CN102119926B - Valsartan self-emulsifying medicament transfer system and preparation method thereof - Google Patents
Valsartan self-emulsifying medicament transfer system and preparation method thereof Download PDFInfo
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- CN102119926B CN102119926B CN 201110053556 CN201110053556A CN102119926B CN 102119926 B CN102119926 B CN 102119926B CN 201110053556 CN201110053556 CN 201110053556 CN 201110053556 A CN201110053556 A CN 201110053556A CN 102119926 B CN102119926 B CN 102119926B
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Abstract
The invention relates to a valsartan self-emulsifying medicament transfer system and a preparation method thereof, belonging to the technical field of medicine. According to the valsartan self-emulsifying medicament transfer system, a liquid or (semi-) solid oil mixture formed from valsartan, an oil phase, a surfactant and a cosurfactant and an auxiliary component can form an emulsion in the gastrointestinal tract or under the conditions of ambient temperature and slight stirring. The preparation method comprises the following steps of: at the water bath temperature of 20-50 DEG C, stirring the mixture of prescribed amounts of oil, surfactant and cosurfactant to form an even settled solution, then adding a prescribed amount of valsartan, and stirring to dissolve the medicament. The invention has the advantages that the valsartan self-emulsifying medicament transfer system improves the oral bioavailability of valsartan, and the preparation process is simple and easy to realize industrialized production.
Description
Technical field
The invention belongs to medical technical field, be specifically related to a kind of valsartan self-emulsifying medicament transfer and preparation method.
Background technology
Valsartan is non-peptideangiotensinⅱ receptor antagonist of new generation, can stop the caused blood vessel of angiotensinⅡ to tighten up and aldosterone release, and is remarkable to the antihypertensive effect of light moderate essential hypertension.This medicine safety of clinical research confirmation is good, and blood pressure lowering is steady, curative effect is strong, long action time, and patient tolerability is good, has been widely used in treating at present hypertension in the whole world.
The valsartan dosage form of listing is more single at present, mainly be capsule and tablet, because valsartan is the Equations of The Second Kind that belongs in the biopharmaceutics categorizing system, be low-solubility and high transmittance film, because dissolubility is low in water, affected medicine absorption in vivo, the bioavailability of oral administration is lower.
The liquid or solid preparation that self-emulsifying drug delivery system (SEDDS) is comprised of medicine, oil phase, surfactant and cosurfactant, spontaneous emulsification forms Emulsion under the gastrointestinal motility or under the gentle agitation of ambient temperature (being generally 37 ℃) in vivo.Along with increasing of emulsifier, particle diameter can further reduce (particle diameter≤100 nm), is called self-emulsifying microemulsion drug delivery system (SMEDDS) this moment.Medicine is present in the tiny oil droplet, is distributed in fast whole gastrointestinal tract, has reduced owing to medicine and gastrointestinal wall direct contacts the stimulation that causes.The distribution of medicine between oil/water is biphase, the stripping and the absorption that rely on the huge specific surface area of tiny oil droplet greatly to improve water-insoluble drug, thus improve bioavailability and the therapeutic effect of medicine.SEDDS and SMEDDS have great advantage at tool aspect raising drug solubility and the bioavailability.So develop the self-emulsified drug delivery system of valsartan, can improve the bioavailability of valsartan oral administration, better meet the market demand.
Summary of the invention
The purpose of this invention is to provide a kind of valsartan self-emulsifying medicament transfer, comprise the liquid or solid preparation, to improve the bioavailability of valsartan oral administration.
Another object of the present invention is to provide the preparation method of valsartan self emulsifying liquid or solid preparation.
The present invention is achieved through the following technical solutions:
Valsartan self-emulsifying medicament transfer provided by the present invention comprises following Main Ingredients and Appearance: valsartan is active component; Oil phase is crude vegetal, the vegetable oil through structure of modification, one or more mixture in the middle long-chain fatty acid glyceride type, such as one or more mixture in soybean oil, Oleum Arachidis hypogaeae semen, Oleum Ricini, hydrogenated corn oil, sad capric acid triglyceride (GTCC), middle carbochain triglyceride (MCT), Polyethylene Glycol glyceryl laurate ester (Gelucire44/14), glyceryl linoleate (Maisine), olein, the Oleum Cocois C8/C10 triglyceride (Captex 355) etc.; Surfactant is one or more mixture in polyoxyethylene glyceride, polyoxyethylene oleate, polyoxyethylene castor oil and derivant, the polyethyleneglycol glyceride etc., such as one or more mixture among Polyethylene Glycol 660-12-hydroxy stearic acid (Solutol HS-15), Pluronic F68, PEG-8-caprylic/capric ester (labrasol), lecithin, polyoxyethylene castor oil, polyoxyethylene hydrogenated Oleum Ricini, Tween80, the Tween20 etc.; Cosurfactant be in, one or more mixture in alcohol of short chain, ether etc., such as one or more mixture in Macrogol 200-600, ethanol, isopropyl alcohol, propylene glycol, the ethylene glycol monomethyl ether (Transcutol) etc.; Also can add the auxiliary elements such as vitamin E, citric acid.
