CN103156812A - Dextrorotation ibuprofen dried suspension and preparation method thereof - Google Patents

Abstract

The invention relates to a dextrorotation ibuprofen dried suspension which uses magnesium hydroxide as a bitterness covering agent, wherein the magnesium hydroxide can effectively cover bitterness of the dextrorotation ibuprofen, plays a role of adjusting a pH value due to alkalinity of the magnesium hydroxide, improves dissolvability of the dextrorotation ibuprofen and increases bioavailability of drugs. In traditional dried suspension, sweeteners, essence and the like are added to improve taste, however, adding the sweetener and the essence cannot completely cover bitterness or adverse taste of the drugs.

Description

(S)-ibuprofen dry suspension and preparation method thereof

Technical field

The present invention relates to field of medicine preparations, relate in particular to nonsteroidal antiinflammatory drug, particularly (S)-ibuprofen dry suspension and preparation method thereof.

Background technology

Ibuprofen is non-steroidal anti-inflammatory, analgesic, the analgesic of a kind of determined curative effect, safety.Within 1964, at first developed by U.S. Boots company and go on the market in Britain in 1969.For the long-term treatment of rheumatic, rheumatoid arthritis and osteoarthritis, also be widely used in the diseases such as the various moderate pains for the treatment of and inflammation, heating clinically, its therapeutic effect is obvious, little than aspirin, indomethacin to gastral side effect.Ibuprofen has 30 years as antiinflammatory and analgesic clinical practice, is considered to safest nonsteroidal antiinflammatory drug (NSAID), and is a kind of nonprescription drugs.

Ibuprofen is comprised of (S)-ibuprofen and the left-handed ibuprofen of equivalent, and S-ibuprofen ((S)-ibuprofen) has activity in vitro and in vivo, and R – ibuprofen is invalid.(S)-ibuprofen has the effect that suppresses COX under clinical effective dose, and left-handed ibuprofen does not have this effect.Therefore these two kinds of space corresponding compounds are fully different on the pharmacology, can regard two kinds of different medicines as.People in animal experiment, have confirmed the high efficiency of current understood (S)-ibuprofen than left-handed ibuprofen with the COX-1 separated and COX-2 isozyme.Left-handed ibuprofen does not almost have activity to COX-2.In Mice Body, the absorption of DL ibuprofen and (S)-ibuprofen does not have difference.But relatively, (S)-ibuprofen is with respect to DL ibuprofen bioavailability average out to 0.66 for pure (S)-ibuprofen and DL ibuprofen human bioavailability.When the DL ibuprofen enters human body, 50%～60% left-handed ibuprofen becomes (S)-ibuprofen by " metabolic reversion ".Therefore have the people to propose, obtain the identical clinical efficacy of a certain dosage DL ibuprofen, the dosage of (S)-ibuprofen should be 75% of DL ibuprofen.But, in calendar year 2001, Evans points out, above-mentioned " reversion " ignored in this reasoning according to pharmacokinetics is not that such fact occurs at once.And the degree that between individuality, reversion occurs has transmutability, and the kinetics of reversion has difference according to the dosage saturation.Recently research shows, only needs the (S)-ibuprofen of DL ibuprofen one half-value dose just can obtain the clinical efficacy identical with the former.

The metabolic characteristic of (S)-ibuprofen and left-handed ibuprofen is also different, left-handed ibuprofen is relevant with the lipid metabolism path, and be incorporated into together on triglyceride with the endogenous fatty acid, and (S)-ibuprofen and these special metabolic responses are irrelevant, therefore, (S)-ibuprofen is removed more thoroughly than DL ibuprofen in body.

At first (S)-ibuprofen is developed successfully by Austrian Gebro-Broscheh Gmbh company, and 1994 through the approval listing.The dosage form of listing has the ordinary preparations such as tablet, capsule, dispersible tablet at present, exist equally absorption difference, bioavailability low, absorb relatively slow, and the patient to child, old people and dysphagia makes troubles, the oral administration mixed suspension listing is also arranged, but do not take effective odor masking device, the bitterness of raw material is taken and has been brought misery to the patient.

CN101077343 discloses a kind of (s)-ibuprofen granules and preparation method, it is characterized in that the raw material that contains following weight proportion in its composition: (S)-ibuprofen 1, alkaline auxiliary solvent 0-100, filler 0.1-100, binding agent 0.1-12, correctives 0.01-0.5, lubricant 0.1-2.Its principal right item is to add the alkaline auxiliary solvent, is convenient to (S)-ibuprofen and dissolves in water rapidly, forms transparent and delicious solution, compares with the common liq preparation also to have and carries advantage more easily.But it is only by adding sweeting agent to improve effectively taste masking of taste, and the bitterness of (S)-ibuprofen still exists.

