CN103830193A - Indacaterol tablets and preparation method thereof - Google Patents

Abstract

The invention belongs to the field of medical technology, and particularly discloses indacaterol tablets and a preparation method thereof. In the invention, active ingredients including indacaterol and lactose are subjected to micropowder treatment, and povidone K90 is added into the prescription as an adhesive to obtain the tablets. By adopting the method, the content uniformity of the obtained preparation meets the requirements, a new option is provided to COPD (chronic obstructive pulmonary disease) patients with different illness characteristics, and the needs for treating asthma and COPD are met to the greatest degree.

Description

QAB-149 tablet preparation and preparation method thereof

Invention field

The invention belongs to drug world, be specifically related to comprise QAB-149 tablet and preparation method thereof.

Background of invention

QAB-149 is bronchodilators, belongs to long-acting suction beta 2-adrenergic receptor agonist (LABA) class, chronic obstructive pulmonary disease (COPD) patient's that is applicable to be grown up the treatment that maintains.There is onset in 5 minutes, continue the feature of 24 hours.QAB-149 is produced by Novartis of Switzerland, more than 70 the countries and regions listing in the whole world since 2009; In China's listing, be the LABA class unitary agent of the first granted COPD of being used for the treatment of of China through the approval of national Bureau of Drugs Supervision in June, 2012.Clinical trial shows, QAB-149 is taken and once can make more than bronchodilatation reaches 24h every day, and its diastole bronchus time is longer than salmaterol and formoterol; Onset is faster than salmaterol.

The nearly forty-two million asthma patient in the whole world and 2,800 ten thousand COPD (chronic obstructive pulmonary disease) patients.Nearly ten years, along with the air pollution in global range and ecological deterioration, the M & M of asthma is in rising trend, has every year to exceed 180,000 people and die from asthma.Separately have to analyze to show, to the year two thousand twenty, COPD rises to the 3rd by the 6th of the global cause of the death from present.Conservative estimation, the whole world will be every year because the number of CCffD death will reach more than 3,500,000 till that time.At home, an Epidemiological study result of being presided over by Zhong Nanshan academician shows, the overall prevalence of current Chinese COPD is 8.2%, and wherein male sicken rate is 12.4%, and women's prevalence is 5.1%.COPD patient has exceeded 4,000 ten thousand in China, estimates 2003---and during 2033, China will have 6,500 ten thousand people and die from COPD.

Application number is CN200910000910 pharmaceutical composition of disclosing QAB-149 and ciclesonide and preparation method thereof.This pharmaceutical composition comprises QAB-149, ciclesonide and one or more pharmaceutically acceptable carriers.

Application number is CN201110240358 pharmaceutical composition of disclosing QAB-149 and budesonide and preparation method thereof.This pharmaceutical composition also comprises one or more pharmaceutically acceptable adjuvants, as glycine or lactose.

But existing document is the unexposed QAB-149 that comprises all filler binding agent

and lubricant

the pharmaceutical preparation of QAB-149 sheet, do not provide any prompting about its pharmaceutical preparation component ratio yet.

The present invention is by studying for a long period of time, find to adopt by QAB-149 and lactose with certain proportion micropowder after, can significantly improve the dissolution of insoluble drug QAB-149, and in prescription, the ratio, the concentration of PVP K90 aqueous solution of newborn sugar and starch there is appreciable impact to the dissolution of QAB-149 sheet.Adopt QAB-149 sheet uniformity of dosage units prepared by method disclosed by the invention to conform with the regulations, and prescription composition, disintegration, disintegration phenomenon and stripping behavior all with former triturate-cause.

Because the drafting of many pH value stripping curve has become the important means that dissects and express solid preparation interior quality, therefore the scientific evaluation ever more important to stripping curve comparison.So far, report has multiple comparative approach.But from the official mission of the states such as the U.S. and Japan assert adopt one of model non-dependence method " similar factors relative method " afterwards, be now substantially unified and adopt.This method feature is that stripping curve is carried out to the overall evaluation, by calculating similar factors (f ₂) similarity of stripping behavior relatively.

