CN107854445A - 一种盐酸鲁拉西酮分散片及其制备方法 - Google Patents
一种盐酸鲁拉西酮分散片及其制备方法 Download PDFInfo
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- CN107854445A CN107854445A CN201711358052.6A CN201711358052A CN107854445A CN 107854445 A CN107854445 A CN 107854445A CN 201711358052 A CN201711358052 A CN 201711358052A CN 107854445 A CN107854445 A CN 107854445A
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- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
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- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
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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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K9/20—Pills, tablets, discs, rods
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- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
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- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
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Abstract
本发明公开了一种含有盐酸鲁拉西酮‑亲水性材料共混物的分散片的制备方法。该分散片含有盐酸鲁拉西酮‑亲水性材料共混物以及其它药学上可接受的辅料，采用湿法制粒压片制备分散片，其分散均匀性良好，可有效地提高盐酸鲁拉西酮固体制剂的溶出速度，提高了患者服用的依从性以及药品的生物利用度，工艺简便，适于工业化生产。
Description
技术领域
本发明属于药物制剂技术领域，具体涉及一种提高盐酸鲁拉西酮在固体制剂中溶出度的技术及其固体制剂分散片的制备方法。
背景技术
1、药品概况
盐酸鲁拉西酮精神***症成年的四项6周对照研究证实盐酸鲁拉西酮的有效性和安全性。在这些研究中，盐酸鲁拉西酮在主要疗效指标方面相对安慰剂显示明显大的改善, 其中包括在研究终结时阳性和阴性症状量表(PANSS) 总分和简明精神病评定量表( 从PANSS量表衍生)，共有5 项试验证实了盐酸鲁拉西酮的耐受性和安全性。最突出症状包括幻觉，妄念，思维和行为紊乱，和多疑。听到其他人听不到的声音是最常见类型的幻觉。、
2、市场前景
盐酸鲁拉西酮(lurasidone HCI) 属于非典型抗精神病药物类，是由日本住友制药公司开发的一种具有双重作用的非典型抗精神病药，2010年10月28日美国FDA批准上市，用于精神***症患者的治疗，其商品名为Latuda，推荐剂量每日1次片剂，用于精神***症患者的一线治疗。
2012年5月大日本制药制药报告，Latuda®（盐酸鲁拉西酮）在两项I型双相情感障碍抑郁症的III期试验中达到主要终点和关键的次要终点，并计划年底向美国食品药品管理局(FDA)递交盐酸鲁拉西酮治疗I型双相情感障碍抑郁症的补充新药申请(sNDA)。
