CN104940128A - Lamotrigine oral liquid preparation and preparation method thereof - Google Patents
Lamotrigine oral liquid preparation and preparation method thereof Download PDFInfo
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- CN104940128A CN104940128A CN201510288845.XA CN201510288845A CN104940128A CN 104940128 A CN104940128 A CN 104940128A CN 201510288845 A CN201510288845 A CN 201510288845A CN 104940128 A CN104940128 A CN 104940128A
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Abstract
The invention discloses a lamotrigine oral liquid preparation. Each 1000ml of the lamotrigine oral liquid preparation contains 0.4-2g of lamotrigine, 10-500g of a sweetener, 0.5-1.5ml of a perfume, 0.5-1.5g of an antiseptic, 0.001-0.1g of a coloring agent, a proper amount of a pH adjusting agent, and the balance of purified water, and the pH value of the lamotrigine oral liquid preparation is 2.5-4.0. The invention also discloses a preparation method of the lamotrigine oral liquid preparation. The lamotrigine oral liquid preparation can effectively cover the bad taste of medicines, can be conveniently swallowed, can be accepted by patients (especially children), and has good administration compliance.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, be specifically related to a kind of lamotrigine oral liquid, the invention still further relates to a kind of preparation method of lamotrigine oral liquid.
Background technology
Lamotrigine is New-type wide-spectrum health AED.Be used for the treatment of partial seizures, constitutional and Secondary cases tonic-clonic seizures, also can be used for the epilepsy relevant to Lennox-Gastaut syndrome.Single therapy or elements addition are grown up and child's all kinds epilepsy has good efficacy and saferry, especially have certain effect to intractable epilepsy.The defects such as existing lamotrigine dosage form dysphagia, dose fractionation are inaccurate, drug compliance difference.Current lamotrigine there is no the dosage form listing of applicable special population (particularly child), also has no relevant report.
Summary of the invention
The object of this invention is to provide a kind of lamotrigine oral liquid, solve the problem of dose titration complicated in the medication process existed in prior art and the segmentation of preparation consumption.
Another object of the present invention is to provide a kind of preparation method of lamotrigine oral liquid.
First technical scheme of the present invention is, a kind of lamotrigine oral liquid, every 1000ml lamotrigine oral liquid comprises following component: lamotrigine 0.4g-2g, sweeting agent 10g-500g, aromatic 0.5ml-1.5ml, antiseptic 0.5g-1.5g, coloring agent 0.001g-0.1g, pH value regulator, surplus is purified water, and pH value is 2.5-4.0.
Sweeting agent is one or more in sucrose, sucralose, glucose, fructose, maltose, Nulomoline, hydroxyl isomaltulose, starch sugar, lactose, galactose, stevioside, ammonium glycyrrhizinate, D-MANNOSE, Radix Glycyrrhizae, disodium glycyrrhizinate, D-Sorbitol, sorbitol, tripotassium glycyrrhetate and trisodium, glucide, saccharin sodium, sodium cyclamate, acesulfame potassium, LaspartylLphenylalanine methylester, alitame, xylitol, sorbitol, aspartame.
Aromatic is one or more in flavoring banana essence, Fructus Citri tangerinae essence, flavoring pineapple essence, Fructus Citri Limoniae essence, strawberry essence, cherry essence, milk flavour, chocolate essence, apple essence.
Antiseptic is one or more in p-hydroxybenzoic acid esters, benzoic acid and sodium benzoate, sorbic acid, potassium sorbate and calcium sorbate, calcium propionate, dehydro sodium acetate, sodium diacetate or sodium lactate.
Coloring agent is that amaranth, carmine, erythrosine, newly red, lemon yellow, sunset yellow, indigo, beet red, lac are red, red pigment of cowberry, capsanthin, red rice red in one or more.
PH adjusting agent be citric acid, adipic acid, lemon acid potassium, lactic acid, fumaric acid, sodium sesquicarbonate, tartaric acid, sodium hydroxide, sodium dihydrogen citrate, malic acid, potassium carbonate, lemon acid potassium, phosphoric acid, sodium carbonate, sodium citrate, acetic acid, sodium citrate, citric acid, hydrochloric acid one or more.
