CN108078962A - 一种盐酸多奈哌齐口腔速溶膜剂及其制备方法 - Google Patents
一种盐酸多奈哌齐口腔速溶膜剂及其制备方法 Download PDFInfo
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- 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
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- Prior art keywords
- donepezil hydrochloride
- instant film
- film
- preparation
- hydrochloride orally
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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。
Description
技术领域
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。
背景技术
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。
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。
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。
发明内容
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。
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。
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％。
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。
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：
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。
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。
具体实施方式
下面对本发明进行进一步的阐述。
实施例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。
实施例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。
实施例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。
实施例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。
实施例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。
实施例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。
实施例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。
实施例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。
实施例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。
盐酸多奈哌齐口腔速溶膜剂评价方法
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。
根据外观与感官评价为考察指标评分标准
评价结果如下
Claims (7)
1.一种盐酸多奈哌齐口腔速溶膜剂及其制备方法，其特征在于该口腔速溶膜剂是由盐酸多奈哌齐、成膜材料、增塑剂、填充剂、掩味剂、遮光剂和其他辅料组成。
2.根据权利要求1所述的盐酸多奈哌齐口腔速溶膜剂，其特征在于其中各组分的重量百分含量为：盐酸多奈哌齐1-40％、成膜材料20-80％、增塑剂1-20％、填充剂10-30％、掩味剂1-20％、遮光剂和其他辅料0-5％。
3.根据权利要求1所述的盐酸多奈哌齐口腔速溶膜剂，其特征在于所述成膜材料选自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，优选Kollicoat IR、HPMC。
4.根据权利要求1所述的盐酸多奈哌齐口腔速溶膜剂，其特征在于所述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，优选甘油、1，2-丙二醇。
5.根据权利要求1所述的盐酸多奈哌齐口腔速溶膜剂，其特征在于所述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，优选甘露糖醇、赤藓糖醇、山梨醇。
6.根据权利要求1所述的盐酸多奈哌齐口腔速溶膜剂，其特征在于所述掩味剂选自小分子甜味剂如三氯蔗糖、甘露醇、阿斯巴甜、甜菊糖、甘草甜素、糖精钠、薄荷醇、香精，掩味树脂类如聚克立林及其钾盐树脂、丙烯酸树脂类以及掩味包合物如环糊精类中的一种或多种，优选三氯蔗糖、甘草甜素、薄荷醇。
7.根据权利要求1所述的盐酸多奈哌齐口腔速溶膜剂，其特征在于制备方法包括如下步骤：
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，切割成一定大小膜片，即得盐酸多奈哌齐口腔速溶膜剂。
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| CN113082005A (zh) * | 2021-04-07 | 2021-07-09 | 青岛科技大学 | 纳米纤维素基掩味口腔速溶膜的制备 |
| CN115569122A (zh) * | 2022-10-20 | 2023-01-06 | 深圳善康医药科技股份有限公司 | 一种多奈哌齐缓释植入剂及其制备方法和用途 |
| CN116712415A (zh) * | 2023-07-07 | 2023-09-08 | 力品药业(厦门)股份有限公司 | 一种多奈哌齐口溶膜及其制备方法 |
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| CN115569122B (zh) * | 2022-10-20 | 2024-05-31 | 深圳善康医药科技股份有限公司 | 一种多奈哌齐缓释植入剂及其制备方法和用途 |
| CN116712415A (zh) * | 2023-07-07 | 2023-09-08 | 力品药业(厦门)股份有限公司 | 一种多奈哌齐口溶膜及其制备方法 |
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