CN113069418A - 一种阿莫西林颗粒的制备方法 - Google Patents
一种阿莫西林颗粒的制备方法 Download PDFInfo
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- CN113069418A CN113069418A CN202110429638.7A CN202110429638A CN113069418A CN 113069418 A CN113069418 A CN 113069418A CN 202110429638 A CN202110429638 A CN 202110429638A CN 113069418 A CN113069418 A CN 113069418A
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- amoxicillin
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- LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 title claims abstract description 92
- 229960003022 amoxicillin Drugs 0.000 title claims abstract description 92
- LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 title claims abstract description 92
- 239000008187 granular material Substances 0.000 title claims abstract description 72
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- 238000001035 drying Methods 0.000 claims description 34
- 239000000243 solution Substances 0.000 claims description 29
- 238000002156 mixing Methods 0.000 claims description 23
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 20
- 239000002994 raw material Substances 0.000 claims description 20
- 238000003756 stirring Methods 0.000 claims description 18
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical group O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 15
- 229920001983 poloxamer Polymers 0.000 claims description 15
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- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 14
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- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 6
- 229930195725 Mannitol Natural products 0.000 claims description 6
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- UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UEDUENGHJMELGK-HYDKPPNVSA-N 0.000 claims description 6
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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 6
- 235000019202 steviosides Nutrition 0.000 claims description 6
- 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 description 5
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 4
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
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- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
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- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
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- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 1
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- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
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- A61K31/425—Thiazoles
- A61K31/429—Thiazoles condensed with heterocyclic ring systems
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Abstract
本发明公开了一种阿莫西林颗粒的制备方法,以质量百分含量计,其各组分的用量为:阿莫西林固体分散体20%‑30%、填充剂70%‑80%、粘合剂1%‑1.5%、甜味剂0.5%‑1.5%、助流剂0.05%‑0.25%。本发明不仅解决了目前阿莫西林颗粒制剂溶出度差的问题,而且还减少制剂的副作用,提高安全性,使其能够更好的被儿童患者所接受。
Description
技术领域
本发明涉及药物制剂技术领域,具体涉及一种阿莫西林颗粒的制备方法。
背景技术
阿莫西林适用于敏感菌(不产生β内酰胺酶菌株)溶血链球菌、肺炎链球菌、葡萄球菌或流感嗜血杆菌所致中耳炎、鼻窦炎、咽炎、扁桃体炎等上呼吸道感染,大肠埃希菌、奇异变形杆菌或粪肠球菌所致的泌尿生殖道感染,溶血链球菌、肺炎链球菌、葡萄球菌或流感嗜血杆菌所致急性支气管炎、肺炎等下呼吸道感染,急性单纯性淋病等,对于上呼吸道、下呼吸道的严重感染都具有良好的抗菌作用。其制剂有胶囊、片剂、颗粒剂、分散片等。
阿莫西林颗粒具有服用方便、患者依从性好等优点,广泛应用于儿童呼吸系统、泌尿生殖系统、消化系统感染。
由于阿莫西林在水中微溶,在乙醇中几乎不溶,较差的溶解性决定了其颗粒剂的溶出度较差,解决溶出度问题,成为了阿莫西林颗粒剂目前面临的难题,有资料报道加入吐温80、十二烷基硫酸钠等表面活性剂,其不仅对人体有很大的毒副作用,而且效果不明显,均匀性很差,如何制备一种溶出度好、稳定性高、副作用小的阿莫西林颗粒制剂,一直是药品生产企业亟待解决的问题。
