CN107519134B - 一种热熔离心制备固体分散体的方法 - Google Patents
一种热熔离心制备固体分散体的方法 Download PDFInfo
- Publication number
- CN107519134B CN107519134B CN201710623367.2A CN201710623367A CN107519134B CN 107519134 B CN107519134 B CN 107519134B CN 201710623367 A CN201710623367 A CN 201710623367A CN 107519134 B CN107519134 B CN 107519134B
- Authority
- CN
- China
- Prior art keywords
- solid dispersion
- medicine
- powder
- water
- centrifugation
- 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.)
- Active
Links
- 239000007962 solid dispersion Substances 0.000 title claims abstract description 51
- 238000000034 method Methods 0.000 title claims abstract description 34
- 238000002844 melting Methods 0.000 title claims abstract description 19
- 230000008018 melting Effects 0.000 title claims abstract description 14
- 238000005119 centrifugation Methods 0.000 title abstract description 11
- 239000003814 drug Substances 0.000 claims abstract description 44
- 239000000843 powder Substances 0.000 claims abstract description 35
- 229940079593 drug Drugs 0.000 claims abstract description 23
- 239000012876 carrier material Substances 0.000 claims abstract description 8
- 239000002198 insoluble material Substances 0.000 claims abstract description 4
- 238000002156 mixing Methods 0.000 claims abstract description 4
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 claims description 4
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 claims description 4
- 235000021355 Stearic acid Nutrition 0.000 claims description 3
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 3
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 3
- 239000008117 stearic acid Substances 0.000 claims description 3
- 239000000263 2,3-dihydroxypropyl (Z)-octadec-9-enoate Substances 0.000 claims description 2
- RZRNAYUHWVFMIP-GDCKJWNLSA-N 3-oleoyl-sn-glycerol Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](O)CO RZRNAYUHWVFMIP-GDCKJWNLSA-N 0.000 claims description 2
- 229940075507 glyceryl monostearate Drugs 0.000 claims description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 claims description 2
- RZRNAYUHWVFMIP-UHFFFAOYSA-N monoelaidin Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC(O)CO RZRNAYUHWVFMIP-UHFFFAOYSA-N 0.000 claims description 2
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 claims description 2
- 239000012943 hotmelt Substances 0.000 abstract description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 9
