CN111214447A - Solid composition of safinamide mesylate and preparation method thereof - Google Patents
Solid composition of safinamide mesylate and preparation method thereof Download PDFInfo
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- CN111214447A CN111214447A CN201811407735.0A CN201811407735A CN111214447A CN 111214447 A CN111214447 A CN 111214447A CN 201811407735 A CN201811407735 A CN 201811407735A CN 111214447 A CN111214447 A CN 111214447A
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- Prior art keywords
- solid composition
- safinamide mesylate
- safinamide
- solution
- preparation
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
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- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention relates to a safinamide mesylate solid composition and a preparation method thereof, belonging to the field of medicines. The safinamide mesylate is a novel oral medicament for treating the Parkinson's disease, and has low in vivo absorption rate due to low solubility. In order to improve the bioavailability, the invention provides a solution or suspension prepared from safinamide mesylate by using a solvent, wherein the solvent adopted by the solution or suspension is prepared from purified water or an ethanol water solution; the concentration of the safinamide mesylate is 10 to 40 percent; spraying the solution or suspension onto the excipient by fluidized bed granulation process to obtain pharmaceutical granules containing safinamide mesylate, and preparing into preparation; can be free from pH value, and can improve dissolution rate, thereby improving bioavailability.
Description
Technical Field
The invention belongs to the field of pharmaceutical preparations, and particularly relates to a safinamide mesylate solid composition and a preparation method thereof.
Background
The safinamide is a sodium channel and calcium channel compound blocker, and is used as a levodopa single drug or an auxiliary treatment drug for treating intermediate and advanced idiopathic parkinsonism by combining with other parkinsonian drugs. Safinamide mesylate was a new oral drug developed by Newron and Zambon thereof for the treatment of parkinson's disease and was first marketed in the european union in 2015.
The solubility of the safinamide in an aqueous medium is very low, particularly the solubility is only 10 micrograms/ml when the pH =7, which causes the bioavailability of the safinamide in gastrointestinal tract administration to be low, so that the improvement of the dissolution rate of the safinamide to improve the bioavailability thereof is a technical problem to be solved at present.
Disclosure of Invention
The invention aims to solve the defect of low bioavailability of the existing safinamide preparation, and invents fluidized bed spray granulation, so that the safinamide is uniformly distributed on a carrier, the surface area is enlarged, the dissolution rate is improved, and the bioavailability is improved.
The invention provides a method for preparing a solid composition containing hydrophilic safinamide mesylate, which comprises the following steps:
the safinamide mesylate is prepared into a solution or suspension containing the active substance by using a solvent, and the aqueous solution of the active substance is sprayed on the excipient by adopting a fluidized bed granulation process to obtain granules containing the active ingredient.
Mixing the granules containing active ingredients with suitable additives, and making into solid composition, tablet, granule, or capsule.
The solution or suspension of safinamide mesylate is prepared by using hydrophilic adhesive and using purified water or ethanol water solution as solvent. The concentration of the ethanol aqueous solution should not be higher than 30% (w/w).
The hydrophilic adhesive is one of hydroxypropyl cellulose EF, hydroxypropyl cellulose LF, hydroxypropyl methylcellulose E5 and hydroxypropyl methylcellulose E15.
The concentration of the solution or suspension of safinamide mesylate is 10-40%, preferably 20-30%. The concentration of safinamide mesylate affects the yield and dissolution rate of fluid bed granulation.
The excipient is one or more of microcrystalline cellulose PH101, microcrystalline cellulose PH102, lactose monohydrate, spray-dried lactose, mannitol, and spray-dried mannitol, preferably microcrystalline cellulose.
The solid composition is in the form of a tablet.
Detailed Description
The following examples further describe the beneficial effects of the present invention, and the examples are for illustrative purposes only and do not limit the scope of the present invention.
Example 1
The prescription composition is as follows:
safinamide mesylate 30.00%
Hydroxypropyl methylcellulose E53.00%
Microcrystalline cellulose 51.00%
Cross-linked polyvidone 15.00%
Magnesium stearate 1.00%
The preparation process comprises the following steps:
the hydroxypropyl methylcellulose E5 and the safinamide mesylate with the prescription amount are dissolved in purified water to ensure that the concentration of the safinamide mesylate is 15% (w/w), and the mixture is stirred to form uniform suspension. Spraying the above solution onto microcrystalline cellulose with fluidized bed to obtain active ingredient granule, adding polyvinylpolypyrrolidone and magnesium stearate, mixing, and tabletting.