发明内容
本发明的目的是针对现有技术的不足而提供一种阿莫西林颗粒的制备方法,该制剂不仅解决了目前阿莫西林颗粒制剂溶出度差的问题,而且还减少制剂的副作用,提高安全性,使其能够更好的被儿童患者所接受。
为了完成上述目的,本发明采用以下技术方案:
一种阿莫西林颗粒的制备方法,具体包括以下步骤:
S1:将阿莫西林原料用气流粉碎机粉碎,过120目筛后备用;
S2:取步骤S1所得的阿莫西林原料溶于适量的水中,得到阿莫西林水溶液,再将泊洛沙姆溶于阿莫西林水溶液中,或者将泊洛沙姆加热至完全熔融后,加入阿莫西林原料,搅拌混合均匀;
S3:将步骤S2所得溶液进行减压干燥、粉碎,即得阿莫西林固体分散体;
S4:取步骤S3所得的阿莫西林固体分散体与填充剂混合均匀,然后加入粘合剂在湿法制粒机中制备软材,过35-50目筛制粒;
S5:将步骤S4中的湿颗粒置于沸腾干燥机进行烘干;
S6:烘干后用35-50目筛进行整粒,得到干颗粒;
S7:将步骤S6所得的干颗粒中加入甜味剂、助流剂,通过三维运动混合机混合均匀,即得阿莫西林颗粒,将上述颗粒分装为0.125克或0.25克/每单位剂量的包装,用铝塑复合膜进行包装。
本发明的进一步改进点在于,所述泊洛沙姆为泊洛沙姆124、泊洛沙姆188、泊洛沙姆237、泊洛沙姆338、泊洛沙姆407中的一种。
本发明的进一步改进点在于,所述步骤S5中沸腾干燥机温度为40-50℃,干燥水分控制1%以下。
本发明的进一步改进点在于,以质量百分含量计,其各组分的用量为:阿莫西林固体分散体20%-30%、填充剂70%-80%、粘合剂1%-1.5%、甜味剂0.5%-1.5%、助流剂0.05%-0.25%。
本发明的进一步改进点在于,所述填充剂为乳糖、微晶纤维素、蔗糖、甘露醇中的一种或几种的混合。
本发明的进一步改进点在于,所述填充剂为乳糖和微晶纤维素按照质量比为5-6:1的比例组成。
本发明的进一步改进点在于,所述粘合剂为羟丙基纤维素、聚乙烯吡咯烷酮、丙烯酸乙酯-甲基丙烯酸甲酯共聚物水分散体中的一种或几种的混合。
本发明的进一步改进点在于,所述粘合剂按质量比为聚乙烯吡咯烷酮:乙醇:纯化水=8:2:90的比例配制成质量体积百分含量为8%的聚乙烯吡咯烷酮溶液。
本发明的进一步改进点在于,所述甜味剂为甜菊苷、糖精钠、阿斯巴甜中的一种或两种的混合。
本发明的进一步改进点在于,所述助流剂为二氧化硅。
与现有技术相比,本发明的有益效果是:
1、本发明的阿莫西林颗粒通过泊洛沙姆作为固体载体材料,使主药处于高度分散状态,一是可以增加药物的溶解度和溶出速率,提高生物利用度;二是可以通过载体来掩盖药物的不良气味,改善药物的口感;三是可以利用载体的包蔽作用,延缓药物的水解或氧化,增加药物的稳定性。
2、颗粒剂的杂质低,外观均匀,流动性良好,装量准确,含量均一。
3、颗粒剂服用方便,容易确定儿童患者的给药剂量。
4、生产工艺简便易行,成本低廉。
具体实施方式
为了使本技术领域的人员更好地理解本申请方案,下面结合实施例对本发明进行详细的说明,但并不限制本发明的内容。
实施例1
一种阿莫西林颗粒的制备方法,其包括以下组分含量(g):阿莫西林10、泊洛沙姆15、乳糖60、微晶纤维素12、聚乙烯吡咯烷酮1.25、甜菊苷1.5、二氧化硅0.25。
具体包括以下步骤:
(1)将阿莫西林原料用气流粉碎机粉碎,过120目筛后备用;
(2)取步骤(1)所得的阿莫西林原料溶于适量的水中,得到阿莫西林水溶液,再将泊洛沙姆溶于阿莫西林水溶液中,或者将泊洛沙姆188于60°加热至完全熔融变成熔融态液体,然后往熔融态溶液中加入阿莫西林原料,搅拌混合均匀;
(3)将步骤(2)所得溶液进行减压干燥、粉碎,即得阿莫西林固体分散体;其中,也可通过减压蒸除、真空干燥、冷冻干燥、喷雾干燥等方法进行干燥;
(4)取步骤(3)所得的阿莫西林固体分散体与乳糖、微晶纤维素混合均匀,取聚乙烯吡咯烷酮,按照聚乙烯吡咯烷酮:乙醇:纯化水=8:2:90的比例配制成质量体积百分含量为8%的聚乙烯吡咯烷酮溶液,然后加入聚乙烯吡咯烷酮溶液在湿法制粒机中制备软材,过40目筛制粒;
