Ibuprofen suspension drops and preparation method thereof

Abstract

The invention relates to ibuprofen suspension drops, wherein a prescription of the suspension drops is
composed of the components by weight: 4.0% of ibuprofen, 1.0-3.5% of pregelatinized starch, 1.0-5.0%
of sorbitol, 4.0-5.0% of glycerol, 15.0-30.0% of fructose, 0.1-0.2% of citric acid, 0.1-0.2% of sodium
benzoate, 0.05-0.1% of Tween 80, 0.05-0.5% of an essence, 0.6-1.5% of a suspending aid, and a proper
amount of purified water. The dosage of the suspending aid used in the ibuprofen suspension drops is
small, but an unexpected suspending effect is achieved, the suspending state stability can be kept in a
wider temperature range, and the pungent taste of ibuprofen in mouthfeel is overcome. The invention also
relates to a preparation method of the ibuprofen suspension drops.
Description

A kind of ibuprofen suspension drop and preparation method thereof

Technical field

The present invention relates to prescription composition of a kind of pharmaceutical preparation and
preparation method thereof, particularly a kind of ibuprofen suspension drop and preparation method
thereof.

Background technology

Ibuprofen (Ibuprofen) was researched and developed by Boots companies of Britain in 1964, it is to use
one of most common ntipyretic analgesic medicine in recent years, it is in addition to antiinflammatory
action, have significant analgesia, antipyretic effect and good safety again, with lower toxicity, body
accumulation is not likely to produce, is not only adapted to adult, old people, is particularly suited for
infant.Ratified ibuprofen from 1989 and can be clinically used for the antipyretic of infant in 6 months in
the U.S..

Based on oral, an a piece of or medicine need to be divided into several parts and be taken the dosage
form of the Motrin for having listed at present both at home and abroad by child's oral tablet or capsule,
dosage is difficult to accurately control, secondly because the acid of ibuprofen, child is reluctant
actively to take, and greatly affects it to use.The preparation of suspension formation has the
advantages that taking convenience, drug absorption effect are good compared with the preparation of
other forms, is particularly suitable for child and has the patient of dysphagia.

The ibuprofen mixed suspension preparation for having listed is divided into suspension drop and
suspension, there is two kinds of concentration, three kinds of specifications：1) 15ml: 0.6g ibuprofen
suspension drop；2) 100ml: 2g ibuprofen suspension；3) 30ml: 0.6g ibuprofen suspension.

Wherein the concentration of suspension drop is 2 times of suspension, and such design fully takes into
account the convenience for using of infant, but, insoluble ibuprofen pharmaceutical concentration is
higher, and to formulation and technology higher requirement is researched and proposed.For
suspension, the suspension drop of higher concentration may be needed in scattered uniformity, the
stability of suspension, mobility, and the aspect such as accuracy of divided dose has higher
requirement.

However, suspension and suspension drop belong to thermodynamic unstable system, commercially
available ibuprofen oral suspension long term storage or meet and easily occur after the conditions such
as high temperature the wild effects such as layering, flocculation, sedimentation.The accuracy of
dosage is affected, particularly to child patient, safety and the effectiveness of its medication is have
impact on.
The content of the invention

In order to overcome the above-mentioned deficiencies of the prior art, the invention provides a kind of
ibuprofen suspension drop and preparation method thereof.By two kinds of suspending agents of low
dose of addition, adjust its proportioning, and addition can improve other adjuvants of mouthfeel,
realizing can be while good mouthfeel, more preferable suspending effect can be reached, uniformity is
good, and mobility is good, and enables suspension drop that stablizing for suspension is kept within the
scope of wider temperature.

The ibuprofen suspension drop that the present invention is provided, it is characterised in that the
prescription of the suspensoid constitutes the weight ratio ingredient for including and is：Ibuprofen
4.0%, pregelatinized Starch 1.0～3.5%, Sorbitol 1.0～5.0%, glycerol 4.0～5.0%, Fructose 15.0～30.0%,
citric acid 0.1～0.2%, sodium benzoate 0.1～0.2%, Tween 80 0.05～0.1%, essence 0.05～0.5%,
suspending agent 0.6～1.5%, Purified Water q. s；

Wherein, described suspending agent is the combination of xanthan gum 0.1%～0.5% and
Microcrystalline Cellulose and Carboxymethylcellulose Sodium complex 0.5%～1.0%.

Microcrystalline Cellulose and Carboxymethylcellulose Sodium complex is also referred to as Colloidal

microcrystalline cellulose, and at present, commercially available has 4 types：Avicel RC-501, Avicel RC-
581, Avicel RC-591 and Avicel CL-611.

Preferably, above-mentioned Microcrystalline Cellulose and Carboxymethylcellulose Sodium complex is

Avicel RC-591.

In test it was found that suspending agent only xanthan gum is the dispersibility that suspension
dropping liquid cannot be kept good, and increase Microcrystalline Cellulose and
Carboxymethylcellulose Sodium complex, particularly Avicel RC-591 and serve unexpected suspending
effect.And, it has been found that only when both consumptions are in certain proportion scope, the
suspending effect that can be optimal.