Second technical scheme of the present invention is, a kind of preparation method of lamotrigine oral liquid is specifically implemented according to following steps:
Step 1, weighing, weigh following component, lamotrigine 0.4g-2g, sweeting agent 10g-500g, aromatic 0.5ml-1.5ml, antiseptic 0.5g-1.5g, coloring agent 0.001g-0.1g, and pH value regulator is appropriate, and surplus is purified water, and above total amount is 1000ml;
Step 2, get appropriate purified water and put in Agitation Tank, be heated to 40 DEG C ~ 60 DEG C, under stirring condition, add the sweeting agent being insoluble in water successively, lamotrigine adds in Agitation Tank after being uniformly dispersed with a small amount of hot water, after heated and boiled a period of time, cooling, mixing time is 5min-15min;
Step 3, by load weighted antiseptic, sweeting agent soluble in water, coloring agent respectively with a small amount of temperature be 40 DEG C ~ 60 DEG C warm water dissolve after add in Agitation Tank, add aromatic, stir after adding purified water;
Step 4, use pH adjusting agent adjust ph, to 2.5-4.0, then add purified water and are settled to full dose, and stir 20min-40min, filter, fill, sterilizing, prepare lamotrigine oral liquid with the plate filter that aperture is 0.45 μm.
The invention has the beneficial effects as follows: the present invention is directed to current epileptic group huge, the antiepileptic market demand obviously increases, and the antiepileptic of safe, effective and applicable special population is under-supply, dosage form lacks, there is the present situation of potential safety hazard in clinical practice, develop lamotrigine oral liquid and preparation method thereof, under the prerequisite ensureing principal agent appropriate dosage, by selecting adjuvant and formulation method, lamotrigine is made oral solution, be conducive to the absorption of medicine, the accuracy of raising bioavailability, dosage and drug safety.Also provide more, renewal, better dosage form selection for clinical, the availability of treat special population and compliance will have very big improvement simultaneously.
Detailed description of the invention
Below in conjunction with detailed description of the invention, the present invention is described in detail.The present invention is further illustrated for specific embodiment, but be not limited thereto.
The invention provides a kind of lamotrigine oral liquid, every 1000ml lamotrigine oral liquid contains following component: lamotrigine 0.4g-2g, sweeting agent 10g-500g, aromatic 0.5ml-1.5ml, antiseptic 0.5g-1.5g, coloring agent 0.001g-0.1g, pH value regulator is appropriate, surplus is purified water, and pH value is 2.5-4.0.
Wherein, sweeting agent is one or more in sucrose, sucralose, glucose, fructose, maltose, Nulomoline, hydroxyl isomaltulose, starch sugar, lactose, galactose, stevioside, ammonium glycyrrhizinate, D-MANNOSE, Radix Glycyrrhizae, disodium glycyrrhizinate, D-Sorbitol, sorbitol, tripotassium glycyrrhetate and trisodium, glucide, saccharin sodium, sodium cyclamate (cyclamate), acesulfame potassium, LaspartylLphenylalanine methylester (aspartame, sweetener), alitame, xylitol, sorbitol, aspartame.
Aromatic is one or more in flavoring banana essence, Fructus Citri tangerinae essence, flavoring pineapple essence, Fructus Citri Limoniae essence, strawberry essence, cherry essence, milk flavour, chocolate essence, apple essence.
Antiseptic is one or more in p-hydroxybenzoic acid esters, benzoic acid and sodium benzoate, sorbic acid, potassium sorbate and calcium sorbate, calcium propionate, dehydro sodium acetate, sodium diacetate or sodium lactate.
Coloring agent is that amaranth, carmine, erythrosine, newly red, lemon yellow, sunset yellow, indigo, beet red, lac are red, red pigment of cowberry, capsanthin, red rice red in one or more.
PH adjusting agent be citric acid, adipic acid, lemon acid potassium, lactic acid, fumaric acid, sodium sesquicarbonate, tartaric acid, sodium hydroxide, sodium dihydrogen citrate, malic acid, potassium carbonate, lemon acid potassium, phosphoric acid, sodium carbonate, sodium citrate, acetic acid, sodium citrate, citric acid, hydrochloric acid one or more.
