CN104306338A - Granule containing acrylic acid resin and desloratadine, and preparation method thereof - Google Patents
Granule containing acrylic acid resin and desloratadine, and preparation method thereof Download PDFInfo
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- CN104306338A CN104306338A CN201410489302.XA CN201410489302A CN104306338A CN 104306338 A CN104306338 A CN 104306338A CN 201410489302 A CN201410489302 A CN 201410489302A CN 104306338 A CN104306338 A CN 104306338A
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- desloratadine
- acrylic resin
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- granule
- essence
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Abstract
The present invention discloses a method for preparing desloratadine particles by using a solvent drying method, wherein the method is characterized in that the drug and an acrylic acid resin are prepared into a clathrate through a solvent drying method, and then the particle and an appropriate auxiliary material (such as a filler, a flavoring agent, a disintegrating agent, a suspending aid and the like) are completely mixed to granulate. With the process, the taste can be significantly improved, and the drug stability can be increased.
Description
Technical field
The invention belongs to field of medicaments, be specifically related to a kind of solvent seasoning legal system that adopts for the method for Desloratadine granule.
Background technology
Along with social development, environmental pollution is on the rise, and rhythm of life accelerates, and pressure becomes large, and these factors all cause anaphylactic disease sickness rate to remain high, and have a strong impact on the quality of life of people, wherein allergic rhinitis, the anaphylaxis dermatosis such as urticaria are particularly remarkable.
The long-acting tricyclic antidepressants antihistaminic that Desloratadine (Desloratadine) is non-sedating is the active metabolite of loratadine, by optionally antagonism peripheral H1-receptor, alleviates the related symptoms of allergic rhinitis or chronic idiopathic urticaria.
Research display, Desloratadine not easily passs through blood brain barrier, be applicable to the related symptoms of rapid recovery allergic rhinitis, as sneeze, rhinorrhea and rhinocnesmus, nasal decongestion/nasal obstruction, and ophthalmic pruritus, to shed tears and congested, palate is itched and is coughed, also can be used for the related symptoms of relieve chronic idiopathic urticaria as pruritus, and welt quantity and the size of urticaria can be reduced, and the symptom of other anaphylaxis dermatosis.
The promising tablet of dosage form, syrup etc. that Desloratadine is common on market at home.But because tablet is not suitable for patient and the children taking of dysphagia, syrup is not easy to store and carry, perishable in the process of storage, the careless slightly curative effect that will affect medicine, therefore develop granule to increase the portability of patient's compliance and shipping storage, improve the stability of medicine simultaneously.Due to this medicine bitter in the mouth, and less stable, domesticly mainly contain powder coating for current technology used, but powder coating yield is lower, and requires equipment and process harsh, common working condition cannot meet.The solvent seasoning legal system that this method is is for clathrate, and technique is simple, and institute's use equipment is conventional equipment, and normal productive plant can meet.Desloratadine is slightly soluble in water, and taste is extremely bitter, adopts common correctives, cannot reach the effect of taste masking, and easily and saccharide react, as sucrose, lactose etc., cause related substance to raise.And in granule, generally all need to add soluble saccharide as filler, the preparation method of therefore plain particles agent is not suitable for Desloratadine granule.This patent adopts acrylic resin and Desloratadine to form clathrate, can cover its bad mouthfeel on the one hand, on the other hand by the parcel by acrylic resin, medicine and sugar bulking agents is isolated, and ensures the stability of medicine.
Summary of the invention
The object of the invention is to prepare a kind of good mouthfeel, preparation technology's simple possible, the Desloratadine granule of good stability.The present invention relates to a kind of solvent seasoning legal system that adopts for the method for Desloratadine granule.Medicine and acrylic resin is it is characterized in that to make solid dispersion by solvent seasoning method, i.e. clathrate, and then by this clathrate and suitable adjuvant (as: filler, correctives, disintegrating agent, suspending agent etc.) fully mixing granulation.Can significantly improve Desloratadine mouthfeel by this technique, increase the stability of medicine simultaneously.
The preparation method of clathrate is solvent seasoning method, it is characterized in that, acrylic resin and Desloratadine is fully disperseed in organic solvent, and the weight ratio of Desloratadine and acrylic resin is 1:1 ~ 1:10, and solid-liquid ratio is 1:5 ~ 1:40; Drug solution is formed after stirring, then by the organic solvent in this solution: dry removal, obtain the clathrate of Desloratadine-acrylic resin, the organic solvent added is selected from ethanol, acetone, isopropyl alcohol, chloroform, wherein preferred alcohol.Solvent drying processes is selected from spraying dry, drying under reduced pressure, and a conventional oven is dry, wherein preferably spray drying method.
