CN102670570B - Microporous spongy ondansetron hydrochloride film agent and preparation method thereof - Google Patents
Microporous spongy ondansetron hydrochloride film agent and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a microporous spongy ondansetron hydrochloride film agent and a preparation method thereof. The microporous spongy ondansetron hydrochloride film agent comprises ondansetron hydrochloride, water-soluble polymer materials and water insoluble micro powder; according to the film agent, two kinds of polymer materials are matched for used, wherein the molecular weight of one kind of the polymer material is 10,000 to 200,000 Daltons, and the molecular weight of the other kind of the polymer material is 200,000 to 10,000,000 Daltons; and the ratio of one kind of the polymer material to the other kind of the polymer material is (1:4) to (4:1). By the polymer material with the low molecular weight, a film can be dissolved quickly; by the polymer material with the high molecular weight, the physical intensity and toughness of the film can be guaranteed; and the aim of quick release is fulfilled, and the intensity of the film is guaranteed.
Description
Technical field
The present invention relates to a kind of Ondansetron Hydrochloride preparation.
Background technology
Ondansetron (Ondansetron) is a kind of 5-hydroxytryptamine receptor antagonist, and the clinical nausea and vomiting that is mainly used in chemotherapy or caused by radiation also can be used for the rear nausea and vomiting of performing the operation.The effect of the existing periphery of its emesis mechanism has again the effect of maincenter.Mainly to bring into play curative effect by the 5-hydroxytryptamine receptor that suppresses the oblongata chemoreceptor trigger zone.And have the gastric motility effect, accelerate gastric emptying, thereby be beneficial to emesis.
The clinical practice of ondansetron is fit to make membrane very much.Because membrane does not need water delivery service, especially be fit to the patient of dysphagia; Be placed on tongue instantly, and be difficult for after sticking spuing.Compare with liquid preparations such as drop, syrups, dosage is accurate; Compare with the lyophilizing sheet with oral cavity quick disintegrating slice, production technology is simple, and cost is lower.
The medicine film preparation is as far back as i.e. existing many researchs of nineteen seventies, as tranquilizer film (Chinese Journal of Pharmaceuticals, 1976,12(19)), diphenoxylate medicine film (Chinese Journal of Pharmaceuticals, 1976,12(22)), external applied contraceptive film (Chinese Journal of Pharmaceuticals, 1977,4-5(45)), nitroglycerin medicine film (Chinese Journal of Pharmaceuticals, 1977,12(5)), rhodexin film (Chinese Journal of Pharmaceuticals, 1980,4(18)), clonidine sustained release film formulation (Chinese Journal of Pharmaceuticals, 1981,3(141)) etc.Chinese Pharmacopoeia is also recorded (Pharmacopoeia of People's Republic of China 1995 editions, 2000 editions, 2005 editions, 2010 editions) to membrane as official preparation.This dosage form for various reasons at home, development is not fast arranged so far, also get permission to produce at home there are no new medicine film, may with lack modern production machine, lack packing attractive in appearance easy to use relevant, for this reason, the inventor has applied for the patent of new packaged form of packaging machine, the membrane of production machine, the membrane of membrane, to promote membrane development at home.
By contrast, abroad membrane in development rapidly and vigorously, as the membrane of nonprescription drugs, the U.S. FDA approved 9 products and going on the market, as the breath freshening membrane, antianaphylactic diphenhydramine membrane etc.
Membrane as prescription drugs also easily manufactured because of it, adjuvant is few, easy to carry, do not need water clothes, rapid-action, more the economic dispatch many merits is replacing the oral formulations such as oral cavity disintegration tablet, lyophilizing sheet, dispersible tablet, and present many patents, as paste mucoadhesive films (US pat on oral mucosa, 6750,921), can be bonded at and slowly lose again molten membrane (USpat in the oral cavity, 5800,832), double-deck membrane (US pat is also arranged, the membrane (WO 2008040534(A2) that non-oral cavity adhesion, meeting disintegrate in the oral cavity 5700,478), are also arranged).Numerous membrane are used for pain relieving, sleep disorder etc., be particularly suitable for engulfing patient, child, the easy patient that vomiting occurs of difficulty, U.S. FDA has been ratified the famotidine film in 2005, ratified again the production of ondansetron film in 2010, sign prescriptions film will come into the market with speed faster.
