CN104922075A - Solid preparation for treating pediatric epilepsy and preparation method thereof - Google Patents
Solid preparation for treating pediatric epilepsy and preparation method thereof Download PDFInfo
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- CN104922075A CN104922075A CN201510288906.2A CN201510288906A CN104922075A CN 104922075 A CN104922075 A CN 104922075A CN 201510288906 A CN201510288906 A CN 201510288906A CN 104922075 A CN104922075 A CN 104922075A
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Abstract
The invention discloses a solid preparation for treating pediatric epilepsy and a preparation method thereof. The solid preparation is a dispersed preparation and comprises active agent core particles, wherein the core particles just comprise medicines for treating epilepsy or comprise the medicines for treating epilepsy and one or several excipients. Through the adoption of a taste masking mixture coating comprises the core particles of anti-epileptic medicines, coating particles are formed. The solid preparation is capable of masking the uncomfortable taste, has the function of improving the stability of the medicines, and can be used for solving the problem that children have difficulty in swallowing the bitter medicines.
Description
Technical field
The invention belongs to medical art, be specifically related to a kind of solid preparation for the treatment of epilepsy in childhood and preparation method thereof.
Background technology
At present, typical oral dosage form comprises tablet, capsule etc., and these conventional solid dosage forms are mainly applicable to adult.And child, old man and some especial patients are had any problem at swallow tablet and capsule, therefore usually expect to provide liquid form or can chewable solid dosage forms, when the physicochemical property of medicine is not suitable for making liquid preparation, good selection is just to provide masticable solid dosage forms, as the microgranule on papmeat (as child's food) can be sprinkling upon, because its administration is usually more convenient and simple.
To there is disintegrate result of extraction poor for the oral formulations of magnesium valproate, topiramate, lamotrigine in the market, the defect that bioavailability is low, simultaneously due to the side effect of antiepileptic, for antiepileptic or the blank of child, for injection, children's has and kind fears sense, is difficult to consciously to use with doctor, parental cooperation on time; For employing bottled oral liquid or syrup, there is the drawback of secondary or repeatedly repeated contamination; For tablet, when the not enough a slice of pediatric dose, artificially need split, cause divided dose inaccurate, some coated tablet, slow releasing tablet, dispersible tablet lose its specifically effect such as effect as protection, taste masking, controlled release, isolation after artificially splitting.In order to the unstability of the poor taste and medicine thing of covering antiepileptic, object of the present invention is exactly that provide convenience child and the inconvenient patient of swallow regular solid dosage forms takes and can the stable solid preparation of biological utilisation.
Summary of the invention
The invention provides epilepsy solid pharmaceutical preparation that a kind of patient that maybe can not swallow for child uses and preparation method thereof.
The present invention realizes especially by following technical scheme:
One treats epilepsy in childhood solid pharmaceutical preparation, this solid dosage forms is for dispensing type preparation, comprise activating agent slug particle, slug particle only comprises AED or comprises AED and one or more excipient, AED is sodium valproate, valpromide, magnesium valproate, lamotrigine, carbamazepine, oxcarbazepine, gabapentin, non-ammonia ester, phenobarbital, phenytoin Sodium, primidone, ethosuximide, levetiracetam, acetazolamide, zonisamide, mesuximide, vigabatrin, diazepam, nitrazepam, clonazepam, chlorine lorazepam and comprise the ilepcimide of plant origin, vanillin, Cornu Saigae Tataricae, one or more in asarone.
The method for the treatment of epilepsy in childhood solid pharmaceutical preparation of the present invention is as follows:
A) preparation is containing the slug particle of AED, the dry slug particle obtaining particle diameter 0.100mm-2.5mm;
B) dry slug particle 20 ~ 40 parts, solvent 20 ~ 30 parts, mask agent 2 ~ 3 parts, binding agent 1 ~ 2 part is taken by quality;
C) by after solvent and binding agent in a mixer mix homogeneously, add mask agent and form Coating Solution;
D) the slug particle Coating Solution containing AED is sprayed in fluid bed, obtain and respond with granule;
Described slug particle can form granule or globule by technology well known by persons skilled in the art, the roll extrusion and pulverizing, extruding balling-up or other method that form granule or globule as adopted.
