CN117137868A

CN117137868A - Ibuprofen rectal foam agent and preparation method and application thereof

Info

Publication number: CN117137868A
Application number: CN202210560742.4A
Authority: CN
Inventors: 柴立; 李霞; 高滔; 贾金艳; 王心永
Original assignee: Guizhou Holy Pharmaceutical Co ltd
Current assignee: Guizhou Holy Pharmaceutical Co ltd
Priority date: 2022-05-23
Filing date: 2022-05-23
Publication date: 2023-12-01

Abstract

The invention belongs to the technical field of pharmaceutical preparations, discloses an ibuprofen rectal foam agent, a preparation method and application thereof, and solves the problems that an ibuprofen oral preparation is inconvenient to use and a solid suppository for rectal administration has slow effect in the prior art. The ibuprofen rectal foam agent comprises a liquid medicine and a propellant, wherein the liquid medicine comprises 5-30 parts of ibuprofen and 10-95 parts of a carrier; the ratio of the propellant to the liquid medicine is 0.30:1-1.7:1. The preparation method of the invention comprises the following steps: preparing raw materials in parts by weight; preparing auxiliary materials into a solution, and adding ibuprofen to prepare a solution type liquid medicine or a suspension type liquid medicine; adopting a single-dose or multi-dose filling mode; filling into container, selecting non-quantitative valve or drug delivery device, capping, and filling propellant. The invention relates to an application of ibuprofen rectal administration foaming agent in preparing children high fever emergency medicines. The invention has large dosage, the content of ibuprofen in each 100g of liquid medicine can reach 30g, the stability is good, and the onset time is quick.

Description

Ibuprofen rectal foam agent and preparation method and application thereof

Technical Field

The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to an ibuprofen rectal foam agent and a preparation method and application thereof.

Background

The medicinal foam aerosol is a unique medicine formulation, and the medicine can be in a dissolved state or a suspension state in the emulsion, so that the foam aerosol can be deeply administered, the ejected matters of the foam aerosol do not flow, the foam is stable and has long duration, the foam is uniformly dispersed in a cavity, the coating surface is wide, the medicine can effectively permeate into folds of mucous membranes, the medicine has quick response, and the curative effect is better than that of other formulations.

The ibuprofen preparation is a common antipyretic analgesic preparation in clinic at present, and the conventional preparations in foreign market at present comprise tablets, capsules, suspensions and injections, and the preparation formulations in domestic market comprise tablets, capsules, syrups, oral liquids and suppositories. The common antipyretic dosage forms for children are clinically applied in a plurality of suspension and suppositories, but the oral suspension is inconvenient to use when the children are high in fever, and the solid suppositories for rectal administration are slow in drug release, so that the development and administration are convenient, and the antipyretic dosage forms for children with rapid drug release have good clinical value.

Disclosure of Invention

The invention aims to provide an ibuprofen rectal foam agent, which solves the problems that an ibuprofen oral preparation in the prior art is inconvenient to use when the ibuprofen oral preparation is high in heat and a solid suppository for rectal administration has slow effect.

The second object of the invention is to provide a preparation method of the ibuprofen rectal foam agent.

It is a further object of the present invention to provide the use of the ibuprofen rectal foam.

In order to achieve the above purpose, the technical scheme adopted by the invention is as follows:

the ibuprofen rectal foam agent comprises a liquid medicine and a propellant, wherein the liquid medicine is prepared from the following raw materials in parts by weight: 5-30 parts of ibuprofen and 10-95 parts of carrier; the ratio of the propellant to the liquid medicine is 0.30:1-1.7:1.

In some embodiments of the present invention, the liquid medicine further comprises 0.05-20 parts of a surfactant, or/and 0.01-10 parts of a pH regulator, or/and 0.01-10 parts of a thickener, or/and 0.01-10 parts of an emulsifier, or/and 0.01-5 parts of a stabilizer.

In some embodiments of the invention, the medical fluid comprises a solution-type medical fluid, a suspension-type medical fluid.