3、产品优势
1）每日一片，口服方便。
2）疗效确切。对5-HT2A受体和多巴胺D2受体均具有高度亲和力。对精神病患者的阳性和阴性症状均具有显著疗效。
3）有研究报道鲁拉西酮可以改善认知功能。
4）第二适应症用于治疗双相情感障碍正处于三期临床。计划年底递交补充申请。
发明内容
本发明的目的在于提供一种工艺简单、溶出速度快、药物生物利用度高的分散片。本发明涉及了一种利用亲水性材料与盐酸鲁拉西酮预混，内外法加入崩解剂，使制剂溶出速率增加的方法。其特征是先将原料药盐酸鲁拉西酮粉碎过200目筛，然后和亲水性材料过80目筛混合若干次，其中亲水性材料为乳糖、甘露醇、山梨醇中的一种或几种；盐酸鲁拉西酮与亲水性材料的重量比为1：1~1：40，优选1：15~1：50；过80目筛混合3~8次，优选5~6次，形成盐酸鲁拉西酮-亲水性材料共混物。加入其余内加辅料混合均匀，其中填充剂为乳糖、甘露醇、山梨醇、微晶纤维素、木糖醇、果糖、淀粉及淀粉衍生物中的一种或几种，优选乳糖和微晶纤维素；崩解剂为预胶化淀粉、羧甲基淀粉钠、羧甲基纤维素钠、交联聚维酮、低取代羟丙基纤维素、交联羧甲基纤维素钠中的一种或几种，优选羧甲基淀粉钠和交联聚维酮；内加崩解剂量为30%~70%，优选40%~50%。加入粘合剂，粘合剂为羟丙纤维素、聚维酮、乙醇、水中的一种或几种，优选羟丙纤维素和水，过24目筛制粒。50 ℃鼓风干燥，水分烘至1~3%。将烘干颗粒称重，折算收率外加，外加崩解剂为预胶化淀粉、羧甲基淀粉钠、羧甲基纤维素钠、低取代羟丙基纤维素、交联羧甲基纤维素钠中的一种或几种，优选羧甲基淀粉钠和交联聚维酮；外加润滑剂为硬脂酸镁、硅酸铝镁、硬脂富马酸钠、蔗糖脂肪酸酯、单硬脂酸甘油酯、滑石粉、硬脂酸、二氧化硅中的一种或几种，优选硬脂酸镁和二氧化硅；外加矫味剂为阿司帕坦、薄荷脑、安赛蜜、甜菊苷、薄荷香精、香草香精中的一种或几种，优选阿司帕坦、薄荷香精。
采用本方法制备的分散片服用方便，口感良好，分散均匀性良好，15min溶出度大于85%，属于快速溶出。
具体实施方式
以下实施例进一步描述本发明的有益效果，实施例仅用于例证的目的，不限制本发明的范围，同时本领域普通技术人员根据本发明所做的显而易见的改变和修饰也包含在本发明范围之内。
（一）分散片的制备
实施例1：
制备工艺：
将盐酸鲁拉西酮粉碎过200目筛，然后与29倍重量乳糖过80目筛混合3次，加入剩余乳糖、微晶纤维素和羧甲基淀粉钠过80目筛3次混匀，2%羟丙基纤维素作为粘合剂，24目筛制粒，50 ℃鼓风干燥，水分烘至1~3%，将烘干颗粒过24目筛整粒，称重，折算收率，外加羧甲基淀粉钠、二氧化硅、阿司帕坦、薄荷香精和硬脂酸镁，Φ8平冲压片，片重200 mg，硬度20-40N。
实施例2：
制备工艺：
将盐酸鲁拉西酮粉碎过200目筛，然后与24倍重量甘露醇过80目筛混合3次，加入剩余甘露醇、微晶纤维素和羧甲基淀粉钠过80目筛3次混匀，2%羟丙基纤维素作为粘合剂，24目筛制粒，50 ℃鼓风干燥，水分烘至1~3%，将烘干颗粒过24目筛整粒，称重，折算收率，外加羧甲基淀粉钠、二氧化硅、阿司帕坦、薄荷香精和硬脂酸镁，Φ8平冲压片，片重200 mg，硬度20-40 N。
实施例3：
制备工艺：
将盐酸鲁拉西酮粉碎过200目筛，然后与37倍重量乳糖过80目筛混合5次，加入剩余乳糖、微晶纤维素和羧甲基淀粉钠过80目筛3次混匀，2%羟丙基纤维素作为粘合剂，24目筛制粒，50 ℃鼓风干燥，水分烘至1~3%，将烘干颗粒过24目筛整粒，称重，折算收率，外加羧甲基淀粉钠、二氧化硅、阿司帕坦、薄荷香精和硬脂酸镁，Φ8平冲压片，片重200 mg，硬度20-40N。
实施例4：
制备工艺：
将盐酸鲁拉西酮粉碎过200目筛，然后与47倍重量乳糖过80目筛混合3次，加入剩余乳糖、微晶纤维素和羧甲基淀粉钠过80目筛3次混匀，2%羟丙基纤维素作为粘合剂，24目筛制粒，50 ℃鼓风干燥，水分烘至1~3%，将烘干颗粒过24目筛整粒，称重，折算收率，外加羧甲基淀粉钠、二氧化硅、阿司帕坦、薄荷香精和硬脂酸镁，Φ8平冲压片，片重200 mg，硬度20-40N。
