CN104013602A - Olanzapine oral instant film and preparation method thereof - Google Patents
Olanzapine oral instant film and preparation method thereof Download PDFInfo
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- CN104013602A CN104013602A CN201410190122.1A CN201410190122A CN104013602A CN 104013602 A CN104013602 A CN 104013602A CN 201410190122 A CN201410190122 A CN 201410190122A CN 104013602 A CN104013602 A CN 104013602A
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Abstract
The invention belongs to the field of pharmaceutical preparations and relates to an olanzapine oral instant film preparation and a preparation method thereof. The non-swallow oral instant film consists of novel dosage forms such as solid dispersion, complex, micelle and lipidosome prepared from low-dosage chemical medicines, and auxiliary components which can be accepted in the oral instant film. The olanzapine oral instant film is good in taste, rapid in oral disintegration and dissolution, fast in effectiveness, high in bioavailability and small in volume, is not needed to be taken with water and is suitable for the children, old and patients which are completely bedridden and suffer from severe disablement, and the olanzapine oral instant film preparation can be taken at any time under the condition that people are inconvenient to drink water.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, be specifically related to a kind of dosage form that solubilising technology is combined with oral instant thin film technique and preparation method thereof, more relate to a kind of olanzapine oral instant membrane and preparation method thereof.
Background technology
Oral instant membrane belongs to the membrane in pharmaceutical dosage form, is also a kind of immediate release oral solid dosage form, and it is the breath freshening thin film evolution from confection and mouth care market, has been applied to abroad at present in over-the-counter drug and prescription drug.Oral instant membrane is a kind of safe and effective dosage form, common product is designed to the size of a stamp, on tongue, can dissolve fast, and swallow with normal swallowing act, patient can take without drinking-water in the situation that, thereby realizes the quick release of one or more effective ingredients.Oral instant membrane can be realized in the situation that being inconvenient to drink water or there is no drinking water supply, take medicine exactly easily and fast,, and compared with common box-packed or bottled medicine, volume is less, be easy to carry, can meet better fast pace, high pressure city crowd's demand, especially be applicable to child, old people and critical patient and use.Therefore, pharmaceutical producing enterprise and consumer unanimously think, oral instant membrane be a kind of alternative conventional dosage forms as the desirable novel form of liquid preparation, tablet and capsule, will there is wide marketing advantage.
Olanzapine is applicable to schizophrenia and other has the psychotic acute stage of the serious positive symptom and/or negative symptoms and the treatment of maintenance phase, also can alleviate the Secondary cases emotion symptom of schizophrenia and relevant disease.Olanzapine untoward reaction is few, seldom occurs the dyskinesia.The main adverse reaction of olanzapine is drowsiness and body weight increases.The accidental medication initial stage occurs that a property crossed of liver aminotransferase ALT and AST slightly raises, but does not accompany clinical symptoms.Olanzapine oral absorption is good, within 5 to 8 hours, reaches plasma peak concentration, and not affected by feed.The olanzapine formulations using clinically is at present mainly tablet, and olanzapine is by gastrointestinal absorption, and onset needs certain hour, is difficult to control rapidly schizophrenia acute stage symptom; And when schizophrenic's acute stage and two-way affective disorder stadium maniacale, usually there is patient's Refuse to take medicine, Tibetan medicine and the FAQs of telling medicine in oral cavity, schizophrenic's compliance problem ubiquity.Therefore, the dosage form that this volume of Tablet and Capsula agent is larger usually cannot play a role to this class patient, should consider to use wieldy dosage form for schizophrenic.Oral instant membrane is a kind of dosage form that can better improve patient compliance.But generally speaking, what oral instant membrane adopted is that hydrophilic matrix material is prepared and obtains, and olanzapine is almost insoluble in water, be difficult to be dispersed in hydrophilic glue, and in blade coating drying course, due to the hydrophobicity of olanzapine, in drying course, can there is agglomeration in olanzapine principal agent, affect the uniformity of dosage units of principal agent.Therefore, prepare the good olanzapine dissolving films of drug effect, solve olanzapine homodisperse problem in preparation aqueous matrix, and in blade coating, drying course principal agent to disperse the problems such as reunion be the technical problem that such dosage form is needed solution badly.
