CN105641677A - Stable telaprevir capsule pharmaceutical composition - Google Patents
Stable telaprevir capsule pharmaceutical composition Download PDFInfo
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- CN105641677A CN105641677A CN201410634013.4A CN201410634013A CN105641677A CN 105641677 A CN105641677 A CN 105641677A CN 201410634013 A CN201410634013 A CN 201410634013A CN 105641677 A CN105641677 A CN 105641677A
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- capsule
- microcrystalline cellulose
- croscarmellose sodium
- telaprevir
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Abstract
The present invention discloses a stable telaprevir capsule pharmaceutical composition, which is characterized in that the components in the formula for preparing 1000 stable telaprevir capsule pharmaceutical compositions comprise 375-700 g of telaprevir, 70-140 g of microcrystalline cellulose, 0.5-1 g of micro-powder silica gel, 50-100 g of cross-linked sodium carboxymethyl cellulose, and a proper amount of a 10% pre-gelatinized starch solution. The present invention further relates to a telaprevir capsule preparation method. According to the present invention, the telaprevir capsule prepared by using the formula and the preparation method has characteristics of good fluidity, good dissolution, low loading difference, high bioavailability, and good treatment effect.
Description
Technical field
The present invention relates to a kind of stable VX-960 pharmaceutical capsules composition and its preparation method.
Background technology
VX-960
English name: Telaprevir;
Structural formula:
Molecular formula: C36H53N7O6;
Molecular weight: 679.85;
VX-960 is a kind of reversibility proteinase inhibitor, with polyoxyethylene glycol alpha-interferon and ribavirin conbined usage, can effectively suppress the duplication of HVC virus, for the treatment of chronic hepatitis C.
By the research to prior art, VX-960 bioavailability in human body is low is still puzzlement people's urgent problem. In addition, the kind of suitable preparation method and processing condition, weighting agent and consumption are most important to the result of extraction of capsule, mobility, content uniformity. Conventional weighting agent lactose, Microcrystalline Cellulose, starch etc., conventional disintegrating agent has Microcrystalline Cellulose, sodium starch glycolate etc. But, how to obtain more excellent solubility rate by the dissolution rate adjustment formula of described VX-960 and technique adjustment, how to improve its mobility, content uniformity by the processing method examined, problem, the prior aries such as the degraded of VX-960 all do not provide further prompting to avoid how to select suitable processing condition, in view of this, this invention of special proposition.
Summary of the invention
The present invention is intended to overcome the problem such as the mobility of existing VX-960 pharmaceutical composition is not good, dissolution rate is low, content uniformity is obvious, change the dissolution rate of VX-960 capsule and the low shortcoming of bioavailability, improve curative effect, and the good fluidity of the VX-960 capsule provided, content uniformity is little. According to existing auxiliary material and working condition, in guarantee, there is lower production cost and simple preparation technology, under being suitable for the prerequisite of large-scale industrial production, it is necessary to study out a kind of suitable prescription composition and preparation technology, make VX-960 have good bioavailability.
Therefore, it is an object of the invention to provide a kind of VX-960 capsule, it is characterised in that, the formula making 1000 is hired a car as follows:
VX-960 250-500g
Croscarmellose sodium 50-100g
Microcrystalline Cellulose 70-140g
Micropowder silica gel 0.5-1g
10% pregelatinized Starch solution is appropriate.
Preferably, to make the formula of 1000 composed as follows for the VX-960 capsule of the present invention:
VX-960 250g
Croscarmellose sodium 50g
Microcrystalline Cellulose 70g
Micropowder silica gel 0.5g
10% pregelatinized Starch solution is appropriate.
In the present invention, Microcrystalline Cellulose does weighting agent, and pregelatinized Starch plays dual parts bonding and disintegration, promotes capsule disintegration.
The present invention determines the assembly application of Microcrystalline Cellulose and pregelatinized Starch by prescription screening, and prepared VX-960 capsule dissolubility is better, and content uniformity is little, and determines the optimizing prescriptions of the present invention through auxiliary material shaker test. Prescription screening is tested and be the results are shown in down:
From above test-results: prescription 1 no matter content uniformity or stripping trend is all better than other prescription.
