CN102000026A - Naproxen orally-taken micro-emulsion preparation and preparation method thereof - Google Patents
Naproxen orally-taken micro-emulsion preparation and preparation method thereof Download PDFInfo
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- CN102000026A CN102000026A CN 201010530797 CN201010530797A CN102000026A CN 102000026 A CN102000026 A CN 102000026A CN 201010530797 CN201010530797 CN 201010530797 CN 201010530797 A CN201010530797 A CN 201010530797A CN 102000026 A CN102000026 A CN 102000026A
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- naproxen
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- microemulsion
- oil
- oral
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- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 title claims abstract description 67
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 title claims abstract description 67
- 229960002009 naproxen Drugs 0.000 title claims abstract description 67
- 239000004530 micro-emulsion Substances 0.000 title claims abstract description 66
- 238000002360 preparation method Methods 0.000 title claims abstract description 45
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 34
- 239000003995 emulsifying agent Substances 0.000 claims abstract description 18
- 239000008215 water for injection Substances 0.000 claims abstract description 15
- 239000003921 oil Substances 0.000 claims description 40
- 238000003756 stirring Methods 0.000 claims description 21
- 239000007957 coemulsifier Substances 0.000 claims description 11
- 239000000203 mixture Substances 0.000 claims description 10
- DNIAPMSPPWPWGF-UHFFFAOYSA-N propylene glycol Substances CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 10
- 230000001954 sterilising effect Effects 0.000 claims description 10
- 238000004659 sterilization and disinfection Methods 0.000 claims description 10
- 210000004907 gland Anatomy 0.000 claims description 9
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 claims description 8
- 229940068918 polyethylene glycol 400 Drugs 0.000 claims description 8
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 7
- -1 polyoxyethylene Polymers 0.000 claims description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 6
- 125000005456 glyceride group Chemical group 0.000 claims description 6
- ZEMPKEQAKRGZGQ-AAKVHIHISA-N 2,3-bis[[(z)-12-hydroxyoctadec-9-enoyl]oxy]propyl (z)-12-hydroxyoctadec-9-enoate Chemical class CCCCCCC(O)C\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CC(O)CCCCCC)COC(=O)CCCCCCC\C=C/CC(O)CCCCCC ZEMPKEQAKRGZGQ-AAKVHIHISA-N 0.000 claims description 5
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims description 5
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 claims description 4
- OIQOAYVCKAHSEJ-UHFFFAOYSA-N 2-[2,3-bis(2-hydroxyethoxy)propoxy]ethanol;hexadecanoic acid;octadecanoic acid Chemical compound OCCOCC(OCCO)COCCO.CCCCCCCCCCCCCCCC(O)=O.CCCCCCCCCCCCCCCCCC(O)=O OIQOAYVCKAHSEJ-UHFFFAOYSA-N 0.000 claims description 4
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 claims description 4
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 claims description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- 239000005642 Oleic acid Substances 0.000 claims description 4
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 claims description 4
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 4
- 239000002202 Polyethylene glycol Substances 0.000 claims description 4
- 229920002685 Polyoxyl 35CastorOil Polymers 0.000 claims description 4
- 238000009472 formulation Methods 0.000 claims description 4
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 claims description 4
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 4
- QUANRIQJNFHVEU-UHFFFAOYSA-N oxirane;propane-1,2,3-triol Chemical compound C1CO1.OCC(O)CO QUANRIQJNFHVEU-UHFFFAOYSA-N 0.000 claims description 4
- 239000008389 polyethoxylated castor oil Substances 0.000 claims description 4
- 229920001223 polyethylene glycol Polymers 0.000 claims description 4
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 claims description 3
- 239000003963 antioxidant agent Substances 0.000 claims description 3
- 230000003078 antioxidant effect Effects 0.000 claims description 3
- 230000001804 emulsifying effect Effects 0.000 claims description 3
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 claims description 3
- 229940093471 ethyl oleate Drugs 0.000 claims description 3
- 238000007731 hot pressing Methods 0.000 claims description 3
- 238000007689 inspection Methods 0.000 claims description 3