Summary of the invention
The present invention aims to provide a kind of dosage form that can address the above problem, and realizes quick disintegrate and absorbs, conveniently takes, and improves patient's compliance, and bioavailability is higher, and then indirect improves the object of disease control rate.Particularly, be to provide one can be in oral cavity rapidly-soluble pharmaceutical dosage form, to overcome the problems such as the administration inconvenience that olanzapine exists as tablet.
First the present invention makes olanzapine the dosage forms such as solid dispersion, bag and thing, micelle and liposome, to improve dissolubility and the degree of scatter of olanzapine.
Feature of the present invention be macromolecular material by selecting good water solubility as filmogen, ensured that medicine film can dissolve fast in oral cavity; The simple filmogen that uses good water solubility can not meet the requirement that oral instant membrane dissolves rapidly in oral cavity, adds appropriate disintegrating agent in the present invention, utilizes the capillarity of disintegrating agent and expansion can solve this technical barrier.
The prescription of olanzapine oral instant membrane provided by the invention is composed as follows:
Olanzapine novel form lyophilized powder, filmogen, disintegrating agent, filler, sweeting agent, plasticizer and pH adjusting agent, also can add coloring agent and essence as required.
The component that other is medically acceptable:
Account for 0 ~ 50% at least one flavoring agent or sweeting agent of described film weight;
Account at least one bitter tasting retarding agent of 0 ~ 50% of described film weight;
Account at least one coloring agent of 0% ~ 10% of described film weight;
Account at least one plasticizer of 0% ~ 25% of described film weight;
Account at least one antiseptic of 0% ~ 20% of described film weight;
Account at least one saliva stimulant of 0% ~ 30% of described film weight;
Account at least one disintegrating agent of 0% ~ 50% of described film weight;
Account for 0% ~ 30% water of described film weight.
The described filmogen of preparing novel form comprises polyethylene glycols, polyvidone class, surfactant-based, organic acid, saccharide and alcohols, cellulose derivative, cyclodextrin and derivant thereof, amphipathic nature block polymer, cholesterol etc.
Described filmogen is not only pharmaceutical carrier, also needs by film forming performance thickening, figuration effect.Its stable in properties, not with drug interaction, also should there is good aqueous solubility, be convenient to human body dissolve, absorb.Filmogen of the present invention is most preferably from Kollicoat IR, xanthan gum, sodium alginate, gelatin, dextrin, Lac, arabic gum, polyvidone, methylcellulose, hydroxypropyl cellulose, high one or more that replace in hypromellose, chitosan, agar and alginic acid.
Described filler is selected from one or more in mannitol, sucrose, glucose, maltose, lactose, sorbitol, xylitol, maltose alcohol, galactitol, erythritol, dextrin, trehalose; Preferably microcrystalline cellulose and mannitol.Because microcrystalline Cellulose has disintegration, mannitol is water miscible, so select these two kinds of components can promote this oral instant membrane in intraoral dissolving.
Disintegrating agent has capillarity and expansion, has pore structure after making film dry, forms the capillary channel that is easy to moistening, can be by water-wet, and contact water afterwards with water and can enter film inside with capillary channel rapidly, impel the rapid disintegrate of film.Disintegrating agent of the present invention is selected from one or more in microcrystalline Cellulose, pregelatinized Starch, low-substituted hydroxypropyl cellulose, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, crosslinked carboxymethyl fecula sodium and starch.
Described sweeting agent is selected from one or more in aspartame, sucralose, fructose, sucrose, stevioside, glycyrrhizin, essence, spice, glucide and saccharin sodium; Preferably sucralose.
Described plasticizer is selected from one or more in Polyethylene Glycol, glycerol, propylene glycol, silicone oil, polypropylene glycol, hexanediol; Preferably glycerine.