Another object of the present invention is to provide the preparation method of VX-960 capsule of the present invention, it is characterised in that the method comprises the steps:
1) respectively by dry to VX-960, croscarmellose sodium, Microcrystalline Cellulose, pulverize, sieve, obtain VX-960 powder, croscarmellose sodium powder and Microcrystalline Cellulose powder respectively;
2) get the VX-960 of recipe quantity, croscarmellose sodium and Microcrystalline Cellulose, mix, then add 10% pregelatinized Starch solution and make softwood in right amount, cross 20 eye mesh screens and granulate, obtain VX-960 wet granular;
3) above-mentioned VX-960 wet granular is dried to moisture under 60 DEG C of conditions and it is less than 5%, obtain the dry particle of VX-960;
4) dry for above-mentioned VX-960 particle being crossed the 20 whole grains of eye mesh screen, then add lubricant, mix, after quality inspection is qualified, dress capsule, obtains VX-960 capsule.
In above-mentioned preparation method, sieving of step 1) was 100 order sieves.
Preferably, the object of screening is the material in order to obtain relatively uniform particle size. This has important meaning smoothly to what drug quality and preparation were produced. The unit operations such as mixing, granulation, dress capsule sieve the mobility on mixedness, particle, Packing character, content uniformity etc. and has obvious impact. Remix after former, auxiliary material being pulverized, sieved in the present invention, former, auxiliary material can be made to be evenly distributed, what mix is more even, and the present invention adopts Microcrystalline Cellulose and major ingredient pulverize rear remix respectively, the mobility of mixedness, particle, Packing character and content uniformity can be made to be significantly improved thus make medicine better play drug effect.
In addition, heating can cause the degraded of VX-960, therefore, it is determined that the drying temperature being applicable to is very important. VX-960 particle is dried to moisture by the present invention under 60 DEG C of conditions and is less than 5%, obtain the dry particle of VX-960, not only avoid and heat the degraded to VX-960, and drying effect is good.
The present invention using Microcrystalline Cellulose as weighting agent, croscarmellose sodium is as disintegrating agent, 10% pregelatinized Starch as tackiness agent; Lubricant is micropowder silica gel. Make VX-960 capsule, have following advantage:
1) stability of VX-960 can be improved: because medicine is wrapped in capsule, therefore medicine and the contact of light, air and moisture can be completely cut off, it is to increase medicine stability;
2) higher than tablet bioavailability: because vehicle is not generally added in the preparation of capsule, also not add pressure, therefore in stomach and intestine, relatively pill, tablet disperse fast, good absorption;
3) the VX-960 capsule good fluidity prepared by preparation method of VX-960 capsule provided by the present invention, dissolution rate is good, content uniformity is not obvious.
Embodiment
Below in conjunction with embodiment, the present invention is described in further detail, it should be appreciated that the non-scope being only limitted to these embodiments of the scope of the present invention.
Embodiment 1
It is composed as follows that the formula of 1000 made by VX-960 capsule:
VX-960 250g
Croscarmellose sodium 50g
Microcrystalline Cellulose 70g
Micropowder silica gel 0.5g
10% pregelatinized Starch solution is appropriate
Preparation method
1) VX-960, croscarmellose sodium and Microcrystalline Cellulose is dry, pulverizing, excessively 100 orders sieve respectively, obtains VX-960 powder, croscarmellose sodium and Microcrystalline Cellulose powder respectively;
2) get the VX-960 of recipe quantity, croscarmellose sodium and Microcrystalline Cellulose, mix, then add 10% pregelatinized Starch solution and make softwood in right amount, cross 20 eye mesh screens and granulate, obtain VX-960 wet granular;
3) above-mentioned VX-960 wet granular is dried to moisture under 60 DEG C of conditions and it is less than 5%, obtain the dry particle of VX-960
4) dry for above-mentioned VX-960 particle being crossed the 20 whole grains of eye mesh screen, then add lubricant, mix, after quality inspection is qualified, dress capsule, obtains VX-960 capsule.