(5)将步骤(4)中的湿颗粒置于沸腾干燥机进行烘干,烘干温度为45℃,干燥水分控制1%以下;
(6)烘干后40目筛进行整粒,得到干颗粒;
(7)将步骤(6)所得的干颗粒中加入甜菊苷、二氧化硅,通过三维运动混合机混合均匀,即得阿莫西林颗粒,将上述颗粒分装为0.125克或0.25克/每单位剂量的包装,用铝塑复合膜进行包装。
实施例2
一种阿莫西林颗粒的制备方法,其包括以下组分含量(g):阿莫西林12、泊洛沙姆15、甘露醇70、羟丙基纤维素1.25、糖精钠1.5、二氧化硅0.25。
具体包括以下步骤:
(1)将阿莫西林原料用气流粉碎机粉碎,过120目筛后备用;
(2)取步骤(1)所得的阿莫西林原料溶于适量的水中,得到阿莫西林水溶液,再将泊洛沙姆溶于阿莫西林水溶液中,或者将泊洛沙姆188于60°加热至完全熔融变成熔融态液体,然后往熔融态溶液中加入阿莫西林原料,搅拌混合均匀;
(3)将步骤(2)所得溶液进行减压干燥、粉碎,即得阿莫西林固体分散体;其中,也可通过减压蒸除、真空干燥、冷冻干燥、喷雾干燥等方法进行干燥;
(4)取步骤(3)所得的阿莫西林固体分散体与甘露醇混合均匀,取羟丙基纤维素融入溶剂配制成羟丙基纤维素溶液,然后加入羟丙基纤维素溶液在湿法制粒机中制备软材,过40目筛制粒;
(5)将步骤(4)中的湿颗粒置于沸腾干燥机进行烘干,烘干温度为45℃,干燥水分控制1%以下;
(6)烘干后40目筛进行整粒,得到干颗粒;
(7)将步骤(6)所得的干颗粒中加入糖精钠、二氧化硅,通过三维运动混合机混合均匀,即得阿莫西林颗粒,将上述颗粒分装为0.125克或0.25克/每单位剂量的包装,用铝塑复合膜进行包装。
实施例3
一种阿莫西林颗粒的制备方法,其包括以下组分含量(g):阿莫西林10、泊洛沙姆12、蔗糖75、羟丙基纤维素1.5、阿斯巴甜1.25、二氧化硅0.25。
具体包括以下步骤:
(1)将阿莫西林原料用气流粉碎机粉碎,过120目筛后备用;
(2)取步骤(1)所得的阿莫西林原料溶于适量的水中,得到阿莫西林水溶液,再将泊洛沙姆溶于阿莫西林水溶液中,或者将泊洛沙姆188于60°加热至完全熔融变成熔融态液体,然后往熔融态溶液中加入阿莫西林原料,搅拌混合均匀;
(3)将步骤(2)所得溶液进行减压干燥、粉碎,即得阿莫西林固体分散体;其中,也可通过减压蒸除、真空干燥、冷冻干燥、喷雾干燥等方法进行干燥;
(4)取步骤(3)所得的阿莫西林固体分散体与阿斯巴甜混合均匀,取羟丙基纤维素融入溶剂配制成羟丙基纤维素溶液,然后加入羟丙基纤维素溶液在湿法制粒机中制备软材,过40目筛制粒;
(5)将步骤(4)中的湿颗粒置于沸腾干燥机进行烘干,烘干温度为45℃,干燥水分控制1%以下;
(6)烘干后40目筛进行整粒,得到干颗粒;
(7)将步骤(6)所得的干颗粒中加入糖精钠、二氧化硅,通过三维运动混合机混合均匀,即得阿莫西林颗粒,将上述颗粒分装为0.125克或0.25克/每单位剂量的包装,用铝塑复合膜进行包装。
对比例1
一种阿莫西林颗粒(作为参比制剂),其制备方法如下:1)按配方比例称取阿莫西林、蔗糖、羧甲淀粉钠、阿司帕坦、柠檬黄、桔子香精、乙醇,蔗糖先用装有60目筛网的粉碎机粉碎;2)将95%乙醇加纯化水配成50%乙醇溶液作为润湿剂;加入柠檬黄溶解;3)将阿莫西林与蔗糖、羧甲基淀粉钠、阿司帕坦投入湿法混合制粒机中干混5分钟;4)加入包含柠檬黄的乙醇溶液,高速搅拌、高速切割约25秒钟,制成软材;5)将软材加入摇摆制粒机中,用24目尼龙筛网制粒;6)将湿颗粒移入沸腾干燥机中,进风温度40±5℃,进行干燥;7)将干燥后的颗粒进行过筛操作,上层筛网目数为18目,下层筛网目数为60目,并喷桔子香精;8)将颗粒置三维运动混合机中混合15分钟;(9)分装。
对比例2
