CN1709231A - Tolterodine tartrate soft capsule and its preparing method - Google Patents
Tolterodine tartrate soft capsule and its preparing method Download PDFInfo
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- CN1709231A CN1709231A CN 200510080363 CN200510080363A CN1709231A CN 1709231 A CN1709231 A CN 1709231A CN 200510080363 CN200510080363 CN 200510080363 CN 200510080363 A CN200510080363 A CN 200510080363A CN 1709231 A CN1709231 A CN 1709231A
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- tolterodine tartrate
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Abstract
The present invention relates to a troterodine tartrate soft capsule and its preparation method. The content of described soft capsule is solution type or suspension type obtained by mixing troterodine tartrate and one and/or several kinds of solubilization agent, solubility promoter, suspension adjuvant, solubiliser and surfactant and dissolving them, then it is used for preparing soft capsule.
Description
Technical field
The present invention relates to tolterodine tartrate soft capsule and preparation method thereof,, make the soft capsule that content is solution-type or suspension type by selection to its composition.
Background technology
Tolterodine tartrate (tolterodine tartrate) is a kind of novel potent striving property M nachr antagonist unexpectedly, poisonous weeds alkali (M) receptor is had only high-affinity and specificity, is the medicine that a kind of curative effect is treated unstability or hyperkinesia wing skin inflammation preferably.Be mainly used in frequent micturition, urgent micturition and the urgent urinary incontinence symptom alleviated due to the wing skin over-activity.Clinical practice has good curative effect and the low characteristics of untoward reaction.
At present existing Tolterodine tartrate peroral dosage form is a tablet, and the disintegrate of solid orally ingestibles such as tablet is slow, absorption difference in the body, bioavailability are low.Soft capsule dosage form has been accelerated the process of disintegrate in the body, decomposition, stripping with respect to tablet, makes the easier absorption of active ingredient.
Summary of the invention
The present invention is intended to overcome problems such as the poor stability, the bioavailability that have the Tolterodine tartrate solid orally ingestible are low, has changed the dissolution and the low shortcoming of bioavailability of Tolterodine tartrate oral formulations, has improved curative effect.
Tolterodine tartrate soft capsule of the present invention can prepare by the various appropriate method of soft capsule preparation, the preparation method of preferred tolterodine tartrate soft capsule is as follows: one in Tolterodine tartrate and lytic agent, cosolvent, solubilizing agent, suspending agent, the surfactant and/or a plurality of mixed dissolution are made solution-type or suspension type content, adopt pressed film method to prepare soft capsule, soft capsule is through solidifying by cooling in wind, drying, wash ball, do eventually with appropriate solvent, promptly get product.
Tolterodine tartrate soft capsule content described in the preparation method of the present invention composed as follows: form by Tolterodine tartrate and adjuvant.Wherein said adjuvant comprises in lytic agent, cosolvent, solubilizing agent, suspending agent, the surfactant one and/or a plurality of.Wherein lytic agent is Polyethylene Glycol, fish oil, soybean oil, refining Oleum Arachidis hypogaeae semen, Radix Oenotherae erythrosepalae oil, Herba Silybi mariani oil, Oleum Vitis viniferae, Oleum Helianthi, safflower oil, the Fructus Hippophae wet goods vegetable and animals oils of PEG400 or PEG600 liquid state, preferred PEG400 or soybean oil, the addition of lytic agent is 10%--95%, preferably: 20%-80%, more preferably: 30%-70%; Cosolvent is mixture, pluronic F-68, monostearate, zein, hydrogenated palm oil, soybean lecithin, lecithin, polyglycerol ester, sucrose fat of lower alcohols such as propylene glycol, glycerol, isopropyl alcohol and/or several alcohol etc., preferred propylene glycol or monostearate, the addition of cosolvent is 1%--60%, preferably: 2%-50%, more preferably: 3%-40%; Suspending agent is the solid-state Polyethylene Glycol of PEG4000, PEG6000, aerosil, liquid paraffin, lanoline, Cera Flava, glyceryl monostearate, high fatty alcohol, preferred PEG4000 or Cera Flava, addition is 1%～10%, and is preferred: 1.5%-8%, more preferably: 2%-6%; Solubilizing agent is sodium hydroxide solution or sodium bicarbonate solution or unsaturated fatty acid, preferred sodium hydroxide solution or oleic acid, and addition is 0.1%～10% preferred: 0.5%-8%, more preferably: 1%-5%; Surfactant is sorbester p17, sorbester p18, Tween 80, polysorbate60, sodium lauryl sulphate, neutral liquid fat, preferred neutral liquid fat, and the addition of surfactant is 1%～30%, and is preferred: 3%-25%, more preferably: 3%-20%; Wherein the content of Tolterodine tartrate is 0.1%～10%, and is preferred: 0.2-5%, more preferably: 0.2-2%; Each component sum of content is 100%.It is primary raw material that softgel shell adopts gelatin, glycerol and/or sorbitol etc., can add 0.2～0.8% titanium dioxide and make as opacifier.