The water solublity of Ondansetron Hydrochloride is relatively poor, need to be dispersed in macromolecular material; And its bitter in the mouth need to add correctives and odor mask; Add adding of insoluble micropowder in pore creating material, the large percentage of the water insoluble active ingredient in prescription.The inventor finds, when the large percentage of water insoluble active ingredient in the film prescription, film is more crisp, and is frangible.Be unfavorable for producing, transport, preserve and use.Common way is the plasticizer that adds q.s, but when increasing the plasticizer ratio, the ratio of macromolecular material reduces relatively, is unfavorable for the molding of film.If will in the macromolecule ratio hour guarantee film strength, will use higher molecular weight, material that viscosity is larger, like this, the dissolving of film will be slowed down, and does not reach the effect of rapid onset.
And when adopting the inventor when the disclosed technology of the patent of first to file prepares the Ondansetron Hydrochloride membrane, test finds, also exist film more crisp, cut with packaging process in frangible defective, need to be improved.
Summary of the invention
One of purpose of the present invention is to provide a kind of spongiform Ondansetron Hydrochloride membrane with micropore and preparation method thereof, and the defective that exists to overcome prior art satisfies clinical needs.
Spongiform Ondansetron Hydrochloride membrane with micropore of the present invention, its component comprises Ondansetron Hydrochloride, water-soluble high-molecular material and water-insoluble micropowder;
In the gross weight of membrane, the weight content of Ondansetron Hydrochloride is 1～40%, preferably 7～30%;
Described water-soluble high-molecular material is any two kinds in HPMC, PVA, HPC, CMC-Na, PVP, sodium alginate or PEO, and wherein, a kind of is the lower molecular weight water-soluble high-molecular material, and its molecular weight is 10,000～200,000 dalton, another kind is the higher molecular weight water-soluble high-molecular material, and its molecular weight is 200,000～10,000,000 dalton;
The weight average molecular weight that described molecular weight refers to;
The chemical name of HPMC is hypromellose, the chemical name of PVA is polyvinyl alcohol, and the chemical name of HPC is hydroxypropyl cellulose, and the chemical name of CMC-Na is sodium carboxymethyl cellulose, the chemical name of PVP is polyvinylpyrrolidone, and the chemical name of PEO is polyoxyethylene;
Weight ratio is:
Lower molecular weight water-soluble high-molecular material: higher molecular weight water-soluble high-molecular material=1: 4～4: 1;
Preferably, described water-soluble high-molecular material is that molecular weight is that 130,000 daltonian PVA and molecular weight are the mixture of 600,000 daltonian HPC, and weight ratio is 4: 1;
Be perhaps:
Molecular weight is that 20,000 daltonian HPMC and molecular weight are the mixture of 7,000,000 daltonian PEO, and weight ratio is 1: 4;
Be perhaps:
Molecular weight is that 32,000 daltonian sodium alginates and molecular weight are 700,000 daltonian mixture, and weight ratio is 1: 2;
Be perhaps:
Molecular weight is that 100,000 daltonian PEO and molecular weight are 360,000 daltonian PVP mixture, and weight ratio is 1: 1;
Be perhaps
Molecular weight is that 10,000 daltonian PVP and molecular weight are the mixture of 1,000,000 daltonian HPC, and weight ratio is 2: 1.