一种阿莫西林颗粒(作为参比制剂),其制备方法如下:1)称取阿莫西林;2)将枸橼酸、枸橼酸钠、柠檬黄和蔗糖混合粉碎过80目筛;3)制备黏合剂溶液,按比例配制成1.0wt%的羧甲基纤维素钠的95%乙醇溶液和66.52wt%的糖浆;4)将阿莫西林和辅料混合,加入黏合剂溶液,置于高效湿法制粒机料斗内,封闭料箱,开启转桨和切刀低速搅切混合5分钟,停止搅切,加入95%乙醇适量,开启转桨搅拌和切刀,慢速搅切120秒,停止搅切,加入1%羧甲基纤维素钠浆,高速搅切至60秒时,从观察口中加入糖浆,高速搅切至180秒~240秒,用经清洗消毒的物料桶接收湿颗粒,再用YK-160型摇摆式颗粒机过14目筛网制粒;5)颗粒干燥:先在沸腾干燥机的干燥锅中加入一薄层已干燥好的颗粒,将制粒后的湿颗粒置沸腾干燥机中,将进风温度设定为55℃,进风温度显示在55±5℃(若进风温度显示在30秒内超出温度范围,视为在可接受范围内),将每锅约2/3量湿颗粒倒入锅内开启搅拌55℃预烘3分钟,颗粒稍成型后倒入每锅剩余量湿颗粒,开始计时,开启搅拌,烘干27分钟(开始、10min、20min、结束时各记录进风出风温度一次)。干燥结束取出颗粒;6)经55℃干燥后整粒,加香精总混。
对比例3
一种阿莫西林颗粒(作为参比制剂),其制备方法如下:1)称取阿莫西林,乳糖、甘露醇、甜菊甙、蔗糖、羧甲基纤维素钠备用;2)黏合剂溶液的配置:将聚维酮K30、尼泊金乙酯、柠檬黄、甜橙香精,置于80g的纯化水中搅拌溶解,配制粘合剂溶液;3)将阿莫西林、乳糖、甘露醇、蔗糖、羧甲基纤维素钠、甜菊甙投入湿法制粒机中,开启搅拌浆电机,搅拌混合时间10分钟;打开机盖,加入粘合剂溶液,制粒时间约3分钟;4)制粒完成后,打开出料活塞,点动搅拌浆将湿颗粒排出。湿颗粒用湿法造粒机制粒(筛网目数为16目);5)开动鼓风机将物料吸入沸腾干燥机内,进风温度设定在60℃±5℃,出风温度设定在50℃±5℃,物料温度≤55℃,干燥时间约25分钟;6)将M-1000型振荡筛装上16目和40目筛网,投料过筛,将大于16目的颗粒投入粉碎整粒机中,将整粒过的颗粒再次投入到振荡筛中,所收集的16目到40目颗粒;7)总混,袋装。
实验例4溶出度测定
将实施例1、实施例2、实施例3分别与参考例1、参考例2、参考例3的样品于水、pH1.2盐酸溶液、pH4.0醋酸盐缓冲液、pH6.8磷酸盐缓冲液中进行溶出度比较,溶出度分别由如下表1、表2、表3和表4所示。
表1水中溶出度对比
时间(min) | 10 | 20 | 30 | 40 | 50 | 60 |
对比例1溶出率(%) | 25.2 | 48.1 | 68.5 | 75.1 | 88.3 | 93.6 |
对比例2溶出率(%) | 30.2 | 50.0 | 65.3 | 73.6 | 86.2 | 92.5 |
对比例3溶出率(%) | 28.4 | 46.0 | 58.6 | 76.5 | 89.0 | 95.6 |
实施例1 | 33.5 | 52.6 | 70.0 | 82.3 | 90.2 | 99.1 |
实施例2 | 31.1 | 55.6 | 72.4 | 84.0 | 91.3 | 98.9 |
实施例3 | 32.6 | 51.6 | 69.8 | 78.4 | 89.2 | 98.1 |
表2pH1.2盐酸溶液溶出度对比
时间(min) | 10 | 20 | 30 | 40 | 50 | 60 |
对比例1溶出率(%) | 23.2 | 45.1 | 66.0 | 72.1 | 84.7 | 94.5 |
对比例2溶出率(%) | 28.1 | 47.6 | 63.4 | 70.5 | 85.2 | 95.3 |
对比例3溶出率(%) | 32.1 | 49.2 | 67.6 | 78.5 | 88.0 | 93.7 |
实施例1 | 35.2 | 53.5 | 71.2 | 84.3 | 89.8 | 99.5 |
实施例2 | 33.2 | 51.3 | 73.7 | 82.6 | 90.3 | 98.5 |
实施例3 | 32.3 | 54.5 | 71.8 | 79.8 | 88.9 | 98.7 |
表3pH4.0醋酸盐缓冲液溶出度对比
时间(min) | 15 | 25 | 35 | 45 |
对比例1溶出率(%) | 41.2 | 68.6 | 82.4 | 95.1 |
对比例2溶出率(%) | 43.6 | 70.2 | 85.7 | 92.2 |
