CN101269222A - Smell concealing composition of hydrochloric selegiline, and preparation containing the composition - Google Patents
Smell concealing composition of hydrochloric selegiline, and preparation containing the composition Download PDFInfo
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- CN101269222A CN101269222A CNA2007100645849A CN200710064584A CN101269222A CN 101269222 A CN101269222 A CN 101269222A CN A2007100645849 A CNA2007100645849 A CN A2007100645849A CN 200710064584 A CN200710064584 A CN 200710064584A CN 101269222 A CN101269222 A CN 101269222A
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- selegilinehydrochloride
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Abstract
The invention provides a Selegiline hydrochloride smell covering compound, which contains sugar alcohol, corrective agent, gelatin, and xanthan gum, and is treated by special process and is evenly dispersed with Selegiline hydrochloride. The compound covers the stimulating taste of Selegiline hydrochloride, is used for preparing the orally disintegrating tablet, and is used for treating Parkinsons disease.
Description
Technical field
The present invention relates to a kind of taste masking compositions of SelegilineHydrochloride and the oral cavity disintegration tablet that uses said composition to prepare.
Background technology
Parkinson is the common refreshing smart system of maincenter degenerative disease, be mainly in person in middle and old age, prevalence is approximately 1% among the over-65s crowd, parkinson disease in late period levodopa class preparation on probation for a long time, often occur that curative effect goes down and long-term DOPA treatment syndrome, comprise that motion is bad, symptom fluctuation, agent end phenomenon, on-off phenomenon etc.Use catechol oxygen position monomethyl transferring enzyme (COMT) inhibitor at present, as Tolcapone and Entacapone.The former suppresses in the brain and the COMT of brain outer (intestinal regulating liver-QI); The latter suppresses the outer COMT of brain.The dopamine degraded is reduced, thereby increase DOPAMINE CONTENT IN RABBIT in the brain relatively, make disturbances in patients with Parkinson disease doing well,improving in late period.But Tolcapone has serious hepatotoxicity, and Entacopane is also owing to other reason not seen widespread use.SelegilineHydrochloride is a selectivity β MAO-B B inhibitor, and it can selectivity irreversibly suppresses dopamine and is degraded to 4-hydroxy-3-methoxy-.alpha.-toluic acid., thereby has increased accumulating of dopamine; Simultaneously also can reduce the reuptake of presynaptic membrane to dopamine, promote the release of dopamine, these have all prolonged action time exogenous and the endogenous dopamine, and the clinical symptoms of disturbances in patients with Parkinson disease is improved.In addition; the neuroprotective of SelegilineHydrochloride has received increasing concern in recent years; manyly studies confirm that it can resist the Oxidation of oxygen-derived free radicals; raise superoxide dismutase and hydrogen peroxide enzyme level; the apoptosis that postpones cell under the serum-free condition, the decline of the mitochondrial membrane potential that the prevention apoptosis brings out.
The effect of taking medicine for the patient that guarantees to suffer from parkinson, prepare and a kind ofly in the oral cavity, need not obey water, also need not to chew, place on the tongue, after meeting rapid dissolving of saliva or disintegrate, the SelegilineHydrochloride oral cavity disintegration tablet of borrowing swallowing act to go into the stomach onset is a research topic highly significant.
In the oral cavity disintegration tablet kind of FDA listing, preparation process is mainly taked following two kinds of methods: freeze-drying (Zydis method) and direct compression process (Orasolv method).Wherein freeze-drying and common freeze drying process, for example powder pin technology difference mainly is that principal agent and adjuvant quantitatively are divided in the fixed mold, lyophilizing is anhydrated, and makes the solid preparation of high porosity.This method is a Britain R.P.Scherer house journal, and each drugmaker takes the mode of consigned processing to carry out the oral cavity disintegration tablet preparation by Scherer company; And the Orasolv method is to take to become the granule taste masking with gelatin, microcrystalline Cellulose parcel principal agent earlier, adds the mannitol of more amount, and other adds a small amount of effervescent, disintegrating agent, correctives and lubricant, forms with less pressure direct compression.Cima company has this patent technology, and each drugmaker adopts the mode of consigned processing to be processed by Cima company.Present above two kinds of methods Orally disintegrating piece preparation method that is comparative maturities, but its particularity is all arranged, to process conditions and equipment requirements than higher.Research and develop at home in the process of this type of preparation, as copy above-mentioned two kinds of technologies to should be taken into account the patent infringement problem.
