CN105640900A - Perampanel medicinal composition - Google Patents

Abstract

The invention relates to a perampanel medicinal composition and a preparation method of the perampanel medicinal composition. According to the perampanel medicinal composition and the preparation method, auxiliary ingredients, namely, pregelatinized starch and mannitol at a certain ratio are selected, so that the release degree in vitro is improved to a great extent, thus the bioavailability is improved, and further, a preparation with good stability is provided.

Description

A kind of pyrrole Lun Panai pharmaceutical composition

Technical field

The present invention relates to field of pharmaceutical preparations, it is specifically related to a kind of pyrrole Lun Panai pharmaceutical composition and its preparation method.

Background technology

Pyrrole Lun Panai is a kind of alpha-amino group-3-hydroxyl-5 methyl-4-different azoles propionic acid (AMPA) receptor antagonist, the perampanel(trade(brand)name of Wei Cai company of U.S. FDA approval on October 22nd, 2012 Japan research and development: Fycompa) list in the U.S., it is used for the treatment of the local outbreak of more than 12 years old epilepsy patient, it reduces neurone be overexcited by suppressing postsynaptic AMPA receptors glutamate activity. This is the first antiepileptic drug with this mechanism of action of FDA approval.

Present inventor is by the research to pyrrole Lun Panai preparation in prior art, the astonishing pharmaceutical composition having found a kind of new pyrrole Lun Panai, dissolution rate in pyrrole Lun Panai body can not only be improved, and said composition is under preparation, storage, super-humid conditions, it is possible to ensure the stability of long-term storage. At ambient temperature, after the time of 36 months, measuring it has related substance, does not substantially degrade, and has more excellent quality stability in the present invention. Said preparation quality and stability thereof is substantially increased by it is carried out art breading. Meanwhile, to have prescription, technique simple for said composition, it is not necessary to special processing production unit, the advantage such as with low cost, thus the extensive popularization being this medicine in clinical, serve more positive effect.

Summary of the invention

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, the preparation technology being necessary to study out a kind of stable prescription composition, makes pyrrole Lun Panai have good stability of drug products and dissolution rate.

The present invention provides a kind of pharmaceutical composition containing pyrrole Lun Panai, and containing pyrrole Lun Panai, disintegrating agent, pregelatinized Starch and N.F,USP MANNITOL, and the weight ratio of pregelatinized Starch and N.F,USP MANNITOL is between 1.6-3.5.

Pregelatinized Starch and N.F,USP MANNITOL are the weighting agents of pharmaceutical composition of the present invention.

One or more the mixture that wherein said disintegrating agent is selected from polyvinylpolypyrrolidone, CCMS-Na or cross-linked carboxymethyl cellulose sodium.

Preferred above-mentioned disintegrating agent is polyvinylpolypyrrolidone.

Appropriate micropowder silica gel and Magnesium Stearate can be contained as required.

The feature of the present invention, for have been selected by weighting agent, finds the necessary proportion relation of two kinds of weighting agents so that obtained tablet has good dissolution rate, has good stability simultaneously, and obtained tablet hardness height, can carry out industrial amplification and produce. The key completing the present invention is: the control of the selection of disintegrating agent, the selection of weighting agent, pregelatinized Starch and N.F,USP MANNITOL ratio.

Specifically the pyrrole Lun Panai pharmaceutical composition of the present invention, described component and weight percent thereof be:

Pyrrole Lun Panai 1 ~ 3.33%

Pregelatinized Starch 40 ~ 52.5%

N.F,USP MANNITOL 15 ~ 25%

Disintegrating agent 20-25%

Preferably each component and weight percent thereof are:

Pyrrole Lun Panai 2 ~ 3.33%

Pregelatinized Starch 40 ~ 50%

N.F,USP MANNITOL 15 ~ 20%

Polyvinylpolypyrrolidone 20 ~ 25%

Magnesium Stearate 2 ~ 6%

Micropowder silica gel 2 ~ 6%

More preferred described component and weight percent thereof be:

Pyrrole Lun Panai 3.33%

Pregelatinized Starch 50%

N.F,USP MANNITOL 20%

Polyvinylpolypyrrolidone 21.67%

Magnesium Stearate 2.5%

Micropowder silica gel 2.5%

In addition, the present invention also provides a kind of pyrrole Lun Panai sheet and its preparation method, and preparation method is through following step:

1) putting in mortar by pyrrole Lun Panai, pregelatinized Starch, N.F,USP MANNITOL, add a small amount of water and grind to form mashed prod, less than 50 DEG C dry, pulverizes into 60-80 order fine powder, for subsequent use;

2) polyvinylpolypyrrolidone is sieved, for subsequent use;

3) by the auxiliary material 2 of recipe quantity) add 1) in, mix, for subsequent use;

4) 3 are got) middle employing 80% ethanolic soln, mixed even, make 30-40 order particle, dry below 50 DEG C, whole grain, adds lubricant, mixes, and compressing tablet to obtain final product.

