KR20090077302A - Excellent stability of megestrol acetate acetate composition and its manufacturing method - Google Patents

Abstract

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to pharmaceutical compositions comprising megestrol acetate as a main component, and more particularly to megestrol acetate as ethylene oxide-propylene oxide block copolymer, hydrogenated polyoxyl castor oil, and polyethylene glycol-15-hydroxystearic acid. At least one surfactant selected from the group consisting of and at least one humectant selected from the group consisting of propylene glycol and glycerin is dispersed together to a pharmaceutical composition excellent in stability.

The pharmaceutical composition containing megestrol acetate in accordance with the present invention has excellent dispersibility and excellent stability, as well as excellent redispersibility. In addition, by controlling the interfacial activity of the poorly soluble megestrol acetate drug particles and hydrating the particles sufficiently to remove the air between the particles, it is easily manufactured through a relatively simple manufacturing method such as a homomixer, homogenizer, etc., rather than a special preparation facility. It is possible.

Description

A Pharmaceutical Composition Comprising Megestrol Acetate with Great Stability and the Preparing Method Thereof}

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to pharmaceutical compositions comprising megestrol acetate as a main component, and more particularly to megestrol acetate as ethylene oxide-propylene oxide block copolymer, hydrogenated polyoxyl castor oil, and polyethylene glycol-15-hydroxystearic acid. At least one surfactant selected from the group consisting of and at least one humectant selected from the group consisting of propylene glycol and glycerin are dispersed together to provide excellent pharmaceutical composition.

Megestrol acetate is useful in the management of cachexia (lack of nutrition), anorexia, weight loss, etc., which are common in cancer patients undergoing chemotherapy, and are known in European Patent No. 0338404 A1 and US Patent No. 4,370,321. Has a 17 alpha-acetoxy-6-methylpregna-4,6-diene-3,20-dione structure as shown in Chemical Formula 1 below.

Megestrol acetate is a synthetic derivative of natural progesterone. Cancer patients with chemotherapy (lack of nutrition), anorexia, weight loss, or people with acquired immunodeficiency syndrome (AIDS) may find it difficult or impossible to take large amounts of tablets or capsules. If the dosage is large, it should be designed a liquid formulation, not a tablet or capsule. Since megestrol acetate is poorly soluble in water, it is suitable in the form of a suspension in which undissolved solid particles in such liquid formulations are evenly dispersed in the liquid medium. Pharmaceutically useful suspensions require that the atomized drug particles disperse well in water to maintain a stable suspension during storage and facilitate redispersion.

Methoxy sold under the current product geyiseu ^® (Megace oral solution, Bristol-Myers Squibb Company, NJ, USA) is form stable suspensions in water, through which can contain gum acetate megestrol as polyethylene glycol, polysorbate and xanthan (Korean Patent No. 10-0211192).

However, megestrol acetate can be used to prepare a stable suspension due to the fact that the drug is very poorly soluble in water, the effect of drug concentration is excessively large, and the interfacial tension of the drug particles is so large that air is contained between the particles. Was not easy to prepare as a suspension. Therefore, in the case of the existing product, a process of firstly mixing and hydrating polyethylene glycol and polysorbate aqueous solution by melting the megestrol acetate acetate particles with heat for a long time, and adding a viscosity modifier to the polyethylene glycol solution which is heated and melted again. In addition, the process of dissolving other excipients such as mating agents, preservatives, etc. was separated and separately prepared, followed by complicated processes such as mixing again. In this process, the megestrol acetate drug particles were exposed to high temperature heat, and problems caused by long working processes were generated.

In general, the dissolution rate of the drug in particulate form is known to increase with increasing surface area, ie, decreasing particle size. In this respect, various techniques for reducing the size of fine particles have been used, which can be largely classified into dry grinding, wet grinding, and air jet grinding. Such grinding methods are well known in the art.