实施例5：
制备工艺：
将盐酸鲁拉西酮粉碎过200目筛，然后与35倍重量乳糖过80目筛混合3次，加入剩余乳糖、微晶纤维素和羧甲基淀粉钠过80目筛3次混匀，水作为粘合剂，24目筛制粒，50 ℃鼓风干燥，水分烘至1~3%，将烘干颗粒过24目筛整粒，称重，折算收率，外加羧甲基淀粉钠、二氧化硅、阿司帕坦、薄荷香精和硬脂酸镁，Φ8平冲压片，片重230 mg，硬度20-40 N。
实施例6：
制备工艺：
将盐酸鲁拉西酮粉碎过200目筛，然后与34倍重量乳糖过80目筛混合7次，加入剩余乳糖、微晶纤维素和羧甲基淀粉钠过80目筛3次混匀，水作为粘合剂，24目筛制粒，50 ℃鼓风干燥，水分烘至1~3%，将烘干颗粒过24目筛整粒，称重，折算收率，外加羧甲基淀粉钠、二氧化硅、阿司帕坦、薄荷香精和硬脂酸镁，Φ8平冲压片，片重230 mg，硬度20-40 N。
实施例7：
制备工艺：
将盐酸鲁拉西酮粉碎过200目筛，然后与24倍重量乳糖过80目筛混合5次，加入剩余乳糖、微晶纤维素和羧甲基淀粉钠过80目筛3次混匀，水作为粘合剂，24目筛制粒，50 ℃鼓风干燥，水分烘至1~3%，将烘干颗粒过24目筛整粒，称重，折算收率，外加羧甲基淀粉钠、二氧化硅、阿司帕坦、薄荷香精和硬脂酸镁，Φ8平冲压片，片重260 mg，硬度20-40 N。
对比实施例：
制备工艺：
将盐酸鲁拉西酮粉碎过200目筛，然后与与44倍重量乳糖内加辅料过80目筛3次混匀，2%羟丙基纤维素作为粘合剂，24目筛制粒，50 ℃鼓风干燥，水分烘至1~3%，将烘干颗粒过24目筛整粒，称重，折算收率，外加羧甲基淀粉钠、二氧化硅、阿司帕坦、薄荷香精和硬脂酸镁，Φ8平冲压片，片重260mg，硬度20-40 N。
Claims (10)
1.一种盐酸鲁拉西酮分散片，其特征在于：含有盐酸鲁拉西酮-亲水性材料共混物，此外还有填充剂、崩解剂、粘合剂、润滑剂和矫味剂。
2.据权利要求1所述的盐酸鲁拉西酮-亲水性材料共混物，其特征在于：亲水性材料为乳糖、甘露醇、山梨醇中的一种或几种。
3.据权利要求1所述的盐酸鲁拉西酮-亲水性材料共混物，其特征在于：盐酸鲁拉西酮与亲水性材料的重量比为1：1~1：40。
4.据权利要求4所述的盐酸鲁拉西酮-亲水性材料共混物，其特征在于：盐酸鲁拉西酮与亲水性材料的重量比为1：10~1：20。
5.据权利要求1所述，盐酸鲁拉西酮-亲水性材料共混物的制备方法为：将原料药盐酸鲁拉西酮和亲水性材料过80目筛混合若干次，形成盐酸鲁拉西酮-亲水性材料共混物。
6.据权利要求6所述，其特征在于：盐酸鲁拉西酮和亲水性材料过80目筛混合3~8次。
7.据权利要求1所述，其特征在于：填充剂为乳糖、甘露醇、山梨醇、微晶纤维素、淀粉及淀粉衍生物、果糖中的一种或几种。
8.据权利要求1所述，其特征在于：崩解剂为羧甲基淀粉钠、交联聚维酮、羧甲基纤维素钠、低取代羟丙基纤维素、交联羧甲基纤维素钠中的一种或几种。
9.据权利要求8所述，其特征在于：内加崩解剂为30%~70%。
10.据权利要求1所诉，其特征在于：粘合剂为羟丙纤维素、聚维酮、乙醇、水中的一种或几种。
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| CN106377514A (zh) * | 2016-09-24 | 2017-02-08 | 万全万特制药江苏有限公司 | 盐酸鲁拉西酮分散片 |
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| CN106109430A (zh) * | 2016-07-28 | 2016-11-16 | 北京万全德众医药生物技术有限公司 | 一种含有来曲唑的分散片及其制备方法 |
| CN106377514A (zh) * | 2016-09-24 | 2017-02-08 | 万全万特制药江苏有限公司 | 盐酸鲁拉西酮分散片 |
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