Embodiment 2
It is composed as follows that the formula of 1000 made by VX-960 capsule:
VX-960 500g
Croscarmellose sodium 100g
Microcrystalline Cellulose 140g
Micropowder silica gel 1g
10% pregelatinized Starch solution is appropriate
Preparation method
1) VX-960, croscarmellose sodium and Microcrystalline Cellulose is dry, pulverizing, excessively 100 orders sieve respectively, obtains VX-960 powder and Microcrystalline Cellulose powder respectively;
2) get the VX-960 of recipe quantity, croscarmellose sodium and Microcrystalline Cellulose, mix, then add 10% pregelatinized Starch solution and make softwood in right amount, cross 20 eye mesh screens and granulate, obtain VX-960 wet granular;
3) above-mentioned VX-960 wet granular is dried to moisture under 60 DEG C of conditions and it is less than 5%, obtain the dry particle of VX-960;
4) dry for above-mentioned VX-960 particle being crossed the 20 whole grains of eye mesh screen, then add lubricant, mix, after quality inspection is qualified, dress capsule, obtains VX-960 capsule.
The useful effect of the VX-960 capsule of the present invention is described below by way of test example, comparative example.
The study on the stability of [test example 1] product of the present invention
Adopt the VX-960 capsule that prescription of the present invention and preparation method obtain, through the test of study of pharmacy influence factor, investigate and the results are shown in down:
Conclusion: factors influencing under high temperature, high wet, illumination condition, product appearance of the present invention observe unchanged, disintegration time and content all stable.
Claims (5)
1. a stable VX-960 pharmaceutical capsules composition, it is characterised in that the formula making 1000 is composed as follows:
VX-960 250-500g
Croscarmellose sodium 50-100g
Microcrystalline Cellulose 70-140g
Micropowder silica gel 0.5-1g
10% pregelatinized Starch solution is appropriate.
2. VX-960 pharmaceutical capsules composition according to claim 1, it is characterised in that the formula making 1000 is composed as follows:
VX-960 250g
Croscarmellose sodium 50g
Microcrystalline Cellulose 70g
Micropowder silica gel 0.5g
10% pregelatinized Starch solution is appropriate.
3. VX-960 pharmaceutical capsules composition according to claim 1, it is characterised in that the formula making 1000 is composed as follows:
VX-960 500g
Croscarmellose sodium 100g
Microcrystalline Cellulose 140g
Micropowder silica gel 1g
10% pregelatinized Starch solution is appropriate.
4. the preparation method of VX-960 capsule described in claim 1 or 2 or 3, it is characterised in that described preparation method comprises the steps:
1) respectively by dry to VX-960, croscarmellose sodium, Microcrystalline Cellulose, pulverize, sieve, obtain VX-960 powder, croscarmellose sodium powder and Microcrystalline Cellulose powder respectively;
2) get the VX-960 of recipe quantity, croscarmellose sodium and Microcrystalline Cellulose, mix, then add 10% pregelatinized Starch solution and make softwood in right amount, cross 20 eye mesh screens and granulate, obtain VX-960 wet granular;
3) above-mentioned VX-960 wet granular is dried to moisture under 60 DEG C of conditions and it is less than 5%, obtain the dry particle of VX-960;
4) dry for above-mentioned VX-960 particle being crossed the 20 whole grains of eye mesh screen, then add lubricant, mix, after quality inspection is qualified, dress capsule, obtains VX-960 capsule.
5. preparation method according to claim 4, it is characterised in that sieving in step 1) referred to 100 order sieves.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410634013.4A CN105641677A (en) | 2014-11-12 | 2014-11-12 | Stable telaprevir capsule pharmaceutical composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410634013.4A CN105641677A (en) | 2014-11-12 | 2014-11-12 | Stable telaprevir capsule pharmaceutical composition |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105641677A true CN105641677A (en) | 2016-06-08 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410634013.4A Pending CN105641677A (en) | 2014-11-12 | 2014-11-12 | Stable telaprevir capsule pharmaceutical composition |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105641677A (en) |
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2014
- 2014-11-12 CN CN201410634013.4A patent/CN105641677A/en active Pending
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Application publication date: 20160608 |