In obtained clathrate, add other adjuvant again granulate, the adjuvant that can add comprises, filler, suspending agent, binding agent, correctives, lubricant, pigment etc.Wherein, filler is selected from mannitol, lactose, sucrose, maltose, soluble starch or microcrystalline Cellulose; Correctives is selected from essence, comprises apple essence, flavoring banana essence, grape essence, orange flavor; Binding agent is one or more in HPMC, PVPK30, starch, purified water and ethanol; Suspending agent is selected from xanthan gum, hypromellose, sodium carboxymethyl cellulose; Pigment comprises lemon yellow, setting sun Huang, carmine.
Adopt granule prepared by this method, good mouthfeel, dissolution rate is fast, and in 15min, stripping can reach more than 90%, and medicine stability is good, and acceleration environment places June, and related substance is qualified.
Detailed description of the invention
Below in conjunction with embodiment, the present invention is described in further detail, but be not limited to following embodiment.Wherein " % " refers to " % by weight ".
Embodiment 1
In this embodiment, the ratio of Desloratadine and acrylic resin is 1:1, and the ratio of acrylic resin and Desloratadine solid and organic solvent is 1:2, and selected organic solvent is ethanol.Each component proportion is:
| Component | Percentage ratio (%) |
| Desloratadine | 0.5 |
| Acrylic resin | 0.5 |
| Mannitol | 20 |
| Sucrose | 65 |
| Microcrystalline Cellulose | 9.0 |
| PVP K30 | 1.5 |
| Magnesium stearate | 1.0 |
| Sunset yellow | 0.5 |
| Xanthan gum | 1.0 |
| Orange flavor | 1.0 |
| Total | 100 |
Preparation technology: by the acrylic resin 5g of recipe quantity, Desloratadine 5g, join in 20g ethanol and stir 30 minutes, it is made fully to disperse, and form complex, this inclusion complex in solution is adopted spray drying method 50 DEG C of dryings, collect dried clathrate granule, add 200g mannitol again, 650g sucrose, 90g microcrystalline Cellulose, with the PVP K30 of 10%, for binding agent adopts wet granulation technology to granulate, wet granular is dry under 50 DEG C of conditions again, the solid content of binding agent accounts for 1.5% of prescription total amount, finally add 10g magnesium stearate, 5g sunset yellow, 10g xanthan gum, 10g orange flavor, mix homogeneously, according to Desloratadine content in granule, carry out packed, every bag of weight is about 1g.Cool taste band Fructus Citri sinensis fragrance, dissolution reaches more than 90%, acceleration environment June, and related substance is qualified.
Embodiment 2
In this embodiment, the ratio of Desloratadine and acrylic resin is 1:10, and the ratio of acrylic resin and Desloratadine solid and ethanol is 1:10.Each component proportion is:
| Component | Percentage ratio (%) |
| Hydrochloric acid Desloratadine | 0.5 |
| Acrylic resin | 5 |
| Mannitol | 20 |
| Sucrose | 60 |
| Microcrystalline Cellulose | 9.0 |
| Hypromellose | 1.5 |
| Magnesium stearate | 1.0 |
| Lemon yellow | 0.5 |
| Sodium carboxymethyl cellulose | 1.0 |
| Apple essence | 1.0 |
| Total | 100 |
Preparation technology: by the acrylic resin 50g of recipe quantity, Desloratadine 5g, join in 550g ethanol and stir 30 minutes, it is made fully to disperse, and form complex, this inclusion complex in solution is adopted spray drying method 70 DEG C of dryings, collect dried clathrate granule, add 200g mannitol again, 600g sucrose, 90g microcrystalline Cellulose, hypromellose with 10% is the granulation of binding agent employing wet granulation technology, wet granular is dry under 50 DEG C of conditions again, the solid content of binding agent accounts for 1.5% of prescription total amount, finally add 10g magnesium stearate, 5g lemon yellow, 10g sodium carboxymethyl cellulose, 10g apple essence, mix homogeneously, according to Desloratadine content in granule, carry out packed, every bag of weight is about 1g.Cool taste band apple aroma, dissolution reaches more than 90%, acceleration environment June, and related substance is qualified.