Solid dosage forms of the present invention to dispense the microspheres form that papmeat (as child's food) is swallowed with food by patient.
Excipient of the present invention refers to be mixed with the inert substance of regular dosage form with activating agent, comprises such as diluent, binding agent, lubricant, disintegrating agent, coloring agent, flavoring agent and sweeting agent.
Described diluent includes, but is not limited to sulphuric acid dicalcium, calcium sulfate, lactose, sorbitol, microcrystalline Cellulose, Kaolin, mannitol, sodium chloride, dried starch, powdered sugar or sugared ball.
Described binding agent includes, but is not limited to paragutta, as hydroxypropyl emthylcellulose (HPMC), PVP, carboxymethyl cellulose, ethyl cellulose and methylcellulose, starch, starch,pregelatinized, gelatin, sugar (as molasses) or natural gum (as acacin, sodium alginate, panwar natural gum).Be good to use PVP (being specially American Pharmacopeia PVP) as binding agent.
Described disintegrating agent includes, but is not limited to methylcellulose, cellulose, carboxymethyl cellulose, crosslinked sodium carboxymethyl cellulose, aluminium-magnesium silicate, PVP, starch, sodium starch glycollate, starch,pregelatinized, alginic acid or guar gum.
Described mask agent includes, but is not limited to cellulose acetate, cellulose acetate-butyrate, methylcellulose, methylcellulose.
Described solvent includes, but is not limited to water, acetone, alcohols (as methanol, ethanol, isopropyl alcohol), dichloromethane, ethyl acetate, methyl ethyl ketone or its mixture.
Taste masking coating of the present invention is containing when accounting for the about 7-15% of final pharmaceutical composition weight, and what the particle diameter of Dragees granule fixed on that about 0.100mm-2.5mm obtains having satisfied taste masking and bioavailability does not spread preparation.Taste masking coating is good containing the about 9-13% of the pharmaceutical composition weight accounting for drying, accounts for about 11% for best.
Beneficial effect of the present invention is: the present invention dispenses type preparation contains antiepileptic slug particle by taste masking coating parcel, masks the poor taste of antiepileptic, can play the effect strengthening medicine stability simultaneously, solve the difficult problem that child swallows suffering.
Detailed description of the invention
Below in conjunction with embodiment, the present invention is described further, the following stated, only to preferred embodiment of the present invention, not do other forms of restriction to the present invention, any those skilled in the art may utilize the technology contents of above-mentioned announcement to be changed to the Equivalent embodiments of equal change.Everyly do not depart from the present invention program's content, any simple modification done following examples according to technical spirit of the present invention or equivalent variations, all drop in protection scope of the present invention.
The invention provides the AED solid dosage forms that a kind of patient that maybe can not swallow for child uses.More particularly, this solid dosage forms dispenses type preparation, comprises activating agent slug particle, and the second layer that this granule covers the poor taste of AED does taste coverage.Slug particle only can comprise AED, or comprises AED and one or more excipient, and they can form granule or globule by technology well known by persons skilled in the art, the roll extrusion and pulverizing, extruding balling-up or other method that form granule or globule as adopted.Again the granule of formation or globule taste masking mixture are carried out coating.Preferably solid dosage forms of the present invention to dispense the microspheres form that papmeat (as child's food) is swallowed with food by patient.
The method that preparation dispenses type preparation comprises as follows: by only containing AED granule or crystallization or also containing the slug particle taste masking mixture coating of one or more excipient, then drying.The preparation method of slug particle comprises:
First method, first AED material powder is placed in fluid unit, then the spray adhesive liquid pharmaceutically formed in acceptable solvent (as water, ethanol, acetone etc.) as PVP, starch, sucrose, syrup, HPMC by excipient well known by persons skilled in the art or spraying suspension are on powder, form granule, then dry, until solvent volatilization, obtain slug particle.
Second method, is mixed to form wet feed by Powdered or graininess AED and diluent or filler and water or pharmaceutically acceptable solvent (as water, ethanol).Mixture is mixed, until form wet feed and the good group of kneading.Then wet feed is placed in extruder and is squeezed into elongate strip.Then can be dry by mixture, suitably pulverize, maybe can be placed in suitable nodulizer and make circular medicated core, then dry.