In some embodiments of the present invention, the solution-type medicine liquid comprises 5-10 parts of ibuprofen;

or/and the suspension type liquid medicine comprises 10-30 parts of ibuprofen.

In some embodiments of the invention, the carrier comprises an aqueous carrier, or/and a non-aqueous carrier;

preferably, the aqueous carrier comprises at least one of propylene glycol, purified water, glycerol, ethanol, polyethylene glycol, polypropylene glycol, propylene glycol glyceride;

preferably, the non-aqueous carrier comprises at least one of light mineral oil, olive oil, soybean oil, corn oil, ethyl oleate.

In some embodiments of the present invention, the surfactant comprises at least one of polyoxyethylene fatty acid ester, polysorbate, isopropyl myristate, glycerol monooleate, glycerol monostearate, glycerol trioctanoate/decanoate, glycerol trioleate, polyoxyethylene butyl ether, polyoxyethylene cetyl ether, polyoxyethylene oleyl cetyl ether, sorbitan trioleate, tween, laureth-4;

the surfactant is preferably at least one of polyoxyethylene fatty acid ester, polysorbate and isopropyl myristate;

the polyoxyethylene fatty acid ester is preferably at least one of polyoxyl (10) stearyl ether and polyoxyl 20 whale stearyl ether.

In some embodiments of the present invention, the pH adjuster comprises at least one of disodium phosphate, citric acid, sodium bicarbonate, sodium carbonate, arginine, triethanolamine, triethylamine;

or/and the thickener comprises at least one of carboxymethyl cellulose, polyoxyethylene-polyoxypropylene copolymer, xanthan gum, agar, guar gum, hydroxyethyl cellulose, hydroxypropyl cellulose, methyl cellulose, cetyl alcohol, polyvinyl alcohol, polyethylene glycol and emulsifying wax;

or/and the emulsifier at least comprises at least one of linear fatty acid, branched fatty acid, propylene glycol stearate, glycerol stearate, polyethylene glycol, aliphatic alcohol and polyethylene oxide-propylene oxide block copolymer;

or/and the stabilizer at least comprises at least one of ethylene diamine tetraacetic acid and edetate disodium.

In some embodiments of the invention, the propellant is a pharmaceutically acceptable gas;

preferably, the propellant comprises at least one of a low molecular weight alkane, chlorofluorocarbon, hydrochlorofluorocarbon, hydrofluoroalkane;

more preferably, the low molecular weight alkane comprises at least one of isobutane, n-butane, propane;

more preferably, the hydrofluoroalkane comprises at least one of HFA134a and HFA 227.

In some embodiments of the invention, the ibuprofen rectal foam is in a multi-dose package or a single-dose package.

The preparation method of the ibuprofen rectal administration foaming agent comprises the following steps:

s1, preparing raw materials in parts by weight;

s2, mixing all auxiliary materials except ibuprofen to prepare a solution;

s3, adding ibuprofen into the solution to prepare solution type liquid medicine or suspension type liquid medicine;

s4, filling the solution type liquid medicine or the suspension type liquid medicine into a container, capping, and then filling the propellant to obtain the medicine;

preferably, the liquid medicine is filled in a single-dose or multi-dose filling mode;

preferably, the gland is a fixed-quantity-pressing valve or a non-fixed-quantity-pressing valve.

In some embodiments of the present invention, the multi-dose filling method includes: the liquid medicine is filled into pressure-resistant spray bottles, the filling amount is larger than the dosage for one time, quantitative valves with different quantitative volumes (the quantitative volume is 0.5-2 ML) are pressed and fixed on the different spray bottles, and the propellant is pressed into the bottles. When the medicine is administered, the pressing valve is used once, and the medicine administration can be completed by pressing the valve for a plurality of times according to the use instruction of the product.