Described water-insoluble micropowder is preferably microcrystalline Cellulose micropowder, starch, fine silica powder, CaCO3 micropowder, kayexalate micropowder, CMC micropowder or chitosan micropowder, and the particle diameter of micropowder is 0.1～100 μ m, preferred 1～50 μ m;
The weight ratio of water-soluble high-molecular material and water-insoluble micropowder is:
Water-soluble high-molecular material: water-insoluble micropowder=1: 0.05～1.5;
Preferably:
Water-soluble high-molecular material: water-insoluble micropowder=1: 0.1～1.25;
The aperture of described micropore is 10～100nm, and the thickness of thin film is 0.01～0.2mm;
Further, in described membrane, also comprise other adjuvants, described other adjuvants are more than one in antioxidant, correctives, plasticizer or pigment, and in the gross weight of membrane, the weight content of other adjuvants is 0.01～30%;
Described antioxidant is vitamin C, BHA, BHT, vitamin E, EDTA, fumaric acid, maleic acid, tartaric acid, lysine, arginine, sodium sulfite, sodium sulfite etc.;
Described correctives comprises more than one in sweeting agent, acidic flavoring agent, aromatic, effervescent, gummy macromolecular material, lecithin, cephalin or phosphatidic acid etc.;
Described sweeting agent such as xylitol, leaf dulcin, Radix Glycyrrhizae ester glycosides, stevioside, saccharin sodium, aspartame, sucralose, acesulfame potassium or cyclamate etc.;
Described acidic flavoring agent such as citric acid, malic acid, ascorbic acid or glycine etc.;
Described aromatic such as Eucalyptus oil, oleum Citri sinensis, Oleum menthae, Oleum menthae, MENTHOL or vanillin etc.;
Described effervescent is sodium bicarbonate, sodium carbonate etc.;
Described gummy macromolecular material such as xanthan gum, guar gum, tragakanta, cover its glue, locust bean gum, Radix Acaciae senegalis etc.;
Described plasticizer is selected from more than one in Polyethylene Glycol (PEG), glycerol, triacetyl glycerine, triethyl citrate or Tween 80;
Described pigment is titanium dioxide, shellac color, alkermes, beet red, carthamin, curcumin, beta-carotene, chlorophyll, sunset yellow, lemon yellow, viride nitens or fast green etc.
The preparation method of described Ondansetron Hydrochloride membrane comprises the steps:
(1) pore creating material and Ondansetron Hydrochloride are added the water slip of described water-soluble high-molecular material, the weight concentration of the water slip of water-soluble high-molecular material is 10～30%;
The component of described pore creating material comprises described water-insoluble micropowder and absorption solvent thereon, and the parts by weight of water-insoluble micropowder and the weight portion of solvent are:
100 parts of water-insoluble micropowders
100～900 parts of solvents
Described solvent is selected from more than one in ethanol or acetone, preferred alcohol;
Pore creating material add weight, with the weighing scale of butt water-soluble high-molecular material and water-insoluble micropowder, water-soluble high-molecular material: water-insoluble micropowder=1: 0.05～1.5;
Preferably:
Water-soluble high-molecular material: water-insoluble micropowder=1: 0.1～1.25;
(2) then be coated with masking, obtain the medicine carrying thin film;
Described coating masking is the method for this area routine, and as the method for research (Chinese Journal of Pharmaceuticals, 1977,12 (5)) bibliographical information of nitroderm TTS, the present invention repeats no more;
(3) the medicine carrying thin film that step (2) is obtained is dry at higher than the temperature of solvent evaporates, obtain described microporous sponge shape medicine film preparation, solvent volatilizees from the water-insoluble micropowder and disengages, and stay next micropore at every water-insoluble micropowder place, and due to water-insoluble micropowder capillarity, solvent disengages and is slowly, be conducive to keep uniform bubble formation, because the water-insoluble micropowder is distributed in the macromolecule serosity, thereby just can form bubble comparatively uniformly, the aperture that how much has determined again micropore of the particle diameter of water-insoluble micropowder and amount of alcohol, what of the amount of micropore,
Preferably, in step (1), pore creating material, Ondansetron Hydrochloride and other adjuvants are added the water slip of described water-soluble high-molecular material, and then the coating masking, the medicine carrying thin film obtained;
The present invention adopts macromolecular material to consist of network structure, and medicament mixed then with joining in the aqueous solution of macromolecular material after the insoluble micropowder absorption of water used in solvent, forms a large amount of micropores by pore creating material in material.