When taking owing to oral cavity disintegration tablet simultaneously is disintegrate in the oral cavity, so adopt necessary method to cover the bad sense of taste that medicine produces in the oral cavity, patient can not produced conflict psychology to become research when medication and produce one of matter of utmost importance that oral cavity disintegration tablet institute must solution.Yet, taste beastly is arranged all for most drug.In the pharmaceutics field, mainly be by the beta-cyclodextrin inclusion compound effect, utilize solid dispersion technology or in compositions, add means such as correctives and reach the effect that medicine hides flavor.But those skilled in the art know when adopting beta-cyclodextrin inclusion compound effect and solid dispersion technology to hide flavor, and condition is wayward, and final products must verify that as X-diffraction, differential thermal analysis (DSC) etc., process is numerous and diverse through any special measures.
The method that adds correctives in compositions only is applicable to that also crude drug not have under the lighter situation of big zest and bitterness, and for the zest of some crude drug own especially greatly or bitterness when heavier, this method does not then have great role.
Patent CN00807309.0 discloses the preparation method of the fast-dispersing type that comprises fish glue, this patent adopts the fish glue of not gelation to do carrier, fish glue is preferably obtained by cold water fish simultaneously, and is the fish glue of not gelation type, has increased production cost and technology difficulty greatly.
Patent CN01822381 provides a kind of preparation that is used for active component, can cover the disagreeable taste of medicine, but its technology difficulty is bigger, and the particle size that requires separate unit increases technology difficulty between 50-80 μ m, and process is wayward.
Summary of the invention
It is simple to the purpose of this invention is to provide a kind of technology, and the SelegilineHydrochloride taste masking compositions that product hardness is higher can be covered the zest taste of SelegilineHydrochloride.Said composition can be further used for preparing oral cavity disintegration tablet, and the intraoral disintegration time of oral cavity disintegration tablet is not had influence; But not only be confined to oral cavity disintegration tablet, also can be used in other oral formulations, as dispersible tablet, buccal tablet, dry suspension etc.This oral cavity disintegration tablet need not be obeyed water in the oral cavity, also need not to chew, and places on the tongue, after rapid dissolving of chance saliva or the disintegrate, borrows swallowing act to go into the stomach onset and gets final product.
A kind of effective and technology is easy, be easy to the Orally disintegrating piece preparation method of molding in order to find to taste masking, the applicant is through discovering in a large number, SelegilineHydrochloride is mixed with sugar alcohol and a spot of correctives, gelatin and xanthan gum and handle through special process, after SelegilineHydrochloride is uniformly dispersed, find to cover effectively the zest mouthfeel of SelegilineHydrochloride pleasantly surprisedly, simultaneously intraoral disintegration time of oral cavity disintegration tablet of preparation is not had influence.This method also can be used for the medicine that other bitterness is heavier or zest is bigger.
Technical scheme of the present invention can be done the binding agent granulation with the aqueous solution or the alcoholic solution of xanthan gum for behind SelegilineHydrochloride and sugar alcohol, correctives and the gelatin mix homogeneously, promptly gets SelegilineHydrochloride taste masking compositions behind the wet grain drying.
Technical scheme of the present invention also can for SelegilineHydrochloride, sugar alcohol, correctives, gelatin and xanthan gum common water-soluble after, be spin-dried for or remove to desolvate in Rotary Evaporators and obtain the taste masking compositions by spray drying process.
The above-mentioned two kinds of taste masking compositionss that obtain all can further prepare the SelegilineHydrochloride oral cavity disintegration tablet by adding other conventional adjuvant such as filler, disintegrating agent, correctives and lubricant.
In said composition, amount of sugar alcohol is 2～8 times of principal agent SelegilineHydrochloride; The correctives consumption is 0.004～0.02 times of SelegilineHydrochloride; The gelatin consumption is 0.04～0.2 times of SelegilineHydrochloride; The xanthan gum consumption is 0.004～0.02 times of SelegilineHydrochloride.
Sugar alcohols described in the said composition comprises one or more mixture in mannitol, sorbitol, the xylitol.
Correctives described in the said composition comprises one or more mixture in sucralose, Ai Saimi, stevioside, the aspartame.
Add filler such as sugar alcohols, starch, microcrystalline Cellulose during the pressing port cavity disintegrating tablet.
Disintegrating agent such as low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone and carboxymethyl starch sodium.