对比例3溶出率(%) | 43.1 | 71.3 | 86.5 | 94.5 |
实施例1 | 51.3 | 78.6 | 88.2 | 99.8 |
实施例2 | 50.2 | 75.6 | 87.7 | 98.9 |
实施例3 | 52.0 | 77.4 | 86.9 | 98.8 |
表4pH6.8磷酸盐缓冲液溶出度对比
时间(min) | 15 | 25 | 35 | 45 |
对比例1溶出率(%) | 42.3 | 69.8 | 84.2 | 95.8 |
对比例2溶出率(%) | 44.5 | 72.2 | 86.5 | 93.4 |
对比例3溶出率(%) | 45.3 | 73.1 | 88.5 | 95.2 |
实施例1 | 53.4 | 79.3 | 90.0 | 99.8 |
实施例2 | 52.1 | 76.5 | 88.9 | 99.1 |
实施例3 | 52.3 | 78.2 | 87.5 | 99.0 |
由以上表格可知,通过实施例1、实施例2、实施例3的方法所制备的样品相对于对比例1、对比例2、对比例3中所制备的样品来讲溶出速度明显提高,由此可看出,本发明所制备的产品的溶解度和溶出速率都有所增加,提高了生物的利用度。
虽然本发明已利用上述较佳实施例进行说明,但其并非用以限定本发明的保护范围,任何本领域技术人员在不脱离本发明的精神和范围之内,相对上述实施例进行各种变动与修改仍属于本发明所保护的范围。
Claims (10)
1.一种阿莫西林颗粒的制备方法,其特征在于,具体包括以下步骤:
S1:将阿莫西林原料用气流粉碎机粉碎,过120目筛后备用;
S2:取步骤S1所得的阿莫西林原料溶于适量的水中,得到阿莫西林水溶液,再将泊洛沙姆溶于阿莫西林水溶液中,或者将泊洛沙姆加热至完全熔融后,加入阿莫西林原料,搅拌混合均匀;
S3:将步骤S2所得溶液进行减压干燥、粉碎,即得阿莫西林固体分散体;
S4:取步骤S3所得的阿莫西林固体分散体与填充剂混合均匀,然后加入粘合剂在湿法制粒机中制备软材,过35-50目筛制粒;
S5:将步骤S4中的湿颗粒置于沸腾干燥机进行烘干;
S6:烘干后用35-50目筛进行整粒,得到干颗粒;
S7:将步骤S6所得的干颗粒中加入甜味剂、助流剂,通过三维运动混合机混合均匀,即得阿莫西林颗粒,将上述颗粒分装为0.125克或0.25克/每单位剂量的包装,用铝塑复合膜进行包装。
2.根据权利要求1所述的一种阿莫西林颗粒的制备方法,其特征在于,所述泊洛沙姆为泊洛沙姆124、泊洛沙姆188、泊洛沙姆237、泊洛沙姆338、泊洛沙姆407中的一种。
3.根据权利要求1所述的一种阿莫西林颗粒的制备方法,其特征在于,所述步骤S5中沸腾干燥机温度为40-50℃,干燥水分控制1%以下。
4.根据权利要求1所述的一种阿莫西林颗粒的制备方法,其特征在于,以质量百分含量计,其各组分的用量为:阿莫西林固体分散体20%-30%、填充剂70%-80%、粘合剂1%-1.5%、甜味剂0.5%-1.5%、助流剂0.05%-0.25%。
5.根据权利要求4所述的一种阿莫西林颗粒的制备方法,其特征在于,所述填充剂为乳糖、微晶纤维素、蔗糖、甘露醇中的一种或几种的混合。
6.根据权利要求5所述的一种阿莫西林颗粒的制备方法,其特征在于,
所述填充剂为乳糖和微晶纤维素按照质量比为5-6:1的比例组成。
7.根据权利要求4所述的一种阿莫西林颗粒的制备方法,其特征在于,所述粘合剂为羟丙基纤维素、聚乙烯吡咯烷酮、丙烯酸乙酯-甲基丙烯酸甲酯共聚物水分散体中的一种或几种的混合。
8.根据权利要求7所述的一种阿莫西林颗粒的制备方法,其特征在于,所述粘合剂按质量比为聚乙烯吡咯烷酮:乙醇:纯化水=8:2:90的比例配制成质量体积百分含量为8%的聚乙烯吡咯烷酮溶液。
9.根据权利要求4所述的一种阿莫西林颗粒的制备方法,其特征在于,所述甜味剂为甜菊苷、糖精钠、阿斯巴甜中的一种或两种的混合。
10.根据权利要求4所述的一种阿莫西林颗粒的制备方法,其特征在于,所述助流剂为二氧化硅。
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