The present invention also provides a kind of preparation method of lamotrigine oral liquid, specifically implements according to following steps:
Step 1, weighing, weigh following component, lamotrigine 0.4g-2g, sweeting agent 10g-500g, aromatic 0.5ml-1.5ml, antiseptic 0.5g-1.5g, coloring agent 0.001g-0.1g, pH value is appropriate, surplus is purified water, and pH value is 2.5-4.0, and above total amount is 1000ml;
Step 2, get appropriate purified water and put in Agitation Tank, be heated to 40 DEG C ~ 60 DEG C, under stirring condition, add indissoluble sweeting agent successively, lamotrigine adds in Agitation Tank after being uniformly dispersed with a small amount of hot water, after heated and boiled a period of time, cooling, mixing time is 5min-15min;
Step 3, by load weighted antiseptic, easy molten sweeting agent, coloring agent respectively with a small amount of temperature be 40 DEG C ~ 60 DEG C warm water dissolve after add in Agitation Tank, add aromatic, stir after adding purified water;
Step 4, use pH adjusting agent adjust ph, to 2.5-4.0, then add purified water and are settled to full dose, and stir 20min-40min, filter, fill, sterilizing, prepare lamotrigine oral liquid with the plate filter that aperture is 0.45 μm.
Lamotrigine oral liquid, have be convenient to take, good absorbing, bioavailability high.Divided dose is accurate, and Clinical efficacy and safety is higher, is specially adapted to the gerontal patient of child and dysphagia.
Lamotrigine oral liquid can adopt low dose of independent packaging, improve the accuracy of dosage, reduce the generation of over administration (or not enough) and Medication error and untoward reaction, solve a difficult problem for dose titration complicated in medication process and the separation of preparation consumption.
The present invention has enriched dosage form and the specification of antiepileptic preparation, for clinical provide more, upgrade, better dosage form selection, simultaneously to the availability of special population Antiepileptic Drugs and compliance significant.
Embodiment 1 (oral liquid)
The preparation method of the lamotrigine oral liquid of the present embodiment 1, specifically implement according to following steps: weigh following component: lamotrigine 2g, sodium benzoate 1g, sorbitol 50g, sucrose 100g, aspartame 0.5g, strawberry essence 1ml, sodium lactate 0.5g, amaranth 0.01g, hydrochloric acid is appropriate, and surplus is purified water, and above total amount is 1000ml; Getting purified water puts in Agitation Tank, is heated to 50 DEG C, under stirring condition, adds sorbitol successively, and lamotrigine adds in Agitation Tank after being uniformly dispersed with a small amount of hot water, after heated and boiled a period of time, and cooling, mixing time is 10min; Add in Agitation Tank after load weighted sodium lactate, sucrose soluble in water and aspartame, amaranth are dissolved with the warm water that a small amount of temperature is 50 DEG C respectively, add aromatic, stir after adding purified water; With pH adjusting agent salt acid for adjusting pH value to 2.5-4.0, then add purified water and be settled to full dose, and stir 20min-40min, filter with the plate filter that aperture is 0.45 μm, fill, sterilizing, prepare lamotrigine oral liquid.
Embodiment 2 (syrup)
The preparation method of the lamotrigine oral liquid of the present embodiment 2, specifically implement according to following steps: weigh following component: lamotrigine 2g, sodium benzoate 1g, sorbitol 50g, sucrose 450g, strawberry essence 1ml, amaranth 0.0025g, hydrochloric acid is appropriate, and surplus is purified water, and above total amount is 1000ml; Getting appropriate purified water puts in Agitation Tank, is heated to 40 DEG C, adds sucrose and sorbitol under agitation, and heated and boiled is to dissolving completely, for subsequent use; By load weighted lamotrigine in small beaker, complete with hot water dissolving, join in Agitation Tank; By load weighted sodium benzoate, strawberry essence, amaranth, join respectively in Agitation Tank, add purified water, stir 3min; By load weighted pH adjusting agent, join in Agitation Tank, adjust ph is within the scope of 2.5-4.0; Add to full dose in purified water to Agitation Tank, stir, filter with the plate filter that aperture is 0.45 μm, fill, sterilizing, prepare lamotrigine oral liquid.