Correctives such as sweeting agent (aspartame, cyclamate, sucralose etc.) and essence.
Lubricant such as magnesium stearate, Pulvis Talci, calcium stearate, hydrogenated vegetable oil and light silicic acid anhydride.
SelegilineHydrochloride Orally disintegrating piece preparation method of the present invention can for:
(1) with SelegilineHydrochloride taste masking compositions and filler, disintegrating agent mix homogeneously.
(2) granulate by common wet granulation technology.
(3) add correctives, lubricant or disintegrating agent mixing, tabletting gets final product.
Embodiment
The present invention is further elaborated by following examples, but does not limit the scope of the invention.
Embodiment 1
1. SelegilineHydrochloride taste masking preparation of compositions:
| SelegilineHydrochloride | 3g |
| Mannitol | 6g |
| Sucralose | 0.012g |
| Gelatin | 0.12g |
| Xanthan gum | 0.012g |
| Water | 80mL |
Preparation technology: take by weighing SelegilineHydrochloride, mannitol, sucralose, gelatin and xanthan gum mix homogeneously by above-mentioned prescription, behind water dissolution, be spin-dried for by rotation thin film evaporation instrument under 50 ℃～70 ℃ conditions.It is standby that the dry thing of gained is crossed 80 mesh sieves.
2. the preparation of SelegilineHydrochloride oral cavity disintegration tablet:
| SelegilineHydrochloride taste masking compositions | 9.144g |
| Mannitol | 117.86g |
| Microcrystalline Cellulose | 60.0g |
| Low-substituted hydroxypropyl cellulose | 10.0g |
| Mentholum | 0.80g |
| Magnesium stearate | 2.00g |
| Water | In right amount |
Preparation technology: take by weighing SelegilineHydrochloride taste masking compositions and auxiliary materials and mixing according to prescription, water is granulated, and dry back adds the magnesium stearate mixing, tabletting gets final product.
Embodiment 2
1. SelegilineHydrochloride taste masking preparation of compositions:
| SelegilineHydrochloride | 5g |
| Mannitol | 20g |
| Sucralose | 0.05g |
| Gelatin | 0.5g |
| Xanthan gum | 0.05g |
| Water | 100mL |
Preparation technology: take by weighing SelegilineHydrochloride, mannitol, sucralose, gelatin and xanthan gum mix homogeneously by above-mentioned prescription, behind water dissolution, promptly in 180 ℃ of spray dryinges.
2. the preparation of SelegilineHydrochloride oral cavity disintegration tablet:
| SelegilineHydrochloride taste masking compositions | 25.6g |
| Mannitol | 118g |
| Starch | 39.2g |
| Cross-linking sodium carboxymethyl cellulose | 12.0g |
| Sucralose | 0.08g |
| Pulvis Talci | 4.00g |
| Polyvidone | In right amount |
Preparation technology: take by weighing SelegilineHydrochloride compositions and auxiliary materials and mixing according to prescription, 5% polyvidone aqueous solution is granulated, and mix with Pulvis Talci dry back, tabletting gets final product.
Embodiment 3
1. SelegilineHydrochloride taste masking preparation of compositions:
| SelegilineHydrochloride | 3g |
| Mannitol | 24g |
| Ai Sai honey | 0.06g |
| Gelatin | 0.6g |
| Xanthan gum | 0.06g |
| Water | 100mL |
Preparation technology: take by weighing SelegilineHydrochloride, mannitol, Ai Saimi, gelatin and xanthan gum mix homogeneously by above-mentioned prescription, behind water dissolution, promptly in 180 ℃ of spray dryinges.
2. the preparation of SelegilineHydrochloride oral cavity disintegration tablet:
| SelegilineHydrochloride taste masking compositions | 27.7g |
| Mannitol | 80.0g |
| Microcrystalline Cellulose | 76.7g |
| Polyvidone | 12g |
| Flavoring orange essence | 1.6g |
| Magnesium stearate | 2.0g |
| Water | In right amount |
Preparation technology: take by weighing SelegilineHydrochloride taste masking compositions and auxiliary materials and mixing according to prescription, water is granulated, and dry back adds the magnesium stearate mixing, tabletting gets final product.
