, stir and dissolve in a water bath at 60°C, add donepezil hydrochloride, sucralose, glycyrrhizin, menthol, and titanium dioxide and continue stirring to fully dissolve and disperse, and disperse evenly, then sonicate for 30 minutes Degassed, evenly coated on a glass plate, dried at 60°C, cut into 2×1.5cm2 size membranes to obtain donepezil hydrochloride oral fast-dissolving film.
实施例7Example 7
具体制备过程：称取Kollicoat IR、1，2-丙二醇在60℃水浴中搅拌溶解，加入盐酸多奈哌齐、甘露醇、三氯蔗糖、甘草甜素、薄荷醇、二氧化钛继续搅拌，使其充分溶解分散，分散均匀后超声30min脱气，均匀涂布于玻璃板上，60℃干燥，切割成2×1.5cm2大小膜片，得盐酸多奈哌齐口腔速溶膜剂。Specific preparation process: Weigh Kollicoat IR and 1,2-propanediol, stir and dissolve in a 60°C water bath, add donepezil hydrochloride, mannitol, sucralose, glycyrrhizin, menthol, and titanium dioxide and continue stirring to fully dissolve and disperse. After uniform dispersion, it was degassed by ultrasonication for 30 minutes, evenly spread on a glass plate, dried at 60°C, and cut into 2×1.5cm2 size membranes to obtain donepezil hydrochloride oral instant film.
实施例8Example 8
具体制备过程：称取Kollicoat IR、1，2-丙二醇在60℃水浴中搅拌溶解，加入盐酸多奈哌齐、赤藓糖醇、三氯蔗糖、甘草甜素、薄荷醇、二氧化钛继续搅拌，使其充分溶解分散，分散均匀后超声30min脱气，均匀涂布于玻璃板上，60℃干燥，切割成2×1.5cm2大小膜片，得盐酸多奈哌齐口腔速溶膜剂。Specific preparation process: Weigh Kollicoat IR, 1,2-propanediol, stir and dissolve in a 60°C water bath, add donepezil hydrochloride, erythritol, sucralose, glycyrrhizin, menthol, and titanium dioxide and continue stirring to fully dissolve Disperse, after uniform dispersion, degas by ultrasonication for 30 minutes, evenly spread on a glass plate, dry at 60°C, cut into 2×1.5cm2 size membranes, and obtain donepezil hydrochloride oral fast-dissolving film.
实施例9Example 9
具体制备过程：称取Kollicoat IR、1，2-丙二醇在60℃水浴中搅拌溶解，加入盐酸多奈哌齐、山梨醇P60、三氯蔗糖、甘草甜素、薄荷醇、二氧化钛继续搅拌，使其充分溶解分散，分散均匀后超声30min脱气，均匀涂布于玻璃板上，60℃干燥，切割成2×1.5cm2大小膜片，得盐酸多奈哌齐口腔速溶膜剂。Specific preparation process: Weigh Kollicoat IR, 1,2-propanediol, stir and dissolve in a 60°C water bath, add donepezil hydrochloride, sorbitol P60, sucralose, glycyrrhizin, menthol, titanium dioxide and continue stirring to fully dissolve and disperse , dispersed evenly, degassed by ultrasonication for 30 minutes, evenly coated on a glass plate, dried at 60°C, cut into 2×1.5cm2 size membranes to obtain donepezil hydrochloride oral fast-dissolving film.
盐酸多奈哌齐口腔速溶膜剂评价方法Evaluation method of donepezil hydrochloride oral fast-dissolving film
口腔速溶膜剂的评价方法根据外观与感官评价为考察指标，从均匀度、成膜性、脱模难易程度三个方面进行考察；根据膜剂的物理性质为考察指标，从耐折度、抗拉强度和百分伸长率三个方面进行考察；另外考察其崩解时间。The evaluation method of oral instant film is based on the appearance and sensory evaluation as the inspection index, and is investigated from three aspects: uniformity, film formation, and demolding difficulty; according to the physical properties of the film as the inspection index, the folding resistance, The three aspects of tensile strength and percent elongation are investigated; in addition, the disintegration time is investigated.
根据外观与感官评价为考察指标评分标准Scoring criteria for inspection indicators based on appearance and sensory evaluation
评价结果如下The evaluation results are as follows
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