- 238000000034 method Methods 0.000 claims description 3
- 239000005426 pharmaceutical component Substances 0.000 claims description 3
- JQWAHKMIYCERGA-UHFFFAOYSA-N (2-nonanoyloxy-3-octadeca-9,12-dienoyloxypropoxy)-[2-(trimethylazaniumyl)ethyl]phosphinate Chemical compound CCCCCCCCC(=O)OC(COP([O-])(=O)CC[N+](C)(C)C)COC(=O)CCCCCCCC=CCC=CCCCCC JQWAHKMIYCERGA-UHFFFAOYSA-N 0.000 claims description 2
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 claims description 2
- JVKUCNQGESRUCL-UHFFFAOYSA-N 2-Hydroxyethyl 12-hydroxyoctadecanoate Chemical compound CCCCCCC(O)CCCCCCCCCCC(=O)OCCO JVKUCNQGESRUCL-UHFFFAOYSA-N 0.000 claims description 2
- 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 claims description 2
- 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 claims description 2
- DCXXMTOCNZCJGO-UHFFFAOYSA-N Glycerol trioctadecanoate Natural products CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 0.000 claims description 2
- 229920001304 Solutol HS 15 Polymers 0.000 claims description 2
- NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 claims description 2
- NWGKJDSIEKMTRX-BFWOXRRGSA-N [(2r)-2-[(3r,4s)-3,4-dihydroxyoxolan-2-yl]-2-hydroxyethyl] (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)C1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-BFWOXRRGSA-N 0.000 claims description 2
- LDVVMCZRFWMZSG-UHFFFAOYSA-N captan Chemical compound C1C=CCC2C(=O)N(SC(Cl)(Cl)Cl)C(=O)C21 LDVVMCZRFWMZSG-UHFFFAOYSA-N 0.000 claims description 2
- 239000004359 castor oil Substances 0.000 claims description 2
- 235000019438 castor oil Nutrition 0.000 claims description 2
- 239000000306 component Substances 0.000 claims description 2
- FMMOOAYVCKXGMF-MURFETPASA-N ethyl linoleate Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(=O)OCC FMMOOAYVCKXGMF-MURFETPASA-N 0.000 claims description 2
- 229940031016 ethyl linoleate Drugs 0.000 claims description 2
- 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
- FMMOOAYVCKXGMF-UHFFFAOYSA-N linoleic acid ethyl ester Natural products CCCCCC=CCC=CCCCCCCCC(=O)OCC FMMOOAYVCKXGMF-UHFFFAOYSA-N 0.000 claims description 2
- 229920001993 poloxamer 188 Polymers 0.000 claims description 2
- 229940044519 poloxamer 188 Drugs 0.000 claims description 2
- 229920001992 poloxamer 407 Polymers 0.000 claims description 2
- 229940044476 poloxamer 407 Drugs 0.000 claims description 2
- 239000000600 sorbitol Substances 0.000 claims description 2
- 239000008347 soybean phospholipid Substances 0.000 claims description 2
- PHYFQTYBJUILEZ-IUPFWZBJSA-N triolein Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CCCCCCCC)COC(=O)CCCCCCC\C=C/CCCCCCCC PHYFQTYBJUILEZ-IUPFWZBJSA-N 0.000 claims description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims 1
- 229920000053 polysorbate 80 Polymers 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 7
- 229940079593 drug Drugs 0.000 abstract description 3
- 238000010579 first pass effect Methods 0.000 abstract description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 abstract description 3
- 210000004185 liver Anatomy 0.000 abstract description 3
- 210000001365 lymphatic vessel Anatomy 0.000 abstract description 3
- 238000011068 loading method Methods 0.000 abstract description 2
- 241000198210 Epithele Species 0.000 abstract 1
- 210000000170 cell membrane Anatomy 0.000 abstract 1
- 239000004615 ingredient Substances 0.000 abstract 1
- 229920002521 macromolecule Polymers 0.000 abstract 1
- 230000000144 pharmacologic effect Effects 0.000 abstract 1
- 238000002156 mixing Methods 0.000 description 12
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 8
- 235000010265 sodium sulphite Nutrition 0.000 description 4
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 230000002496 gastric effect Effects 0.000 description 3
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 3
- 229920000136 polysorbate Polymers 0.000 description 3
- 239000000811 xylitol Substances 0.000 description 3
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 3
- 229960002675 xylitol Drugs 0.000 description 3
- 235000010447 xylitol Nutrition 0.000 description 3
- 229940121363 anti-inflammatory agent Drugs 0.000 description 2
- 239000002260 anti-inflammatory agent Substances 0.000 description 2
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 210000001842 enterocyte Anatomy 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 2
- 235000010262 sodium metabisulphite Nutrition 0.000 description 2