Embodiment 4
1. SelegilineHydrochloride taste masking preparation of compositions:
| SelegilineHydrochloride | 5g |
| Mannitol | 10g |
| Sucralose | 0.02g |
| Gelatin | 0.2g |
| Xanthan gum | 0.02g |
Preparation technology: take by weighing SelegilineHydrochloride, mannitol, sucralose, gelatin mix homogeneously by above-mentioned prescription, granulate, under 50 ℃～70 ℃ conditions, dry wet granular, sieve promptly with xanthan gum solution.
2. the preparation of SelegilineHydrochloride oral cavity disintegration tablet:
| SelegilineHydrochloride taste masking compositions | 9.144g |
| Sorbitol | 120.0g |
| Starch | 57.1g |
| Low-substituted hydroxypropyl cellulose | 8.8g |
| Aspartame | 1.0g |
| Magnesium stearate | 2.00g |
| Water | In right amount |
Preparation technology: take by weighing SelegilineHydrochloride taste masking compositions and auxiliary materials and mixing according to prescription, water is granulated, and the mixing of 50 ℃～70 ℃ dry back adding magnesium stearate, tabletting get final product.
Embodiment 5
1. SelegilineHydrochloride taste masking preparation of compositions:
| SelegilineHydrochloride | 3g |
| Mannitol | 12g |
| Sucralose | 0.03g |
| Gelatin | 0.3g |
| Xanthan gum | 0.03g |
Preparation technology: take by weighing SelegilineHydrochloride, mannitol, sucralose, gelatin mix homogeneously by above-mentioned prescription, granulate, under 50 ℃～70 ℃ conditions, dry wet granular, sieve promptly with the xanthan gum alcoholic solution.
2. the preparation of SelegilineHydrochloride oral cavity disintegration tablet:
| SelegilineHydrochloride taste masking compositions | 24.6g |
| Sorbitol | 119g |
| Microcrystalline Cellulose | 38.2g |
| Low-substituted hydroxypropyl cellulose | 13.0g |
| Sucralose | 0.08g |
| Magnesium stearate | 4.00g |
| Water | In right amount |
Preparation technology: take by weighing SelegilineHydrochloride taste masking compositions and auxiliary materials and mixing according to prescription, water is granulated, and the mixing of 50 ℃～70 ℃ dry back adding magnesium stearate, tabletting get final product.
Embodiment 6,
1. SelegilineHydrochloride taste masking preparation of compositions:
| SelegilineHydrochloride | 5g |
| Mannitol | 40g |
| Sucralose | 0.1g |
| Gelatin | 1g |
| Xanthan gum | 0.1g |
Preparation technology: take by weighing SelegilineHydrochloride, mannitol, sucralose, gelatin mix homogeneously by above-mentioned prescription, granulate, under 50 ℃～70 ℃ conditions, dry wet granular, sieve promptly with xanthan gum solution.
2. the preparation of SelegilineHydrochloride oral cavity disintegration tablet:
| SelegilineHydrochloride taste masking compositions | 27.7g |
| Mannitol | 86.0g |
| Microcrystalline Cellulose | 74.7g |
| Polyvidone | 8g |
| Flavoring orange essence | 1.6g |
| Magnesium stearate | 2.0g |
| Water | In right amount |
Preparation technology: take by weighing SelegilineHydrochloride taste masking compositions and auxiliary materials and mixing according to prescription, water is granulated, and the mixing of 50 ℃～70 ℃ dry back adding magnesium stearate, tabletting get final product.
Embodiment 7 (comparative example)
1. SelegilineHydrochloride taste masking preparation of compositions:
| SelegilineHydrochloride | 5g |
| Mannitol | 40g |
| Sucralose | 0.1g |
| Gelatin | 1g |
| Xanthan gum | 0.1g |
Preparation technology: take by weighing the simple mix homogeneously of SelegilineHydrochloride, mannitol, sucralose, gelatin and xanthan gum promptly by above-mentioned prescription.
2. the preparation of SelegilineHydrochloride oral cavity disintegration tablet:
| SelegilineHydrochloride taste masking compositions | 27.7g |
| Mannitol | 86.0g |
| Microcrystalline Cellulose | 74.7g |
| Polyvidone | 8g |
| Flavoring orange essence | 1.6g |
| Magnesium stearate | 2.0g |
| Water | In right amount |
Preparation technology: take by weighing SelegilineHydrochloride taste masking compositions and auxiliary materials and mixing according to prescription, aqueous solution is granulated, and the mixing of 50 ℃～70 ℃ dry back adding magnesium stearate, tabletting get final product.