- 238000004519 manufacturing process Methods 0.000 abstract description 6
- 239000003960 organic solvent Substances 0.000 abstract description 3
- 238000009776 industrial production Methods 0.000 abstract description 2
- 241001061264 Astragalus Species 0.000 description 15
- 235000006533 astragalus Nutrition 0.000 description 15
- 150000004676 glycans Chemical class 0.000 description 15
- 229920001282 polysaccharide Polymers 0.000 description 15
- 239000005017 polysaccharide Substances 0.000 description 15
- 210000004233 talus Anatomy 0.000 description 15
- HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 13
- 229960001597 nifedipine Drugs 0.000 description 13
- 229920001223 polyethylene glycol Polymers 0.000 description 11
- 239000002202 Polyethylene glycol Substances 0.000 description 10
- DJGAAPFSPWAYTJ-UHFFFAOYSA-M metamizole sodium Chemical compound [Na+].O=C1C(N(CS([O-])(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 DJGAAPFSPWAYTJ-UHFFFAOYSA-M 0.000 description 8
- 238000010521 absorption reaction Methods 0.000 description 7
- 238000009474 hot melt extrusion Methods 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 238000004090 dissolution Methods 0.000 description 6
- 238000000338 in vitro Methods 0.000 description 6
- 230000000694 effects Effects 0.000 description 5
- 239000002245 particle Substances 0.000 description 5
- 239000006069 physical mixture Substances 0.000 description 4
- 102000002151 Microfilament Proteins Human genes 0.000 description 3
- 108010040897 Microfilament Proteins Proteins 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000001186 cumulative effect Effects 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 210000003632 microfilament Anatomy 0.000 description 3
- 238000007873 sieving Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000007613 slurry method Methods 0.000 description 2
- 238000001694 spray drying Methods 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- 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 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- RCEAADKTGXTDOA-UHFFFAOYSA-N OS(O)(=O)=O.CCCCCCCCCCCC[Na] Chemical compound OS(O)(=O)=O.CCCCCCCCCCCC[Na] RCEAADKTGXTDOA-UHFFFAOYSA-N 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000016383 Zea mays subsp huehuetenangensis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 235000009973 maize Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 239000004570 mortar (masonry) Substances 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- -1 polyoxyethylene Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