- 230000004206 stomach function Effects 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 238000013271 transdermal drug delivery Methods 0.000 description 2
- 206010070840 Gastrointestinal tract irritation Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 229920002690 Polyoxyl 40 HydrogenatedCastorOil Polymers 0.000 description 1
- 230000000146 antalgic effect Effects 0.000 description 1
- 229940114079 arachidonic acid Drugs 0.000 description 1
- 235000021342 arachidonic acid Nutrition 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000000820 nonprescription drug Substances 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 239000013037 reversible inhibitor Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- RZWIIPASKMUIAC-VQTJNVASSA-N thromboxane Chemical compound CCCCCCCC[C@H]1OCCC[C@@H]1CCCCCCC RZWIIPASKMUIAC-VQTJNVASSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention relates to an orally-taken micro-emulsion preparation and a preparation method thereof, in particular a naproxen orally-taken micro-emulsion preparation and a preparation method thereof, belonging to the technical field of medicines. The orally-taken micro-emulsion preparation uses naproxen as the main pharmacological ingredient and contains medicinal oil, emulsifier, assistant emulsifier and water for injection. The naproxen orally-taken micro-emulsion preparation is orally administrated and has clear appearance; the grain diameter evenly ranges within 10nm-100nm; all phase are of the same property and have thermodynamic stability; the medicine loading rate ranges from 0.0%-3.5%; the preparation process is simple; and the quality is stable and can be easily controlled. The naproxen prepared into the orally-taken micro-emulsion preparation can be absorbed through lymphatic vessels as a result of lower surface tension of the micro-emulsion, therefore, the first-pass effect of the liver and obstacles for macromolecule to pass through the gastrointestinal tract epithele cell membranes can be overcome.
Description
Technical field
The present invention relates to oral microemulsion of a kind of technical field of pharmaceuticals and preparation method thereof, particularly relate to a kind of naproxen oral microemulsion preparation and preparation method thereof.
Background technology
Naproxen, chemistry (+) Alpha-Methyl by name-6-methoxyl group-2-naphthalene acetic acid is a kind of fragrant propionic non-steroid antipyretic-antalgic anti-inflammatory agent of being succeeded in developing by U.S. Xin Disi drugmaker (Syntex Co.).Naproxen is the reversible inhibitor of Cycloxygenase, works by the arachidonic acid that suppresses Cycloxygenase mediation conversion plain to thromboxane and various prostaglandins.Its chemical structural formula is as follows:
Naproxen is because hot antalgic and inflammation relieving is respond well, and untoward reaction is little, and existing worldwide extensive use becomes one of global topmost antipyretic-antalgic anti-inflammatory agent and nonprescription drugs.Because oral administration is convenient, dosage is easy to control, is the most frequently used clinically route of administration, so naproxen is mainly oral administration in clinical practice.The main dosage form of naproxen administration at present comprises: tablet, capsule, suppository, enteric-coated pellet capsule, drop pill [.CN1939293A such as Shen Lingjia, 2007], the gel transdermal drug-delivery preparation [Xu Zhen etc. the Chinese Hospitals pharmaceutical journal, 2009,29 (19): 1636-1638], transdermal patch [Hu Jinhong, Chen Yan .CN1387842A, 2003] etc.Because naproxen is almost insoluble in water, biological half-life is short, and oral administration dosage is big, so gastrointestinal side effect in various degree can occur behind the oral administration, kidney and heart are also had certain toxicity, and bioavailability is low.Naproxen is made slow releasing preparation or enteric coated preparation can alleviate gastrointestinal side effect, but because production process adopts the method for coating more, so preparation process is more loaded down with trivial details relatively; Make conventional tablet and capsule, oral administration artifact availability is not high; Make suppository administration inconvenience; It is simple to make the drop pill preparation, but the medicament contg instability; Gel transdermal drug-delivery preparation and transdermal patch use inconvenience, easy pollution clothes, and onset is slow.Therefore, develop that the naproxen oral formulations is particularly outstanding safely and efficiently.