US Patent No. 7,101,576 discloses a formulation for reducing the dosage by increasing the bioavailability through the nano-particles of megestrol acetate drug particles. The formulations are acetate methoxy guest roll HPMC, Elan with sodium Tokyu glyphosate using a Nano Mill ^® (NanoMill) of (Elan Corporation, USA) in 125 higher concentration than the concentration of the ^® conventional methoxy geyiseu milligrams / Milliliters of megestrol acetate suspension were prepared.

Despite the advantages of high bioavailability and low dosage, however, the preparation of such formulations requires special equipment such as colloid mills and nanomills ^® and long process times from hours to days. In addition, this method is to increase the bioavailability by reducing the particle size, which is less related to the composition for maintaining a stabilized suspended phase.

Therefore, it is easy to manufacture and does not clump or agglomerate due to the attraction between particles through a manufacturing method other than a method that can cause physical and chemical modifications to megestrol acetate drug particles. There is a need for pharmaceutical compositions in a more stable form, including drug particles, which do not cause precipitation during shelf life and that have less variation in pharmaceutical form.

Accordingly, the present inventors easily disperse the megestrol acetate acetate particles without using a method of causing physical and chemical modifications to the megestrol acetate drug particles, excellent dispersibility, excellent stability and redispersibility To provide.

The present invention to achieve the above object megestrol acetate; At least one surfactant selected from the group consisting of ethylene oxide-propylene oxide block copolymers, hydrogenated polyoxyl castor oils and polyethylene glycol-15-hydroxystearic acid; And it provides a stable oral pharmaceutical composition comprising at least one humectant selected from the group consisting of propylene glycol and glycerin.

In the pharmaceutical composition according to the present invention, the surfactant is preferably included in 0.005 to 10% by weight based on the total weight of the pharmaceutical composition. When the amount of the surfactant is less than the present weight%, not only the difficulty of preparing the suspension due to the interfacial tension of the hydrophobic megestrol acetate, but also the precipitation easily occurs when the suspension is left, and the amount of the surfactant is the weight% In case of exceeding a large amount of bubbles, it is difficult to prepare a suspension and may cause hypersensitivity reactions such as anaphylaxis during human administration.

The amount of the surfactant was set in consideration of other inherent physical properties (critical micelle concentration, toxicity, etc.) according to the type of the surfactant, solubility in megestrol acetate, stability of the suspension, and the like.

In particular, the ethylene oxide-propylene oxide block copolymer as the surfactant is preferably contained in 0.005 to 5.0% by weight, preferably 0.02 to 3.0% by weight based on the pharmaceutical composition.

In addition, the hydrogenated polyoxyl castor oil as the surfactant is preferably contained in 0.01 to 5.0% by weight, preferably 0.05 to 1.0% by weight relative to the total weight of the pharmaceutical composition.

In addition, the polyethylene glycol-15-hydroxystearic acid as the surfactant is preferably contained in 0.01 to 10.0% by weight, preferably 0.05 to 5.0% by weight relative to the total weight of the pharmaceutical composition.

In the pharmaceutical composition according to the present invention, the humectant is preferably contained in an amount of 0.5 to 30.0% by weight, preferably 2.0 to 20.0% by weight, based on the total weight of the pharmaceutical composition.

Megestrol acetate is very poorly soluble in water, so when a wetting agent is mixed in the above weight% when preparing a suspension, the affinity with water increases the convenience of preparation and an appropriate amount of wetting agent is added to the interface of the present patent. When used in combination with an active agent, it was confirmed that the suspension state lasted longer and the resuspension was improved.

The megestrol acetate acetic acid pharmaceutical composition according to the present invention may preferably contain a thickener in addition to the surfactant and the wetting agent in the crude suspension prepared stably.

The thickener may be included in 0.1 to 30% by weight based on the total weight of the megestrol acetate pharmaceutical composition. This is why maintaining the proper viscosity due to the use of thickeners in the formulation design of suspensions is essential for the formation of physicochemically stable formulations during the shelf life of the suspensions. Therefore, if the concentration of the suspending agent exceeds 30% by weight, the viscosity is too high to lose the fluidity, which is the main property of the liquid formulation, if less than 0.1% by weight it may be difficult to expect a distinct effect of suspension stability because the concentration is too low. to be.