The third method, the independent or roll extrusion together with one or more excipient by AED.Such as, Powdered or graininess AED and excipient can be mixed together, suitable binding agent and lubricant (as microcrystalline Cellulose, magnesium stearate or Pulvis Talci etc.) be provided, by a press, make mixture be pressed into wet feed.Then wet feed is pressed through a particle diameter and reduce machine, be reduced to suitable particle diameter, obtain slug particle.
The method for the treatment of epilepsy in childhood solid pharmaceutical preparation is: the drying of obtained slug particle is formed dry slug particle, coated granule is formed with taste masking mixture coating, coated granule drying is formed pharmaceutical composition, wherein the amount of taste masking mixture is the 7%-15% of pharmaceutical composition weight, and the particle diameter of dry heart granule fixes on about 0.100mm-2.5mm.
Embodiment 1 taste masking coat level is on the impact of pharmaceutical preparation
Utilize the inventive method to obtain magnesium valproate and dispense type preparation, its Chinese medicine contains the taste masking coating of 7-15% weight, and in the water of pharmaceutical composition bioavailability, solubility test the results are shown in Table 1.
Solubility test result in table 1 water
Be below specific embodiments of the invention, but scope of the present invention is not limited to following examples.
The preparation of embodiment 2 slug particle
Accurate weighing often plants the batch of core pearl composition.Suitable batch pure water is put in the jacketed pan that purging device, homogenizer and blender are housed.Add batch PVP, the mixture of gained at least 15 minutes, makes PVP be dispersed in water.Add sodium valproate (75kg), within least 15 minutes, make it disperse mixture mixing.Water is passed through interlayer.By blender and homogenizer by sodium valproate suspension homogenize about 90 minutes (scope: 80-100 minute).Proceed to stir in the follow-up each step preparing core pearl.
Prepare that there is the pump that three are sprayed pump head.The sugared ball of batch, NF are installed in fluid bed.By sugared ball fluidisation, according to certain parameter through nozzles spray sodium valproate suspension.After bed temperature reaches 60 DEG C by slug particle in 60 DEG C of dryings at least 15 minutes.
The preparation of embodiment 2 coated granule
Batch acetone and dehydrated alcohol are proceeded to suitable stainless steel cask mix.Batch PVP is added with suitable blender.With being added in whirlpool by batch cellulose acetate in suitable blender mixed process, naked eyes detect Coating Solution clarity.Refill in the Glatt fluidized bed processor of Wurster post (or equivalent), the 16/25 order core pearl (150kg) obtained in embodiment 1 is carried out fluidisation.Core pearl is sprayed until full dose Coating Solution is finished with Coating Solution.By coated pearl in about 60 DEG C of dry 28-32 minute.
Sweco sieves (or equal equipment) top and installs 16 mesh sieves, and 20 mesh sieves are installed in bottom.The coating pearl of whole batch is sieved, the extraneous coating pearl of 516-20 order.
Embodiment 3 clinical practice
The solid pharmaceutical preparation of invention effectively can treat epilepsy.Clinical experiment for many years by carrying out countless patient, its result all achieves significant curative effect.Now with the situation of 100 routine patient's pertinent clinical treatments, details are as follows.
Clinical data: collect 100 the typical patients of symptom suffering from epilepsy throughout the country, carry out the clinical experiment of preparation of the present invention.These 100 patient male 64 people, women 36 people, oldest 35 years old, minimum 3 years old, 7 years old mean age.
Therapeutic Method: treat according to embodiment 2 gained preparation, therapeutic modality is oral, and take three times on 1st, each 0.4g, the course for the treatment of is 6 months, follows up a case by regular visits to 1 year.Set up matched group, oral Carbamazepine Tablets (0.1g/ sheet)+clonazepam sheet (2mg/ sheet) and sodium valproate sheet (0.2g/ sheet)+clonazepam sheet (2mg/ sheet) simultaneously.