Computing formula:

$f_2=50\log \left[\frac{100}{\sqrt{1+\frac{\underset{i=1}{\overset{n}{\mathrm{\Σ}}}{(R_t-T_t)}^2}{n}}}\right]$

R _tand T _trepresent respectively the average accumulated dissolution rate of two preparations in the time of n sample point.

Time point interval selected when calculating is without equating, but two time points that preparation is got must be consistent; And computation time, point should be no less than 3; Because this result of calculation has the characteristic that depends on comparison time point number, therefore the time point more than dissolution rate 85% (adjusting release formulation more than 80%) is answered no more than one.

Suggestion researcher can, according to the concrete condition of reference preparation dissolution rate, be chosen dissolution rate interval close

individual (as can be for tune release formulation individual, do not advise exceeding 7 points) time point calculates.

Conventionally, work as f ₂numerical value thinks that between 50-100 two stripping curves are similar.

Summary of the invention

The invention provides a kind of pharmaceutical preparation formula and preparation method of QAB-149 sheet, concrete technical scheme is as follows:

On the one hand, the invention provides a kind of QAB-149 tablet preparation, wherein, the component that described preparation comprises following weight percentage ratio: QAB-149

filler

binding agent

and lubricant

In some embodiments, QAB-149 tablet preparation of the present invention, wherein, described filler is lactose, starch or its combination, and described binding agent is 30 POVIDONE K 30 BP/USP 90 (PVP K90), and described lubricant is magnesium stearate.

In other embodiments, QAB-149 tablet preparation of the present invention, wherein, the ratio of described filler breast sugar and starch is

described binding agent PVP K90 is that concentration is

aqueous solution.

In other embodiments, QAB-149 tablet preparation of the present invention, is characterized in that described QAB-149 and lactose are for subsequent use after the ratio micropowder with 1:20.

In other embodiments, QAB-149 tablet preparation of the present invention, the component that it comprises following percentage by weight:

On the other hand, the invention provides a kind of preparation method of QAB-149 tablet preparation, wherein, QAB-149 and a certain proportion of lactose micropowder, for subsequent use; Prepare certain density PVP K90 aqueous solution, for subsequent use; Take QAB-149, lactose, the starch mix homogeneously of recipe quantity, add PVP K90 aqueous solution to granulate, dry, add the magnesium stearate mix homogeneously of corresponding recipe quantity, measure mixture content, calculate sheet weight, tabletting, to obtain final product.

QAB-149 sheet prepared by the present invention has following advantage: 1, its uniformity of dosage units meets the requirements; 2, its disintegrate completely in 5min.

Carrier of the present invention comprises, but be not limited to, ion-exchanger, aluminum, aluminium stearate, lecithin, serum albumin, as human albumin, buffer substance is as phosphate, glycine, sorbic acid, potassium sorbate, the partial glycerol ester admixture of saturated vegetable fatty acid, water, salt or electrolyte, as protamine sulfate, sodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salt, colloid silicon, magnesium trisilicate, polyvinylpyrrolidone, polyacrylate, wax, polyethylene-polyoxypropylene-blocking-up polymer, lanoline, sugar, as lactose, dextrose plus saccharose, starch is as corn starch and potato starch, the derivant of cellulose and it is as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate, natural gum powder, Fructus Hordei Germinatus, gelatin, Pulvis Talci, adjuvant is as cocoa butter and suppository wax, oily as Oleum Arachidis hypogaeae semen, Oleum Gossypii semen, safflower oil, Oleum Sesami, olive oil, Semen Maydis oil and Oleum Glycines, glycols compound, as propylene glycol and Polyethylene Glycol, esters is as ethyl oleate and ethyl laurate, agar, buffer agent is as magnesium hydroxide and aluminium hydroxide, alginic acid, pyrogen-free water, Deng oozing salt, Lin Ge (family name) solution, ethanol, phosphate buffer solution, and other nontoxic proper lubrication agent are as sodium laurylsulfate and magnesium stearate, coloring agent, releasing agent, coating dress material, sweeting agent, flavoring agent and spice, antiseptic and antioxidant.