Single dose filling mode: the liquid medicine is filled into a pressure-resistant spray bottle, the filling amount is equal to the dosage for one time, a non-quantitative valve is pressed and fixed on the spray bottle, and the propellant is pressed into the bottle. The valve is pressed down until the liquid medicine is completely sprayed out during administration. When in administration, one bottle of liquid medicine is used at one time.

In some embodiments of the present invention, a liquid drug (volume 100. Mu.L, 200. Mu.L, 300. Mu.L, 400. Mu.L, or 500. Mu.L) is filled into a pressure-resistant spray bottle in an amount equal to the single use dose, a non-metering valve is press-fitted to the spray bottle, and a propellant is injected into the bottle. The valve is pressed down until the liquid medicine is completely sprayed out during administration. When in administration, one bottle of liquid medicine is used at one time. The ibuprofen rectal administration foaming agent is applied to preparation of high-heat first-aid medicines, preferably, pediatric high-heat first-aid medicines.

Compared with the prior art, the invention has the following beneficial effects:

the invention has ingenious conception and scientific design, and prepares the foam agent for rectal administration of ibuprofen for the first time.

The ibuprofen rectal administration foaming agent has large administration amount, the content of ibuprofen in each 100g of liquid medicine can reach 30g, the stability is good, the onset time is quick, and the pharmacodynamic test shows that the ibuprofen rectal administration foaming agent is consistent with the peak time of injection administration.

Drawings

Figure 1 is a graph of the rabbit drug substitution of pediatric ibuprofen suppository, ibuprofen solution type foam, ibuprofen suspension type foam.

Detailed Description

In order to make the objects, technical solutions and advantages of the embodiments of the present invention more clear, the technical solutions of the embodiments of the present invention will be clearly and completely described below. The specific conditions are not noted in the examples and are carried out according to conventional conditions or conditions recommended by the manufacturer. The reagents or apparatus used were conventional products commercially available without the manufacturer's attention.

The homogenizer used in the examples of the present invention was manufactured by Shanghai Instrument relaxation industry Co.

Example 1

This example discloses a preparation method of ibuprofen rectal foam solution type, the raw materials of which are shown in table 1:

TABLE 1

The components	Dosage (weight portions)
		Ibuprofen	10
Arginine (Arg)	5
		Sodium carbonate	2.5
Polyoxyethylene (10) stearyl ether	0.5
		Emulsifying wax	0.3
Cetyl alcohol	0.5
		Propylene glycol	13
PEG200	5
		Edetic acid disodium salt	0.04
Purified water	63.2

The propellant is butane, and the dosage of the propellant is 5.0g butane per 15g liquid medicine.

The preparation method comprises the following steps: weighing arginine, sodium carbonate, polyoxyethylene (10) stearyl ether, emulsifying wax, cetyl alcohol, propylene glycol, PEG200, edetate disodium and purified water according to the prescription, heating in water bath at 65deg.C for 30min, taking out, stirring to dissolve completely, adding ibuprofen, stirring until ibuprofen is dissolved completely, and obtaining medicinal liquid.

Multi-dose filling mode: the liquid medicine is filled into pressure-resistant spray bottles, the filling amount is larger than the dosage for one time, and quantitative valves with different quantitative volumes (quantitative volumes of 0.5ML, 1ML, 1.5ML or 2 ML) are pressed and fixed on the different spray bottles, and the propellant is pressed into the bottles. When in administration, the pressing valve is used for one-time dosage, and each bottle can be used for multiple times according to the product use instructions.

Single dose filling mode: filling the medicinal liquid (volume of 0.5ML, 1ML, 1.5ML or 2 ML) into pressure-resistant spray bottle, with filling amount equal to one-time dosage, pressing and fixing non-quantitative valve on spray bottle, and pressing propellant into bottle. The valve is pressed down until the liquid medicine is completely sprayed out during administration. When in administration, one bottle of liquid medicine is used at one time.