Described pH adjusting agent is selected from a kind of or its mixture in citric acid or tartaric acid.
The preparation method of olanzapine oral instant membrane provided by the invention comprises the steps:
A, employing new technology is prepared into solid dispersion, bag and thing, micelle by property medicine olanzapine hard to tolerate, or liposome, and lyophilizing must contain the olanzapine lyophilized powder of active component;
B, by soluble in water the water soluble ingredient except water-soluble polymer, obtain aqueous solution;
C, add the lyophilized powder that contains olanzapine to stir;
D, at least one biological acceptable aqueous polymer is joined in aqueous solution under stirring, fully dispersed with stirring obtains olanzapine polymer gel;
E, degassed, evenly coats olanzapine polymer gel on flat board;
F, blast heating are dried, and heat drying temperature is 70 ~ 80 DEG C, and cutting, obtains described olanzapine oral instant membrane.
detailed description of the invention:
The present invention is further elaborated by following examples, but scope of the present invention is not limited to these embodiment.So, under method prerequisite of the present invention, simple modifications of the present invention is all belonged to the scope of protection of present invention.
Embodiment 1:
Recipe quantity is 2000 (specification 5mg) or 1000 (specification 10mg):
Olanzapine (solid dispersion) 10g
Mannitol 20g
Polyvidone 15g
Sodium carboxymethyl cellulose 15g
Microcrystalline Cellulose 5g
Sucralose 0.5g
Purified water * 160g
* in blade coating dry run, remove.
Technique:
Olanzapine is carried out to pretreatment, obtain olanzapine solid dispersion lyophilized powder.Take mannitol 20g, be placed in appropriate containers, add 160g purified water.Add microcrystalline Cellulose 5g, sucralose 0.5g, stirs.Then add olanzapine solid dispersion lyophilized powder (containing 10g olanzapine), stir homogeneous, add polyvidone 15g, sodium carboxymethyl cellulose 15g, stirs homogeneous.High speed shear 2 minutes under (10000rpm), 5 times repeatedly, under vacuum condition, leave standstill 8h to remove bubble, obtain blade coating gel.By this glue blade coating, to plastic sheeting, the temperature between 70 DEG C to 80 DEG C is dried.Then the membrane that blade coating obtains is peeled off from plastic sheeting, shears subpackage, can obtain membrane.
Embodiment 2
Recipe quantity is 2000 (specification 5mg) or 1000 (specification 10mg):
Olanzapine (clathrate) 10g
Mannitol 20g
Hypromellose 30g
Sucralose 0.5g
Purified water * 200g
* in blade coating dry run, remove.
Technique:
1) olanzapine is carried out to pretreatment, obtain olanzapine clathrate lyophilized powder;
2) take mannitol 20g, be placed in appropriate containers, add 40g purified water.Stir and add until completely dissolved olanzapine clathrate lyophilized powder (containing olanzapine 10g), stir homogeneous, be designated as A;
3) take hypromellose 30g, be placed in appropriate containers, add 85 DEG C of-95 DEG C of distilled water 160g, stir homogeneous, be cooled to completely and dissolve, obtain glue liquid B;
4) glue liquid B is added in A, add sucralose 0.5g.High speed shear 2 minutes under (10000rpm), 5 times repeatedly, under vacuum condition, leave standstill 8h to remove bubble, obtain blade coating gel.By this glue blade coating, to plastic sheeting, the temperature between 70 DEG C to 80 DEG C is dried.Then the membrane that blade coating obtains is peeled off from plastic sheeting, shears subpackage, can obtain membrane.
Embodiment 3
Recipe quantity is 2000 (specification 5mg) or 1000 (specification 10mg):
Olanzapine (clathrate) 10g
Mannitol 20g
Gelatin 10g
Arabic gum 10g
Chitosan 10g
Saccharin sodium 0.5g
Purified water * 200g
* in blade coating dry run, remove.