Clinic Case of the present invention:
1, Lee, 8 years old, clinical definite was epileptic, and medical history 5 years, once took the medicines such as multiple epilepsy, effectively can not control outbreak.While taking sodium valproate, add the compositions taking the embodiment of the present invention 1, predose is 25mg, and the next day takes, and serve on two weeks; Two weeks subsequently once a day, each 25mg.After this, every 1-2 week increases dosage, and maximum recruitment is 25-50mg.After 3 months, substantially eliminate drowsiness, the headache of patient, dizzy phenomenon, taste is good, and swallowing property is good, and drug compliance is good.
2, Yan, 12 years old, clinical definite was epileptic, medical history 5 years, showed effect by the moon about 11 times.Take the compositions of the embodiment of the present invention 2, adopt this product single therapy, predose is 25mg, once a day, serve on two weeks; Use 50mg subsequently, once a day, serve on two weeks.After this, every 1-2 week increases dosage, and maximum recruitment is 50-100mg, until reach optimum curative effect.After 3 months, simultaneously patient substantially eliminates drowsiness, the headache because taking that other drug occurs, dizzy phenomenon, and well, swallowing property is good, and drug compliance is good for taste.
3, king so-and-so, female, 16 years old, clinical definite was epileptic, and medical history is shown effect about 8 times in the moon, 6.Take the compositions of the embodiment of the present invention 3, adopt this product single therapy, predose is 25mg, once a day, serve on two weeks; Use 50mg subsequently, once a day, serve on two weeks.After this, every 1-2 week increases dosage, and maximum recruitment is 50-100mg, until reach optimum curative effect.Carry out spirit to dredge simultaneously.After 5 months, patient substantially eliminates drowsiness, the headache because taking that other drug occurs, dizzy phenomenon, and taste is good, and swallowing property is good, and drug compliance is good.
4, Song, man, 9 years old, clinical definite was epileptic, and medical history 4 years, once took the medicines such as multiple epilepsy, effectively can not control outbreak.While taking sodium valproate, add the compositions taking the embodiment of the present invention 5, predose is 25mg, and the next day takes, and serve on two weeks; Two weeks subsequently once a day, each 25mg.After this, every 1-2 week increases dosage, and maximum recruitment is 25-50mg.It is show effect by the moon 3 times that second month plays record number of incidences.Simultaneously patient substantially eliminate because of take that other drug occurs drowsiness, have a headache, dizzy phenomenon, readme can be felt good, and swallowing property is good, and drug compliance is good.
Above test example proves that the present composition has outstanding synergy to treatment epileptic condition.
Claims (7)
1. a lamotrigine oral liquid, it is characterized in that, every 1000ml lamotrigine oral liquid comprises following component: lamotrigine 0.4g-2g, sweeting agent 10g-500g, aromatic 0.5ml-1.5ml, antiseptic 0.5g-1.5g, coloring agent 0.001g-0.1g, pH value regulator is appropriate, and surplus is purified water, and pH value is 2.5-4.0.
2. lamotrigine oral liquid according to claim 1, it is characterized in that, described sweeting agent is sucrose, sucralose, glucose, fructose, maltose, Nulomoline, hydroxyl isomaltulose, starch sugar, lactose, galactose, stevioside, ammonium glycyrrhizinate, D-MANNOSE, Radix Glycyrrhizae, disodium glycyrrhizinate, D-Sorbitol, sorbitol, tripotassium glycyrrhetate and trisodium, glucide, saccharin sodium, sodium cyclamate, acesulfame potassium, LaspartylLphenylalanine methylester, alitame, xylitol, sorbitol, one or more in aspartame.
3. lamotrigine oral liquid according to claim 1, it is characterized in that, described aromatic is one or more in flavoring banana essence, Fructus Citri tangerinae essence, flavoring pineapple essence, Fructus Citri Limoniae essence, strawberry essence, cherry essence, milk flavour, chocolate essence, apple essence.