Select 6 volunteers that the sample of the various embodiments described above is carried out mouthfeel and Orally disintegrating time detecting, comprehensively its result, average, mouthfeel and Orally disintegrating time detecting the results are shown in Table 1.
The detection method of Orally disintegrating time is: select different experimenters, put into oral cavity disintegration tablet on the tongue and pick up counting, the slight friction of maxillary and tongue last slice is taken away the sheet surface by the part of saliva dissolves, stops timing in mouth when no solid or grittiness.
The mouthfeel of each embodiment of table 1 and mouth collapse the time limit
[notes] +++: it is fabulous, ++: good ,+: general ,-: it is relatively poor,--: poor,---: extreme difference
Conclusion: after SelegilineHydrochloride and mannitol, sucralose, gelatin and xanthan gum be prepared into the taste masking compositions by special process, covered the zest of medicine effectively, and to there not being influence the disintegration of using the oral cavity disintegration tablet that said composition is prepared from.Its preparation method is simple and easy to do simultaneously, and cost is low, has proved that this taste masking compositions has excellent characteristic.
Claims (9)
1. the taste masking compositions of a SelegilineHydrochloride is characterized in that it contains sugar alcohol, correctives, gelatin and xanthan gum, and said composition can be covered the zest mouthfeel of SelegilineHydrochloride.
2. taste masking compositions as claimed in claim 1, it is characterized in that the consumption of sugar alcohol wherein is 2～8 times of SelegilineHydrochloride, the acesulfame potassium consumption is 0.004～0.02 times of SelegilineHydrochloride, the gelatin consumption is 0.04～0.2 times of SelegilineHydrochloride, and the xanthan gum consumption is 0.004～0.02 times of SelegilineHydrochloride.
3. taste masking compositions as claimed in claim 1 is characterized in that described sugar alcohol comprises in mannitol, sorbitol, the xylitol one or more mixture.
4. taste masking compositions as claimed in claim 1 is characterized in that described correctives comprises sucralose, stevioside, acesulfame potassium, the mixture of one or more of aspartame.
5. taste masking compositions as claimed in claim 1, it is characterized in that in its preparation process with SelegilineHydrochloride, sugar alcohol, acesulfame potassium, gelatin and xanthan gum common water-soluble after, be spin-dried for or spray drying process removes and desolvates in Rotary Evaporators.
6. taste masking compositions as claimed in claim 1 is characterized in that in its preparation process xanthan gum is made binding agent behind the water-soluble or ethanol, and the powder mixture of SelegilineHydrochloride, mannitol, sucralose, gelatin is granulated.
7. an oral cavity disintegration tablet is characterized in that containing the described SelegilineHydrochloride taste masking of claim 1 compositions, in intraoral disintegration time less than 60 seconds and have the mouthfeel of sense.
8. oral cavity disintegration tablet as claimed in claim 7, the taste masking combination system that it is characterized in that its contained SelegilineHydrochloride with SelegilineHydrochloride, sugar alcohol, acesulfame potassium, gelatin and xanthan gum common water-soluble after, be spin-dried for or spray drying process removes to desolvate and obtains in Rotary Evaporators.
9. oral cavity disintegration tablet as claimed in claim 7, described sugar alcohol comprise mannitol, sorbitol, one or more mixture of xylitol.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007100645849A CN101269222A (en) | 2007-03-21 | 2007-03-21 | Smell concealing composition of hydrochloric selegiline, and preparation containing the composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007100645849A CN101269222A (en) | 2007-03-21 | 2007-03-21 | Smell concealing composition of hydrochloric selegiline, and preparation containing the composition |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101269222A true CN101269222A (en) | 2008-09-24 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2007100645849A Pending CN101269222A (en) | 2007-03-21 | 2007-03-21 | Smell concealing composition of hydrochloric selegiline, and preparation containing the composition |
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| Country | Link |
|---|---|
| CN (1) | CN101269222A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105193748A (en) * | 2015-10-28 | 2015-12-30 | 陈跃坚 | Freeze-drying preparation of PD (Parkinson's disease) treatment drug and preparation method of freeze-drying preparation |
-
2007
- 2007-03-21 CN CNA2007100645849A patent/CN101269222A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105193748A (en) * | 2015-10-28 | 2015-12-30 | 陈跃坚 | Freeze-drying preparation of PD (Parkinson's disease) treatment drug and preparation method of freeze-drying preparation |
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Open date: 20080924 |