According to antiepileptic criterion of therapeutical effect in " drugs for nervous guideline of clinical investigations " that Ministry of Public Health is formulated:
Effective: seizure frequency reduces more than 75%, or compare prolongation more than 1 year with the intermittent time of showing effect before treatment, electroencephalogram change is clearly better, and integration reduces 70% ~ 90% before comparatively treating;
Effective: seizure frequency reduces 35% ~ 75%, or outbreak symptom obviously weakens, decreased duration more than 1/2, and electroencephalogram change take a favorable turn, and integration reduces 35% ~ 69% before comparatively treating;
Invalid: seizure frequency, degree, symptom and electroencephalogram change all without improvement or deterioration, and integration only reduces less than 35% before comparatively treating.
Therapeutic outcome statistics is as table 2:
Table 2 clinical treatment outcome
| Standard | Treatment group | Matched group |
| Effective | 78 people | 50 people |
| Effectively | 15 people | 30 people |
| Invalid | 7 people | 20 people |
Claims (8)
1. treat a preparation method for the solid preparation of epilepsy in childhood, it is characterized in that comprising the following steps:
1) preparation is containing the slug particle of AED, the dry slug particle obtaining particle diameter 0.100mm-2.5mm;
2) dry slug particle 20 ~ 40 parts, solvent 20 ~ 30 parts, mask agent 2 ~ 3 parts, binding agent 1 ~ 2 part is taken by quality;
3) by after solvent and binding agent in a mixer mix homogeneously, add mask agent and form Coating Solution;
4) the slug particle Coating Solution containing AED is sprayed in fluid bed, obtain and respond with granule;
Described slug particle is the granule that mixed liquor by being formed by excipient and antiepileptic are mixed to form.
2. a kind of preparation method for the treatment of the solid preparation of epilepsy in childhood according to claim 1, it is characterized in that: described excipient refers to be mixed with the inert substance of regular dosage form with activating agent, comprises diluent, binding agent, lubricant, disintegrating agent, coloring agent, flavoring agent or sweeting agent.
3. a kind of preparation method for the treatment of the solid preparation of epilepsy in childhood according to claim 2, is characterized in that: described diluent comprises sulphuric acid dicalcium, calcium sulfate, lactose, sorbitol, microcrystalline Cellulose, Kaolin, mannitol, sodium chloride, dried starch, powdered sugar or sugared ball.
4. a kind of preparation method for the treatment of the solid preparation of epilepsy in childhood according to claim 2, is characterized in that: described binding agent comprises hydroxypropyl emthylcellulose, PVP, carboxymethyl cellulose, ethyl cellulose and methylcellulose, starch, starch,pregelatinized, gelatin, sugar or natural gum.
5. a kind of preparation method for the treatment of the solid preparation of epilepsy in childhood according to claim 2, is characterized in that: described disintegrating agent comprises methylcellulose, cellulose, carboxymethyl cellulose, crosslinked sodium carboxymethyl cellulose, aluminium-magnesium silicate, PVP, starch, sodium starch glycollate, starch,pregelatinized, alginic acid or guar gum.
6. a kind of preparation method for the treatment of the solid preparation of epilepsy in childhood according to claim 2, is characterized in that: described mask agent comprises cellulose acetate, cellulose acetate-butyrate, methylcellulose or methylcellulose.
7. a kind of preparation method for the treatment of the solid preparation of epilepsy in childhood according to claim 2, is characterized in that: described solvent comprises one or more in water, acetone, alcohols, dichloromethane, ethyl acetate or methyl ethyl ketone.
8. the solid preparation for the treatment of epilepsy in childhood that obtains of preparation method according to claim 1, is characterized in that: in said preparation, taste masking coating is containing the 7-15% accounting for final pharmaceutical composition weight.