Technique:
1) olanzapine is carried out to pretreatment, obtain olanzapine clathrate lyophilized powder;
2) take mannitol 20g, be placed in appropriate containers, add 40g purified water.Stir and add until completely dissolved olanzapine clathrate lyophilized powder (containing olanzapine 10g), stir homogeneous, be designated as A;
3) take gelatin 10g, arabic gum 10g, chitosan 10g, be placed in appropriate containers, add distilled water 160g.Stir 2h above to glue homogeneous, obtain glue liquid B;
4) glue liquid B is added in A, add saccharin sodium 0.5g.High speed shear 2 minutes under (10000rpm), 5 times repeatedly, under vacuum condition, leave standstill 8h to remove bubble, obtain blade coating gel.By this glue blade coating, to plastic sheeting, the temperature between 70 DEG C to 80 DEG C is dried.Then the membrane that blade coating obtains is peeled off from plastic sheeting, shears subpackage, can obtain membrane.
Embodiment 4
Recipe quantity is 2000 (specification 5mg) or 1000 (specification 10mg):
Olanzapine (micelle) 10g
Lactose 20g
Polyvinyl alcohol 30g
Sucralose 0.5g
Purified water * 160g
* in blade coating dry run, remove.
Technique:
Olanzapine is carried out to pretreatment, obtain olanzapine micelle freeze-drying powder.Take lactose 20g, be placed in appropriate containers, add 160g purified water.Stir and add until completely dissolved olanzapine micelle freeze-drying powder (containing olanzapine 10g), stir homogeneous, add polyvinyl alcohol 30g, stir homogeneous; Add sucralose 0.5g.High speed shear 2 minutes under (10000rpm), 5 times repeatedly, under vacuum condition, leave standstill 8h to remove bubble, obtain blade coating gel.By this glue blade coating, to plastic sheeting, the temperature between 70 DEG C to 80 DEG C is dried.Then the membrane that blade coating obtains is peeled off from plastic sheeting, shears subpackage, can obtain membrane.
Embodiment 5
Recipe quantity is 2000 (specification 5mg) or 1000 (specification 10mg):
Olanzapine (liposome) 10g
Xylitol 20g
Polyvinylpyrrolidone 15g
Methylcellulose 15g
Saccharin sodium 0.5g
Purified water * 160g
* in blade coating dry run, remove.
Technique:
Olanzapine is carried out to pretreatment, obtain olanzapine micelle freeze-drying powder.Take xylitol 20g, be placed in appropriate containers, add 160g purified water.Stir and add until completely dissolved olanzapine lipid freeze-dry powder (containing olanzapine 10g), stir homogeneous, add polyvinylpyrrolidone and methylcellulose, stir homogeneous; Add saccharin sodium 0.5g.High speed shear 2 minutes under (10000rpm), 5 times repeatedly, under vacuum condition, leave standstill 8h to remove bubble, obtain blade coating gel.By this glue blade coating, to plastic sheeting, the temperature between 70 DEG C to 80 DEG C is dried.Then the membrane that blade coating obtains is peeled off from plastic sheeting, shears subpackage, can obtain membrane.
Claims (10)
1. an olanzapine oral instant membrane, it is characterized in that first olanzapine being made the novel forms such as solid dispersion, bag and thing, micelle, liposome, then add filmogen, and the necessary acceptable filler of pharmacy, sweeting agent, disintegrating agent, plasticizer and pH adjusting agent, also can add as required coloring agent and essence.
2. olanzapine oral instant membrane according to claim 1, is characterized in that described filmogen comprises polyethylene glycols, polyvidone class, surfactant-based, organic acid, saccharide and alcohols, cellulose derivative, cyclodextrin and derivant thereof, amphipathic nature block polymer, cholesterol etc.
3. according to the olanzapine oral instant membrane described in claim 1 and 3, it is characterized in that described filmogen is selected from Kollicoat IR, xanthan gum, sodium alginate, gelatin, dextrin, Lac, arabic gum, polyvidone, methylcellulose, hydroxypropyl cellulose, high one or more that replace in hypromellose, chitosan, agar and alginic acid.