Summary of the invention
The objective of the invention is provides a kind of naproxen oral microemulsion preparation and preparation method thereof for overcoming above-mentioned the deficiencies in the prior art part.The present invention be with naproxen as main pharmaceutical component, and contain medicinal oil, emulsifying agent, help emulsifying, the microemulsion formulation of water for injection preparation.Naproxen oral microemulsion preparation route of administration of the present invention is an oral administration, the outward appearance clarification, and particle diameter is evenly distributed on 10nm-100nm, and each homogeny and Thermodynamically stable, drug loading are 0.0%-3.5%, and preparation technology is simple, steady quality and control easily.After naproxen is prepared into the administration of oral microemulsion preparation,, can absorb, so the obstacle can overcome the first pass effect of liver and macromole by the gastrointestinal tract epithelial cell film time through lymphatic vessel because the surface tension of microemulsion is lower.In addition, naproxen oral microemulsion preparation makes directly stomach function regulating enterocyte contact of naproxen, thereby alleviate naproxen gastrointestinal is stimulated, and improves the oral bioavailability of naproxen; Simultaneously, the hydrophobic drug naproxen is made the microemulsion oral drug-supplying system, also be fit to the child or take because of can not the swallow patient of solid dosage medicine of all physiology and pathology reason.Therefore, naproxen oral microemulsion preparation has broad application prospects.
The present invention realizes with following technical scheme: a kind of naproxen oral microemulsion preparation, described naproxen oral microemulsion preparation with naproxen as main pharmaceutical component, and contain medicinal oil, emulsifying agent, help emulsifying, the microemulsion of water for injection preparation, it is characterized in that: the weight/volume percent of this each component of microemulsion formulation (W/V) is:
Naproxen 0.0%-3.5%
Medicinal oil 0.0%-15.0%
Emulsifying agent 10.0%-40.0%
Co-emulsifier 0.5%-20.0%
All the other are water for injection.
Described medicinal oil is ethyl oleate, olein, Ethyl linoleate, oleic acid polyethyleneglycol glyceride (Labrafil M 1944 CS), chain length C
6-C
12Between one or more of the fatty glyceride of medium chain such as Arlacel 80, Arlacel 86, Captex 355 (oil), Myvacet (oil), median chain triglyceride oil.
Described emulsifying agent is soybean phospholipid, egg yolk lecithin, poloxamer 188 (F68), poloxamer 407, tell 80, in the polysorbas20, polyoxyethylene castor oil (Cremophor EL), polyoxyethylene hydrogenated Oleum Ricini (Cremophor RH40), polyethyleneglycol-12-hydroxy stearin (Solutol HS 15) one or more.
Described co-emulsifier is an ethanol, 1, one or more in 2-propylene glycol, Polyethylene Glycol-400 (PEG-400), sorbitol, glycerol, the TC.
A kind of method for preparing a kind of naproxen oral microemulsion preparation as claimed in claim 1 is characterized in that comprising the steps:
(1) gets recipe quantity emulsifying agent, co-emulsifier and medicinal oil, mix, make oil phase;
(2) get the recipe quantity naproxen and be added in the oil phase and mix, make evenly, standby;
(3) recipe quantity correctives, antioxidant are dissolved in the water for injection, make water, standby;
(4) water is slowly joined in the oil phase, stir, filter and make microemulsion;
(5) microemulsion qualified on inspection after, fill is jumped a queue, gland; The hot pressing steam sterilization promptly gets naproxen oral microemulsion preparation.