Example 2

This example discloses a preparation method of ibuprofen rectal foam solution type, the raw materials of which are shown in table 2:

TABLE 2

The components	Dosage (weight portions)
		Ibuprofen	5
Sodium carbonate	5
		Polyoxyethylene (10) stearyl ether	0.5
Emulsifying wax	0.2
		Cetyl alcohol	0.8
Propylene glycol	8
		PEG200	5
Edetic acid disodium salt	0.03
		Glycerol	8
Purified water	67.5

The preparation method comprises the following steps: weighing arginine, sodium carbonate, polyoxyethylene (10) stearyl ether, emulsifying wax, cetyl alcohol, propylene glycol, PEG200, edetate disodium, glycerol and purified water according to the prescription, heating in water bath at 65deg.C for 30min, taking out, stirring to dissolve completely, adding ibuprofen, stirring until ibuprofen is dissolved completely, and obtaining medicinal liquid.

Multi-dose filling mode: the liquid medicine is filled into a pressure-resistant spray bottle, the filling amount is larger than the dosage for one time, quantitative valves with different quantitative volumes (quantitative volumes of 0.5ML, 1ML, 1.5ML or 2 ML) are pressed and fixed on the spray bottle, and the propellant is pressed into the bottle. When in administration, the pressing valve is used for one-time dosage, and each bottle can be used for multiple times according to the product use instructions.

Single dose filling mode: the liquid medicine (volume 0.5ML, 1ML, 1.5ML or 2 ML) is filled into a pressure-resistant spray bottle, the filling amount is equal to the dosage of one time use, a non-quantitative valve is pressed and fixed on the spray bottle, and the propellant is pressed into the bottle. The valve is pressed down until the liquid medicine is completely sprayed out during administration. When in administration, one bottle of liquid medicine is used at one time.

Example 3

This example discloses a preparation method of ibuprofen rectal foam solution type, the raw materials of which are shown in table 3:

TABLE 3 Table 3

The components	Dosage (weight portions)
		Ibuprofen	8
Arginine (Arg)	6
		Hydroxypropyl methylcellulose	5
Emulsifying wax	0.3
		Cetyl alcohol	0.5
Propylene glycol	13
		PEG400	10
Edetic acid disodium salt	0.02
		Purified water	57.2

The preparation method comprises the following steps: weighing arginine, hydroxypropyl methylcellulose, emulsifying wax, cetyl alcohol, propylene glycol, PEG400, disodium edentate and purified water according to the prescription, heating in water bath at 65deg.C for 30min, taking out, stirring to dissolve completely, adding ibuprofen, stirring to dissolve completely, and obtaining medicinal liquid.

Example 4

This example discloses a preparation method of ibuprofen rectal foam solution type, the raw materials of which are shown in table 4:

TABLE 4 Table 4

The propellant is butane, the dosage of the propellant is 5.0g butane per 15g of liquid medicine

The preparation method comprises the following steps: and weighing hydroxypropyl methylcellulose, emulsifying wax, cetyl alcohol, propylene glycol, PEG400, disodium edentate, triethanolamine and purified water according to the prescription, heating in water bath at 65deg.C for 30min, taking out, stirring to dissolve completely, adding ibuprofen, and stirring to dissolve completely to obtain medicinal liquid.

Filling liquid medicine:

Example 5

The example discloses a preparation method of ibuprofen rectal foam suspension, which comprises the following raw materials in table 5:

TABLE 5

The propellant is tetrafluoroethane, and the dosage of the propellant is 12.0g of tetrafluoroethane filled in every 20g of liquid medicine.

The preparation method comprises the following steps: arginine, sodium carbonate, polyoxyethylene (10) stearyl ether, emulsifying wax, cetyl alcohol, propylene glycol, PEG400, edetate disodium and purified water are weighed according to the prescription, heated for 30 minutes in a water bath at 65 ℃, taken out, stirred until fully dissolved, added with ibuprofen, homogenized for 30 minutes by using a homogenizer at 1000 revolutions per minute, and the suspension type liquid medicine is obtained.