The megestrol acetate composition according to the present invention, in addition to the excipients such as pH adjusters, preservatives, artificial and natural sweeteners, flavoring agents, colorants, dispersants, solubilizers, etc., has good stability and properties and prevents aggregation and sedimentation between particles. It can be suppressed to prepare a pharmaceutical composition excellent in redispersibility.

In particular, thickeners and pH adjusting agents play a major role in maintaining stable and redispersible formulations evenly suspended with surfactants and wetting agents. Suitable thickeners include xanthan gum, guar gum, and the like, or natural or synthetic polymers such as carboxymethyl cellulose, povidone, carrageenan, methylcellulose, and the like.

The present invention also provides a composition comprising (a) at least one surfactant selected from the group consisting of ethylene oxide-propylene oxide block copolymers, hydrogenated polyoxyl castor oils and polyethylene glycol-15-hydroxystearic acid, and glycerin and Preparing a crude suspension by adding and stirring to an aqueous solution in which at least one humectant selected from the group consisting of propylene glycol is dissolved; And (b) at least one surfactant selected from the group consisting of ethylene oxide-propylene oxide block copolymer, hydrogenated polyoxyl castor oil and polyethylene glycol-15-hydroxystearic acid in the crude suspension prepared in step (a). And it provides a method for preparing acetic acid megestrol pharmaceutical composition comprising the step of adding and mixing the excipient dissolved in an aqueous solution in which at least one humectant is selected from the group consisting of glycerin and propylene glycol.

In the manufacturing method of the megestrol acetate acetate composition according to the present invention as described above, the preparation of the crude suspension first acts to remove the bubbles between the particles and simplifies the process, while reducing the process time while the acetate megest into small enough particles This is to disperse the roll drug particles.

The pharmaceutical composition containing megestrol acetate in accordance with the present invention has excellent dispersibility and excellent stability, as well as excellent redispersibility. In addition, by controlling the surface activity of the poorly soluble megestrol acetate drug particles and hydrating the particles sufficiently to remove the air between the particles, it is easy to manufacture through a relatively simple manufacturing method such as homomixers, homogenizers, etc. It is possible.

In the present invention, ethylene oxide-propylene oxide block copolymer, hydrogenated polyoxyl castor oil, and polyethylene glycol-15-hydroxystearic acid are particularly non-hydrophilic among a myriad of pharmaceutically acceptable surfactants for solubilizing poorly water-soluble or non-hydrophilic drugs. Particularly useful for evenly dispersing the drug megestrol in water, the addition of glycerin or propylene glycol as a humectant facilitates the manufacture and minimizes the time and effort during the manufacturing process. It was confirmed that it is easy to maintain and does not easily precipitate and has excellent redispersibility.

Hereinafter, the present invention will be described in more detail with reference to the following examples and test examples. In conclusion, these examples are only for illustrating the present invention in more detail, it is to those skilled in the art that the scope of the present invention is not limited by these examples and test examples according to the gist of the present invention. Will be self-evident.

<Example 1>

Acetate megestrol to 4.44 w / v%, the concentration of the ethylene oxide-propylene oxide block copolymer (trade name: root roll ^® BASF Co.) to 0.1 w / v%, containing glycerol 10 wt / put in% by volume aqueous solution of a homomixer to The mixture was stirred for 2 hours and the like to prepare a crude suspension in which bubbles were hardly generated. The preparation of the crude suspension serves to remove bubbles between the particles and to simplify the process to shorten the process time and to disperse the megestrol acetate drug particles into sufficiently small particles.

Ethylene oxide-propylene oxide block copolymer (trade name: root roll ^® BASF Co.) to 0.1 w / v% glycerol 10 wt / vol% aqueous solution of each glass in 100 ml containing tangeom was dissolved 4g, sodium benzoate 1g and sucrose 50g 900 ml of the crude suspension is added and mixed again with a homomixer. Finally, the orange essence was added to pH 4.0 with citric anhydride, sodium citrate and the like.