Embodiment 3
In this embodiment, the ratio of Desloratadine and acrylic resin is 1:5, and the ratio of acrylic resin and Desloratadine solid and ethanol is 1:5.Each component proportion is:
| Component | Percentage ratio (%) |
| Hydrochloric acid Desloratadine | 0.5 |
| Acrylic resin | 2.5 |
| Mannitol | 20 |
| Sucrose | 60 |
| Microcrystalline Cellulose | 11.5 |
| Magnesium stearate | 1.0 |
| Lemon yellow | 0.5 |
| Sodium carboxymethyl cellulose | 1.0 |
| Apple essence | 1.0 |
| Total | 100 |
Preparation technology: by the acrylic resin 25g of recipe quantity, Desloratadine 5g, join in 150 ethanol and stir 30 minutes, it is made fully to disperse, and form complex, this inclusion complex in solution is adopted spray drying method 60 DEG C of dryings, collect dried clathrate granule, add 200g mannitol again, 600g sucrose, 10g microcrystalline Cellulose, employing dry granulation process is granulated, finally add 10g magnesium stearate, 5g lemon yellow, 10g sodium carboxymethyl cellulose, 10g apple essence, mix homogeneously, according to Desloratadine content in granule, carry out packed, every bag of weight is about 1g.Cool taste band apple aroma, dissolution reaches more than 90%, acceleration environment June, and related substance is qualified.
Embodiment 4
In this embodiment, the ratio of Desloratadine and acrylic resin is 1:1, and the ratio of acrylic resin and Desloratadine solid and organic solvent is 1:2, and selected organic solvent is ethanol, adopts hypobaric drying method to remove organic solvent.Each component proportion is:
| Component | Percentage ratio (%) |
| Desloratadine | 0.5 |
| Acrylic resin | 0.5 |
| Mannitol | 20 |
| Sucrose | 65 |
| Microcrystalline Cellulose | 9.0 |
| PVP K30 | 1.5 |
| Magnesium stearate | 1.0 |
| Sunset yellow | 0.5 |
| Xanthan gum | 1.0 |
| Orange flavor | 1.0 |
| Total | 100 |
Preparation technology: by the acrylic resin 5g of recipe quantity, Desloratadine 5g, join in 20g ethanol and stir 30 minutes, it is made fully to disperse, and form complex, this inclusion complex in solution is adopted hypobaric drying method 50 DEG C of dryings, collect dried clathrate granule, add 200g mannitol again, 650g sucrose, 90g microcrystalline Cellulose, with the PVP K30 of 10%, for binding agent adopts wet granulation technology to granulate, wet granular is dry under 50 DEG C of conditions again, the solid content of binding agent accounts for 1.5% of prescription total amount, finally add 10g magnesium stearate, 5g sunset yellow, 10g xanthan gum, 10g orange flavor, mix homogeneously, according to Desloratadine content in granule, carry out packed, every bag of weight is about 1g.Cool taste band Fructus Citri sinensis fragrance, dissolution reaches more than 90%, acceleration environment June, and related substance is qualified.
Embodiment 5
Do not adopt acrylic resin to process raw material in this embodiment prescription, adopt common odor mask, the acrylic resin of 5% is changed into the mannitol of 5%, all the other adjuvants are identical with prescription 2.Each component proportion is:
| Component | Percentage ratio (%) |
| Hydrochloric acid Desloratadine | 0.5 |
| Mannitol | 25 |
| Sucrose | 60 |
| Microcrystalline Cellulose | 9.0 |
| Hypromellose | 1.5 |
| Magnesium stearate | 1.0 |
| Lemon yellow | 0.5 |
| Sodium carboxymethyl cellulose | 1.0 |
| Apple essence | 1.0 |
| Total | 100 |
Preparation technology: by the Desloratadine 5g of recipe quantity, mannitol 250g, sucrose 600g, microcrystalline Cellulose 90g, the hypromellose with 10% is the granulation of binding agent employing wet granulation technology, and wet granular is dry under 50 DEG C of conditions again, the solid content of binding agent accounts for 1.5% of prescription total amount, finally adds 10g magnesium stearate, 5g lemon yellow, 10g sodium carboxymethyl cellulose, 10g apple essence, mix homogeneously, according to Desloratadine content in granule, carry out packed, every bag of weight is about 1g.Mouthfeel is extremely bitter, and dissolution reaches more than 90%, and within 0 day, related substance exceeds standard.