Multi-dose filling mode: the liquid medicine is filled into a pressure-resistant spray bottle, the filling amount is larger than the dosage for one time, and quantitative valves with different quantitative volumes (the quantitative volumes are 100 mu L, 200 mu L, 300 mu L, 400 mu L or 500 mu L) are pressed and fixed on the spray bottle, and the propellant is pressed into the bottle. When in administration, the pressing valve is used for one-time dosage, and each bottle can be used for multiple times according to the product use instructions.

Single dose filling mode: the medicinal liquid (volume of 100. Mu.L, 200. Mu.L, 300. Mu.L, 400. Mu.L or 500. Mu.L) is filled into a pressure-resistant spray bottle, the filling amount is equal to the single-use dose, a non-quantitative valve is pressed and fixed on the spray bottle, and the propellant is pressed into the bottle. The valve is pressed down until the liquid medicine is completely sprayed out during administration. When in administration, one bottle of liquid medicine is used at one time.

Example 6

The example discloses a preparation method of ibuprofen rectal foam suspension, which comprises the following raw materials in table 6:

TABLE 6

The propellant is tetrafluoroethane, the dosage of which is 20g per liquid medicine, and the propellant is 12.0g of tetrafluoroethane

The preparation method comprises the following steps: arginine, polyoxyethylene (10) stearyl ether, hydroxypropyl methylcellulose, emulsifying wax, cetyl alcohol, propylene glycol, PEG400, edetate disodium and purified water are weighed according to the prescription, heated in a water bath at 65 ℃ for 30 minutes, taken out, stirred until fully dissolved, ibuprofen is added, and the mixture is homogenized for 30 minutes by using a homogenizer at 1000 revolutions per minute to obtain suspension type liquid medicine.

Example 7

The example discloses a preparation method of ibuprofen rectal foam suspension, which comprises the following raw materials in table 7:

TABLE 7

The preparation method comprises the following steps: heating and dissolving hypromellose and water, standing at room temperature to obtain clear and transparent solution, adding arginine and disodium edentate, and stirring; heating cetyl alcohol, propylene glycol and polyethylene glycol 400, lauryl alcohol 400 to dissolve, adding into the above solution while it is hot, stirring, adding ibuprofen, homogenizing for 30min at 1000 rpm with a homogenizer to obtain ibuprofen suspension; and (5) filling the ibuprofen suspension solution into the liquid medicine under the stirring state.

Example 8

The example discloses a preparation method of ibuprofen rectal foam suspension, which comprises the following raw materials in table 8:

TABLE 8

The preparation method comprises the following steps: heating and dissolving hypromellose and water, standing at room temperature to obtain clear and transparent solution, adding arginine and disodium edentate, and stirring; heating cetyl alcohol, propylene glycol and polyethylene glycol 400, tween 80 to dissolve, adding into the above solution while it is hot, stirring, adding ibuprofen, homogenizing with homogenizer to obtain ibuprofen suspension.

Example 9

This example discloses an examination of the homogeneity experimental conditions of the present invention.

Homogenizing refers to extruding the material liquid of the material, and refining the material under the triple actions of strong impact and decompression expansion, so that the material can be mixed with each other more uniformly.

The ibuprofen suspension solution is prepared according to a determined prescription, the content of the ibuprofen suspension solution before and after homogenization is measured, and the ibuprofen content at different sampling points is 297.1mg/g and 197.6mg/g when the ibuprofen suspension solution is not homogenized, so that the content difference is obvious; after homogenizing for 2 hours with a homogenizer at 500 rpm, the homogeneity of the solution is significantly improved with the results of 309.10mg/g, 314.26mg/g and 302.63 mg/g.

The particle size is reduced by homogenization, so that the suspension is more stable and uniform, and the uniformity of filling and good redispersibility in the use process are facilitated. The homogenizing time and the rotating speed are determined by parameters such as sedimentation volume ratio, redispersibility, content and the like.