The specific embodiment:
Tolterodine tartrate soft capsule of the present invention can prepare by the various appropriate method of soft capsule preparation, preferably make: get Tolterodine tartrate by being prepared as follows method, (lytic agent is the Polyethylene Glycol of PEG400 or PEG600 liquid state to lytic agent, fish oil, soybean oil, refining Oleum Arachidis hypogaeae semen, Radix Oenotherae erythrosepalae oil, Herba Silybi mariani oil, Oleum Vitis viniferae, Oleum Helianthi, safflower oil, Fructus Hippophae wet goods vegetable and animals oils, preferred PEG400 or soybean oil), cosolvent (propylene glycol, glycerol, the mixture of lower alcohols such as isopropyl alcohol and/or several alcohol, pluronic F-68, monostearate, zein, hydrogenated palm oil, soybean lecithin, lecithin, polyglycerol ester, sucrose fat etc., preferred propylene glycol or monostearate), suspending agent (PEG4000, the Polyethylene Glycol that PEG6000 is solid-state, aerosil, liquid paraffin, lanoline, Cera Flava, glyceryl monostearate, high fatty alcohol, preferred PEG6000 or Cera Flava), solubilizing agent (sodium hydroxide solution or sodium bicarbonate solution or unsaturated fatty acid, preferred sodium hydroxide solution or oleic acid), surfactant (sorbester p17, sorbester p18, Tween 80, polysorbate60, sodium lauryl sulphate, neutral liquid fat, preferred neutral liquid fat) in one and/or a plurality of mixed dissolution make solution-type or suspension type content; Get gelatin, purified water, the abundant mixing of glycerol and get glue, it is standby to regulate the adhesive tape that is compressed to 0.5-2.0mm thickness by press; Adopt pressed film method to prepare soft capsule,, wash ball, do eventually, promptly with appropriate solvent through solidifying by cooling in wind, drying.
Enumerate several embodiment that are used to that the invention process process is described rather than are used for limiting protection domain, as follows:
Embodiment 1)
Soybean oil 312g
Tolterodine tartrate 5g
Hydrogenated palm oil 54g
Oleic acid 15g
Tween 80
20g
Granulate 1000
Softgel shell glue prescription:
Gelatin: glycerol: water=1: 0.6: 0.7
The soft capsule that adopts above prescription to adopt preparation method to make, through study of pharmacy influence factor test, it is as follows to investigate the result:
| The investigation factor | Appearance character | Disintegration (min) | Content (%) |
| 0 day | Oval soft capsule | ??13 | ??98.8 |
| High temperature 10 days | Oval soft capsule | ??12 | ??99.1 |
| High humidity 10 days | Oval soft capsule | ??14 | ??99.2 |
| High light 10 days | Oval soft capsule | ??15 | ??97.9 |
Conclusion: investigate through high temperature, high humidity, high light condition effect factor, this product visual examination no change, disintegration time and content are all stable.
Embodiment 2)
PEG600???????????????????????320g
Tolterodine tartrate 5g
Isopropyl alcohol 41g
Sodium hydroxide solution 18g
Gas silica 1 6g
Granulate 1000
Softgel shell glue prescription:
Gelatin: sorbitol: water :=1: 0.6: 0.7
The soft capsule that adopts above prescription to adopt preparation method to make, through study of pharmacy influence factor test, it is as follows to investigate the result:
| The investigation factor | Appearance character | Disintegration (min) | Content (%) |
| 0 day | Oval soft capsule | ??13 | ??98.7 |
| High temperature 10 days | Oval soft capsule | ??14 | ??98.1 |
| High humidity 10 days | Oval soft capsule | ??15 | ??98.2 |
| High light 10 days | Oval soft capsule | ??15 | ??99.0 |
Conclusion: investigate through high temperature, high humidity, high light condition effect factor, this product visual examination no change, disintegration time and content are all stable.