But the water solublity of Ondansetron Hydrochloride is relatively poor, and bitter in the mouth, need to add correctives and odor mask, adds the insoluble micropowder in pore creating material, the large percentage of the water insoluble active ingredient in prescription.Adopt common way masking, film is crisp, and is frangible, can't normally produce, transports, preserves and use.If strengthen the consumption of plasticizer, the ratio of macromolecule filming material further reduces, and is difficult to film forming.If will in the macromolecule ratio hour guarantee film strength, will use higher molecular weight, material that viscosity is larger, like this, the dissolving of film will be slowed down, and onset is slow.
The inventor finds by a large amount of experiments, if two or more macromolecular material is used in conjunction with, wherein the molecular weight of at least a macromolecular material is 10,000～200,000 dalton, the molecular weight of at least a macromolecular material is 200,000～10,000,000 dalton, the ratio of bi-material is 1:4～4:1, just can solve the problems referred to above.The effect of this invention is very significant, and the macromolecular material by lower molecular weight comparatively fast dissolves film, guarantees physical strength and the toughness of film by the macromolecular material of higher molecular weight, has both reached the purpose of rapid release, has guaranteed again film strength.
Description of drawings
Fig. 1 is the Dissolution Rate Testing data.
The specific embodiment
Embodiment 1
Be that 130,000 daltonian PVA and 20g molecular weight are that 600,000 daltonian HPC are dissolved in 500g water with the 80g molecular weight, be made into the water slip.
100g pore creating material, 10g Ondansetron Hydrochloride, 1g aspartame, 1g arginine, 5g glycerol and 3g titanium dioxide are added in above-mentioned water slip, fully stirring, mix homogeneously.
The component of described pore creating material comprises that particle diameter is chitosan and the absorption acetone thereon of 0.5 μ μ m, and the parts by weight of chitosan and the weight portion of solvent are:
100 parts of chitosans
400 parts, acetone
(2) then adopt the method for research (Chinese Journal of Pharmaceuticals, 1977,12 (5)) bibliographical information of nitroderm TTS, the coating masking obtains the thin film presoma;
(3) the thin film presoma that step (2) is obtained obtains described thin film for the medicine film preparation in 80 ℃ of dryings, and thickness is 0.07mm.
(4) measure content according to high performance liquid chromatography (two appendix V D of Chinese Pharmacopoeia version in 2010), cut into the specification of every hydrochloric ondansetron 4mg or 8mg.
The weight ratio of each component:
Low-molecular weight water-soluble macromolecular material: high molecular weight water-soluble macromolecular material=4: 1;
Water-soluble high-molecular material: water-insoluble micropowder=1: 0.2;
The aperture of described micropore is 30nm.
Performance evaluation: outward appearance is even, bright and clean.Film strength and toughness are all better.
Be that 20,000 daltonian HPMC and 64g molecular weight are that 7,000,000 daltonian PEO is dissolved in 500g water with the 16g molecular weight, be made into the water slip.
200g pore creating material, 50g Ondansetron Hydrochloride, 5g cyclamate and 0.1g sunset yellow are added in above-mentioned water slip, fully stirring, mix homogeneously.
The component of described pore creating material comprises that particle diameter is CaCO3 and the absorption ethanol thereon of 50 μ m, and the parts by weight of CaCO3 and the weight portion of solvent are:
100 parts of CaCO3
100 parts of ethanol
Other are with embodiment 1.