Valsartan of the present invention is as follows from the percentage by weight of each chief component composition of (little) emulsification preparation:
Valsartan 1%-10%
Oil phase 10%-60%
Surfactant 10%-70%
Cosurfactant 0-30%
Auxiliary composition 0-5%
Valsartan self emulsifying medicinal liquid directly fill becomes soft capsule, also can add some absorbent, comprise one or more mixture in microcrystalline Cellulose, lactose, cellulose acetate, ethyl cellulose, polyacrylic resin, silicone rubber, gelatin, Hydroxypropyl Methyl Cellulose Phthalate, CAP, micropowder silica gel, mannitol, dichloromethane and the aerosil etc., be made into solid self-emulsifying tablet, micropill, microsphere, powder, granule etc.Prepared valsartan self-emulsifying medicament transfer can spontaneous formation Emulsion in gastrointestinal tract or in the situation of ambient temperature and gentle agitation.
The preparation process of valsartan self-emulsifying medicament transfer is: under 20 ℃-50 ℃ bath temperature, the mixture of oil, surfactant and the cosurfactant of recipe quantity stirred to make becomes uniform settled solution, the valsartan that adds again recipe quantity, stirring makes medicine dissolution and get final product.Can be further with its embedding in soft capsule, also can add some solid absorbents and be made into solid self-emulsifying tablet, micropill, microsphere, powder, granule etc.
The invention has the advantages that self-emulsifying drug delivery system has improved the contact area of medicine and gastrointestinal wall, thereby accelerate the absorption rate of medicine, can improve the oral administration biaavailability of valsartan; And preparation technology is simple, is easy to suitability for industrialized production; The forward position of self-emulsifiable preparation development has been expanded in the simultaneously research of solid self-emulsifying preparation, makes its application more convenient.
Description of drawings
Fig. 1 is the particle size data figure of embodiment 1, and measured particle diameter is 42nm.
The specific embodiment
The preparation of embodiment 1 self-emulsifying soft capsule
It is composed as follows to write out a prescription: (g)
Valsartan 40
Miglyol 812 165
Tween80 235
1,2-PD 110
550g makes 1000 soft capsules altogether.
Preparation technology: under 40 ℃, with recipe quantity MCT, Tween80 and the mixture of 1,2-PD stir to make and become uniform settled solution, add again the valsartan of recipe quantity, stir and make medicine dissolution, its embedding is in soft capsule afterwards.
Embodiment 2 is from the preparation of (little) emulsification preparation
It is composed as follows to write out a prescription: (g)
Valsartan 10
Miglyol 812 220
Tween80 320
550g makes 1000 soft capsules altogether.
Preparation technology is with embodiment 1.
Embodiment 3 is from the preparation of (little) emulsification preparation
It is composed as follows to write out a prescription: (g)
Valsartan 80
Miglyol 812 240
Tween80 220
1,2-PD 60
600g makes 1000 soft capsules altogether.
Preparation technology is with embodiment 1.
Embodiment 4 is from the preparation of (little) emulsification preparation
It is composed as follows to write out a prescription: (g)
Valsartan 40
Ethyl oleate 200
Tween80 260
Ethylene glycol monomethyl ether 100
600g makes 1000 soft capsules altogether.
Preparation technology is with embodiment 1.
Embodiment 5: from the preparation of (little) emulsification preparation
It is composed as follows to write out a prescription: (g)
Valsartan 40
Gelucire44/14 200
Solutol HS-15 180
Transcutol P 180
600g makes 1000 soft capsules altogether.
Preparation technology: take by weighing Gelucire44/14, Solutol HS-15 and the Transcutol P of recipe quantity, 40 ℃ stirring in water bath is even, takes by weighing the valsartan of recipe quantity again, stirs and makes medicine dissolution, and fill becomes soft capsule.
Embodiment 6: from the preparation of (little) emulsification preparation
It is composed as follows to write out a prescription: (g)
Valsartan 40
Gelucire44/14 180
F68 200
Transcutol P 180
600g makes 1000 soft capsules altogether.
Preparation technology is with embodiment 5.
Embodiment 7: from the preparation of (little) emulsification preparation
It is composed as follows to write out a prescription: (g)
Valsartan 40
Gelucire44/14 140
Miglyol 812 40
F68 200
Transcutol P 180
600g makes 1000 soft capsules altogether.
Preparation technology is with embodiment 5.
Embodiment 8:
Particle size determination:
Measure the particle diameter of above-described embodiment 1-8 Emulsion with particle size analyzer.Particle diameter adopts Ma Erwen laser light scattering particle size determination instrument (Zetasizer 3000) to measure, and the light scattering degree is decided to be 90 °, and measuring temperature is 25 ± 1 ℃.Record the particle diameter of self emulsifying solution of each embodiment in 200 nm.Wherein the particle diameter of embodiment 1 is 42nm, accompanying drawing.