4. lamotrigine oral liquid according to claim 1, it is characterized in that, described antiseptic is one or more in p-hydroxybenzoic acid esters, benzoic acid and sodium benzoate, sorbic acid, potassium sorbate and calcium sorbate, calcium propionate, dehydro sodium acetate, sodium diacetate or sodium lactate.
5. lamotrigine oral liquid according to claim 1, it is characterized in that, described coloring agent is that amaranth, carmine, erythrosine, newly red, lemon yellow, sunset yellow, indigo, beet red, lac are red, red pigment of cowberry, capsanthin, red rice red in one or more.
6. lamotrigine oral liquid according to claim 1, it is characterized in that, pH adjusting agent be citric acid, adipic acid, lemon acid potassium, lactic acid, fumaric acid, sodium sesquicarbonate, tartaric acid, sodium hydroxide, sodium dihydrogen citrate, malic acid, potassium carbonate, lemon acid potassium, phosphoric acid, sodium carbonate, sodium citrate, acetic acid, sodium citrate, citric acid, hydrochloric acid one or more.
7. a preparation method for lamotrigine oral liquid, is characterized in that, specifically implements according to following steps:
Step 1, weighing, weigh following component, lamotrigine 0.4g-2g, sweeting agent 10g-500g, aromatic 0.5ml-1.5ml, antiseptic 0.5g-1.5g, coloring agent 0.001g-0.1g, pH value regulator is appropriate, surplus is purified water, and pH value is 2.5-4.0, and above total amount is 1000ml;
Step 2, get appropriate purified water and put in Agitation Tank, be heated to 40 DEG C ~ 60 DEG C, under stirring condition, add the sweeting agent being insoluble in water successively, lamotrigine adds in Agitation Tank after being uniformly dispersed with a small amount of hot water, after heated and boiled a period of time, cooling, mixing time is 5min-15min;
Step 3, by load weighted antiseptic, sweeting agent soluble in water, coloring agent respectively with a small amount of temperature be 40 DEG C ~ 60 DEG C warm water dissolve after add in Agitation Tank, add aromatic, stir after adding purified water;
Step 4, use pH adjusting agent adjust ph, to 2.5-4.0, then add purified water and are settled to full dose, and stir 20min-40min, filter, fill, sterilizing, prepare lamotrigine oral liquid with the plate filter that aperture is 0.45 μm.
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| CN201510288845.XA CN104940128A (en) | 2015-05-31 | 2015-05-31 | Lamotrigine oral liquid preparation and preparation method thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106491539A (en) * | 2016-12-19 | 2017-03-15 | 上海奥科达生物医药科技有限公司 | A kind of lamotrigine dry suspension and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997000681A1 (en) * | 1995-06-23 | 1997-01-09 | The Wellcome Foundation Limited | Pharmaceutical composition containing lamotrigine |
| CN102743333A (en) * | 2012-07-27 | 2012-10-24 | 万特制药(海南)有限公司 | Levetiracetam oral liquid and preparation method of levetiracetam oral liquid |
| CN104161733A (en) * | 2007-07-02 | 2014-11-26 | 阿普塔利斯制药股份有限公司 | Orally disintegrating tablet compositions of lamotrigine |
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2015
- 2015-05-31 CN CN201510288845.XA patent/CN104940128A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997000681A1 (en) * | 1995-06-23 | 1997-01-09 | The Wellcome Foundation Limited | Pharmaceutical composition containing lamotrigine |
| CN104161733A (en) * | 2007-07-02 | 2014-11-26 | 阿普塔利斯制药股份有限公司 | Orally disintegrating tablet compositions of lamotrigine |
| CN102743333A (en) * | 2012-07-27 | 2012-10-24 | 万特制药(海南)有限公司 | Levetiracetam oral liquid and preparation method of levetiracetam oral liquid |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106491539A (en) * | 2016-12-19 | 2017-03-15 | 上海奥科达生物医药科技有限公司 | A kind of lamotrigine dry suspension and preparation method thereof |
| CN106491539B (en) * | 2016-12-19 | 2019-03-26 | 上海奥科达生物医药科技有限公司 | A kind of Lamotrigine dry suspensoid agent and preparation method thereof |
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