CN103933001A - Stable silodosin oral solid pharmaceutical composition and preparation method thereof - Google Patents

Abstract

The invention provides a stable silodosin oral solid pharmaceutical composition and a preparation method thereof. The composition comprises silodosin or a medical salt thereof, an antioxidant and one or more medical auxiliary materials among a filling agent, a disintegrating agent, a binding agent and a lubricating agent.

Description

A kind of stable how pungent oral solid drug composition of celo and preparation method thereof

Technical field

The invention belongs to medical technical field, be specifically related to a kind of stable how pungent oral solid drug composition of celo and preparation method thereof.

Background technology

The how pungent capsule of celo (Silodosin Capsule) is the alpha 1-receptor antagonist by the invention of Japanese Kissei drugmaker, can be used for the symptom that treatment is relevant with benign prostatic hyperplasia (BPH) or hypertrophy, and specification is 2mg, 4mg.Its commodity are called excellent vertical good fortune.Obtain listing approval in May, 2006 in Japan, and successively went on the market in US and European various countries in 2009 and 2010.Its molecular structural formula is as follows:

How pungent celo is is a kind of active substance with potential viscosity and electrostatic property, and has consistency problem and produce unwanted degradation impurity with the conventional pharmaceutic adjuvant of major part.This has brought challenge for preparing the stable how pungent oral drug preparation of celo.

Patent CN1726028A discloses the how pungent oral solid drug composition of a kind of celo, is primarily characterized in that it can reach Fast Stripping in aqueous medium, and does not disclose pharmaceutical preparation how to prepare stable applicable storage.Adopt wet granulation to prepare the how pungent preparation of celo although mention in its description example, in fact adopt traditional wet granulation technology to prepare the stable how pungent preparation of applicable celo and have huge difficulty.

Patent WO2014006635 discloses a kind of how pungent pharmaceutical composition of celo containing lubricant sodium stearyl fumarate.And provide and adopted straight mixed technique to prepare the method for the pharmaceutical composition that uniformity of dosage units is qualified.It is partially slow that its progress compared with prior art maximum is to have solved the stripping causing because of magnesium stearate over-lubrication.Do not mention and how to obtain the how pungent pharmaceutical composition of stable celo.

Patent CN102283816A has introduced a kind of containing the how pungent slow releasing tablet of celo, and this slow releasing tablet is taking hydrogel matrix and waxiness class framework material as mixed-matrix, taking Eudragit E 100 as release regulator.Listing capsule comparison with common, it is advantageous that and reduced administration number of times, and the release of medicine is more tended to be steady.The also not mentioned how pungent preparation stabilization of celo that how to make in entire chapter patent.

Summary of the invention

In order to solve the impurity degradation problem of the how pungent preparation of celo in preparation and storage process, the invention provides a kind of composition simple, the how pungent oral solid drug composition of easy to prepare, stay-in-grade celo.

This stable combination of oral medication comprises how pungent or its officinal salt of celo and antioxidant and is selected from one or more pharmaceutic adjuvants in filler, binding agent, disintegrating agent and lubricant.

As a kind of preferred version, described antioxidant be in BHT (2,6-di-tert-butyl-4-methy phenol), BHA (BHA), gallate ester, ascorbic acid any one or multiple.More preferably BHT or BHA.

As a kind of preferred version, it is 0.02%～0.5% that described antioxidant accounts for prescription weight ratio, more preferably 0.02%～0.2%.

As a kind of preferred version, described pharmaceutic adjuvant comprises a class or a few class in filler, binding agent, disintegrating agent and lubricant.Wherein, described filler is one or more in starch, lactose, sugar alcohol, more preferably mannitol or sorbitol; Described binding agent be in methylcellulose, hydroxypropyl cellulose, hypromellose, polyvidone, starch, pregelatinized Starch in one or more, more preferably pregelatinized Starch or starch;

Described disintegrating agent is one or more in low-substituted hydroxypropyl cellulose, sodium carboxymethyl cellulose, partially pregelatinized starch, more preferably partially pregelatinized starch.Described lubricant is one or more in magnesium stearate, Talcum, hard fumaric acid sodium, more preferably magnesium stearate or Talcum.

As a kind of preferred version, the how pungent particle diameter d of described celo (90)≤50 μ m, more preferably d (90)≤20 μ m.

As a kind of preferred version, the type processed of described compositions is but is not limited to capsule or tablet.

The method that the invention provides the above-mentioned solid composite medicament of preparation, concrete steps are as follows:

(1) antioxidant is dissolved in applicable solvent, for subsequent use;

(2) mix and sieve with other adjuvants except lubricant how pungent celo; Solution Dispersion prepared by step 1, to wherein, mixes soft material processed;

(3) soft material of step 2 is crossed to 14～30 sieves, 40～80 DEG C dry, and particle drying moisture Control is 1～3%, 14～40 orders dry granule that sieves to obtain;

(4) the dry granule of step 3 is added to lubricant, mix homogeneously; Filled capsules or tabletting.

The how pungent oral solid drug composition of celo provided by the invention, adopts conventional wet granulation technology, steady quality in preparation and storage process.

Detailed description of the invention

By following specific embodiment, can more specific description the present invention.But the present invention is not limited to following examples.