The invention also discloses it is a kind of in order that suspension drop reaches the ibuprofen
suspension drop formula of optimal mouthfeel, the pungent mouthfeel of ibuprofen itself can be
generally overcome, additionally, xanthan gum and Avicel RC-591 can also cause its mouthfeel more to
lubricate：It is preferred that specifically, the weight ratio ingredient that the prescription composition
of the suspension drop includes is：Ibuprofen 4.0%, pregelatinized Starch 1.0%, Sorbitol 5.0%, glycerol
4.0%, Fructose 18.0%, citric acid 0.2%, sodium benzoate 0.2%, Tween 80 0.05%, essence 0.05%, xanthan
gum 0.1%, Avicel RC-591 0.5%, Purified Water q. s.

Above-mentioned ibuprofen is micropowder, and mean diameter is 4～10 μm.

The method for preparing above-mentioned ibuprofen suspension drop, comprises the steps of：

1) Microcrystalline Cellulose and Carboxymethylcellulose Sodium complex is added in appropriate hot

purified water (60～80 DEG C), homogenizing；

2) xanthan gum is mixed with glycerol, adds appropriate purified water, and stirring makes swelling；

3) pregelatinized Starch is added in appropriate purified water, stirring makes to be uniformly

dispersed；

4) by Fructose, Sorbitol, citric acid, sodium benzoate, essence, in adding appropriate purified water,
homogenizing makes dissolving；

5) by above-mentioned steps 2), 3), 4) resulting solution adds step 1) in resulting solution, stir；
6) Tween 80 is added in appropriate purified water and is dissolved, added ibuprofen and stir evenly,
then homogenizing；

7) by step 6) resulting solution is added to step 5) in resulting solution, stir, plus remaining purified
water is settled to 100%, mix homogeneously；

8) standing, gas removal bubble, fill is obtained final product.

We are on the basis of xanthan gum, Microcrystalline Cellulose and Carboxymethylcellulose Sodium
complex (and more preferably Avicel RC-591) be increased as suspending agent, and investigated by
dissolved corrosion similarity, suspension character, long-time stability etc., filter out the suitable ratio
of suspending agent.Meanwhile, we are also by substantial amounts of research, it is determined that a
kind of optimal ibuprofen suspension drop formula of mouthfeel.

Compared with prior art, the invention has the beneficial effects as follows ensureing that the ibuprofen
micro powder granule in oral administration mixed suspension is dispersed, significantly improve
common suspension liquid long-time or meet the high viscosity and agglomeration problems produced
after the extreme conditions such as high temperature are placed, stability is high.And it is in good taste,
convenient for children and use with the adult patient for swallowing difficulty, it is ensured that the
accuracy of dosage, improve Drug safety and effectiveness.

Specific embodiment

Further below present disclosure is illustrated by specific embodiment.However, it will be appreciated

that present disclosure and claimed scope include but is not limited to the content of following
examples.

Embodiment 1

The composition and its consumption of 100mL ibuprofen oral suspensions：

Preparation method：

1) weigh Microcrystalline Cellulose and Carboxymethylcellulose Sodium complex to add in about 25%
prescription calorimetric purified water (60～80 DEG C), homogenizing (10000rpm) 15min；

2) xanthan gum and glycerol are weighed, is mixed, add about 15% recipe quantity purified water,
magnetic agitation makes swelling；

3) pregelatinized Starch is weighed, in adding 15% recipe quantity purified water, is stirred 5 minutes,
make to be uniformly dispersed；

4) Fructose, Sorbitol, citric acid, sodium benzoate, essence are weighed respectively, and in adding
about 25% recipe quantity purified water, homogenizing (8500～10000rpm) makes dissolving；

5) during above-mentioned three kinds of solution is added 1), mixing and stirring, appropriate purified
water wash bottle is added, stirring homogenizing (8500～10000rpm)；

6) weigh Tween 80, in adding about 15% recipe quantity purified water, make dissolving, add ibuprofen
raw material, stirred evenly with glass rod, then homogenizing (8500rpm) 2 minutes；

7) in 6) adding 5), stir, plus remaining purified water is settled to 100%, homogenizing (8500～
10000rpm) 5～30 minutes, mix homogeneously.

8) standing, gas removal bubble, fill.

Embodiment 2
The composition and its consumption of 100mL ibuprofen oral suspensions：

Preparation method is with embodiment 1.

Embodiment 3

The composition and its consumption of 100mL ibuprofen oral suspensions：

Preparation method is with embodiment 1.

Embodiment 4

The composition and its consumption of 100mL ibuprofen oral suspensions：

Preparation method is with embodiment 1.

The ibuprofen suspension drop stability checking test that the present invention of embodiment 5 is
provided

Test method：

1～sample of sample 4 prepared by 1～embodiment of Example 4, and ibuprofen suspension drop

(Shanghai pharmaceutical Co. Ltd of Johnson ＆ Johnson, the trade name ground with original：Merrill
Lynch) as reference substance.Separately sampled about 7ml, in putting 10ml vials, sealing bottleneck is
positioned over 10 days under the conditions of room temperature, 40 DEG C of high temperature, 60
DEG C of high temperature, illumination 4500lx, investigates the change of appearance character.