Embodiment 3)
PEG600???????????????????????320g
Tolterodine tartrate 5g
Propylene glycol 40g
Sodium bicarbonate solution 17g
PEG6000??????????????????????18g
Granulate 1000
Softgel shell glue prescription:
Gelatin: sorbitol: water=1: 0.5: 0.8
The soft capsule that adopts above prescription to adopt preparation method to make, through study of pharmacy influence factor test, it is as follows to investigate the result:
| The investigation factor | Appearance character | Disintegration (min) | Content (%) |
| 0 day | Oval soft capsule | ??14 | ??98.8 |
| High temperature 10 days | Oval soft capsule | ??13 | ??99.2 |
| High humidity 10 days | Oval soft capsule | ??14 | ??98.6 |
| High light 10 days | Oval soft capsule | ??15 | ??98.7 |
Conclusion: investigate through high temperature, high humidity, high light condition effect factor, this product visual examination no change, disintegration time and content are all stable.
Embodiment 4)
PEG600???????????????????????320g
Tolterodine tartrate 5g
Isopropyl alcohol 38g
Sodium hydroxide solution 20g
PEG4000??????????????????????17g
Granulate 1000
Softgel shell glue prescription:
Gelatin: glycerol: water=1: 0.4: 0.9
The soft capsule that adopts above prescription to adopt preparation method to make, through study of pharmacy influence factor test, it is as follows to investigate the result:
| The investigation factor | Appearance character | Disintegration (min) | Content (%) |
| 0 day | Oval soft capsule | ??12 | ??98.9 |
| High 10 days | Oval soft capsule | ??14 | ??99.1 |
| High humidity 10 days | Oval soft capsule | ??13 | ??98.9 |
| High light 10 days | Oval soft capsule | ??15 | ??99.2 |
Conclusion: investigate through high temperature, high humidity, high light condition effect factor, this product visual examination no change, disintegration time and content are all stable.
Embodiment 5)
Herba Silybi mariani oil 320g
Tolterodine tartrate 5g
Monostearate 45g
Oleic acid 20g
Neutral liquid fat 15g
Granulate 1000
Softgel shell glue prescription:
Gelatin: sorbitol: water :=1: 0.6: 0.7
The soft capsule that adopts above prescription to adopt preparation method to make, through study of pharmacy influence factor test, it is as follows to investigate the result:
| The investigation factor | Appearance character | Disintegration (min) | Content (%) |
| 0 day | Oval soft capsule | ??15 | ??99.1 |
| High temperature 10 days | Oval soft capsule | ??14 | ??98.9 |
| High humidity 10 days | Oval soft capsule | ??15 | ??99.0 |
| High light 10 days | Oval soft capsule | ??13 | ??99.1 |
Conclusion: investigate through high temperature, high humidity, high light condition effect factor, this product visual examination no change, disintegration time and content are all stable.
3, the stripping characteristics according to the tolterodine tartrate soft capsule of this prepared are as follows:
Compare with existing preparation Tolterodine tartrate sheet dissolution:
| Sample time (min) | ??5 | ??10 | ??20 | ??30 | ??45 | ??60 |
| The Tolterodine tartrate sheet | ??55.1 | ??68.9 | ??75.4 | ??87.3 | ??93.2 | ??98.1 |
| Tolterodine tartrate soft capsule | ??64.3 | ??75.6 | ??87.5 | ??95.8 | ??97.7 | ??99.8 |
Conclusion: the dissolution of tolterodine tartrate soft capsule agent is better than tablet, the dissolution rate height.
Claims (11)
1. a tolterodine tartrate soft capsule is characterized in that content contains Tolterodine tartrate and other adjuvants.
2. the described soft capsule of claim 1 is characterized in that content is solution-type, suspension type.
3. the described soft capsule of claim 1, wherein said adjuvant comprise in lytic agent, cosolvent, solubilizing agent, suspending agent, the surfactant one and/or a plurality of.
4. the described soft capsule of claim 3, wherein said lytic agent is liquid polyethylene glycol and/or vegetable and animals oils.