<Example 2>

Megestrol acetate at a concentration of 4.44 w / v%, hydrogenated polyoxyl castor oil: containing (trade name Crescent mode pore ^® BASF Co., Ltd.) 0.25 w / v%, and polyethylene glycol 15-hydroxy stearic acid (trade name: Solutol HS ^® BASF) was prepared in a 10 wt% / vol% aqueous solution of propylene glycol containing 0.5 wt% / vol% and stirred for 2 hours with a homomixer to produce a crude suspension with little bubbles.

Polyoxyl hydrogenated castor oil (trade name: Pore Crescent Mo ^® BASF Co., Ltd.) 0.25 w / v%, and containing polyethylene glycol 15-hydroxy stearic acid (trade name: HS ^® solution toll BASF Co.) to 0.5 w / v%, containing 4 g of xanthan gum, 1 g of sodium benzoate and 50 g of white sugar are dissolved in 100 ml of 10 wt / vol% aqueous solution of propylene glycol, and then 900 ml of the crude suspension is added and mixed again with a homomixer. Finally, the orange essence was added to pH 4.0 with citric anhydride, sodium citrate and the like.

<Example 3>

4.44 w / v% polyethylene megestrol acetate at a concentration of glycol 15-hydroxystearic acid (trade name: HS ^® solution toll BASF Co., Ltd.) 0.25 w / v% glycerol containing 10 wt / vol% aqueous solution into a homopolymer of The mixture was sufficiently stirred with a mixer to prepare a crude suspension.

Polyethylene glycol 15-hydroxystearic acid (trade name: HS ^® solution toll BASF Co., Ltd.) 0.25 w / v% glycerol containing 10 w / v% aqueous solution of xanthan gum in 100 ml 4g, benzoic acid solution obtained by dissolving sodium 1g and 50g sucrose To this, add 900 ml of the crude suspension and mix again with a homomixer. Finally, the orange essence was added to pH 4.0 with citric anhydride, sodium citrate and the like.

<Example 4>

4.44 weight / acetate megestrol to a concentration of% by volume of ethylene oxide-propylene oxide block copolymer (trade name: root roll ^® BASF Co.) 0.3 w / v% into a containing glycerin 0.5 w / v% aqueous solution of a homomixer etc. The mixture was stirred sufficiently to prepare a crude suspension.

Ethylene oxide-propylene oxide block copolymer: in which (a trade name root roll ^® BASF Co.) to 0.3 w / v%, containing dissolved xanthan gum 4g, sodium benzoate 1g and sucrose 50g in 100 ml glycerol 0.5 w / v% aqueous solution which solution Add 900 ml of the crude suspension and mix again with a homomixer. Finally, the orange essence was added to pH 4.0 with citric anhydride, sodium citrate and the like.

<Example 5>

Hydrogenated polyoxyl castor oil (trade name: Cremophor ^® BASF) was prepared in a 30 wt / vol% aqueous solution of propylene glycol containing 0.3 wt / vol% to 4.44 wt / vol% concentration. Stirring sufficiently to make crude suspension.

In a solution in which 4 g of xanthan gum, 1 g of sodium benzoate and 50 g of sugar were dissolved in 100 ml of an aqueous 30 wt / vol% solution of propylene glycol containing 0.3 wt / vol% of hydrogenated polyoxyl castor oil (trade name: Cremophor ^® BASF), Add 900 ml of the crude suspension and mix again with a homomixer. Finally, the orange essence was added to pH 4.0 with citric anhydride, sodium citrate and the like.

Comparative Example 1

4.44 weight / acetate megestrol to a concentration of% by volume of ethylene oxide-propylene oxide block copolymer: with (trade name root roll ^® BASF Co.) to 0.1 / put in% by volume containing wetting ratio was added an aqueous solution of a homomixer etc. 2 Stirring for a time gave a crude suspension with little bubbles.