The weight ratio of each component:
Low-molecular weight water-soluble macromolecular material: high molecular weight water-soluble macromolecular material=1: 4;
Water-soluble high-molecular material: water-insoluble micropowder=1: 1.25;
The aperture of described micropore is 10nm.
Performance evaluation: outward appearance is even, bright and clean.Film strength and toughness are all better.
Embodiment 3
Be that 32,000 daltonian sodium alginates and 120g molecular weight are that 700,000 daltonian CMC-Na are dissolved in 700g water with the 60g molecular weight, be made into the water slip.
90g pore creating material, 50g Ondansetron Hydrochloride, 5g sucralose, 5g triethyl citrate and 3g titanium oxide are added in above-mentioned water slip, fully stirring, mix homogeneously.
The component of described pore creating material comprises that particle diameter is kayexalate and the absorption ethanol thereon of 10 μ m, and the parts by weight of kayexalate and the weight portion of solvent are:
100 parts of kayexalates
100 parts of ethanol
Other are with embodiment 1.
The weight ratio of each component:
Low-molecular weight water-soluble macromolecular material: high molecular weight water-soluble macromolecular material=1: 2;
Water-soluble high-molecular material: water-insoluble micropowder=1: 0.25;
The aperture of described micropore is 10nm.
Performance evaluation: outward appearance is even, bright and clean.Film strength is better, and toughness meets the demands.
Embodiment 4
Be that 100,000 daltonian PEO and 60g molecular weight are that 360,000 daltonian PVP are dissolved in 600g water with the 60g molecular weight, be made into the water slip.
72g pore creating material, 60g Ondansetron Hydrochloride, 1g citric acid, 2g sodium bicarbonate and 0.1g lemon yellow pigment are added in above-mentioned water slip, fully stirring, mix homogeneously.
The component of described pore creating material comprises that particle diameter is microcrystalline Cellulose and the absorption ethanol thereon of 20 μ m, and the parts by weight of microcrystalline Cellulose and the weight portion of solvent are:
100 parts of microcrystalline Cellulose
300 parts of ethanol
Other are with embodiment 1.
The weight ratio of each component:
Low-molecular weight water-soluble macromolecular material: high molecular weight water-soluble macromolecular material=1: 1;
Water-soluble high-molecular material: water-insoluble micropowder=1: 0.5;
The aperture of described micropore is 20nm.
Performance evaluation: outward appearance is even, bright and clean.The toughness of film is better, and intensity can meet the demands.
Embodiment 5
Be that 10,000 daltonian PVP and 30g molecular weight are that 1,000,000 daltonian HPC is dissolved in 400g water with the 60g molecular weight, be made into the water slip.
90g pore creating material, 20g Ondansetron Hydrochloride, 1g tartaric acid, 3g sodium carbonate, 1g stevioside and 5g titanium oxide are added in above-mentioned water slip, fully stirring, mix homogeneously.
The component of described pore creating material comprises that particle diameter is fine silica powder and the absorption acetone thereon of 50 μ m, and the parts by weight of fine silica powder and the weight portion of solvent are:
100 parts of fine silica powders
900 parts, acetone
Other are with embodiment 1.
The weight ratio of each component:
Low-molecular weight water-soluble macromolecular material: high molecular weight water-soluble macromolecular material=2: 1;
Water-soluble high-molecular material: water-insoluble micropowder=1: 0.1;
The aperture of described micropore is 50nm.
Performance evaluation: outward appearance is even, bright and clean.Film strength and toughness all can meet the demands.
Get embodiment 1 ~ 5 film (specification 7.5mg) each 6, according to dissolution method (two appendix X C first methods of Chinese Pharmacopoeia version in 2010), take 0.1mol/L hydrochloric acid solution 500ml as solvent, rotating speed is per minute 50 to turn, operation in accordance with the law through 1,2,3,5,10, during 15min, is respectively got solution 1ml and is filtered, precision measures subsequent filtrate 20ul, measures according to high performance liquid chromatography (two appendix V D of Chinese Pharmacopoeia version in 2010); Calculate the stripping quantity of different time.Stripping curve is seen Fig. 1.
