CN105520918B

CN105520918B - Pregabalin capsule

Info

Publication number: CN105520918B
Application number: CN201511014317.1A
Authority: CN
Inventors: 胡国宜; 胡锦平; 陈玮琦; 顾冬飞; 汪士金; 奚小金
Original assignee: CHANGZHOU SUNLIGHT PHARMACEUTICAL Co Ltd
Current assignee: CHANGZHOU SUNLIGHT PHARMACEUTICAL Co Ltd
Priority date: 2015-12-31
Filing date: 2015-12-31
Publication date: 2018-12-11
Anticipated expiration: 2035-12-31
Also published as: CN105520918A

Abstract

The invention discloses a kind of Pregabalin capsules, it is made of Pregabalin, lactose and pharmaceutically acceptable carrier, and wherein lactose is screening lactose, spray-dried lactose or lactose compound.Screening lactose preferred size is distributed as being not higher than 10%, less than 100 μm being 20~45%, no less than 85% less than 200 μm and the no less than 99% screening lactose less than 250 μm less than 32 μm.In above-mentioned Pregabalin capsule, the weight percent of Pregabalin is 5%~50%, and the weight percent of lactose is 10%~60%.The present invention is prepared Pregabalin capsule and can be obtained preferable stability using screening lactose or spray-dried lactose or lactose compound and Pregabalin bulk pharmaceutical chemicals and pharmaceutically acceptable carrier, to solve the problems, such as that Pregabalin capsule stability is poor in the prior art, can be suitble to industrialized production.

Description

Pregabalin capsule

Technical field

The invention belongs to technical field of medicine, and in particular to a kind of Pregabalin capsule.

Background technique

Pregabalin belongs to non-γ-aminobutyric acid (GABA) receptor stimulating agent or antagonist, is that a kind of novel agents of calcium ion is logical Road regulator, energy blocking voltage dependent calcium channel, reduces the release of neurotransmitter.Clinic is mainly used for Diabetic Peripheral mind Through the related neuralgia of lesion, postherpetic neuralgia and adjuvant treatment the epileptic attack of adult partial's property, generalized anxiety disorder, in Pivot neuralgia (including spinal cord injury, stroke and the adjoint neuralgia of multiple sclerosis) and fibromyalgia.

On the one hand, since there are primary amino groups and carboxyl for Pregabalin intramolecular, intramolecular condensation easily occurs and generates interior acyl Amine, this intramolecular condensation phenomenon is more obvious especially under wet heat condition.And the primary amino group in Pregabalin is damp and hot Under the conditions of be also easy to and mailland reaction occurs for carboxyl in lactose molecule.Therefore, wet granulation (is especially filling with lactose The wet granulation of agent) be not suitable for preparing Pregabalin capsule.

On the other hand, the very poor compressibility of Pregabalin is but also dry granulation is difficult to reach to form particle improvement mobility Purpose prepares Pregabalin capsule to be not suitable for use in.

Summary of the invention

The purpose of the present invention is to solve the above problem, provides a kind of big raw with preferable stability, suitable industrialization The Pregabalin capsule of production.

Realizing the technical solution of above-mentioned purpose of the present invention is: a kind of Pregabalin capsule, it be by Pregabalin, lactose with And pharmaceutically acceptable carrier is made.

Applicants have unexpectedly found that the lactose nature difference of different process preparation is larger, then, applicant guesses dissimilarity Its mobility of capsule and stability that the lactose and Pregabalin of matter are prepared very likely can also have larger difference.For This, applicant finally found that by many experiments: the grinding lactose that obtains only by common mechanical lapping and by grinding Lactose condensation product (lactose of referred to as pelletizing below) and the capsule made from Pregabalin that lactose is formed after fluidized bed processing Stability is poor；And it is multiple by the lactose that lactose and other auxiliary material (such as starch, microcrystalline cellulose) spray-dried techniques obtain It closes object and capsule stability made from Pregabalin is then preferable；And the lactose of spray-dried technique production (is referred to as below Spray-dried lactose) and the production of screened technique the relatively narrow lactose of size distribution (below referred to as screening lactose) More preferably with capsule stability made from Pregabalin.

Above-mentioned spray-dried lactose is will to grind lactose to be added to the water to obtain suspension, it is then spray-dried again after The crystalline lactose sphere agglomerates formed in unformed lactose substrate.

Above-mentioned screening lactose preferred size be distributed as less than 32 μm not higher than 10%, less than 100 μm be 20~45%, small In 200 μm of no less than 85% and the no less than 99% screening lactose less than 250 μm；Or size distribution is less than 100 μm Not higher than 20%, less than 250 μm be 40%~70% and the no less than 99% screening lactose less than 400 μm；Or granularity It is distributed as the lactose of no less than 75% not higher than 20% and less than 200 μm less than 63 μm.

Above-mentioned pharmaceutically acceptable carrier is mainly adhesive and lubricant.