。
Embodiment 6
Investigate sample indices prepared by embodiment 1,2,3,4,5, comparing result is as follows:
From embodiment 1,2,3,4 result, after adopting acrylic resin to process raw material, four equal arriving of prescription mouthfeel improve, and increase with acrylic resin consumption, bitterness is lighter, when acrylic resin consumption is 1:1, although mouthfeel has good improvement, but still there is certain bitterness, although 0 day and to accelerate after June related substance all lower than required standard, but with prescription 2,3 compare, still larger.And prescription 5 does not process raw material, adopt common odor mask, serious bitter taste, and 0 day related substance just exceeds standard.
Prescription 2,3 adopt the acrylic resin of 1:5 and 1:10 to prepare clathrate respectively, good mouthfeel, mask the bitterness of Desloratadine completely, and 0 day related substance significantly limits lower than regulation, accelerate related substance after 6 months still significantly not increase, prove to use acrylic resin to prepare Desloratadine clathrate, significantly increase the stability of medicine.
Claims (10)
1. one kind contains pharmaceutical composition of acrylic resin and Desloratadine and preparation method thereof, it is characterized in that adopting the standby solid dispersion containing Desloratadine and acrylic resin of solvent seasoning legal system, then add another or multiple auxiliary materials is prepared into granule.
2. preparation method according to claim 1, is characterized in that Desloratadine and acrylic resin to join in organic solvent with certain proportion, then except desolventizing, form solid dispersion particles, add other adjuvants again, mixing granulation, obtain Desloratadine granule.
3. according to claim 2, the part by weight of Desloratadine and acrylic resin is 1:1-1:10.
4. according to claim 3, the part by weight of Desloratadine and propenoic acid resin series compound is 1:5-1:10.
5. according to claim 2, the organic solvent added in solid dispersion preparation process is selected from ethanol, acetone, isopropyl alcohol, chloroform.
6. the organic solvent preferred alcohol according to claim 5, added in solid dispersion preparation process.
7. preparation method according to claim 1, solvent seasoning method comprises spray drying method, hypobaric drying method, oven method.
8. according to claim 7, solvent seasoning method preferably spray drying method.
9. preparation method according to claim 2, other adjuvants added comprise: filler, suspending agent, binding agent, correctives, lubricant, pigment.
10. according to claim 9, filler is selected from mannitol, lactose, sucrose, maltose, soluble starch or microcrystalline Cellulose; Correctives is selected from essence, comprises apple essence, flavoring banana essence, grape essence, orange flavor; Binding agent is one or more in HPMC, PVPK30, starch, purified water and ethanol; Suspending agent is selected from xanthan gum, hypromellose, sodium carboxymethyl cellulose; Pigment comprises lemon yellow, setting sun Huang, carmine.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410489302.XA CN104306338A (en) | 2014-09-24 | 2014-09-24 | Granule containing acrylic acid resin and desloratadine, and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410489302.XA CN104306338A (en) | 2014-09-24 | 2014-09-24 | Granule containing acrylic acid resin and desloratadine, and preparation method thereof |
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| CN104306338A true CN104306338A (en) | 2015-01-28 |
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| CN201410489302.XA Pending CN104306338A (en) | 2014-09-24 | 2014-09-24 | Granule containing acrylic acid resin and desloratadine, and preparation method thereof |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105343009A (en) * | 2015-11-09 | 2016-02-24 | 米克珐玛（苏州）生物医药有限公司 | Rupatadine fumarate taste-masking dry suspension |
| CN105963264A (en) * | 2016-05-16 | 2016-09-28 | 浙江凯润制药有限公司 | Desloratadine sublingual tablet and preparation method thereof |
| WO2022106923A1 (en) | 2020-11-18 | 2022-05-27 | BioPharma Synergies, S. L. | Orodispersible powder composition comprising an antihistamine compound |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105343009A (en) * | 2015-11-09 | 2016-02-24 | 米克珐玛（苏州）生物医药有限公司 | Rupatadine fumarate taste-masking dry suspension |
| CN105343009B (en) * | 2015-11-09 | 2019-02-12 | 苏州维高能生物技术有限公司 | Rupatadine fumarate taste masking dry suspensoid agent |
| CN105963264A (en) * | 2016-05-16 | 2016-09-28 | 浙江凯润制药有限公司 | Desloratadine sublingual tablet and preparation method thereof |
| WO2022106923A1 (en) | 2020-11-18 | 2022-05-27 | BioPharma Synergies, S. L. | Orodispersible powder composition comprising an antihistamine compound |
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Application publication date: 20150128 |