Embodiment 9:
Pharmacokinetic studies in the body:
For being subjected to test preparation, commercially available conventional capsule agent is reference preparation, gets 8 of rats, employing binary cycle trial design according to the preparation of embodiment one described prescription and method preparation, dosage is 8mg/kg, 24h fasting before the administration, gastric infusion, 0 after the administration, 15min, 30min, 60min, 2h, 3h, 4h, 6h, 8h, 10h gets blood, centrifugal, plasma sample is processed, and measures blood drug level with the HPLC method.Experimental result shows, the AUC value of homemade self-emulsifiable preparation and commercially available capsule be respectively 10.38 and 5.32mg/mlh relative bioavailability be about 195%.The bioavailability of self-emulsifiable preparation has reached reduction dosage apparently higher than commercially available capsule, reduces the purpose of side effect.
Claims (5)
1. valsartan self-emulsifying medicament transfer, it is characterized in that: comprise following composition, its weight percent consists of:
Valsartan 1%-10%
Oil phase 10-60%
Surfactant 10%-70%
Cosurfactant 0-30%
Auxiliary composition 0-5%;
Described oil phase is soybean oil, Oleum Arachidis hypogaeae semen, Oleum Ricini, hydrogenated corn oil, three Miglyol 812s, Polyethylene Glycol glyceryl laurate ester, glyceryl linoleate, olein, middle carbochain triglyceride, one or more mixture in the Oleum Cocois C8/C10 triglyceride; Described surfactant is one or more mixture among Polyethylene Glycol 660-12-hydroxy stearic acid, Pluronic F68, PEG-8-caprylic/capric ester, lecithin, polyoxyethylene castor oil, polyoxyethylene hydrogenated Oleum Ricini, Tween80, the Tween20; Described cosurfactant is one or more mixture in Macrogol 200-600, ethanol, isopropyl alcohol, propylene glycol, the ethylene glycol monomethyl ether.
2. valsartan self-emulsifying medicament transfer according to claim 1, it is characterized in that: described auxiliary composition is vitamin E or citric acid.
3. valsartan self-emulsifying medicament transfer according to claim 1 is characterized in that: the homogeneous mixture that described valsartan self-emulsifying medicament transfer forms, directly fill becomes soft capsule.
4. valsartan self-emulsifying medicament transfer according to claim 1 is characterized in that: be made into solid self-emulsifying tablet, micropill, microsphere, powder, granule with adding some absorbent in the prepared self-emulsifying drug delivery system.
5. valsartan self-emulsifying medicament transfer according to claim 4, it is characterized in that: described absorbent comprises one or more mixture in microcrystalline Cellulose, lactose, cellulose acetate, ethyl cellulose, polyacrylic resin, silicone rubber, gelatin, Hydroxypropyl Methyl Cellulose Phthalate, CAP, micropowder silica gel, mannitol, dichloromethane and the aerosil.
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| CN 201110053556 CN102119926B (en) | 2011-03-07 | 2011-03-07 | Valsartan self-emulsifying medicament transfer system and preparation method thereof |
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| CN102119926B true CN102119926B (en) | 2013-01-23 |
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| CN107468650A (en) * | 2016-10-09 | 2017-12-15 | 郑州泰丰制药有限公司 | A kind of Irbesartan self-emulsifying soft capsule and preparation method thereof |
| CN108553417B (en) * | 2018-03-30 | 2022-06-21 | 陕西中医药大学 | Osthole self-emulsifying drug release system and preparation method and application thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101829111A (en) * | 2010-05-23 | 2010-09-15 | 浙江华海药业股份有限公司 | Valsartan-containing solid preparation and preparation method thereof |
| CN101485657B (en) * | 2009-03-04 | 2010-12-01 | 浙江华海药业股份有限公司 | Diovan compound preparation and preparation method thereof |
| CN101732270B (en) * | 2010-01-17 | 2011-11-30 | 鲁南制药集团股份有限公司 | Dispersing tablet of valsartan and preparation method thereof |
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2011
- 2011-03-07 CN CN 201110053556 patent/CN102119926B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101485657B (en) * | 2009-03-04 | 2010-12-01 | 浙江华海药业股份有限公司 | Diovan compound preparation and preparation method thereof |
| CN101732270B (en) * | 2010-01-17 | 2011-11-30 | 鲁南制药集团股份有限公司 | Dispersing tablet of valsartan and preparation method thereof |
| CN101829111A (en) * | 2010-05-23 | 2010-09-15 | 浙江华海药业股份有限公司 | Valsartan-containing solid preparation and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 袁悦等.缬沙坦自微乳化药物传递系统的处方筛选与体外评价.《2008年中国药学会学术年会暨第八届中国药师周论文集》.2008,第1173-1177页. * |
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