Be optimized for:
(1) gets recipe quantity emulsifying agent, co-emulsifier and medicinal oil, mix in 25 ℃, make oil phase;
(2) get the recipe quantity naproxen and be added in the oil phase and mix, make evenly, standby;
(3) recipe quantity correctives, antioxidant are dissolved in 25 ℃ the water for injection, make water, standby;
(4) water is slowly joined in the oil phase, stir, filter and make microemulsion;
(5) microemulsion qualified on inspection after, fill is jumped a queue, gland; The hot pressing steam sterilization, 121 ℃ of sterilization 15min promptly get naproxen oral microemulsion preparation.
Advantage of the present invention is: naproxen oral microemulsion preparation production process is simple, steady quality is easily controlled, can absorb through lymphatic vessel after oral, obstacle in the time of can overcoming the first pass effect of liver and macromole by the gastrointestinal tract epithelial cell film, make directly stomach function regulating enterocyte contact of naproxen, thereby alleviate naproxen to GI irritation, improve the oral bioavailability of naproxen, and have the curative effect of increasing, reduce toxic characteristic.Therefore, naproxen oral microemulsion preparation has broad application prospects.
The specific embodiment
Below by embodiment the present invention is described in further detail:
Embodiment 1,
Get naproxen 1.8g, median chain triglyceride oil 8.0g, emulsifier tween 8030.0g and co-emulsifier Polyethylene Glycol-400 (PEG-400) 10.0g are heated to 25 ℃ of stirring and evenly mixings, get oil phase; Measure water for injection 55.0ml, sodium sulfite 66.7mg, xylitol 69.0mg stirs and makes dissolving, is heated to 25 ℃, gets water.The stirring and evenly mixing under 25 ℃ of temperature with oil phase and water filters and makes microemulsion, and fill is jumped a queue, gland, and 121 ℃ of sterilization 15min get the naproxen oral microemulsion.This microemulsion mean diameter is (38.6 ± 2.0) nm, and naproxen content is 1.77% (W/V), and all other indexs meet medicinal oral microemulsion requirement.
Embodiment 2,
Get naproxen 1.0g, median chain triglyceride oil 5.0g, emulsifier tween 8022.5g and 1,2-propylene glycol 7.5g is heated to 25 ℃ of stirring and evenly mixings, gets oil phase; Measure water for injection 70.0ml, sodium sulfite 69.6mg, A Si BATANG 87.00mg stirs and makes dissolving, is heated to 25 ℃, gets water.The stirring and evenly mixing under 25 ℃ of temperature with oil phase and water filters and makes microemulsion, and fill is jumped a queue, gland, and 121 ℃ of sterilization 15min get the naproxen oral microemulsion.This microemulsion mean diameter is (19.0 ± 2.1) nm, and naproxen content is 0.99% (W/V), and all other indexs meet medicinal oral microemulsion requirement.
Embodiment 3,
Get naproxen 1.0g, oleic acid polyethyleneglycol glyceride (Labrafil M 1944CS) 6.0g, emulsifier polyoxyethylene Oleum Ricini (Cremophor EL) 16.0g and co-emulsifier 1,2-propylene glycol 8.0g is heated to 25 ℃ of stirring and evenly mixings, gets oil phase; Measure water for injection 75.0ml, sodium pyrosulfite 75.0mg, xylitol 80.0mg stirs and makes dissolving, is heated to 25 ℃, gets water.The stirring and evenly mixing under 25 ℃ of temperature with oil phase and water filters and makes microemulsion, and fill is jumped a queue, gland, and 121 ℃ of sterilization 15min get the naproxen oral microemulsion.This microemulsion mean diameter is (29.8 ± 1.5) nm, and naproxen content is 0.96% (W/V), and all other indexs meet medicinal oral microemulsion requirement.