(1) Examination of the homogenization time

The sample solution of ibuprofen suspension foam prepared in the method of example 8 was homogenized by a homogenizer at a rotation speed of 1000 rpm for 10 minutes, 20 minutes and 30 minutes, respectively, and then the sedimentation volume ratio, redispersibility and content of the homogenized liquid were measured.

The sedimentation volume ratio measurement method (CP 2015 edition) in this example is: 50ml of the sample solution was measured with a plug cylinder, sealed, shaken vigorously for 1 minute, the starting height H0 of the suspension was recorded, left to stand for 3 hours, the final height of the suspension was recorded, and the measurement was calculated as follows

Sedimentation volume ratio = H/H0.

The method for examining redispersibility in this example is as follows: taking the homogenized sample, standing for 7 days, and shaking forcefully for 1 minute, wherein the sample is uniform suspension without phase separation.

The content measurement method in this embodiment is as follows: taking homogenized suspension, detecting 5 samples, and examining the average content value and the RSD value.

The specific measurement method comprises the following steps:

the sample solution is precisely measured and a proper amount of the sample is quantitatively diluted by methanol to prepare a solution containing about 0.5mg of ibuprofen in each 1 ml.

The control solution is taken to be a proper amount of ibuprofen control, precisely weighed, dissolved by adding methanol and quantitatively diluted to prepare a solution containing about 0.5mg of ibuprofen in each 1 ml.

Octadecylsilane chemically bonded silica is used as a filler under chromatographic conditions; sodium acetate buffer (6.13 g of sodium acetate, 750ml of water are added to dissolve, and glacial acetic acid is used for regulating the pH value to 2.5) -acetonitrile (40:60) is used as a mobile phase; the detection wavelength is 263nm; the sample volume was 20. Mu.l.

The system applicability requires that the theoretical plate number is not less than 2500 calculated as ibuprofen peak.

The measuring method precisely measures the solution of the sample and the solution of the reference substance, respectively injects the solution into a liquid chromatograph, and records the chromatograms. Calculated as peak area according to the external standard method.

The results are shown in the following table:

TABLE 9 ibuprofen suspension homogenization time investigation results table

The test results show that: the sedimentation volume ratio, redispersibility and content uniformity of 1000 revolutions per minute and 30 minutes of homogenization are determined to be good.

(2) Investigation of the homogeneity rotational speed

Taking a sample solution of the ibuprofen suspension type foaming agent prepared according to the method of the example 8, homogenizing by using a homogenizer for 30 minutes, and respectively taking into consideration the sedimentation volume ratio, redispersibility and content of the homogenized suspension, wherein the homogenizing speed is 1500 rpm, 1000 rpm and 500 rpm; the results are shown in the following table:

table 10 table of results of investigation of the homogenization rotational speed of ibuprofen suspension

The test results show that: under the conditions of 1000 rpm and 1500 rpm, the ibuprofen suspension with good content uniformity can be obtained after 30 minutes of homogenization.

Example 10

This example discloses an examination of the filling process of the present invention.

A 58 x 22 aluminum canister (22 mm diameter, 58mm height, 20mL volume) was used, filled with 6.5g of drug solution, 150 μl of metered dose valve cap, and propellant of different mass. In the experiment, tetrafluoroethane is selected as a propellant, propellants with different dosages (the mass ratio of liquid medicine to the propellant is 1:0.56,1:0.9 and 1:1.69) are designed, the appearance property of the foam aerosol during spraying and the foam collapse time are taken as investigation indexes, and the dosage of the propellant is screened to be better. The medicinal liquid used in this example was the medicinal liquid produced in the same manner as in example 8.