As seen from Figure 1, according to the Ondansetron Hydrochloride film of the prescription of embodiment 1 ~ 5 and technique preparation, the equal dissolve complete of 5min has shown the effect of rapid release.
Embodiment 7
Except not adding the principal agent Ondansetron Hydrochloride, according to prescription and the technique of embodiment 1 ~ 5, the preparation blank film is looked for 10 volunteers, membrane is put into mouth begin timing, if imperceptible obvious membrane fragment is namely thought membrane stripping.Record the dissolution time of membrane.
Result of the test:
Embodiment 1: dissolution time is 4.7 ± 0.3min, and embodiment 2: dissolution time is 4.5 ± 0.4min, and embodiment 3: dissolution time is 4.3 ± 0.6min, and embodiment 4: dissolution time is 4.8 ± 0.3min, and embodiment 5: dissolution time is 4.9 ± 0.3min.
Get the film (specification 4mg) of embodiment 1～5, carry out high temperature, high humidity and exposure experiments to light, investigate the stability of sample.
Hot test: film is put in culture dish, placed 10 days under 60 ℃ of conditions, in the 5th day and sampling in the 10th day, detect content, related substance and the dissolution of Ondansetron Hydrochloride in film.
High wet test: film is put in culture dish, placed 10 days under relative humidity 75% condition at 25 ℃, in the 5th day and sampling in the 10th day, detect content, related substance and the dissolution of Ondansetron Hydrochloride in film.
Exposure experiments to light: film is put in culture dish, is to place 10 days under the condition of 4500Lx ± 500Lx in illumination, in the 5th day and sampling in the 10th day, and content, related substance and the dissolution of Ondansetron Hydrochloride in the detection film.
Testing result sees Table 1 ~ table 5.
Table 1 embodiment 1 stability sample quality inspection result
Hot test (60 ℃) sample quality assay
High wet test (25 ℃, 75%RH) sample quality assay
Exposure experiments to light (4500Lx) sample quality assay
As shown in Table 1, the Ondansetron Hydrochloride film of this prescription and technique preparation is all stable under high temperature, high humidity and illumination condition.
Table 2 embodiment 2 stability sample quality inspection results
Hot test (60 ℃) sample quality assay
High wet test (25 ℃, 75%RH) sample quality assay
Exposure experiments to light (4500Lx) sample quality assay
As shown in Table 2, the Ondansetron Hydrochloride film of this prescription and technique preparation is all stable under high temperature, high humidity and illumination condition.
Table 3 embodiment 3 stability sample quality inspection results
Hot test (60 ℃) sample quality assay
High wet test (25 ℃, 75%RH) sample quality assay
Exposure experiments to light (4500Lx) sample quality assay
As shown in Table 3, the Ondansetron Hydrochloride film of this prescription and technique preparation is all stable under high temperature, high humidity and illumination condition.
Table 4 embodiment 4 stability sample quality inspection results
Hot test (60 ℃) sample quality assay
High wet test (25 ℃, 75%RH) sample quality assay
Exposure experiments to light (4500Lx) sample quality assay
As shown in Table 4, the Ondansetron Hydrochloride film of this prescription and technique preparation is all stable under high temperature, high humidity and illumination condition.
Table 5 embodiment 5 stability sample quality inspection results
Hot test (60 ℃) sample quality assay
High wet test (25 ℃, 75%RH) sample quality assay
Exposure experiments to light (4500Lx) sample quality assay
As shown in Table 5, the Ondansetron Hydrochloride film of this prescription and technique preparation is all stable under high temperature, high humidity and illumination condition.
The comparative example 1
Be that 130,000 daltonian PVA are dissolved in 400g water with the 100g molecular weight, be made into the water slip.All the other are with embodiment 1.
Performance evaluation: outward appearance is even, bright and clean.But film is more crisp, be dried to lick Cheng Zhongyi split, frangible.
Be that 600,000 daltonian HPC are dissolved in 600g water with the 100g molecular weight, be made into the water slip.All the other are with embodiment 1.
Performance evaluation: outward appearance is even, bright and clean.Film strength and toughness are all better.But the film dissolving is slower, and 30min is stripping medicine 58% only, 60min stripping 87%.Do not meet the requirement of clinical use.
The comparative example 2
Be that 20,000 daltonian HPMC are dissolved in 300g water with the 80g molecular weight, be made into the water slip.All the other are with embodiment 2.
Performance evaluation: outward appearance is even, bright and clean.But film is more crisp, be dried to lick Cheng Zhongyi split, frangible.
Be that 7,000,000 daltonian PEO is dissolved in 700g water with the 80g molecular weight, be made into the water slip.All the other are with embodiment 2.
Performance evaluation: film strength and toughness are fine, but the uniformity and fineness are relatively poor.And dissolving slowly, and 30min is stripping medicine 29% only, 60min stripping 52%.Do not meet the requirement of clinical use.
The comparative example 3
Be that 32,000 daltonian sodium alginates are dissolved in 500g water with the 180g molecular weight, be made into the water slip.All the other are with embodiment 3.
Performance evaluation: film is very crisp, and is frangible, is difficult to complete peeling off.
Be that 700,000 daltonian CMC-Na are dissolved in 900g water with the 180g molecular weight, be made into the water slip.All the other are with embodiment 3.
Performance evaluation: film strength and toughness are better, but the uniformity and fineness are not good enough.And dissolving slowly, and 30min is stripping medicine 38% only, 60min stripping 66%.Do not meet the requirement of clinical use.
The comparative example 4
Be that 100,000 daltonian PEO are dissolved in 500g water with the 120g molecular weight, be made into the water slip.All the other are with embodiment 4.
Performance evaluation: outward appearance is even, bright and clean.But film is more crisp, and frangible when cutting packing, outward appearance is imperfect, dosage is inaccurate and cause.
Be that 360,000 daltonian PVP are dissolved in 700g water with the 120g molecular weight, be made into the water slip.All the other are with embodiment 4.
Performance evaluation: outward appearance is even, bright and clean, and film strength and toughness are better.But dissolve slowlyer, 30min is stripping medicine 59% only, 60min stripping 78%.Do not meet the requirement of clinical use.
The comparative example 5
Be that 10,000 daltonian PVP are dissolved in 300g water with the 90g molecular weight, be made into the water slip.All the other are with embodiment 5.
Performance evaluation: film is crisp, and is frangible, can't completely peel off.
Be that 1,000,000 daltonian HPC is dissolved in 500g water with the 90g molecular weight, be made into the water slip.All the other are with embodiment 5.
Performance evaluation: film strength and toughness are better.Outward appearance is bright and clean, but the uniformity is not good enough.And dissolving slowly, and 30min is stripping medicine 36% only, 60min stripping 59%.Do not meet the requirement of clinical use.
Claims (7)
1. have the spongiform Ondansetron Hydrochloride membrane of micropore, it is characterized in that, its component comprises Ondansetron Hydrochloride, water-soluble high-molecular material and water-insoluble micropowder;
Described water-soluble high-molecular material is any two kinds in HPMC, PVA, HPC, CMC-Na, PVP, sodium alginate or PEO, and wherein, a kind of is the lower molecular weight water-soluble high-molecular material, and its molecular weight is 10,000～200,000 dalton, another kind is the higher molecular weight water-soluble high-molecular material, and its molecular weight is 200,000～10,000,000 dalton;
Weight ratio is:
Lower molecular weight water-soluble high-molecular material: higher molecular weight water-soluble high-molecular material=1: 4～4: 1;
The weight ratio of water-soluble high-molecular material and water-insoluble micropowder is: water-soluble high-molecular material: water-insoluble micropowder=1: 0.05～1.5;
Described water-insoluble micropowder is microcrystalline Cellulose micropowder, starch, fine silica powder, CaCO3 micropowder, kayexalate micropowder, CMC micropowder or chitosan micropowder; In the gross weight of membrane, the weight content of Ondansetron Hydrochloride is 1～40%.
2. the spongiform Ondansetron Hydrochloride membrane with micropore according to claim 1, it is characterized in that, described water-soluble high-molecular material is that molecular weight is that 130,000 daltonian PVA and molecular weight are 600, the mixture of 000 daltonian HPC, weight ratio are 4: 1;
Be perhaps:
Molecular weight is that 20,000 daltonian HPMC and molecular weight are the mixture of 7,000,000 daltonian PEO, and weight ratio is 1: 4;
Be perhaps:
Molecular weight is that 100,000 daltonian PEO and molecular weight are 360,000 daltonian PVP mixture, and weight ratio is 1: 1;
Be perhaps:
Molecular weight is that 10,000 daltonian PVP and molecular weight are the mixture of 1,000,000 daltonian HPC, and weight ratio is 2: 1.
3. the spongiform Ondansetron Hydrochloride membrane with micropore according to claim 1, is characterized in that water-soluble high-molecular material: water-insoluble micropowder=1: 0.1～1.25.
4. the spongiform Ondansetron Hydrochloride membrane with micropore according to claim 1, is characterized in that, the aperture of described micropore is 10～100nm, and the thickness of thin film is 0.01～0.2mm.
5. the spongiform Ondansetron Hydrochloride membrane with micropore according to claim 1, it is characterized in that, in described membrane, also comprise other adjuvants, described other adjuvants are more than one in antioxidant, correctives, plasticizer or pigment, in the gross weight of membrane, the weight content of other adjuvants is 0.01～30%.
6. prepare the method for Ondansetron Hydrochloride membrane claimed in claim 1, it is characterized in that, comprise the steps:
(1) pore creating material and Ondansetron Hydrochloride are added the water slip of described water-soluble high-molecular material, the weight concentration of the water slip of water-soluble high-molecular material is 10～30%;
The component of described pore creating material comprises described water-insoluble micropowder and absorption solvent thereon, and the parts by weight of water-insoluble micropowder and the weight portion of solvent are:
100 parts of water-insoluble micropowders
100～900 parts of solvents
Described solvent is selected from more than one in ethanol or acetone;
Pore creating material add weight, with the weighing scale of butt water-soluble high-molecular material and water-insoluble micropowder, water-soluble high-molecular material: water-insoluble micropowder=1: 0.05～1.5;
(2) then be coated with masking, obtain the medicine carrying thin film;
(3) the medicine carrying thin film that step (2) is obtained is dry at higher than the temperature of solvent evaporates, obtains described Ondansetron Hydrochloride membrane.
7. method according to claim 6, is characterized in that, in step (1), pore creating material, Ondansetron Hydrochloride and other adjuvants added the water slip of described water-soluble high-molecular material, and then the coating masking, obtains the medicine carrying thin film.
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| CN101574329A (en) * | 2009-06-12 | 2009-11-11 | 上海现代药物制剂工程研究中心有限公司 | Zolpidem tartrate film agent |
| CN102028672A (en) * | 2010-09-29 | 2011-04-27 | 上海现代药物制剂工程研究中心有限公司 | Microporous spongy film preparation and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101574329A (en) * | 2009-06-12 | 2009-11-11 | 上海现代药物制剂工程研究中心有限公司 | Zolpidem tartrate film agent |
| CN102028672A (en) * | 2010-09-29 | 2011-04-27 | 上海现代药物制剂工程研究中心有限公司 | Microporous spongy film preparation and preparation method thereof |
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