5. the described soft capsule of claim 4, wherein said lytic agent is that described lytic agent is Polyethylene Glycol, fish oil, soybean oil, refining Oleum Arachidis hypogaeae semen, Radix Oenotherae erythrosepalae oil, Herba Silybi mariani oil, Oleum Vitis viniferae, Oleum Helianthi, safflower oil, the Fructus Hippophae wet goods vegetable and animals oils of PEG400 or PEG600 liquid state, preferred PEG400 or soybean oil; The addition of lytic agent is 10%--95%, and is preferred: 20%-80%, more preferably: 30%-70%.
6. each described soft capsule of claim 1-5, wherein said cosolvent is the mixture, pluronic F-68, monostearate, zein, hydrogenated palm oil, soybean lecithin, lecithin, polyglycerol ester, sucrose fat of lower alcohols such as propylene glycol, glycerol, isopropyl alcohol and/or several alcohol etc., preferred propylene glycol or monostearate; The addition of cosolvent is 1%--60%, and is preferred: 2%-50%, more preferably: 3%-40%.
7. each described soft capsule of claim 1-6, wherein said solubilizing agent is sodium hydroxide solution or sodium bicarbonate solution or unsaturated fatty acid, preferred sodium hydroxide solution or oleic acid, addition are 0.1%～10% preferred: 0.5%-8%, more preferably: 1%-5%.
8. each described soft capsule of claim 1-7, wherein said suspending agent is the solid-state Polyethylene Glycol of PEG4000, PEG6000, aerosil, liquid paraffin, lanoline, Cera Flava, glyceryl monostearate, high fatty alcohol, preferred PEG6000 or Cera Flava; Addition is 1%～10%, and is preferred: 1.5%-8%, more preferably: 2%-6%.
9. each described soft capsule of claim 1-8, wherein said surfactant is sorbester p17, sorbester p18, Tween 80, polysorbate60, sodium lauryl sulphate, neutral liquid fat, preferred neutral liquid fat; The addition of surfactant is 1%～30%, and is preferred: 3%-25%, more preferably: 3%-20%.
10. each described soft capsule of claim 1-9, the content of wherein said Tolterodine tartrate is 0.1%～10%, and is preferred: 0.2%-5%, more preferably: 0.2-2%.
11. each described preparation of soft capsule method of claim 1-10, with one in Tolterodine tartrate and lytic agent, cosolvent, solubilizing agent, suspending agent, the surfactant and/or a plurality of, mixed dissolution makes solution-type or suspension type content, the preparation soft capsule.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100803631A CN1330297C (en) | 2005-07-04 | 2005-07-04 | Tolterodine tartrate soft capsule and its preparing method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100803631A CN1330297C (en) | 2005-07-04 | 2005-07-04 | Tolterodine tartrate soft capsule and its preparing method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1709231A true CN1709231A (en) | 2005-12-21 |
| CN1330297C CN1330297C (en) | 2007-08-08 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2005100803631A Expired - Fee Related CN1330297C (en) | 2005-07-04 | 2005-07-04 | Tolterodine tartrate soft capsule and its preparing method |
Country Status (1)
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| CN (1) | CN1330297C (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102961358A (en) * | 2012-11-29 | 2013-03-13 | 重庆医药工业研究院有限责任公司 | Abiraterone acetate liquid capsule |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000012069A1 (en) * | 1998-08-27 | 2000-03-09 | Pharmacia & Upjohn Ab | Therapeutic formulation for administering tolterodine with controlled release |
| EP1227806B1 (en) * | 1999-11-11 | 2005-08-03 | Pfizer Health AB | Pharmaceutical formulation containing tolterodine and its use |
| CN1164265C (en) * | 2002-01-09 | 2004-09-01 | 南京美瑞制药有限公司 | Release controlled tuoteluoding tartrate and its preparing process |
| CN100382794C (en) * | 2004-08-30 | 2008-04-23 | 鲁南制药集团股份有限公司 | Dispersed tablet of tartaric acid tolterodine tartrate |
-
2005
- 2005-07-04 CN CNB2005100803631A patent/CN1330297C/en not_active Expired - Fee Related
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102961358A (en) * | 2012-11-29 | 2013-03-13 | 重庆医药工业研究院有限责任公司 | Abiraterone acetate liquid capsule |
| CN102961358B (en) * | 2012-11-29 | 2017-08-04 | 重庆医药工业研究院有限责任公司 | A kind of abiraterone acetate liquid capsule |
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| Publication number | Publication date |
|---|---|
| CN1330297C (en) | 2007-08-08 |
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Granted publication date: 20070808 |