Images
Classifications
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
- A61K31/4152—1,2-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. antipyrine, phenylbutazone, sulfinpyrazone
-
- 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
- A61K31/4422—1,4-Dihydropyridines, e.g. nifedipine, nicardipine
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Medicinal Preparation (AREA)
Abstract
本发明涉及一种热熔离心制备固体分散体的方法。包括下述步骤：将质量分数1%‑50%的药物与质量分数50‑99%的载体材料熔融混合，高速离心制备固体分散体粉末，其中，药物可以是水溶性药物、难溶性药物或易吸潮药物；载体材料可以是水溶性或水不溶性材料。本发明提供了一种热熔离心直接制备固体分散体的方法。本方法生产过程中无需使用有机溶剂和水为介质，无需后续粉碎操作，设备简单，环保高效，适于工业化生产。本方法在制备难溶性药物速释粉末和中药粉末防潮等领域有良好的应用前景。
Description
技术领域
本发明属于制药技术领域，具体涉及一种热熔离心制备固体分散体的方法。
背景技术
本课题组采用热熔离心法，经处方工艺优化，研制出了载药微丝（直径10μm-500μm），具有速释和缓释等多种功能。相关内容已申请发明专利（一种含药微丝及其制备方法，CN201610110161.5）。经大量实验，我们又发现，采用新的载体和药物，优化处方工艺，热熔离心法可进一步制备载药粉末。经检测药物在载体中高度分散，符合固体分散体特征，具有缓释、速释和防潮等特殊效果，尤其适用于提高难溶性药物溶解度和防止中药成份吸潮。
现有固体分散体常规制备方法主要是：溶剂-熔融法、喷雾干燥法和热熔挤出法。本发明的热熔离心法无需有机溶剂和水为介质，比溶剂-熔融法和喷雾干燥法环保节能和高效。本发明的热熔离心法可以直接制备固体分散体粉末，无需热熔挤出条状物后再次粉碎，生产设备简单生产效率更高。
发明内容
本发明的目的在于解决现有技术的不足，提供了一种固体分散体的制备方法。该方法可以直接制备固体分散体粉末，无需热熔挤出条状物后再次粉碎，生产设备简单生产效率更高。
本发明解决技术问题所采用的技术方案为：
一种固体分散体的制备方法，包括下述步骤：将质量分数1%-50%的药物与质量分数50-99%的载体材料熔融混合，高速离心制备固体分散体粉末，其中，药物可以是水溶性药物、难溶性药物或易吸潮药物；载体材料可以是水溶性或水不溶性材料。
作为优选，所述水溶性载体材料为果糖、半乳糖、木糖醇、乳糖、甘露醇、山梨醇、聚乙二醇类、泊洛沙姆类、卖泽类、聚氧乙烯蓖麻油类、枸橼酸、富马酸、酒石酸、琥珀酸和聚乙烯醇中的任意一种或多种。
作为优选，所述水不溶性材料为单硬脂酸甘油酯、硬脂酸、硬脂醇和单油酸甘油酯中一种或多种。
作为优选，药物与载体重量比为1:3-1:9。
作为优选，药物与载体的重量比为1:3-1:4，用于制备速释的固体分散体。
作为优选，药物与载体的重量比为1:4-1:5，用于制备防潮的固体分散体。
作为优选，熔融温度为40-150℃；离心转速为500-10000 r/min；离心孔径为10-500 μm；固体分散体粉末收集距离10-50 cm。
作为优选，熔融温度为60-80℃；离心转速为1000-1500 r/min；离心孔径为50-100μm, 收集距离为20-40cm。
本发明的有益效果为：
本发明提供了一种热熔离心直接制备固体分散体的方法。本方法生产过程中无需使用有机溶剂和水为介质，无需后续粉碎操作，设备简单，环保高效，适于工业化生产。本方法在制备难溶性药物速释粉末和中药粉末防潮等领域有良好的应用前景。
附图说明
图1药辅比对微观形态的影响，放大90倍
图2药辅比对溶出行为的影响
图3黄芪多糖固体分散体外观，放大90倍
图4 不同制剂吸湿48h后外观图
图 5 不同制剂的吸湿曲线
图6 不同制备方法对溶出行为的影响
图7安乃近固体分散体外观，放大90倍
图8安乃近固体分散体的溶出行为。
具体实施方式
为了使本发明的目的、技术方案及优点更加清楚明白，以下结合实施例对本发明进行进一步详细说明。应当理解，此处所描述的具体实施例仅用以解释本发明，并不用于限定本发明。
实施例1 硝苯地平速释固体分散体(难溶性药物/水溶性载体)
分别取1 g，2 g，3 g，4 g 聚乙二醇在90℃下熔融，分别加入1 g硝苯地平粉末，搅匀，在熔融状态下，快速离心转动，转速为1000 r/min，收集距离为10 cm，则得到硝苯地平：聚乙二醇分别为1:1，1:2，1:3，1:4的硝苯地平固体分散体粉末。显微外观如图1所示。
将上述硝苯地平固体分散体和原料药进行体外释放行为评价，采用浆法，介质为0.5% 的十二烷基硫酸钠溶液，转速75 r/min，介质量为500 mL，每杯试样相当于含药量25mg。定时取样10 mL，补液。取滤液采用分光光度法，于333 nm处测定吸光度，计算药物累计释放百分率，体外释放行为结果如图2所示。
结果显示：硝苯地平固体分散体的释放速率和最大释放百分率随着聚乙二醇含量的提高而提高，其中硝苯地平：聚乙二醇比例为1:4，1:3，1:2，1:1的硝苯地平固体分散体2h的释放百分率分别为89.62%，81.57%，72.05%，64.54%，原料药2 h的释放百分率为54.47%，说明熔融离心法制备的固体分散体粉末可以有效促进硝苯地平的溶出，有利于硝苯地平在体内的吸收。