With the medicament of bitterness, if suspension, drink so in the process of medicine or inevitably can feel immediately bitterness after swallowing.In addition, tablet, capsule or other peroral dosage forms, when taking, if mouthful in overstand, chew unintentionally or be bitterness due to other reasons drug release out contacts with taste bud, also can feel bitterness.

Conventional masking methods is to utilize sweeting agent and spice to cover bitterness, and this method only can be covered the medicine that bitterness is light; The other masking methods has the medicine of bitterness is adopted to packaging technique, this technical matters relative complex, and due to the cause of coating, medicine can not Fast Stripping.

Summary of the invention

The object of the present invention is to provide absorb fast, bioavailability is high, simple, the taste masking effect (S)-ibuprofen dry suspension carefully of preparation method simultaneously .

Another object of the present invention is to provide the preparation method of (S)-ibuprofen dry suspension.

Have (S)-ibuprofen absorption difference, problem that bioavailability is low in order to solve in background technology, the present invention has adopted following technical scheme:

?the (S)-ibuprofen dry suspension comprises the component of following percentage by weight:

(S)-ibuprofen 5% ~ 10% bitterness masking agent 1% ~ 10%

Filler 60% ~ 90% suspending agent 0.1% ~ 5%

Correctives 0.1% ~ 5% fluidizer 0.1% ~ 2%

Antibacterial 0.1% ~ 0.5%.

As of the present invention preferred, comprise the component of following percentage by weight:

(S)-ibuprofen 6.7% bitterness masking agent 5%

Filler 83.5% suspending agent 2%

Correctives 1.5% fluidizer 1%

Antibacterial 0.3%.

Described bitterness masking agent is magnesium hydroxide.

Described filler is one or more in mannitol, lactose, sucrose, glucose, sorbitol, microcrystalline Cellulose, maltodextrin, pregelatinized Starch.

Described suspending agent is one or more in xanthan gum, sodium carboxymethyl cellulose, methylcellulose, hydroxypropyl methylcellulose, carbomer.

Described correctives is one or more in sucrose, aspartame, stevioside, cherry essence, strawberry essence, cream flavour, flavoring banana essence.

Described fluidizer is one or both in micropowder silica gel, Pulvis Talci.

The invention also discloses the preparation method of (S)-ibuprofen dry suspension, comprise the steps:

(1), (S)-ibuprofen, bitterness masking agent, filler, fluidizer are crossed the 50-100 mesh sieve;

(2), (S)-ibuprofen is mixed homogeneously with filler, adopt the 50-95% alcoholic solution to granulate, and dry;

(3), above-mentioned granule is mixed homogeneously with suspending agent, correctives and fluidizer;

(4), packing and get final product.

(S)-ibuprofen dry suspension preparation technology disclosed by the invention is simple, be convenient to realize industrialized great production, without adding organic solvent, safety is good, has adopted magnesium hydroxide as the bitterness masking agent, can effectively cover the poor taste of (S)-ibuprofen, patient compliance is good, because magnesium hydroxide is alkalescence, has regulated pH value simultaneously, increase the dissolubility of (S)-ibuprofen, effectively improved the bioavailability of (S)-ibuprofen.

The specific embodiment

Below by specific embodiment, the present invention is described further.

Embodiment 1: the present embodiment prepares 1000 bags of (S)-ibuprofen dry suspension, adopts following material:

(S)-ibuprofen 200g

Sucrose 2506g

Magnesium hydroxide 150g

Xanthan gum 60g

Stevioside 30g

Cherry essence 15g

Methyl parahydroxybenzoate 9g

Micropowder silica gel 30g

Preparation method:

1, (S)-ibuprofen is crossed to 80 mesh sieves, sucrose was pulverized 50 mesh sieves, and 80 mesh sieves are crossed respectively in magnesium hydroxide, methyl parahydroxybenzoate, micropowder silica gel, standby;

2, (S)-ibuprofen is mixed homogeneously with sucrose, adopt 50% alcoholic solution to granulate, drying, 50 order granulate;

3, (s)-ibuprofen granules is mixed homogeneously with magnesium hydroxide, stevioside, cherry essence, xanthan gum, methyl parahydroxybenzoate and micropowder silica gel;

4, packing.