Spray uniformity (RSD): shaking the product, spraying for 5 times, detecting foam content of each spraying, and calculating RSD

TABLE 11 screening results for fluids and propellants

Table 12 weight per spray results table

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The test results show that: the ratio of the liquid medicine to the propellant is closely related to the spray quantity difference and the foam character, the weight difference of each spray of the liquid medicine to the propellant (1:0.56) is obvious, and the liquid medicine and the propellant do not meet the requirements; the spray difference of the liquid medicine/the propellant (1:0.9) is small, and meets the requirements; the spray difference of the liquid medicine/the propellant (1:1.69) is small, and the requirements are met. Therefore, the filling parameters of the ibuprofen rectal foam agent suspension type traditional Chinese medicine liquid/propellant ratio of 1/0.9 to 1/1.7 are all feasible.

Test example 1

This test example provides a biopharmaceutical evaluation test of rectal administration of ibuprofen of the present invention.

(1) Reagent

Table 13 preliminary drug substitution test drug table

Name of the name	Remarks	Source
			Experimental rabbit	Weight:>2.5kg, male	Chengdu Dashuo experimental animal Co.,Ltd.
Ibuprofen suppository for children	Specification of: 50 mg/grain, lot number: 180603	HUBEI TUNGSHUN PHARMACEUTICAL Co.,Ltd.
			Ibuprofen rectal foam (solution type)	Example 1	Homemade
Ibuprofen rectal foam (suspension)	Example 8	Homemade
			Sterilized water for injection	500 ml/bottle	GUANGDONG SAKE BIOTECH Co.,Ltd.
Remaining needle	Specification of: 26G

(2) Test content

Healthy rabbits were fasted for 12 hours, and the indwelling needle was placed in the auricular vein. After 5 minutes, samples were taken and administered rectally, and blood was collected from the auricular veins at various times (10, 20, 30, 45, 60, 90 minutes). The blood is anticoagulated by 1ml of 1% heparin, centrifugated, separated into plasma, the supernatant of heparin anticoagulated plasma is taken and put into a centrifuge tube, 0.1ml of 0.1mol/L hydrochloric acid is added and mixed evenly, 5ml of methanol is used for extraction, the extract is naturally dried at the water bath of 30 ℃, the residue is dissolved by 1.0ml of mobile phase, and after filtration by a microporous filter membrane of 0.45 mu m, the content is measured by injection and HPLC.

(3) Dosage and prescription

The rectal dosage of the ibuprofen suppository for children is about 25mg, the rectal dosage of the ibuprofen solution foam is about 10mg, and the rectal dosage of the ibuprofen suspension foam is about 25mg.

(4) Test results

The peak time of ibuprofen suppository is about 20 minutes, and the solution foaming agent and the suspension foaming agent reach the maximum value within 10 minutes at the first time point of detection, so that the foaming agent has the advantages of quick onset of action compared with suppositories. The ibuprofen solution foam is similar to the ibuprofen suspension foam in profile. The peak concentration of the ibuprofen suspension foam (6.19. Mu.g/g) was increased (4.44. Mu.g/g) compared to the suppository peak concentration at substantially the same dose.

The test data are shown in the following table.

Table 14 results table of pediatric ibuprofen suppository rabbit drug substitution test data

Numbering device	Blood sampling time (minutes)	Blood collection amount (g)	Ibuprofen blood concentration (μg/g)
				1	10	/	/
2	20	0.4934	2.63
				3	30	0.7828	4.44
4	45	0.1528	2.01
				5	60	0.4219	0.602
6	90	/	/

TABLE 15 ibuprofen rectal foam (solution) Rabbit

Drug generation test data results table (sample number XS 023)

Numbering device	Blood sampling time (minutes)	Blood collection amount (g)	Ibuprofen blood concentration (μg/g)
				1	10	0.277	1.11
2	20	0.487	0.429
				3	30	0.042	0.31
4	45	0.552	0.053
				5	60	0.308	/
6	90	0.422	/

TABLE 16 ibuprofen rectal foam (suspension) rabbit

Drug generation test data result table (sample number hxs 002)

Numbering device	Blood sampling time (minutes)	Blood collection amount (g)	Ibuprofen blood concentration (μg/g)
				1	10	0.244	6.19
2	20	0.195	2.44
				3	30	0.312	1.02
4	45	0.266	0.60
				5	60	0.282	0.32
6	90	0.292	/