实施例2 黄芪多糖防潮固体分散体(易吸潮药物/水溶性载体)
将4 g聚乙二醇在60 ℃下熔融后加入1 g黄芪多糖混匀，转动离心，转速为500 r/min，收集距离为20 cm，得到黄芪多糖固体分散体粉末，显微外观如图3所示。
分别称取0.5 g上述黄芪多糖固体分散体、黄芪多糖与聚乙二醇物理混合物（黄芪多糖与聚乙二醇比例为1:4）、黄芪多糖于称量瓶中，放置在湿度为75%，温度为25摄氏度环境中48 h。吸湿后黄芪多糖、物理混合物、固体分散体外观如图4。吸湿曲线如图5。
结果显示：24h后黄芪多糖吸湿率为13.26%，黄芪多糖与聚乙二醇物理混合物为6.33%，黄芪多糖固体分散体为4.44%。黄芪多糖和物理混合物均产生明显外观变化，而黄芪多糖固体分散体仍为粉末，无明显外观变化。说明黄芪多糖固体分散体能够有效产生防吸潮效用，利于存储和运输。
实施例3 热熔挤出固体分散体与热熔离心固体分散体（不同工艺差异）
取1 g硝苯地平与4 g聚乙二醇混合，采用热熔挤出法制备固体分散体。转速为60r/min，温度控制为70 ℃，挤出物冷却至室温，得到热熔挤出混合物。用研钵分次研磨1 h，过筛，得到热熔挤出固体分散体粉末。平均粒径为321μm，形态为不规则粉末。粉末产率为53.2%，粉末堆密度为1.25g/mL。
取4 g聚乙二醇在70℃下熔融，加入1 g硝苯地平粉末，搅匀，在熔融状态下，快速离心转动，转速为3000 r/min。收集距离为20 cm。过筛直接得热熔离心固体分散体粉末。粉末平均粒径为214μm，形态为类球形或椭球形。粉末产率为86.5%，粉末堆密度为0.94g/mL。同样的处方工艺，改变收集距离为50 cm。过筛直接得热熔离心固体分散体粉末,平均粒径159μm，形态为类球形或椭球形。粉末产率为80.3%，粉末堆密度为0.92g/mL。
分别将上述方法制备的热熔挤出硝苯地平固体分散体粉末、50cm收集距离的热熔离心固体分散体粉末和原料药进行体外释放行为评价。采用溶出仪浆法，介质为0.5% 的十二烷基硫酸钠溶液，转速75 r/min，介质为500 mL，每杯试样相当于含药量25 mg。定时取样10 mL，补液。取滤液采用分光光度法，于333 nm处测定吸光度，计算药物累计释放百分率，体外释放行为结果如图6所示：
结果显示：热熔挤出法与热熔离心法制备的固体分散体的溶出行为无明显差异，但与热熔挤出法相比，热熔离心法可以直接制备粉末状的固体分散体，且制备工艺更简单，平均粒径更细，过筛粉末产率更高，形态相对更接近球形。扩大收集距离，会得到更细更均匀的粉末，就与较大粒子在分离过程中易沉降有关。
实施例4 安乃近缓释固体分散体（水溶性药物/难溶性载体）
取9 g 硬脂酸在80℃下熔融，分别加入1 g安乃近粉末，搅匀，在熔融状态下，快速离心转动，转速为1500 r/min，收集距离为40 cm，则得到安乃近固体分散体粉末。显微外观如图7所示：将上述安乃近固体分散体和原料药进行体外释放行为评价，采用浆法，介质为500 mL纯化水，转速75 r/min，每杯试样相当于含药量5 mg。定时取样10 mL，补液。取滤液采用分光光度法，于258nm处测定吸光度，计算药物累计释放百分率，体外释放行为结果如图8所示：结果显示：安乃近原料药迅速释放，而安乃近的固体分散体在8h处才释放完全，表现出了缓释特性，说明可用热熔离心法制备粉末型的缓释固体分散体。
Claims (3)
1.一种固体分散体的制备方法，其特征在于，所述制备方法包括下述步骤：将质量分数l%-50%的药物与质量分数50-99%的载体材料熔融混合，高速离心制得 ，所述药物为水溶性药物或易吸潮药物；载体材料为水不溶性材料，所述水不溶性载体材料为单硬脂酸甘油酯、硬脂酸、硬脂醇和单油酸甘油酯中一种或多种，所述熔融温度为60-80℃；离心转速为1000-1500r/min；离心孔径为50-100μm；固体分散体粉末收集距离20-40cm。
2.根据权利要求1所述的一种固体分散体的制备方法，其特征在于，所述药物与载体的重量比为1:3-1:9。
3.根据权利要求1所述的一种固体分散体的制备方法，其特征在于，所述药物与载体的重量比为1:4-1:5，用于制备防潮的固体分散体。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710623367.2A CN107519134B (zh) | 2017-07-27 | 2017-07-27 | 一种热熔离心制备固体分散体的方法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710623367.2A CN107519134B (zh) | 2017-07-27 | 2017-07-27 | 一种热熔离心制备固体分散体的方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107519134A CN107519134A (zh) | 2017-12-29 |
| CN107519134B true CN107519134B (zh) | 2021-04-09 |
Family
ID=60680170