4. olanzapine oral instant membrane according to claim 1, is characterized in that the component that can also comprise that other is medically acceptable:
Account for 0 ~ 50% at least one flavoring agent or sweeting agent of described film weight;
Account at least one bitter tasting retarding agent of 0 ~ 50% of described film weight;
Account at least one coloring agent of 0% ~ 10% of described film weight;
Account at least one plasticizer of 0% ~ 25% of described film weight;
Account at least one antiseptic of 0% ~ 20% of described film weight;
Account at least one saliva stimulant of 0% ~ 30% of described film weight;
Account at least one disintegrating agent of 0% ~ 50% of described film weight;
Account for 0% ~ 30% water of described film weight.
5. olanzapine oral instant membrane according to claim 1, is characterized in that described filler is selected from one or more in mannitol, sucrose, glucose, maltose, lactose, sorbitol, xylitol, maltose alcohol, galactitol, erythritol, dextrin, trehalose.
6. according to the olanzapine oral instant membrane described in claim 1,5, it is characterized in that described sweeting agent is selected from one or more in aspartame, sucralose, fructose, sucrose, stevioside, glycyrrhizin, essence, spice, glucide and saccharin sodium, preferably sucralose.
7. according to the olanzapine oral instant membrane described in claim 1,5, it is characterized in that described disintegrating agent is selected from one or more in microcrystalline Cellulose, pregelatinized Starch, low-substituted hydroxypropyl cellulose, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, crosslinked carboxymethyl fecula sodium and starch.
8. according to the olanzapine oral instant membrane described in claim 1,5, it is characterized in that described plasticizer is selected from one or more in glycerol, Polyethylene Glycol, propylene glycol, silicone oil, polypropylene glycol, hexanediol, preferably glycerine.
9. olanzapine oral instant membrane according to claim 1, is characterized in that described pH adjusting agent is selected from a kind of or its mixture in citric acid or tartaric acid.
10. a preparation method for olanzapine oral instant membrane according to claim 1, is characterized in that operating according to the following steps:
A, employing new technology is prepared into solid dispersion, bag and thing, micelle by property medicine olanzapine hard to tolerate, or liposome, and lyophilizing must contain the olanzapine lyophilized powder of active component;
B, by soluble in water the water soluble ingredient except water-soluble polymer, obtain aqueous solution;
C, add the lyophilized powder that contains olanzapine to stir;
D, at least one biological acceptable aqueous polymer is joined in aqueous solution under stirring, fully dispersed with stirring obtains olanzapine polymer gel;
E, degassed, evenly coats olanzapine polymer gel on flat board;
F, blast heating are dried, and heat drying temperature is 70 ~ 80 DEG C, and cutting, obtains described olanzapine oral instant membrane.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410190122.1A CN104013602A (en) | 2014-05-07 | 2014-05-07 | Olanzapine oral instant film and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410190122.1A CN104013602A (en) | 2014-05-07 | 2014-05-07 | Olanzapine oral instant film and preparation method thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102451162A (en) * | 2010-10-21 | 2012-05-16 | 重庆市力扬医药开发有限公司 | Olanzapine medicine absorbed through oral mucosa |
| CN102920683A (en) * | 2012-06-11 | 2013-02-13 | 江苏豪森药业股份有限公司 | Olanzapine oral instant membrane |
-
2014
- 2014-05-07 CN CN201410190122.1A patent/CN104013602A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102451162A (en) * | 2010-10-21 | 2012-05-16 | 重庆市力扬医药开发有限公司 | Olanzapine medicine absorbed through oral mucosa |
| CN102920683A (en) * | 2012-06-11 | 2013-02-13 | 江苏豪森药业股份有限公司 | Olanzapine oral instant membrane |
Non-Patent Citations (1)
| Title |
|---|
| 张劲: "《药物制剂技术》", 31 August 2005 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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: 20140903 |