Example 2
The prescription composition is as follows:
safinamide mesylate 30.00%
Hydroxypropyl methylcellulose E53.00%
Microcrystalline cellulose 31.00%
Spray-dried mannitol 20.00%
Cross-linked polyvidone 15.00%
Magnesium stearate 1.00%
The preparation process comprises the following steps:
the hydroxypropyl methylcellulose E5 and the safinamide mesylate with the prescription amount are dissolved in purified water to ensure that the concentration of the safinamide mesylate is 25 percent (w/w), and the mixture is stirred to form uniform suspension. Spraying the above solution onto microcrystalline cellulose and spray-dried mannitol with fluidized bed to obtain active ingredient granule, adding polyvinylpolypyrrolidone and magnesium stearate, mixing, and tabletting.
Example 3
The tablet core prescription comprises:
safinamide mesylate 30.00%
Hydroxypropyl methylcellulose E152.00%
Microcrystalline cellulose 32.00%
Spray-dried lactose 20.00%
Cross-linked polyvidone 15.00%
Magnesium stearate 1.00%
The preparation process comprises the following steps:
dissolving the hydroxypropyl methylcellulose E5 and the safinamide mesylate in purified water according to the prescription amount to ensure that the concentration of the safinamide mesylate is 30% (w/w), and stirring to obtain a uniform suspension. Spraying the above solution onto microcrystalline cellulose and spray-dried mannitol with fluidized bed to obtain active ingredient granule, adding polyvinylpolypyrrolidone and magnesium stearate, mixing, and tabletting.
0.1NHCL +2% (wt/vol) NaCl according to 100 turns of the second pulping method of the fourth 0931 of the Chinese pharmacopoeia 2015 edition. Dissolution rate detection result:
| time of day | Example 1 | Example 2 | Example 3 | Reference formulation |
| 15min/% | 90.12 | 87.23 | 89.13 | 92.34 |
| 30min/% | 98.60 | 94.25 | 97.65 | 99.87 |
And (4) conclusion: according to the dissolution rate detection results, the dissolution rate of the embodiments 1 to 3 is greater than 85% in 15min, the dissolution rate is rapid, the dissolution rate is consistent with that of a reference preparation, and the dissolution rate is improved, so that the dissolution rate is improved, and the bioavailability of the medicine is enhanced.
Claims (7)
1. A solid composition for the preparation of a hydrophilic safinamide mesylate containing composition,
(1) preparing solution or suspension (I) containing active substances from the safinamide mesylate by using a solvent, and spraying the active substances (I) onto the excipient by adopting a fluidized bed granulation process to obtain granules containing the active ingredients;
(2) mixing the granules containing active ingredients with suitable additives, and making into solid composition, tablet, granule, or capsule.
2. The solid composition of safinamide mesylate according to claim 1, wherein the active agent (I) is formulated with a hydrophilic binder and the solvent is purified water or an aqueous ethanol solution.
3. The solid composition of safinamide mesylate according to claim 2, wherein the concentration of the aqueous ethanol solution is not higher than 30% (w/w).
4. The hydrophilic adhesive of claim 2, wherein the hydrophilic adhesive is one of hydroxypropyl cellulose EF, hydroxypropyl cellulose LF, hypromellose E5, and hypromellose E15.
5. Solid composition of safinamide mesylate according to claim 1, wherein the concentration of active substance (I) is between 10% and 40%, preferably between 20% and 30%.
6. The solid composition of safinamide mesylate according to claim 1, wherein the vehicle is one or more of microcrystalline cellulose PH101, microcrystalline cellulose PH102, lactose monohydrate, spray-dried lactose, mannitol, and spray-dried mannitol.
7. The solid composition of safinamide mesylate according to claim 1, wherein the solid composition is in the form of a tablet.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811407735.0A CN111214447A (en) | 2018-11-23 | 2018-11-23 | Solid composition of safinamide mesylate and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811407735.0A CN111214447A (en) | 2018-11-23 | 2018-11-23 | Solid composition of safinamide mesylate and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN111214447A true CN111214447A (en) | 2020-06-02 |
Family
ID=70830346
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811407735.0A Pending CN111214447A (en) | 2018-11-23 | 2018-11-23 | Solid composition of safinamide mesylate and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111214447A (en) |
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2018
- 2018-11-23 CN CN201811407735.0A patent/CN111214447A/en active Pending
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20200602 |
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| WD01 | Invention patent application deemed withdrawn after publication |