Embodiment 4,
Get naproxen 1.40g, oleic acid polyethyleneglycol glyceride (Labrafil M 1944CS) 7.5g, emulsifier polyoxyethylene Oleum Ricini (Cremophor EL) 18.0g and co-emulsifier 1,2-propylene glycol 9.0g is heated to 25 ℃ of stirring and evenly mixings, gets oil phase; Measure water for injection 70.0ml, sodium pyrosulfite 70.0mg, A Si BATANG 84.0mg stirs and makes dissolving, is heated to 25 ℃, gets water.The stirring and evenly mixing under 25 ℃ of temperature with oil phase and water filters and makes microemulsion, and fill is jumped a queue, gland, and 121 ℃ of sterilization 15min get the naproxen oral microemulsion.This microemulsion mean diameter is (32.0 ± 0.8) nm, and naproxen content is 1.36% (W/V), and all other indexs meet medicinal oral microemulsion requirement.
Embodiment 5,
Get naproxen 1.6g, ethyl oleate 9.0g, emulsifier tween 8025.0g and 1,2-propylene glycol 13.0g is heated to 25 ℃ of stirring and evenly mixings, gets oil phase; Measure water for injection 65.0ml, sodium sulfite 68.90mg, A Si BATANG 79.6mg stirs and makes dissolving, is heated to 25 ℃, gets water.The stirring and evenly mixing under 25 ℃ of temperature with oil phase and water filters and makes microemulsion, and fill is jumped a queue, gland, and 121 ℃ of sterilization 15min get the naproxen oral microemulsion.This microemulsion mean diameter is (36.5 ± 2.1) nm, and naproxen content is 1.56% (W/V), and all other indexs meet medicinal oral microemulsion requirement.
Embodiment 6,
Get naproxen 0.53g, median chain triglyceride oil 4.5g, emulsifier polyoxyethylene Oleum Ricini (CremophorELP) 20.25g and co-emulsifier Polyethylene Glycol-400 (PEG-400) 6.75g are heated to 25 ℃ of stirring and evenly mixings, get oil phase; Measure water for injection 75.0ml, sodium sulfite 59.4mg, xylitol 120.0mg stirs and makes dissolving, is heated to 25 ℃, gets water.The stirring and evenly mixing under 25 ℃ of temperature with oil phase and water filters and makes microemulsion, and fill is jumped a queue, gland, and 121 ℃ of sterilization 15min get the naproxen oral microemulsion.This microemulsion mean diameter is (27.8 ± 1.0) nm, and naproxen content is 0.52% (W/V), and all other indexs meet medicinal oral microemulsion requirement.
Claims (5)
1. naproxen oral microemulsion preparation, described naproxen oral microemulsion preparation with naproxen as main pharmaceutical component, and contain medicinal oil, emulsifying agent, help emulsifying, the microemulsion of water for injection preparation, it is characterized in that: the weight/volume percent of this each component of microemulsion formulation (W/V) is:
Naproxen 0.0%-3.5%
Medicinal oil 0.0%-15.0%
Emulsifying agent 10.0%-40.0%
Co-emulsifier 0.5%-20.0%
All the other are water for injection.
2. a kind of naproxen oral microemulsion preparation according to claim 1 is characterized in that: described medicinal oil is ethyl oleate, olein, Ethyl linoleate, oleic acid polyethyleneglycol glyceride (Labrafil M1944CS), chain length C
6-C
12Between in the fatty glyceride of medium chain such as Arlacel 80, Arlacel 86, Captex 355 (oil), Myvacet (oil), the median chain triglyceride oil one or more.
3. a kind of naproxen oral microemulsion preparation according to claim 1 is characterized in that: described emulsifying agent is one or more in soybean phospholipid, egg yolk lecithin, poloxamer 188 (F68), poloxamer 407, Tween 80, polysorbas20, polyoxyethylene castor oil (Cremophor EL), polyoxyethylene hydrogenated Oleum Ricini (CremophorRH40), the polyethyleneglycol-12-hydroxy stearin (Solutol HS 15).
4. a kind of naproxen oral microemulsion preparation according to claim 1, it is characterized in that: described co-emulsifier is an ethanol, 1, one or more in 2-propylene glycol, Polyethylene Glycol-400 (PEG-400), sorbitol, glycerol, the TC.