Test example 2

The stability of the ibuprofen rectal foam suspension was examined using the sample prepared in example 8. The ibuprofen rectal foam was subjected to conditions of 30 ℃ ± 2 ℃ and a relative humidity of 65% ± 5%, and the ibuprofen content was measured at different time points, respectively, as shown in the following table:

table 17 table for accelerated test of ibuprofen rectal foam

	Ibuprofen content% (W/W)
		0 month	28.9
1 month	28.8
		2 months of	28.5
3 months of	28.4
		6 months of	27.7

Test example 3

The stability of the ibuprofen rectal foam solution was examined using the sample prepared in example 4. The ibuprofen rectal foam was subjected to conditions of 30 ℃ ± 2 ℃ and a relative humidity of 65% ± 5%, and the ibuprofen content was measured at different time points, respectively, as shown in the following table:

table 18 table of the accelerated test of ibuprofen rectal foam

The embodiments described above are some, but not all embodiments of the invention. The detailed description of the embodiments of the invention is not intended to limit the scope of the invention, as claimed, but is merely representative of selected embodiments of the invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.

Claims

1. The ibuprofen rectal foam is characterized by comprising a liquid medicine and a propellant, wherein the liquid medicine is prepared from the following raw materials in parts by weight: 5-30 parts of ibuprofen and 10-95 parts of carrier; the ratio of the propellant to the liquid medicine is 0.30:1-1.7:1.

2. The ibuprofen rectal foam according to claim 1, wherein the liquid medicine further comprises 0.05-20 parts of surfactant, or/and 0.01-10 parts of pH regulator, or/and 0.01-10 parts of thickener, or/and 0.01-10 parts of emulsifier, or/and 0.01-5 parts of stabilizer.

3. An ibuprofen rectal foam according to claim 1 or 2, characterized in that said liquid medicine comprises a solution type liquid medicine, a suspension type liquid medicine.

4. An ibuprofen rectal foam according to claim 3, wherein said solution-type medicinal liquid comprises 5-10 parts of ibuprofen;

or/and the suspension type liquid medicine comprises 10-30 parts of ibuprofen.

5. An ibuprofen rectal foam according to claim 1 or 2, characterised in that said carrier comprises an aqueous carrier, or/and a non-aqueous carrier;

6. The ibuprofen rectal foam according to claim 2, wherein said surfactant comprises at least one of polyoxyethylene fatty acid ester, polysorbate, isopropyl myristate, glycerol monooleate, glycerol monostearate, glycerol tricaprylate/decanoate, glycerol trioleate, polyoxyethylene butyl ether, polyoxyethylene cetyl ether, polyoxyethylene oleyl cetyl ether, sorbitan trioleate, tween, laureth-4;

7. The ibuprofen rectal foam according to claim 2, wherein said pH modifier comprises at least one of disodium phosphate, citric acid, sodium bicarbonate, sodium carbonate, arginine, triethanolamine, triethylamine, and the pH is adjusted to less than 9.0;

or/and the stabilizer at least comprises at least one of ethylene diamine tetraacetic acid and edetate disodium; or/and the propellant is a pharmaceutically acceptable gas;

8. The ibuprofen rectal foam according to claim 1, wherein said ibuprofen rectal foam is in a multi-dose package or a single-dose package.

9. A process for the preparation of an ibuprofen rectal foam according to any one of claims 1 to 8, characterised in that it comprises the steps of:

s1, preparing raw materials in parts by weight;

s2, mixing all auxiliary materials except ibuprofen to prepare a solution;

s4, filling the solution type liquid medicine or the suspension type liquid medicine into a pressure-resistant container, capping, and then filling the propellant to obtain the medicine;

10. Use of an ibuprofen rectal foam according to any one of claims 1-8 in the manufacture of a hyperthermia emergency medicament, preferably in the manufacture of a pediatric hyperthermia emergency medicament.