Applicant further found that the content of Pregabalin is unsuitable excessively high in Pregabalin capsule, it is preferred with 50% or less, otherwise It will affect the stability of Pregabalin capsule, therefore, in above-mentioned Pregabalin capsule, the weight percent of Pregabalin is 5%~ 50%, preferably 20%~30%.

In above-mentioned Pregabalin capsule, the weight percent of lactose is 10%~60%, preferably 25%~35%.

In above-mentioned Pregabalin capsule, the weight percent of adhesive is 20%~80%, preferably 30%~50%；It is described viscous Mixture is in starch, PVP K30, hydroxypropyl cellulose, hypromellose, methylcellulose and ethyl cellulose One or two kinds of, preferably starch.

In above-mentioned Pregabalin capsule, the weight percent of lubricant is 1%~10%, preferably 3%~7%；The lubrication Agent is selected from one of magnesium stearate, talcum powder, silica and hydrogenated vegetable oil or two kinds, preferably magnesium stearate.

The good effect that the present invention has: the present invention is using screening lactose or spray-dried lactose or lactose compound Preferable stability can be obtained by preparing Pregabalin capsule with Pregabalin bulk pharmaceutical chemicals and pharmaceutically acceptable carrier, from And solve the problems, such as that Pregabalin capsule stability is poor in the prior art, industrialized production can be suitble to.

Specific embodiment

(embodiment 1)

The Pregabalin capsule of the present embodiment contains Pregabalin 0.025g, screening lactose 0.030g, as binder Starch 0.040g and magnesium stearate 0.005g as lubricant.

The Pregabalin capsule of the present embodiment the preparation method is as follows:

1. by the screened technique of lactose be made size distribution be less than 32 μm not higher than 10%, be 20 less than 100 μm~ 45%, no less than 85% less than 200 μm and the screening lactose for being no less than 99% less than 250 μm.

2. first 250g Pregabalin bulk pharmaceutical chemicals (crossing 80 meshes) are mixed with 400g starch (crossing 80 meshes) in Multidirectional motion 5min, revolving speed 30rpm are mixed on machine；Then 50g magnesium stearate (sieving with 100 mesh sieve) and 300g step 1. sieve obtained is added Divide lactose, continues to mix 10min, revolving speed 30rpm, is uniformly mixed；Finally uniformly mixed material is filled in fully-automatic capsule Fill out on machine it is directly filling obtain Pregabalin capsule, 10000 (1000g in total), every 0.1g is made.

(2~embodiment of embodiment 4)

The Pregabalin capsule of 2~embodiment of embodiment 4 is substantially the same manner as Example 1, the difference is that used The preparation process of lactose is different, is specifically shown in Table 1.

(1~comparative example of comparative example 2)

The Pregabalin capsule of comparative example 1 and comparative example 2 is substantially the same manner as Example 1, the difference is that used The preparation process of lactose is different, is specifically shown in Table 1.

(test example)

Under conditions of Pregabalin capsule made from each embodiment and each comparative example is placed on 40 DEG C/RH75%, 0 day, 5 days, 10 days, 30 days, 2 months and 3 months point in time sampling detect the stability of each Pregabalin capsule.

Table 1

As can be seen from Table 1: using the stability of Pregabalin capsule made from screening lactose or spray-dried lactose Better than using Pregabalin capsule made from lactose compound, and it is significantly better than that using made from grinding lactose and granulation lactose Pregabalin capsule.

Claims

1. a kind of Pregabalin capsule, it is made of Pregabalin, lactose and pharmaceutically acceptable carrier, and feature exists In: the lactose is screening lactose, spray-dried lactose or lactose compound；

In the Pregabalin capsule, the weight percent of Pregabalin is 5%~50%, the weight percent of lactose is 10%~ 60%。

2. Pregabalin capsule according to claim 1, it is characterised in that: the lactose is screening lactose or does by spraying Dry lactose.

3. Pregabalin capsule according to claim 2, it is characterised in that: the lactose is screening lactose.

4. Pregabalin capsule according to claim 3, it is characterised in that: the size distribution of the screening lactose are as follows: small In 32 μm not higher than 10%, be 20~45%, no less than 85% less than 200 μm and less than 250 μm not less than 100 μm Less than 99%.

5. Pregabalin capsule according to claim 3, it is characterised in that: the size distribution of the screening lactose are as follows: small In 100 μm not higher than 20%, less than 250 μm be 40%~70% and less than 400 μm no less than 99%.

6. Pregabalin capsule according to claim 3, it is characterised in that: the size distribution of the screening lactose are as follows: small In 63 μm of no less than 75% not higher than 20% and less than 200 μm.

7. Pregabalin capsule according to claim 1, it is characterised in that: the lactose compound is that lactose starch is compound Object or lactose microcrystal cellulose composite.

8. Pregabalin capsule according to claim 1, it is characterised in that: in the Pregabalin capsule, Pregabalin Weight percent be 20%~30%, the weight percent of lactose is 25%~35%.