The (S)-ibuprofen dry suspension that the present embodiment makes, adopted magnesium hydroxide as the bitterness masking agent, can effectively cover the bitterness of (S)-ibuprofen, and because magnesium hydroxide is alkalescence, play the effect of regulating pH value, increase the dissolubility of (S)-ibuprofen, improve drug bioavailability.And in traditional dry suspension, add often sweeting agent, essence etc. to improve taste, but the way of this employing sweeting agent and essence can not be covered bitterness or the disagreeable taste that medicine itself possesses fully.

Embodiment 2: prepare 1000 band (S)-ibuprofen dry suspension, adopt following material:

(S)-ibuprofen 250g

Glucose 2251g

Pregelatinized Starch 150g

Magnesium hydroxide 240g

Sodium carboxymethyl cellulose 24g

Aspartame 30g

Strawberry essence 15g

Pulvis Talci 30g

Preparation method:

1, (S)-ibuprofen is crossed to 80 mesh sieves, glucose was pulverized 50 mesh sieves, and 80 mesh sieves are crossed respectively in magnesium hydroxide, pregelatinized Starch, standby;

2, (S)-ibuprofen is mixed homogeneously with glucose, pregelatinized Starch, adopt 50% alcoholic solution to granulate, drying, 50 order granulate;

3, (s)-ibuprofen granules is mixed homogeneously with magnesium hydroxide, aspartame, strawberry essence, sodium carboxymethyl cellulose and Pulvis Talci;

4, packing.

Embodiment 3

(S)-ibuprofen 200g

Sucrose 1985g

Mannitol 450g

Magnesium hydroxide 240g

Xanthan gum 20g

Cream flavour 15g

Micropowder silica gel 30g

95% appropriate amount of ethanol

Purified water is appropriate

Preparation method:

1, (S)-ibuprofen is crossed to 80 mesh sieves, sucrose was pulverized 50 mesh sieves, and 80 mesh sieves are crossed respectively in magnesium hydroxide, micropowder silica gel, pregelatinized Starch, standby;

2, (S)-ibuprofen, sucrose are mixed homogeneously with mannitol, adopt 50% alcoholic solution to granulate, drying, 50 order granulate;

3, by (s)-ibuprofen granules, magnesium hydroxide, stevioside, cream flavour, xanthan gum and micropowder silica gel mix homogeneously;

4, packing.

Claims (8)

1. (S)-ibuprofen dry suspension is characterized in that comprising the component of following percentage by weight:

(S)-ibuprofen 5% ~ 10% bitterness masking agent 1% ~ 10%

Filler 60% ~ 90% suspending agent 0.1% ~ 5%

Correctives 0.1% ~ 5% fluidizer 0.1% ~ 2%

Antibacterial 0.1% ~ 0.5%.

2. (S)-ibuprofen dry suspension according to claim 1 is characterized in that comprising the component of following percentage by weight:

(S)-ibuprofen 6.7% bitterness masking agent 5%

Filler 83.5% suspending agent 2%

Correctives 1.5% fluidizer 1%

Antibacterial 0.3%.

3. (S)-ibuprofen dry suspension according to claim 2, is characterized in that described bitterness masking agent is magnesium hydroxide.

4. (S)-ibuprofen dry suspension according to claim 2, is characterized in that described filler is one or more in mannitol, lactose, sucrose, glucose, sorbitol, microcrystalline Cellulose, maltodextrin, pregelatinized Starch.

5. (S)-ibuprofen dry suspension according to claim 2, is characterized in that described suspending agent is one or more in xanthan gum, sodium carboxymethyl cellulose, methylcellulose, hydroxypropyl methylcellulose, carbomer.

6. (S)-ibuprofen dry suspension according to claim 2, is characterized in that described correctives is one or more in sucrose, aspartame, stevioside, cherry essence, strawberry essence, cream flavour, flavoring banana essence.

7. (S)-ibuprofen dry suspension according to claim 2, is characterized in that described fluidizer is one or both in micropowder silica gel, Pulvis Talci.

8. according to the preparation method of any one described (S)-ibuprofen dry suspension of claim 1 ~ 7, it is characterized in that comprising the steps:

(1), (S)-ibuprofen, bitterness masking agent, filler, fluidizer are crossed the 50-100 mesh sieve;

(2), (S)-ibuprofen is mixed homogeneously with filler, adopt the 50-95% alcoholic solution to granulate, and dry;

(3), above-mentioned granule is mixed homogeneously with suspending agent, correctives and fluidizer;

(4), packing and get final product.