5. a method for preparing a kind of naproxen oral microemulsion preparation as claimed in claim 1 is characterized in that comprising the steps:
(1) gets recipe quantity emulsifying agent, co-emulsifier and medicinal oil, mix, make oil phase;
(2) get the recipe quantity naproxen and be added in the oil phase and mix, make evenly, standby;
(3) recipe quantity correctives, antioxidant are dissolved in the water for injection, make water, standby;
(4) water is slowly joined in the oil phase, stir, filter and make microemulsion;
(5) microemulsion qualified on inspection after, fill is jumped a queue, gland; The hot pressing steam sterilization promptly gets naproxen oral microemulsion preparation.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102793700A (en) * | 2012-08-29 | 2012-11-28 | 郑州后羿制药有限公司 | Compound oil emulsion injection containing flumequine and preparation method thereof |
| CN105343002A (en) * | 2015-11-27 | 2016-02-24 | 济南康和医药科技有限公司 | Etoricoxib oral microemulsion preparation and preparation method thereof |
| CN109044971A (en) * | 2018-07-25 | 2018-12-21 | 浙江中医药大学 | A kind of hydroxyl carthamin yellow A-containing self-micro emulsion formulation and preparation method thereof |
| CN109464670A (en) * | 2017-09-08 | 2019-03-15 | 中国科学院微生物研究所 | Key amino acid sites regulating nuclear export of influenza A and B virus nucleoproteins and their use as anti-influenza virus drug targets |
| CN111184725A (en) * | 2020-02-27 | 2020-05-22 | 慈溪市人民医院医疗健康集团(慈溪市人民医院) | Medicinal preparation for preventing and treating cerebral infarction and preparation method thereof |
| CN114642635A (en) * | 2020-12-18 | 2022-06-21 | 北京远大九和药业有限公司 | Oral emulsion of terpene medicinal composition, its preparation method and application |
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| CN1985802A (en) * | 2006-12-14 | 2007-06-27 | 广州中医药大学 | Cnidiadin emulsion and its preparing method and application |
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| CN1338942A (en) * | 1998-12-11 | 2002-03-06 | 药品处理公司 | Self-emulsifying composition of poorly water-soluble drug |
| CN1985802A (en) * | 2006-12-14 | 2007-06-27 | 广州中医药大学 | Cnidiadin emulsion and its preparing method and application |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102793700A (en) * | 2012-08-29 | 2012-11-28 | 郑州后羿制药有限公司 | Compound oil emulsion injection containing flumequine and preparation method thereof |
| CN102793700B (en) * | 2012-08-29 | 2014-03-12 | 郑州后羿制药有限公司 | Compound oil emulsion injection containing flumequine and preparation method thereof |
| CN105343002A (en) * | 2015-11-27 | 2016-02-24 | 济南康和医药科技有限公司 | Etoricoxib oral microemulsion preparation and preparation method thereof |
| CN105343002B (en) * | 2015-11-27 | 2019-07-26 | 济南康和医药科技有限公司 | A kind of Etoricoxib oral microemulsion preparation and preparation method thereof |
| CN109464670A (en) * | 2017-09-08 | 2019-03-15 | 中国科学院微生物研究所 | Key amino acid sites regulating nuclear export of influenza A and B virus nucleoproteins and their use as anti-influenza virus drug targets |
| CN109044971A (en) * | 2018-07-25 | 2018-12-21 | 浙江中医药大学 | A kind of hydroxyl carthamin yellow A-containing self-micro emulsion formulation and preparation method thereof |
| CN111184725A (en) * | 2020-02-27 | 2020-05-22 | 慈溪市人民医院医疗健康集团(慈溪市人民医院) | Medicinal preparation for preventing and treating cerebral infarction and preparation method thereof |
| CN114642635A (en) * | 2020-12-18 | 2022-06-21 | 北京远大九和药业有限公司 | Oral emulsion of terpene medicinal composition, its preparation method and application |
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