Detailed description of the invention

The detailed description of the invention of form by the following examples, is described in further detail foregoing of the present invention.But this should be interpreted as to the scope of the above-mentioned theme of the present invention only limits to following examples.

Embodiment 1

QAB-149 sheet is prepared by following medicinal component:

Preparation method

QAB-149 and lactose are with the ratio micropowder of 1:20, for subsequent use; Compound concentration is 15% PVP K90 aqueous solution, for subsequent use; Take QAB-149, lactose, the starch mix homogeneously of recipe quantity, add PVP K90 aqueous solution to granulate, dry, add the magnesium stearate mix homogeneously of corresponding recipe quantity, measure mixture content, calculate sheet weight, tabletting, to obtain final product.

The QAB-149 sheet of preparation has following characteristics:

Content uniformity test: qualified.Check disintegration: disintegrate completely in 5min, disintegration phenomenon is identical together with former development.

Embodiment 2

QAB-149 sheet is prepared by following medicinal component:

Preparation method

QAB-149 and lactose are with the ratio micropowder of 1:20, for subsequent use; Compound concentration is 15% PVP K90 aqueous solution, for subsequent use; Take QAB-149, lactose, the starch mix homogeneously of recipe quantity, add PVP K90 aqueous solution to granulate, dry, add the magnesium stearate mix homogeneously of corresponding recipe quantity, measure mixture content, calculate sheet weight, tabletting, to obtain final product.

The QAB-149 sheet of preparation has following characteristics: Content uniformity test: qualified.Check disintegration: disintegrate completely in 5min.

Embodiment 3

QAB-149 sheet is prepared by following medicinal component:

Preparation method

QAB-149 and lactose are with the ratio micropowder of 1:20, for subsequent use; Compound concentration is 15% PVP K90 aqueous solution, for subsequent use; Take QAB-149, lactose, the starch mix homogeneously of recipe quantity, add PVP K90 aqueous solution to granulate, dry, add the magnesium stearate mix homogeneously of corresponding recipe quantity, measure mixture content, calculate sheet weight, tabletting, to obtain final product.

The QAB-149 sheet of preparation has following characteristics: Content uniformity test: qualified.Check disintegration: disintegrate completely in 5min.

The concrete numerical value of stripping curve sees attached list 1.

The each embodiment sample of table 1 stripping curve value

As seen from the above table, QAB-149 tablet provided by the present invention, has good dissolution, and stripping curve is comparatively steady, has the effect of good treatment asthma or COPD.

Claims (6)

1. a QAB-149 tablet preparation, wherein, the component that described preparation comprises following weight percentage ratio: QAB-149 filler

binding agent

and lubricant

2. QAB-149 tablet preparation according to claim 1, wherein, described filler is lactose, starch or its combination, and described binding agent is 30 POVIDONE K 30 BP/USP 90 (PVP K90), and described lubricant is magnesium stearate.

3. QAB-149 tablet preparation according to claim 2, wherein, the ratio of described filler breast sugar and starch is

described binding agent PVP K90 is that concentration is aqueous solution.

4. QAB-149 tablet preparation according to claim 2, is characterized in that described QAB-149 and lactose are for subsequent use after the ratio micropowder with 1:20.

5. QAB-149 tablet preparation according to claim 2, the component that it comprises following percentage by weight:

。

6. according to the preparation method of the QAB-149 tablet preparation described in claim 1-5 any one, wherein, QAB-149 and a certain proportion of lactose micropowder, for subsequent use; Prepare certain density PVP K90 aqueous solution, for subsequent use; Take QAB-149, lactose, the starch mix homogeneously of recipe quantity, add PVP K90 aqueous solution to granulate, dry, add the magnesium stearate mix homogeneously of corresponding recipe quantity, measure mixture content, calculate sheet weight, tabletting, to obtain final product.