The advantage of the present invention is that gained preparation has good dissolution rate and stability.

The advantage of the present invention is technical maturity, simple to operate, is applicable to industrial large-scale production.

Following prescription design and optimization is tested for illustration of the present invention.

The screening (by weight percentage) of different compositions formula:

Prescription forms	1	2	3	4	5	6	7
								Pyrrole Lun Panai	3	1	2	3.33	3.33	3.33	3.33
Pregelatinized Starch	47	52.5	42	50	40.5	59	40
								N.F,USP MANNITOL	15	15	25	20	20	15	40
Polyvinylpolypyrrolidone	25	25	20	21.67	25	20	10
								Magnesium Stearate	4.5	3	5	2.5	6	1.17	2.17
Micropowder silica gel	4.5	3.5	6	2.5	5.17	1.5	4.5
								80% ethanolic soln	In right amount	In right amount	In right amount	In right amount	In right amount	In right amount	In right amount

Technique:

1) putting in mortar by pyrrole Lun Panai, pregelatinized Starch, N.F,USP MANNITOL, add a small amount of water and grind to form mashed prod, less than 50 DEG C dry, pulverizes into 60-80 order fine powder, for subsequent use;

2) polyvinylpolypyrrolidone is sieved, for subsequent use;

3) by the auxiliary material 2 of recipe quantity) add 1) in, mix, for subsequent use;

4) 3 are got) middle employing 80% ethanolic soln, mixed even, make 30-40 order particle, dry below 50 DEG C, whole grain, adds lubricant, mixes, and compressing tablet to obtain final product.

Test-results shows

Prescription number	1	2	3	4	5	6	7
								Compressibility	Good, without sticky punching	Good, without sticky punching	Good, without sticky punching	Good, without sticky punching	Good, without sticky punching	There is sticky punching	There is sticky punching
Unilateral	Bright and clean	Bright and clean	Bright and clean	Bright and clean	Bright and clean	Coarse	Coarse
								Hardness (kg)	6.3	6.4	6.8	7	6.9	3.0	4.0
Dissolution rate	98.5%	98.6%	98.2%	99.9%	99.2%	93.4%	92.0%

In the usage ratio of pregelatinized Starch and N.F,USP MANNITOL, contriver finds through shaker test, and the ratio of pregelatinized Starch and N.F,USP MANNITOL is between 1.6-3.5, and the tablet quality pressed meets the requirements, prescription 1 to prescription 5 obtains good outward appearance and hardness, and dissolution rate is also better.

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(comparative example)

Pyrrole Lun Panai 4g

Lactose 90g

Microcrystalline Cellulose 10220g

Croscarmellose sodium 4g

Magnesium Stearate 1g

Make 1000

Preparation method: take each component by recipe quantity, crosses 60 order sieves, fully mixes, granulate, Singlepunchtabletpress compressing tablet.

Embodiment 2

Composition	1000 consumptions	Weight percent (%)
			Pyrrole Lun Panai	4	3.33
Pregelatinized Starch	60	50
			N.F,USP MANNITOL	24	20
Polyvinylpolypyrrolidone	26	21.67
			Magnesium Stearate	3	2.5
Micropowder silica gel	3	2.5
			80% ethanolic soln	In right amount	In right amount

Preparation method is through following step:

1) putting in mortar by pyrrole Lun Panai, pregelatinized Starch, N.F,USP MANNITOL, add a small amount of water and grind to form mashed prod, less than 50 DEG C dry, pulverizes into 60-80 order fine powder, for subsequent use;

2) polyvinylpolypyrrolidone is sieved, for subsequent use;

3) by the auxiliary material 2 of recipe quantity) add 1) in, mix, for subsequent use;

4) 3 are got) middle employing 80% ethanolic soln, mixed even, make 30-40 order particle, dry below 50 DEG C, whole grain, adds lubricant, mixes, and compressing tablet to obtain final product;