Ethylene oxide-propylene oxide block copolymer (trade name: root roll ^® BASF Co.) to w / v%, containing coal residues in wetting the non-added solution 100ml of gum 4g, put the sodium benzoate 1g and sucrose 50g was dissolved in the crude suspension is 900 ml Mix again with a homomixer or the like. Finally, the orange essence was added to pH 4.0 with citric anhydride, sodium citrate and the like.

Comparative Example 2

A crude suspension was prepared by containing megestrol acetate to a concentration of 4.44% by weight, containing 10% by weight of glycerin as a humectant, and adding it to an aqueous solution without a surfactant and stirring for 2 hours with a homomixer or the like.

It contains 10% by weight of glycerin as a humectant, 4g of xanthan gum, 1g of sodium benzoate, and 50g of white sugar are dissolved in 100ml of the surfactant-free aqueous solution, and 900ml of the crude suspension is mixed again with a homomixer. Finally, the orange essence was added to pH 4.0 with citric anhydride, sodium citrate and the like.

Comparative Example 3

Megestrol acetate was added to an aqueous solution of 10 weight / vol% of glycerin containing 0.5 0.5 weight / vol% of polysorbate to a concentration of 4.44 weight / vol%, and stirred sufficiently with a homomixer to prepare a crude suspension.

In a solution in which 4 g of xanthan gum, 1 g of sodium benzoate and 50 g of white sugar were dissolved in 100 ml of a 10 weight / vol% aqueous solution of glycerin containing 0.5 weight / vol% of polysorbate 80, 900 ml of the crude suspension was added, followed by a homomixer. Mix. Finally, the orange essence was added to pH 4.0 with citric anhydride, sodium citrate and the like.

Test Example  1: Check the stability of the drug

In order to confirm the stability of the drug prepared in Examples 1 to 4 at room temperature (25 ℃, 60% RH) and accelerated (40 ℃, 75% RH) conditions for 6 months while leaving the appearance, pH, viscosity, elution, redistribution Acidity and content were tested.

When evaluating the stability, all the quality control items such as property, content test, pH, and elution were evaluated. In the case of suspension, even if the drug particles are precipitated, the precipitated particles can be easily dispersed and commercialized if the suspension is maintained again. Therefore, it is essential to evaluate the possibility of redispersion (resuspension) when evaluating the suspension.

<Evaluation method>

Appearance: Observation was made with the naked eye.

Content: The content of the standard and the stability sample was measured using HPLC, and the values were calculated by comparing the values.

pH: The pH of the suspension was measured using a pH meter.

Dissolution test: The dissolution test was conducted in accordance with Dissolution Test Method 2 using 900 ml of 0.5% sodium lauryl sulfate aqueous solution.

Redispersibility: The test suspension was marked as good if the sediment was dispersed uniformly within 10 times when gently shaken by hand.

TABLE 1

Comprehensive Table of Long-term Preservation Test Results by Example

(Experimental conditions: temperature 25 ^o C, relative humidity 60% RH)

Test Items Example Early 3 months 6 months Constellation #One fitness fitness fitness #2 fitness fitness fitness # 3 fitness fitness fitness #4 fitness fitness fitness # 5 fitness fitness fitness  pH #One 3.68 3.69 3.65 #2 3.78 3.75 3.77 # 3 3.49 3.43 3.47 #4 3.54 3.51 3.50 # 5 3.64 3.65 3.63  Viscosity (cps) #One 269 269 271 #2 252 251 249 # 3 259 259 257 #4 246 250 247 # 5 272 274 273  Dissolution Test #One 100.5% 99.8% 99.3% #2 100.7% 96.5% 91.2% # 3 100.3% 101.6% 99.7% #4 100.5% 101.4% 100.5% # 5 101.2% 100.6% 100.7%  Redispersibility #One Good Good Good #2 Good Good Good # 3 Good Good Good #4 Good Good Good # 5 Good Good Good  Content test #One 102.9% 101.1% 100.2% #2 100.3% 99.6% 97.4% # 3 103.8% 102.1% 102.2% #4 100.5% 100.3% 100.7% # 5 101.2% 101.6% 100.8%

TABLE 2

Accelerated test results for each megestrol acetate acetate example

(Experimental conditions: temperature 40 ^o C, relative humidity 75% RH)

Test Items Example Early 3 months 6 months Appearance (visually confirmed) #One fitness fitness sedimentation #2 fitness fitness sedimentation # 3 fitness fitness sedimentation #4 fitness fitness sedimentation # 5 fitness fitness sedimentation  pH #One 3.68 3.69 3.72 #2 3.78 3.79 3.83 # 3 3.49 3.43 3.47 #4 3.54 3.52 3.50 # 5 3.64 3.63 3.64 Viscosity (cps) #One 269 271 275 #2 252 249 245 # 3 259 261 262 #4 246 243 241 # 5 272 274 273  Dissolution Test #One 100.5% 98.9% 97.1% #2 100.7% 93.1% 87.6% # 3 100.3% 99.6% 98.7% #4 100.5% 98.7% 97.6% # 5 101.2% 97.5% 97.8%  Redispersibility #One Good Good Good #2 Good Good Good # 3 Good Good Good #4 Good Good Good # 5 Good Good Good  Content test #One 102.9% 100.7% 98.1% #2 100.3% 94.1% 90.6% # 3 103.8% 100.3% 98.7% #4 100.5% 100.2% 99.7% # 5 101.2% 100.3% 98.8%

Through the results shown in Table 1 and Table 2, the megestrol acetate suspension compositions according to Examples 1, 2, 3, 4, and 5 were confirmed to have excellent stability in product evaluation items such as properties, contents, and elution. In addition, it was confirmed that the redispersibility was excellent even when settling.

Test Example  2: Sedimentation and Redispersible  compare

Comparative Example 1 using only a surfactant without adding a wetting agent, Comparative Example 2 using only a wetting agent without adding a surfactant, Polysorbate 80, which is a pharmaceutically widely used surfactant that is not a composition according to the present invention and Each prepared sample was left to stand for 6 months under accelerated conditions (40 ° C, 75% RH) to compare the precipitation of the suspension of Comparative Example 3 with glycerin as a wetting agent and whether the suspensions of Examples 1 and 2 were precipitated and redispersible. It compared and observed and showed in following Table 3, Table 4, and FIG.

TABLE 3

Sedimentation Comparison in Accelerated Preservation Conditions by Example of Megestrol Acetate Suspension

(Experimental conditions: temperature 40 ^o C, relative humidity 75% RH)

Test Items division Early 3 months 6 months Sedimentation degree (visual observation) Example 1 fitness fitness sedimentation Example 2 fitness fitness sedimentation Comparative Example 1 fitness sedimentation sedimentation Comparative Example 2 sedimentation sedimentation sedimentation Comparative Example 3 fitness sedimentation sedimentation

As shown in Table 3 above, the suspension of Examples 1 and 2 was allowed to settle after 6 months as a result of being left for 6 months under accelerated conditions (40 ° C., 75% RH) to confirm precipitation of preparation samples. The preparation liquid of Comparative Example 1 and Comparative Example 3 settled within 3 months. In particular, it was confirmed that the suspension of Preparation Example 2 was settled within one week after preparation.

In addition, as shown in FIG. 1, after three months under accelerated storage conditions, the suspensions of Examples 1 and 2 still maintain a stable suspension, but Comparative Example 1 shows a clear settled state.

* Evaluation of redispersibility: The test suspension was marked as good if the precipitate was dispersed uniformly within 10 times when gently shaken by hand.

Comparison of Redispersibility in Accelerated Preservation Conditions by Example of Megestrol Acetate Suspension Test Items division Early 3 months 6 months Redispersibility Example 1 Good Good Good Example 2 Good Good Good Comparative Example 1 Good Bad Bad Comparative Example 2 Bad Bad Bad Comparative Example 3 Good Bad Bad

As shown in Table 3, after six months of acceleration, each of the suspensions of Examples 1, 2, Comparative Example 1, Comparative Examples 2, and 3 were all settled, but as can be seen from Table 4, The suspensions of Examples 1 and 2 were easily redispersed, whereas Comparative Examples 1, 2 and 3 were completely settled and poorly redispersible.

As such, it has been found that the acetate megestrol suspension composition according to the present invention can easily disperse the megesta acetate particles as a main component, and not only stably maintain the suspended phase, but also redispersible when the suspension is precipitated. Excellent.

These results disperse the drug particles into sufficiently small particles by one or more surfactants selected from the group consisting of ethylene oxide-propylene oxide block copolymers, hydrogenated polyoxyl castor oils and polyethylene glycol-15-hydroxystearic acid. It was confirmed that a stable suspension was maintained by effectively removing bubbles between drug particles by using a humectant and suppressing aggregation between particles.

Figure 1 is a photograph showing the appearance after storage for 3 months under accelerated conditions of the megestrol acetate suspension formulation. (a), (b), and (c) each shows Example 1, Example 2, and Comparative Example 1.

Claims (11)

Oral pharmaceutical composition with excellent stability, including (a) megestrol acetate; (b) at least one surfactant selected from the group consisting of ethylene oxide-propylene oxide block copolymers, hydrogenated polyoxylcaster oils and polyethylene glycol-15-hydroxystearic acid; And (c) at least one wetting agent selected from the group consisting of propylene glycol and glycerin. The method of claim 1, The surfactant is a pharmaceutical composition, characterized in that the content in the composition is 0.005 to 10% by weight. The method of claim 2, Ethylene oxide-propylene oxide block copolymer as the surfactant is a pharmaceutical composition, characterized in that the content in the composition is 0.005 ~ 5.0% by weight. The method of claim 2, Hydrogenated polyoxyl castor oil as the surfactant is a pharmaceutical composition, characterized in that the content in the composition is 0.01 to 5.0% by weight. The method of claim 2, Polyethylene glycol 15-hydroxystearic acid as the surfactant is a pharmaceutical composition, characterized in that the content in the composition is 0.01 to 10.0% by weight. The pharmaceutical composition of claim 1, wherein the humectant has a content in the composition of 0.5 to 30.0 wt%. The method of claim 1, The pharmaceutical composition is a pharmaceutical composition, characterized in that it further comprises one or more excipients selected from the group consisting of thickeners, pH adjusters, preservatives, artificial and natural sweeteners, flavoring agents, colorants, dispersants and solubilizers. The method of claim 7, wherein The thickening agent is a pharmaceutical composition, characterized in that at least one selected from the group consisting of xanthan gum, guar gum, carboxymethyl cellulose, povidone, carrageenan and methyl cellulose. Method for preparing acetic acid megestrol pharmaceutical composition comprising the following steps: (a) megestrol acetate comprising at least one surfactant selected from the group consisting of ethylene oxide-propylene oxide block copolymers, hydrogenated polyoxylcaster oils and polyethylene glycol-15-hydroxystearic acid, and glycerin and propylene glycol Adding at least one humectant selected from the group to an aqueous solution in which it is dissolved and stirring to prepare a crude suspension; And (b) at least one surfactant selected from the group consisting of ethylene oxide-propylene oxide block copolymer, hydrogenated polyoxyl castor oil and polyethylene glycol-15-hydroxystearic acid in the crude suspension prepared in step (a); Adding and mixing the excipients dissolved in an aqueous solution in which at least one humectant is selected from the group consisting of glycerin and propylene glycol. The method of claim 9, The excipient of step (b) is a method for producing a pharmaceutical composition, characterized in that at least one selected from the group consisting of thickeners, pH adjusting agents, preservatives, artificial and natural sweeteners, flavoring agents, colorants, dispersants and solubilizers. The method of claim 10, The thickening agent is xanthan gum, guar gum, carboxymethyl cellulose, povidone, carrageenan, methyl cellulose, and the like.

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