Room temperature：Take one bottle of sample to be positioned in room temperature (25-30 DEG C),
sampling observation in 10 days, and continue storage to 6 months；40 DEG C of high temperature：
Take one bottle of sample and place 40 DEG C of electric heating constant-temperature blowing drying
box (PYX-190-A types) setting, sampling observation in 10 days；

60 DEG C of high temperature：Take one bottle of sample and place 60 DEG C of electric heating
constant-temperature blowing drying box (DHG-9070A types) setting, sampling observation in 10 days；

Illumination 4500lx：Take one bottle of sample and place clarity analyzer (CM-III types), regulation
luminosity is 4500lx, and sampling in 10 days is observed.

As a result it is as follows：

The each ibuprofen suspension drop sample appearance character result of table 1

Can be seen that from above-mentioned investigation result：

1st, original is ground reference substance and there was only xanthan gum as suspending agent, room
temperature is placed with for a long time sedimentation phenomenon, the unstability of dosage when
this can cause to use, and, it is unstable under the high temperature conditions, there is flocculation
phenomenon, illustrate that only xanthan gum is cannot to ensure that ibuprofen is dispersed in the
solution as suspending agent, it may occur that sedimentation and phenomenon of flocculating；

2nd, sample 1 and the dispersibility of sample 2 are fine, although flocculation phenomenon occur, be
somewhat uniformly dispersed again once rocking, and illustrate that this prescription flocculation is
reversible, but occur in that flocculation phenomenon, are also the slightly worse performance of
stability；

3rd, the Microcrystalline Cellulose and Carboxymethylcellulose Sodium complex (Avicel CL-611) that
sample 4 is added, under the high temperature conditions the stability of ibuprofen suspension drop is
fine, but mobility is slightly worse；
 Therefore, the ibuprofen suspension drop even particulate dispersion containing xanthan gum and
Microcrystalline Cellulose and Carboxymethylcellulose Sodium complex that the present invention is
provided, significantly improve the high viscosity and agglomeration problems produced after common
suspension liquid long-time is placed, stability is high, and sample 3 contains the xanthan gum and Avicel
RC-591 of optimal proportion, the stability of optimum is all reached under high temperature and
illumination condition.

Claims (4)

Hide Dependent

1. a kind of ibuprofen suspension drop, it is characterised in that the weight ratio ingredient that the
prescription composition of the suspension drop includes is：Bu Luo Fragrant 4.0%, pregelatinized
Starch 1.0～3.5%, Sorbitol 1.0～5.0%, glycerol 4.0～5.0%, Fructose 15.0～30.0%, citron Acid 0.1～0.2%,
sodium benzoate 0.1～0.2%, Tween 80 0.05～0.1%, essence 0.05～0.5%, suspending agent 0.6～1.5%,
Purified Water q. s；

Wherein, described suspending agent is xanthan gum 0.1%～0.5% and Microcrystalline Cellulose and
Carboxymethylcellulose Sodium complex 0.5%～1.0% Combination.

2. ibuprofen suspension drop according to claim 1, it is characterised in that the Microcrystalline

Cellulose and Carboxymethylcellulose Sodium is answered Compound is preferably Avicel RC-591.

3. ibuprofen suspension drop according to claim 1, it is characterised in that the weight that the
prescription composition of the suspension drop includes Measure and be than component：Ibuprofen
4.0%, pregelatinized Starch 1.0%, Sorbitol 5.0%, glycerol 4.0%, Fructose 18.0%, citron Acid 0.2%, sodium
benzoate 0.2%, Tween 80 0.05%, essence 0.05%, xanthan gum 0.1%, Avicel RC-591 0.5%, Purified Water
q. s.

4. the method for preparing ibuprofen suspension drop described in claim 1 or 3, it is characterised in
that comprise the steps of：

1) Microcrystalline Cellulose and Carboxymethylcellulose Sodium complex is added in appropriate hot

purified water (60～80 DEG C), homogenizing；

2) xanthan gum is mixed with glycerol, adds appropriate purified water, and stirring makes swelling；

3) pregelatinized Starch is added in appropriate purified water, stirring makes to be uniformly

dispersed；

4) by Fructose, Sorbitol, citric acid, sodium benzoate, essence, in adding appropriate purified water,
homogenizing makes dissolving；

5) by above-mentioned steps 2), 3), 4) resulting solution adds step 1) in resulting solution, stir；

6) Tween 80 is added in appropriate purified water and is dissolved, added ibuprofen and stir evenly,
then homogenizing；

7) by step 6) resulting solution is added to step 5) in resulting solution, stir, plus remaining purified
water is settled to 100%, Mix homogeneously；

8) standing, gas removal bubble, fill is obtained final product.

Preparation of Suspensions
1. Reduce drug powder to desired size.
2. Add drug and wetting agent to solution.
3. Prepare solution of suspending agent.
4. Add other ingredients.
5. Homogenize medium.
6. Package.