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710623367.2A Active CN107519134B (zh) | 2017-07-27 | 2017-07-27 | 一种热熔离心制备固体分散体的方法 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107519134B (zh) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111374968A (zh) * | 2018-12-27 | 2020-07-07 | 山东鲁抗医药股份有限公司 | 一种含达格列净的组合物及其制备方法和应用 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101732233B (zh) * | 2009-11-19 | 2011-07-27 | 浙江工业大学 | 一种固体分散体的制备方法 |
| CN102218019B (zh) * | 2011-06-17 | 2013-09-25 | 上海理工大学 | 高压静电喷雾制备疏水性药物纳米颗粒状固体分散体的方法 |
| CN105663025A (zh) * | 2016-02-29 | 2016-06-15 | 浙江工业大学 | 一种含药微丝及其制备方法 |
-
2017
- 2017-07-27 CN CN201710623367.2A patent/CN107519134B/zh active Active
Non-Patent Citations (1)
| Title |
|---|
| Physical and dissolution characterization of cilostazol solid dispersions prepared by hot melt granulation (HMG) and thermal adhesion granulation (TAG) methods;Ying C. C.，et al.;《International Journal of Pharmaceutics》;20140730;第473卷;第458-468页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107519134A (zh) | 2017-12-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Steckel et al. | Production of chitosan pellets by extrusion/spheronization | |
| Yu et al. | Sustained release of antineoplastic drugs from chitosan-reinforced alginate microparticle drug delivery systems | |
| Dukić et al. | Development of starch-based pellets via extrusion/spheronisation | |
| TW200825107A (en) | Low-substituted hydroxypropylcellulose powder and method for producing the same | |
| CN1698901A (zh) | 以壳聚糖及其衍生物作为药物载体负载丹参提取物 | |
| CN102488673B (zh) | 普罗布考纳米分散物及其制备方法 | |
| CN102850268A (zh) | 阿立哌唑ⅰ型微晶、阿立哌唑固体制剂及制备方法 | |
| CN104546666A (zh) | 一种非达霉素固体分散体及其制备方法 | |
| CN101851247B (zh) | 含有硫酸氢氯吡格雷晶体颗粒的组合物 | |
| CN104840430A (zh) | 一种绿原酸壳聚糖微球及其制备工艺和应用 | |
| CN115068424B (zh) | 一种纳米级破壁灵芝孢子粉制备方法及应用 | |
| CN104352441A (zh) | 一种富马酸二甲酯肠溶微丸及其制备方法 | |
| CN106511348B (zh) | 石杉碱甲骨架微粒、口崩片及其制备方法 | |
| CN107519134B (zh) | 一种热熔离心制备固体分散体的方法 | |
| Feng et al. | Comparison of the degradation and release behaviors of poly (lactide‐co‐glycolide)–methoxypoly (ethylene glycol) microspheres prepared with single‐and double‐emulsion evaporation methods | |
| CN103263418B (zh) | 一种双氢青蒿素磷酸哌喹片剂及其制备方法 | |
| CN111346055A (zh) | 一种青蒿素b聚合物胶束制剂及其制备与表征方法 | |
| CN113041220A (zh) | 一种以tpgs为载体的柚皮素纳米混悬剂及其制备方法与应用 | |
| CN101890008B (zh) | 一种阿莫西林钠舒巴坦钠药物组合物微球注射剂 | |
| CN101744772A (zh) | 一种制备兽用药物缓释微粒的方法 | |
| CN108542892B (zh) | 阿莫西林胶囊的制备方法 | |
| CN106389336A (zh) | 液晶纳米粒前体微粒、自组装液晶纳米粒及其制备方法 | |
| CN103536575B (zh) | 乙酰半胱氨酸组合物胶囊 | |
| CN106924192B (zh) | 一种中药颗粒剂及其制备方法 | |
| CN101890007B (zh) | 一种阿莫西林钠克拉维酸钾药物组合物微球注射剂 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |