CN1676130A - Water-soluble medicine sublingual-medicating formulation - Google Patents
Water-soluble medicine sublingual-medicating formulation Download PDFInfo
- Publication number
- CN1676130A CN1676130A CN 200410030748 CN200410030748A CN1676130A CN 1676130 A CN1676130 A CN 1676130A CN 200410030748 CN200410030748 CN 200410030748 CN 200410030748 A CN200410030748 A CN 200410030748A CN 1676130 A CN1676130 A CN 1676130A
- Authority
- CN
- China
- Prior art keywords
- sublingual
- water
- solution time
- sorbitol
- hydrochloride
- Prior art date
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- Granted
Links
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- 239000000203 mixture Substances 0.000 title claims abstract description 19
- 238000009472 formulation Methods 0.000 title 1
- SKYZYDSNJIOXRL-BTQNPOSSSA-N (6ar)-6-methyl-5,6,6a,7-tetrahydro-4h-dibenzo[de,g]quinoline-10,11-diol;hydrochloride Chemical compound Cl.C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 SKYZYDSNJIOXRL-BTQNPOSSSA-N 0.000 claims abstract description 22
- 229960003990 apomorphine hydrochloride Drugs 0.000 claims abstract description 22
- JCCNYMKQOSZNPW-UHFFFAOYSA-N loratadine Chemical compound C1CN(C(=O)OCC)CCC1=C1C2=NC=CC=C2CCC2=CC(Cl)=CC=C21 JCCNYMKQOSZNPW-UHFFFAOYSA-N 0.000 claims abstract description 16
- 229960003088 loratadine Drugs 0.000 claims abstract description 16
- 238000002360 preparation method Methods 0.000 claims abstract description 14
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- 239000000600 sorbitol Substances 0.000 claims description 18
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- 229940079593 drug Drugs 0.000 claims description 11
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- 230000000149 penetrating effect Effects 0.000 claims description 6
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- RMRJXGBAOAMLHD-IHFGGWKQSA-N buprenorphine Chemical compound C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@]11CC[C@]3([C@H](C1)[C@](C)(O)C(C)(C)C)OC)CN2CC1CC1 RMRJXGBAOAMLHD-IHFGGWKQSA-N 0.000 claims description 3
- 239000000470 constituent Substances 0.000 claims description 3
- BRTSNYPDACNMIP-FAWZKKEFSA-N dihydroetorphine Chemical compound O([C@H]1[C@@]2(OC)CC[C@@]34C[C@@H]2[C@](C)(O)CCC)C2=C5[C@]41CCN(C)[C@@H]3CC5=CC=C2O BRTSNYPDACNMIP-FAWZKKEFSA-N 0.000 claims description 3
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- 239000000811 xylitol Substances 0.000 claims description 2
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- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 2
- 229960002675 xylitol Drugs 0.000 claims description 2
- 239000004615 ingredient Substances 0.000 claims 1
- 239000006190 sub-lingual tablet Substances 0.000 abstract description 22
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- 239000003826 tablet Substances 0.000 abstract description 9
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- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 6
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- VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 4
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- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 2
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- UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UEDUENGHJMELGK-HYDKPPNVSA-N 0.000 description 1
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Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention provides a water-soluble medicine sublingual tablet prescription composition. Said medicine tablet can be sublingually slowly-dissolved within 10-20 min. The water-soluble effective component of said tablet preparation can be apomorphine hydrochloride, buprenorphine hydrochloride, dihydroetorphine hydrochloride and loratadine, its optimum is apomorphine hydrochloride.
Description
Invention field
The prescription that the present invention relates to a kind of preparation of the water soluble drug that is used for Sublingual or buccal administration is formed.
Background of invention
First pass effect and active drug for fear of liver play a role fast, and some water soluble drug example hydrochloric acid apomorphine (apomorhine hydrochloride), buprenorphin hydrochloride (burenophinehydrochloride), dihydroetorphine hydrochlorate (dihydroetorphine hydrochloride), loratadine (loratadine) etc. adopt the Sublingual administration.The regulation that existing Chinese Pharmacopoeia version in 2000 is made Sublingual tablet: " principal agent and adjuvant should be soluble in water "; Sublingual tablet needs " dissolving in 5 minutes by the disintegrating method method ", promptly can see through sieve aperture at the disintegration tester Chinese medicine tablet.For satisfying pharmacopeia external " dissolving in 5 minutes " regulation, should select the disintegrate adjuvant, still, and disintegrate adjuvant imbibition, it is interior water-soluble but to be difficult to the short time, runs counter to pharmacopeia and answers regulation soluble in water about principal agent and adjuvant.
Therefore, Sublingual tablet is often selected water soluble adjuvant for use in preparation process, yet the easy moisture absorption of water soluble adjuvant can cause the technological problems of sticking; The normal hardness of selecting to reduce tablet in the big in addition production technology, this has caused practical difficulty to commercial production, packing and transportation.
Apomorphine can be used for the treatment of male sexual disorder, i.e. so-called " sexual impotence ".Sexual impotence refers to male's can not reach and keep to be satisfied with erection of sexual intercourse, is also referred to as " erectile dysfunction ".Erectile dysfunction may be by psychological factor or organ factor, the perhaps composition of the two.The organ factor comprises physiological, neural blood vessel and hormone pathology, the perhaps combination of the two.The neural impulse of loose signal takes place by acting on the central nervous system in apomorphine hydrochloride to some muscle.Can stop blood to flow into penis during these muscular tones.When these were of flaccid muscles, the blood flow that flows into penis obviously increased.The blood flow increase makes three kinds of erectile tissues of penis be full of blood, makes penis become strong, and the full adjacent vein of erectile tissue compressing prevents blood to flow out penis, prevents blood to flow out penis and can keep continuing to erect.
Segraves, R, T, studies show that to follow usually for the dosage that reaches the needed apomorphine that erects of et al.J Urology 145:1174-1175 (1991) felt sick and other undesirable serious adverse such as hypertension flushing and perspiration.In addition, too fast if said preparation dissolves, apomorphine is soluble in water, and sublingual administration is swallowed by the patient easily, and can not fully absorb in the Sublingual.Therefore, medicine should not dissolve too fast in the Sublingual.The slow stripping of Sublingual tablet means medicine at the uniform velocity stripping in 10～20 minutes.
In sum, the prescription that the purpose of this invention is to provide a kind of suitable water soluble drug sublingual administration is formed and preparation technology, should meet 2000 editions regulations of existing Chinese Pharmacopoeia, solve the soft problem of big production technology again, and can slowly dissolve in 10～20 minutes in the Sublingual and make the drug slow stripping to reduce its side effect, improve bioavailability of medicament simultaneously.
Summary of the invention
For solving the difficulty that water soluble drug sublingual administration medicament development exists, the present invention is devoted to overcome in the following aspects:
1. the speed of rate.2000 editions dissolution rates of Sublingual tablet being controlled medicine with the regulation of " press the disintegrating method method, dissolve in 5 minutes " and " principal agent and adjuvant should be soluble in water " of existing Chinese Pharmacopoeia.But the solution time in Sublingual should be more than 10 minutes in vivo in this pharmaceutical preparation, and should the slow corrosion in the Sublingual, to reduce the drug side effect of not expecting and to improve bioavailability of medicament.Therefore there is certain contradiction with in vitro tests in the body.The solution time of the tablet that patent CN1271276A produces in disintegration tester is about 8 minutes, exceeded the regulation of Chinese Pharmacopoeia; And wherein used insoluble microcrystalline cellulose excipients, run counter to the guideline of " principal agent and adjuvant should be soluble in water ".
2. the operability of production technology.This preparation prescription is formed and preparation technology is devoted to reduce difficulty in the suitability for industrialized production, as the combination of sticking, Hardness Control, packing or above several difficulties etc.
3. Sublingual process in leaching.This preparation is dispersed in aqueous soluble active constituent in the compositions of water soluble adjuvant, for example sorbitol, mannitol, sucrose and lactose etc., or the compositions of above several adjuvants, by regulating corrosion speed control medicine slowly stripping in the time range of suitable sublingual administration of adjuvant.
Having developed a kind of prescription of water soluble drug sublingual administration preparation forms.
Biological active substances of the present invention is a water soluble drug, comprises apomorphine hydrochloride, buprenorphin hydrochloride, dihydroetorphine hydrochlorate, loratadine; Preferred apomorphine hydrochloride.
Penetrating agent can be sucrose, lactose, sorbitol, mannitol, fructose, xylitol, glucose or their compositions, and the ratio in prescription is 45%～95%; The compositions of preferred sorbitol, mannitol and lactose, wherein to account for the ratio of compositions be 40%～80% to sorbitol, preferred proportion is 60%.Experimental result shows that the ratio of sorbitol in compositions is vital: the ratio of sorbitol is too high, is easy to generate the problem of sticking, and this is because sorbitol very easily absorbs water; The ratio of sorbitol is too low, and it is too slow to cause Sublingual tablet to dissolve easily, and this is because lactose and mannitol penetrating power are not enough.Also can add glycerol, carbamide, organic salt and inorganic salt such as sodium chloride etc. in case of necessity.
Can further add other conventional adjuvants among the present invention, as correctives, binding agent, coloring agent, lubricant and stabilizing agent etc.
Correctives contains intense sweetener, comprises aspartame, sucralose, saccharin sodium, stevioside, cyclamate or their combination; Essence comprises apple essence, flavoring orange essence, grape essence, strawberry essence, citric acid and their combination.Preferred correctives comprises sucralose, green apple powdered flavor and citric acid.
Binding agent comprises: polyvidone aqueous solution, water, starch slurry, the aqueous solution of hydroxypropyl emthylcellulose.
Coloring agent comprises light green, light blue, and carmine, greyish purple.
Lubricant comprises micropowder silica gel, Pulvis Talci, magnesium stearate, fumaric acid sodium stearyl.Preferred magnesium stearate and Pulvis Talci.
Stabilizing agent comprises: antioxidant, as vitamin C; Complexing of metal ion agent such as disodiumedetate.Preferred stabilizing agent is vitamin C and disodiumedetate.
Preferred version describes in detail:
At apomorphine hydrochloride, apomorphine hydrochloride is a kind of unstable compounds in the presence of light and oxygen.But, test discovery said preparation compositions by the influence factor and give apomorphine hydrochloride stability.And the corrosion of sorbitol, mannitol and lactose can make apomorphine hydrochloride stripping slowly in the Sublingual; Can satisfy in disintegration tester simultaneously and dissolve in five minutes, to meet 2000 editions requirements of Chinese Pharmacopoeia the Sublingual tablet solution time.In addition, the proportioning of suitable penetrating agent makes stripping, suitability for industrialized production sticking and the unmanageable problem of hardness obtain solution.The pressure change of finding solution time and tablet simultaneously is irrelevant, the essentially no difference of external solution time of the tablet of hardness 20N and the tablet of 100N.Cover the bitterness except adding sweeting agent, citric acid and green apple powdered flavor can further improve taste of medicine.The antioxidative effect has also been played in the adding of antioxidant and complexing of metal ion agent.
Embodiment
Be that example illustrates the present invention with apomorphine hydrochloride and loratadine respectively, but be not limited only to following examples.
Table 1:
| Supplementary material | Embodiment 1 (mg) | Embodiment 2 (mg) | Embodiment 3 (mg) |
| Apomorphine hydrochloride sorbierite lactose sweet mellow wine citric acid Sucralose light blue ethanedioic acid triethylammonium tetrakis disodium vitamin C magnesium stearate talc | ????1 ????70 ????10 ????14 ????1 ????0.07 ????0.015 ????0.02 ????1 ????0.5 ????3 | ????15 ????40 ????20 ????20 ????1 ????0.07 ????0.015 ????0.02 ????1 ????0.5 ????3 | ????30 ????20 ????25 ????30 ????1 ????0.07 ????0.015 ????0.02 ????1 ????0.5 ????3 |
| Total sheet is heavy: 100.605mg | |||
Embodiment 1
The supplementary material consumption is with reference to table 1.Apomorphine hydrochloride and citric acid are mixed, and then, the principle and the sorbitol that progressively increase by equivalent mix, and mixed powder is placed on mixing in the quick mixer granulator, adds the lactose and the mannitol of recipe quantity again, mixes fast.Disodiumedetate, sucralose be dissolved in 70% the alcohol-water solution, add an amount of light blue, as binding agent.In the powder of quick stirring, add binding agent.Stirred 5 minutes fast.Soft material is crossed 24 mesh sieves and is granulated.The air blast oven dry.Dried granule 20 mesh sieve granulate.Seven millimeters scrobicula stampings, hardness 50N.
Use digestion instrument, 500ml water, 37 degrees centigrade, basket method 50 is changeed, and does stripping and measures.Stripping curve as shown in Figure 1.
In the disintegration tester, 37 degrees centigrade, do and dissolve test.Get a slice and place the Sublingual, do the oral cavity and dissolve test.The results are shown in Table 2 (n=6).
Embodiment 1
The stripping curve of Fig. 1 apomorphine hydrochloride sublingual tablets
The solution time of table 2 apomorphine hydrochloride sublingual tablets
| The slice, thin piece numbering | Solution time table (min) in the disintegration tester of Chinese Pharmacopoeia regulation | The slice, thin piece numbering | Oral cavity solution time (min) |
| ????1 ????2 ????3 ????4 ????5 ????6 | ????3.9 ????3.8 ????3.1 ????3.1 ????3.2 ????3.9 | ????1 ????2 ????3 ????4 ????5 ????6 | ????12.5 ????13.5 ????14.1 ????13.2 ????12.5 ????14.2 |
| Average solution time | ????3.5 | Average solution time | ????13.3 |
Embodiment 2
The supplementary material consumption is with reference to table 1.Apomorphine hydrochloride and citric acid are mixed, and then, the principle and the sorbitol that progressively increase by equivalent mix, and mixed powder is placed on mixing in the quick mixer granulator, adds the lactose and the mannitol of recipe quantity again, mixes fast.Disodiumedetate, sucralose be dissolved in 70% the alcohol-water solution, add an amount of light blue, as binding agent.In the powder of quick stirring, add binding agent.Stirred 5 minutes fast.Soft material is crossed 24 mesh sieves and is granulated.The air blast oven dry.Dried granule 20 mesh sieve granulate.Seven millimeters scrobicula stampings, hardness 50N.
Use digestion instrument, 500ml water, 37 degrees centigrade, to do stripping and measure, basket method 50 is changeed.Stripping curve as shown in Figure 2.
In the disintegration tester, 37 degrees centigrade, do and dissolve test.Get a slice and place the Sublingual, do the oral cavity and dissolve test.The results are shown in Table 3 (n=6).
Embodiment 2
The stripping curve of Fig. 2 apomorphine hydrochloride sublingual tablets
The solution time of table 3 apomorphine hydrochloride sublingual tablets
| The slice, thin piece numbering | Solution time table (min) in the disintegration tester of Chinese Pharmacopoeia regulation | The slice, thin piece numbering | Oral cavity solution time (min) |
| ????1 ????2 ????3 ????4 ????5 ????6 | ????3.9 ????3.8 ????3.1 ????3.1 ????3.2 ????3.9 | ????1 ????2 ????3 ????4 ????5 ????6 | ????15.6 ????15.3 ????12.1 ????12.2 ????12.8 ????15.6 |
| Average solution time | ????3.5 | Average solution time | ????14.0 |
Embodiment 3
The supplementary material consumption is with reference to table 1.Apomorphine hydrochloride and citric acid are mixed, and then, the principle and the sorbitol that progressively increase by equivalent mix, and mixed powder is placed on mixing in the quick mixer granulator, adds the lactose and the mannitol of recipe quantity again, mixes fast.Disodiumedetate, sucralose be dissolved in 70% the alcohol-water solution, add an amount of light blue, as binding agent.In the powder of quick stirring, add binding agent.Stirred 5 minutes fast.Soft material is crossed 24 mesh sieves and is granulated.The air blast oven dry.Dried granule 20 mesh sieve granulate.Seven millimeters scrobicula stampings, hardness 50N.
Use digestion instrument, 500ml water, 37 degrees centigrade, to do stripping and measure, basket method 50 is changeed.Stripping curve as shown in Figure 3.
In the disintegration tester, 37 degrees centigrade, do and dissolve test.Get a slice and place the Sublingual, do the oral cavity and dissolve test.The results are shown in Table 4 (n=6).
Embodiment 3
The stripping curve of Fig. 3 apomorphine hydrochloride sublingual tablets
The solution time of table 4 apomorphine hydrochloride sublingual tablets
| The slice, thin piece numbering | Solution time table (min) in the disintegration tester of Chinese Pharmacopoeia regulation | The slice, thin piece numbering | Oral cavity solution time (min) |
| ??1 ??2 ??3 ??4 ??5 ??6 | ????3.4 ????3.3 ????3.8 ????3.6 ????3.0 ????3.4 | ??1 ??2 ??3 ??4 ??5 ??6 | ????15.2 ????15.3 ????13.1 ????14.2 ????12.8 ????12.6 |
| Average solution time | ????3.4 | Average solution time | ????13.9 |
Table 5
| Supplementary material | Embodiment 4 (mg) | Embodiment 5 (mg) | Embodiment 6 (mg) |
| Loratadine sorbierite lactose sweet mellow wine citric acid light blue magnesium stearate talc | ????10 ????60 ????14 ????11 ????0.5 ????0.015 ????0.5 ????3 | ????20 ????40 ????18 ????18 ????0.5 ????0.015 ????0.5 ????3 | ????30 ????20 ????23 ????23 ????0.5 ????0.015 ????0.5 ????3 |
| Total sheet is heavy: 100.015mg | |||
Embodiment 4
The supplementary material consumption is with reference to table 5.Loratadine and citric acid are mixed, and then, the principle and the sorbitol that progressively increase by equivalent mix, and mixed powder is placed on mixing in the quick mixer granulator, adds the lactose and the mannitol of recipe quantity again, mixes fast.In 70% the alcohol-water solution, add an amount of light blue, as binding agent.In the powder of quick stirring, add binding agent.Stirred 5 minutes fast.Soft material is crossed 24 mesh sieves and is granulated.The air blast oven dry.Dried granule 20 mesh sieve granulate.Seven millimeters scrobicula stampings, hardness 50N.
Use digestion instrument, 500ml water, 37 degrees centigrade, to do stripping and measure, basket method 50 is changeed.Stripping curve as shown in Figure 4.
In the disintegration tester, 37 degrees centigrade, do the external test of dissolving.Get a slice and place the Sublingual, do the oral cavity and dissolve test.The results are shown in Table 6 (n=6).
Embodiment 4
The stripping curve of Fig. 4 loratadine Sublingual tablet
The solution time of table 6 loratadine Sublingual tablet
| The slice, thin piece numbering | Solution time table (min) in the disintegration tester of Chinese Pharmacopoeia regulation | The slice, thin piece numbering | Oral cavity solution time (min) |
| ????1 ????2 ????3 ????4 ????5 ????6 | ????3.3 ????3.3 ????3.9 ????3.7 ????3.5 ????3.6 | ????1 ????2 ????3 ????4 ????5 ????6 | ????12.4 ????14.2 ????14.3 ????13.9 ????14.4 ????13.5 |
| Average solution time | ????3.6 | Average solution time | ????13.8 |
Embodiment 5
The supplementary material consumption is with reference to table 5.Loratadine and citric acid are mixed, and then, the principle and the sorbitol that progressively increase by equivalent mix, and mixed powder is placed on mixing in the quick mixer granulator, adds the lactose and the mannitol of recipe quantity again, mixes fast.In 70% the alcohol-water solution, add an amount of light blue, as binding agent.In the powder of quick stirring, add binding agent.Stirred 5 minutes fast.Soft material is crossed 24 mesh sieves and is granulated.The air blast oven dry.Dried granule 20 mesh sieve granulate.Seven millimeters scrobicula stamping hardness 50N.
Use digestion instrument, 500ml water, 37 degrees centigrade, to do stripping and measure, basket method 50 is changeed.Stripping curve as shown in Figure 5.
In the disintegration tester, 37 degrees centigrade, do and dissolve test.Get a slice and place the Sublingual, do the oral cavity and dissolve test.The results are shown in Table 7 (n=6).
Embodiment 5
The stripping curve of Fig. 5 loratadine Sublingual tablet
The solution time of table 7 loratadine Sublingual tablet
| The slice, thin piece numbering | Solution time table (min) in the disintegration tester of Chinese Pharmacopoeia regulation | The slice, thin piece numbering | Oral cavity solution time (min) |
| ????1 ????2 ????3 ????4 ????5 ????6 | ????3.5 ????3.2 ????3.4 ????3.9 ????3.7 ????3.6 | ????1 ????2 ????3 ????4 ????5 ????6 | ????13.8 ????11.5 ????11.4 ????14.2 ????14.2 ????12.6 |
| Average solution time | ????3.6 | Average solution time | ????12.9 |
Embodiment 6
The supplementary material consumption is with reference to table 5.Loratadine and citric acid are mixed, then, mix by progressively increase principle and sorbitol of equivalent, mixed powder is placed on mixing in the quick mixer granulator, adds the lactose and the mannitol of recipe quantity again, mixes fast.70% alcohol-water solution adds an amount of light blue, as binding agent.In the powder of quick stirring, add binding agent.Stirred 5 minutes fast.Soft material is crossed 24 mesh sieves and is granulated.The air blast oven dry.Dried granule 20 mesh sieve granulate.Seven millimeters scrobicula stampings, hardness 50N.
Use digestion instrument, 500ml water, 37 degrees centigrade, to do stripping and measure, basket method 50 is changeed.Stripping curve as shown in Figure 6.
In the disintegration tester, 37 degrees centigrade, do and dissolve test.Get a slice and place the Sublingual, do the oral cavity and dissolve test.The results are shown in Table 8 (n=6).
Embodiment 6
The stripping curve of Fig. 6 loratadine Sublingual tablet
The solution time of table 8 loratadine Sublingual tablet
| The slice, thin piece numbering | Solution time table (min) in the disintegration tester of Chinese Pharmacopoeia regulation | The slice, thin piece numbering | Oral cavity solution time (min) |
| ????1 ????2 ????3 ????4 ????5 ????6 | ????4.0 ????3.3 ????4.0 ????3.2 ????3.8 ????4.2 | ????1 ????2 ????3 ????4 ????5 ????6 | ????14.0 ????11.4 ????14.1 ????11.3 ????13.4 ????14.5 |
| Average solution time | ????3.8 | Average solution time | ????13.1 |
Embodiment 7 hardness and the time relationship external, that dissolve in the Sublingual
To be pressed into the different tablet of hardness by the granule of above each prescription, solution time is shown in table 9 and table 10.
Table 9 Sublingual tablet hardness and external, Sublingual solution time table (n=6)
| Embodiment 1 | Embodiment 2 | Embodiment 3 | |
| The external solution time of hardness (N) (min) Sublingual solution time (min) | 20?????50?????100 3.3????3.5????3.5 13.1???13.3???13.4 | ??20?????50?????100 ??3.5????3.5????3.7 ??13.8???14.0???14.3 | ??20?????50????100 ??3.4????3.4???3.5 ??13.7???13.9??14.1 |
Table 10 Sublingual tablet hardness and external, Sublingual solution time table (n=6)
| Embodiment 4 | Embodiment 5 | Embodiment 6 | |
| The external solution time of hardness (N) (min) Sublingual solution time (min) | ?20?????50?????100 ?3.4????3.6????3.5 ?13.1???13.8???13.4 | ???20????50????100 ???3.5???3.6???3.5 ???12.8??12.9??13.2 | ???20????50????100 ???3.4???3.8???3.5 ???13.2??13.1??12.9 |
Claims (4)
1. a water soluble drug sublingual administration preparation prescription is formed, and it is characterized in that comprising aqueous soluble active constituent, penetrating agent; Medicine is slowly dissolved in 10～20 minutes in the Sublingual, and the solution time of medicine and tablet hardness change irrelevant.
2. forming according to the prescription of the described preparation of claim 1, comprise aqueous soluble active constituent, can be apomorphine hydrochloride, buprenorphin hydrochloride, dihydroetorphine hydrochlorate, loratadine; Preferred apomorphine hydrochloride.Effective ingredient consumption is 1mg～30mg.
3. form according to the prescription of the described preparation of claim 1, wherein penetrating agent can be sucrose, lactose, sorbitol, mannitol, fructose, xylitol, glucose or their compositions, and the ratio in prescription is 45%～95%.
4. require the compositions of the preferred sorbitol of penetrating agent, mannitol and lactose in 3, wherein to account for the ratio of compositions be 40%～80% to sorbitol.Preferred proportion is 60%.
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| CNB2004100307482A CN100500151C (en) | 2004-04-02 | 2004-04-02 | Water-soluble medicine sublingual-medicating formulation |
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| CNB2004100307482A CN100500151C (en) | 2004-04-02 | 2004-04-02 | Water-soluble medicine sublingual-medicating formulation |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103476372A (en) * | 2010-12-16 | 2013-12-25 | Cynapsus疗法有限公司 | Sublingual films |
| US9481681B2 (en) | 2008-12-08 | 2016-11-01 | Euro-Celtique S.A. | Dihydroetorphines and their preparation |
| US10898479B2 (en) | 2013-05-30 | 2021-01-26 | Euro-Celtique S.A. | Dihydroetorphine for the provision of pain relief and anaesthesia |
| CN113304177A (en) * | 2021-06-01 | 2021-08-27 | 金华寿仙谷药业有限公司 | Wall-broken ganoderma lucidum spore powder extract and preparation method and application of disintegrating tablet thereof |
-
2004
- 2004-04-02 CN CNB2004100307482A patent/CN100500151C/en not_active Expired - Lifetime
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9481681B2 (en) | 2008-12-08 | 2016-11-01 | Euro-Celtique S.A. | Dihydroetorphines and their preparation |
| US10745406B2 (en) | 2008-12-08 | 2020-08-18 | Euro-Celtique S.A. | Dihydroetorphines and their preparation |
| CN103476372A (en) * | 2010-12-16 | 2013-12-25 | Cynapsus疗法有限公司 | Sublingual films |
| CN103476372B (en) * | 2010-12-16 | 2016-04-27 | Cynapsus疗法有限公司 | sublingual film |
| US10898479B2 (en) | 2013-05-30 | 2021-01-26 | Euro-Celtique S.A. | Dihydroetorphine for the provision of pain relief and anaesthesia |
| CN113304177A (en) * | 2021-06-01 | 2021-08-27 | 金华寿仙谷药业有限公司 | Wall-broken ganoderma lucidum spore powder extract and preparation method and application of disintegrating tablet thereof |
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| Publication number | Publication date |
|---|---|
| CN100500151C (en) | 2009-06-17 |
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