Embodiment 1:

Component	Comparative example, g/ criticizes	Embodiment 1, g/ criticizes
			How pungent celo is	4	4
PEARLITOL 25C	132.4	132.365
			Pregelatinized Starch (Starch1500)	26.0	26.0
Partially pregelatinized starch (PC-10)	9.0	9.0

BHT	——	0.035
			Sodium lauryl sulphate	1.8	1.8
Magnesium stearate	1.8	1.8

Preparation method:

Step 1: BHT is dissolved in 95% ethanol, and making BHT concentration is 1.0%.For subsequent use.

Step 2: comparison example and example 1 are mixed by said ratio, cross 60 mesh sieves.The solution soft material processed that embodiment 1 use step 1 is prepared, and comparison example is directly used the 95% ethanol soft material processed of same amount.

Step 3: cross respectively 20 mesh sieves, 60 DEG C dry, and moisture Control is 1.5%, 40 mesh sieve granulate.

Step 4: the granule that step 3 is obtained adds magnesium stearate, mixes, encapsulating capsule or tabletting.

Comparative example is prescription described in embodiment 2 in the preparation patent CN1726028A of Yuan Yan producer application.

Embodiment 2:

Component	Embodiment 2, g/ criticizes
		How pungent celo is	4
PEARLITOL 25C	132.365
		Pregelatinized Starch (Starch1500)	26.0
Partially pregelatinized starch (PC-10)	9.0
		BHA	0.035
Sodium lauryl sulphate	1.8
		Magnesium stearate	1.8

Preparation method is with embodiment 1.

Embodiment 3:

Component	Embodiment 3, g/ criticizes
		How pungent celo is	4
PEARLITOL 25C	132.225
		Pregelatinized Starch (Starch1500)	26.0
Partially pregelatinized starch (PC-10)	9.0
		Propyl gallate	0.175
Sodium lauryl sulphate	1.8

Magnesium stearate

1.8

Preparation method is with embodiment 1.

Embodiment 4:

Component	Embodiment 4, g/ criticizes
		How pungent celo is	4
PEARLITOL 25C	131.525
		Pregelatinized Starch (Starch1500)	26.0
Partially pregelatinized starch (PC-10)	9.0
		Ascorbic acid	0.875
SDS	1.8
		Magnesium stearate	1.8

Preparation method:

95% ethanol that step 1 in the preparation method of embodiment 1 is used changes purified water into and dissolves, and making ascorbic acid concentrations is 1.0%.Other steps are with embodiment 1.

Experimental result:

5 samples and commercially available sample prepared by above-mentioned 4 embodiment are 40 DEG C in temperature, under humidity 75%RH condition, place, and check respectively related substance at 0,1,2,3,6 month.The particular exam method of related substance is as follows:

Wavelength: 225nm; Chromatographic column model: the C18 post GL science Inertsil ODS-3 processed of Co., Ltd., particle diameter 5 μ m, 4.6mm × 25cm.

Mobile phase: get sodium dihydrogen phosphate dihydrate 3.9g, the 1000mL that adds water dissolves, and adjusting pH to 3.4 with phosphoric acid,diluted (1 → 10) is mobile phase A; Taking acetonitrile as Mobile phase B.

Flow velocity: 1.0mL/min.

Result:

From above result, it is stable that the preparation of producing by 2 prescriptions of embodiment in former triturate patent CN1726028A is not so good as commercially available product in preparation and accelerated test process, and the prescription that contains antioxidant is all stable compared with commercially available product in preparation process and accelerated test process.Wherein, the best results of BHT.

Claims (10)

1. the how pungent oral solid drug composition of stable celo, is characterized in that comprising how pungent or its officinal salt of celo, antioxidant, and be selected from one or more pharmaceutic adjuvants in filler, disintegrating agent, binding agent and lubricant.

2. the how pungent oral solid drug composition of celo according to claim 1, is characterized in that antioxidant is selected from one or more in BHT, BHA, gallate ester, ascorbic acid.

3. the how pungent oral solid drug composition of celo according to claim 2, is characterized in that antioxidant is selected from one or both in BHT or BHA.

4. the how pungent oral solid drug composition of celo according to claim 1, is characterized in that it is 0.02%～0.5% that antioxidant consumption accounts for prescription weight ratio.

5. the how pungent oral solid drug composition of celo according to claim 1, is characterized in that filler is selected from one or both in mannitol or sorbitol.

6. the how pungent oral solid drug composition of celo according to claim 1, is characterized in that disintegrating agent is selected from one or both in starch or pregelatinized Starch.

7. the how pungent oral solid drug composition of celo according to claim 1, is characterized in that binding agent is selected from one or more in hyprolose, hydroxypropyl methylcellulose, starch, pregelatinized Starch.

8. the how pungent oral solid drug composition of celo according to claim 1, is characterized in that how pungent or its officinal salt of celo is through micronized, particle diameter d (90)≤50 μ m.

9. the how pungent oral solid drug composition of celo according to claim 1, is characterized in that this oral solid drug composition can further be prepared into capsule or tablet.

10. a preparation method of preparing the how pungent oral solid drug composition of celo as claimed in claim 1, comprises the steps:

(1) antioxidant is dissolved in applicable solvent, for subsequent use;

(2) mix and sieve with other adjuvants except lubricant how pungent celo; Solution Dispersion prepared by step 1, to wherein, mixes soft material processed;

(3) soft material of step 2 is crossed to 14～30 sieves, 40～80 DEG C dry, and particle drying moisture Control is 1～3%, 14～40 orders dry granule that sieves to obtain;

(4) the dry granule of step 3 is added to lubricant, mix homogeneously; Filled capsules or tabletting.