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| CN201510288906.2A CN104922075A (en) | 2015-05-31 | 2015-05-31 | Solid preparation for treating pediatric epilepsy and preparation method thereof |
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Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105456218A (en) * | 2015-12-07 | 2016-04-06 | 黑龙江省智诚医药科技有限公司 | Magnesium valproate sustained-release tablet and preparing method thereof |
| CN105832684A (en) * | 2016-05-11 | 2016-08-10 | 安徽省逸欣铭医药科技有限公司 | Zonisamide orally disintegrating tablets and preparation method thereof |
| CN108014079A (en) * | 2016-11-04 | 2018-05-11 | 武汉武药科技有限公司 | A kind of sabril chewable tablets and preparation method thereof |
| CN108014085A (en) * | 2016-11-04 | 2018-05-11 | 武汉武药科技有限公司 | A kind of preparation method and applications of sabril solid composite |
| CN108904495A (en) * | 2018-09-29 | 2018-11-30 | 哈尔滨珍宝制药有限公司 | A kind of levetiracetam medicinal composition and its preparation method and application |
| CN108991073A (en) * | 2018-08-23 | 2018-12-14 | 湖南博隽生物医药有限公司 | A kind of medical food and preparation method thereof that suitable epileptic patient is edible |
| CN109864971A (en) * | 2019-04-08 | 2019-06-11 | 西安远大德天药业股份有限公司 | A kind of granule and preparation method thereof of Lamotrigine solid dispersions |
| CN110840863A (en) * | 2019-12-06 | 2020-02-28 | 北京斯利安药业有限公司 | Oral instant film agent of alexanide and preparation method thereof |
| CN112741827A (en) * | 2019-10-31 | 2021-05-04 | 武汉武药科技有限公司 | Vigabatrin solid preparation and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1419444A (en) * | 1998-03-04 | 2003-05-21 | 奥尔托-麦克内尔药品股份有限公司 | Pharmaceutical composition of topiramate |
| CN102114002A (en) * | 2006-12-04 | 2011-07-06 | 苏佩努斯制药公司 | Enhanced immediate release formulations of topiramate |
-
2015
- 2015-05-31 CN CN201510288906.2A patent/CN104922075A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1419444A (en) * | 1998-03-04 | 2003-05-21 | 奥尔托-麦克内尔药品股份有限公司 | Pharmaceutical composition of topiramate |
| CN102114002A (en) * | 2006-12-04 | 2011-07-06 | 苏佩努斯制药公司 | Enhanced immediate release formulations of topiramate |
Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105456218A (en) * | 2015-12-07 | 2016-04-06 | 黑龙江省智诚医药科技有限公司 | Magnesium valproate sustained-release tablet and preparing method thereof |
| CN105832684A (en) * | 2016-05-11 | 2016-08-10 | 安徽省逸欣铭医药科技有限公司 | Zonisamide orally disintegrating tablets and preparation method thereof |
| CN108014079A (en) * | 2016-11-04 | 2018-05-11 | 武汉武药科技有限公司 | A kind of sabril chewable tablets and preparation method thereof |
| CN108014085A (en) * | 2016-11-04 | 2018-05-11 | 武汉武药科技有限公司 | A kind of preparation method and applications of sabril solid composite |
| CN108991073A (en) * | 2018-08-23 | 2018-12-14 | 湖南博隽生物医药有限公司 | A kind of medical food and preparation method thereof that suitable epileptic patient is edible |
| CN108904495B (en) * | 2018-09-29 | 2021-04-13 | 哈尔滨珍宝制药有限公司 | Levetiracetam pharmaceutical composition and preparation method and application thereof |
| CN108904495A (en) * | 2018-09-29 | 2018-11-30 | 哈尔滨珍宝制药有限公司 | A kind of levetiracetam medicinal composition and its preparation method and application |
| CN109864971A (en) * | 2019-04-08 | 2019-06-11 | 西安远大德天药业股份有限公司 | A kind of granule and preparation method thereof of Lamotrigine solid dispersions |
| CN109864971B (en) * | 2019-04-08 | 2021-12-17 | 西安远大德天药业股份有限公司 | Granules of lamotrigine solid dispersion and preparation method thereof |
| CN112741827A (en) * | 2019-10-31 | 2021-05-04 | 武汉武药科技有限公司 | Vigabatrin solid preparation and preparation method thereof |
| CN112741827B (en) * | 2019-10-31 | 2022-07-08 | 武汉武药科技有限公司 | Vigabatrin solid preparation and preparation method thereof |
| CN110840863A (en) * | 2019-12-06 | 2020-02-28 | 北京斯利安药业有限公司 | Oral instant film agent of alexanide and preparation method thereof |
| CN110840863B (en) * | 2019-12-06 | 2022-05-17 | 北京斯利安药业有限公司 | Oral quick-dissolving film agent of alexanide and preparation method thereof |
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Application publication date: 20150923 |