Embodiment 3

Composition	1000 consumptions	Weight percent (%)
			Pyrrole Lun Panai	4	3.33
Pregelatinized Starch	48.6	40.5
			N.F,USP MANNITOL	24	20
Polyvinylpolypyrrolidone	30	25
			Magnesium Stearate	7.2	6
Micropowder silica gel	6.2	5.17
			80% ethanolic soln	In right amount	In right amount

Preparation method is through following step:

1) putting in mortar by pyrrole Lun Panai, pregelatinized Starch, N.F,USP MANNITOL, add a small amount of water and grind to form mashed prod, less than 50 DEG C dry, pulverizes into 60-80 order fine powder, for subsequent use;

2) polyvinylpolypyrrolidone is sieved, for subsequent use;

3) by the auxiliary material 2 of recipe quantity) add 1) in, mix, for subsequent use;

4) 3 are got) middle employing 80% ethanolic soln, mixed even, make 30-40 order particle, dry below 50 DEG C, whole grain, adds lubricant, mixes, and compressing tablet to obtain final product;

Test example 1

The useful effect of the present invention is described below by way of testing data.

This test example is to investigate the stability of pyrrole Lun Panai composition provided by the present invention.

Pyrrole Lun Panai pharmaceutical composition is prepared, according to commercially available packaging, at 40 DEG C �� 2 DEG C according to the method for embodiment of the present invention 1-3, the condition of RH75% �� 5% places 6 months, period respectively at the 1st, sampling in 2,3,6 months, according to the detection of stability inspection item, and compare with 0 day data.

Accelerated test result

Above test-results illustrates, embodiment 1 is being accelerated in placement process, and sample has related substance to be significantly increased, and dissolution rate reduces, and quality is unstable; Adopting embodiment 2 prepared by preparation technology of the present invention and embodiment 3 accelerating in placement process, each monitoring index of sample is all qualified.

Claims (8)

1. one kind contains the pharmaceutical composition of pyrrole Lun Panai, it is characterised in that containing pyrrole Lun Panai, disintegrating agent, pregelatinized Starch and N.F,USP MANNITOL, and the weight ratio of pregelatinized Starch and N.F,USP MANNITOL is between 1.6-3.5.

2. pyrrole Lun Panai pharmaceutical composition according to claim 1, it is characterised in that one or more the mixture that described disintegrating agent is selected from polyvinylpolypyrrolidone, CCMS-Na or cross-linked carboxymethyl cellulose sodium.

3. pyrrole Lun Panai pharmaceutical composition according to claim 2, it is characterised in that described disintegrating agent is polyvinylpolypyrrolidone.

4. pyrrole Lun Panai pharmaceutical composition according to Claims 2 or 3, it is characterised in that also containing micropowder silica gel and Magnesium Stearate.

5. pyrrole Lun Panai pharmaceutical composition according to claim 1, it is characterised in that the weight percent of described component is:

Pyrrole Lun Panai 1 ~ 3.33%

Pregelatinized Starch 40 ~ 52.5%

N.F,USP MANNITOL 15 ~ 25%

Disintegrating agent 20-25%.

6. pyrrole Lun Panai pharmaceutical composition according to claim 4, it is characterised in that the weight percent of described component is:

Pyrrole Lun Panai 2 ~ 3.33%

Pregelatinized Starch 40 ~ 50%

N.F,USP MANNITOL 15 ~ 20%

Polyvinylpolypyrrolidone 20 ~ 25%

Magnesium Stearate 2 ~ 6%

Micropowder silica gel 2 ~ 6%.

7. pyrrole Lun Panai pharmaceutical composition according to claim 6, it is characterised in that the weight percent of described component is:

Pyrrole Lun Panai 3.33%

Pregelatinized Starch 50%

N.F,USP MANNITOL 20%

Polyvinylpolypyrrolidone 21.67%

Magnesium Stearate 2.5%

Micropowder silica gel 2.5%.

8. the preparation method of pyrrole Lun Panai pharmaceutical composition according to any one of claim 5-7, it is characterised in that comprise the following steps:

1) putting in mortar by pyrrole Lun Panai, pregelatinized Starch, N.F,USP MANNITOL, add a small amount of water and grind to form mashed prod, less than 50 DEG C dry, pulverizes into 60-80 order fine powder, for subsequent use;

2) polyvinylpolypyrrolidone is sieved, for subsequent use;

3) by the auxiliary material 2 of recipe quantity) add 1) in, mix, for subsequent use;

4) 3 are got) middle employing 80% ethanolic soln, mixed even, make 30-40 order particle, dry below 50 DEG C, whole grain, adds lubricant, mixes, and compressing tablet to obtain final product.