KR20100122589A - Method for preparing novel alendronate emulsion dried product and pharmaceutical composition containing the same - Google Patents

Abstract

PURPOSE: A method for manufacturing a novel alendronate emulsion dry is provided to produce W/O/W type emulsion by simple process. CONSTITUTION: A method for manufacturing a novel alendronate emulsion dry comprises: a step of adding a solution containing 0.05-5 weight parts of alendronate and 0.05-5 weight parts of chitosan dissolved in 5-100 weight parts of water in a butanol solution in a volume ratio of 2:1-3:1 to prepare W/O type emulsion; a step of adding W/O type emulsion to a solution containing 0.5-2%(w/v) of polyvinyl alcohol solution and 0.7-1%(w/v) sodium chloride solution in a volume ratio of 2:1-10:3 to prepare W/O/W type emulsion; a step of compressing or concentrating the emulsion to remove butanol; a step of adding a solution containing 0.5-20%(w/v) of saccharide selected from a group consisting of mannitol, lactose and glucose in a volume ratio of 2:1-5:1; and a step of drying. A pharmaceutical composition for preventing and treating bone diseases contains alendronate emulsion dry as an active ingredient.

Description

Method for preparing novel alendronate emulsion dried product and pharmaceutical composition containing the same

The present invention relates to a method for preparing a novel alendronate emulsion dried product having improved bioavailability, and a pharmaceutical composition containing the same. The present invention provides fat-soluble by adding a positively charged substance to the negatively charged alendronate as an active ingredient, This is to improve the gastrointestinal side effects of Alendronate while increasing the bioavailability of oral administration of the active ingredient using an adhesive polymer and an enteric polymer, while having an excellent effect on the treatment and prevention of osteoporosis.

In general, solubility in water and permeability through the intestinal membrane have a significant effect on the absorption rate during oral administration of drugs (CA Lipinski, F. Lombardo, BW Dominy, P. Feeney, Experimental and computational approaches to estimate solubility and permeability in drug delivery and development setting, Adv. Drug Deliv. Rev. 46, 3-26, 2001). Drugs with high solubility and high permeability have high absorption in the intestinal tract. However, low solubility and high permeability result in a decrease in particle size of the drug (AB Straughn, MC Meyer, G. Raghow, K. Rotenberg, Bioavailability of microsize and ultamicrosize griseofulvin products in the case of visible drugs because of low absorption in the intestinal tract). man, J. Pharmacokinet.Biopharm. 8, 347-362, 1980), using lipids or surfactants (SA Charman, WN Charman, MC Rogge, TD Wilson, FJ Dutko, CW Pouton, Self-emulsifying drug delivery systems: formulation and biopharmaceutic evaluation of an investigational lipophilic compound, Pharm.Res . 9, 87-93, 1992), or the use of solid dispersions, including amorphous (C. Liu, J. Wu, B. Shi, Y. Zhang, T. Gao, Y. Pei, Enhancing the bioavailability of cyclosporin a using solid dispersion containing polyoxyethylene 40 stearate, Drug Dev.Ind . Pharm. 32, 115-123, 2006) . Increase the rate of drug absorption It can be.

Conversely, drugs with high solubility but low intestinal permeability are also to be overcome. Such drugs are generally listed in various ways to increase intestinal permeability. Method of inducing chemical reaction with fatty acids to impart fat solubility (T. Fujita, T. Fujita, K. Morikawa, H. Tanaka, O. Iemura, A. Yamamoto, S. Muranishi, Improvement of intestinal absorption of human calcitonin by chemical modification with fatty acids: synergistic effects of acylation and absorption enhancers, Int. J. Pharm. 134, 47-57, 1996), increasing drug absorption through H ⁺ / peptide cotransporter, one of the enteric active inlet transporters. Peptidyl derivatives (I. Tamai, T. Nakanishi, H. Nakahara, Y. Sai, V. Ganapathy, FH Leibach, A. Tsuji, Improvement of L-dopa absorption by dipeptidyl derivation, activating peptide transporter PepT1, J. Pharm Sci. 87, 1542-1546, 1998; HK Han, DM Oh, GL Amidon, Cellular uptake mechanism of amino acid ester prodrugs in Caco-2 / hPEPT1 cells overexpressing a human peptide transporter, Pharm.Res . 15, 1382-1386. , 1998), conjugation with specific peptides that can penetrate cell membranes (S. Futaki, Arginine-rich peptides: potential for intracelluar delivery of macromolecules and the mystery of the translocation mechanism, Int. J. Pharm. 245, 1-7, 2002), use of absorption enhancers (VHL Lee, Protease inhibitors and penetration enhancers as approaches to modify peptide absorption, J. Control. Release 13, 213-223, 1990), the use of additives that inhibit the intestinal active drug transporter such as p-glycoprotein (Q. Shen, Y. Lin, T. Handa, M. Doi, M. Sugie, K Wakayama, N. Okada, T. Fujita, A. Yamamoto, Modulation of intestinal p-glycoprotein function by polyethylene glycols and their derivatives by in vitro transport and in situ absorption studies, Int. J. Pharm. 313, 49-56, 2006), colon-specific drug delivery (M. Saffran, GS Kumar, C. Davariar, JC Burnham, F. Williams, DC Neckers, A new approach to the oral administration of insulin and other peptide drugs, Science 233, 1081-1084 , 1986) and mucoadhesive drug delivery (S. Sakuma, M. Hayashi, M. Akashi, Design of nanoparticles composed of graft copolymers for oral peptide delivery, Adv. Drug Deliv. Res. 47, 21-37, 2001) The method can thereby increase the absorption of the drug.

Currently developed bisphosphonate drugs are so polar that they do not penetrate the biological lipid membrane, and have a strong affinity with polyvalent metal ions such as calcium to form an insoluble complex when combined with them in vivo to be absorbed through the cell membrane in the digestive tract Is known to be difficult ( Br . J. Cancer 71, 67, 1995). In addition, since it is anionic in the small intestine at pH 6-8, it is difficult to absorb in the small intestine, so that most drugs have an absorption rate of less than 10%, and in particular, the absorption rate of sodium alindronate is reported to be less than 1% ( Clin. Pharmacol. Therapeutics 58,288-209, 1995).

In addition, Alendronate causes local irritation to the gastrointestinal mucosa of the upper gastrointestinal tract, causing side effects such as esophagitis, esophageal ulcers, and esophageal erosions. (PC De Groen, New Eng. J. Med. 335, 1016-1021, 1996; DO Castell, New Eng. J. Med. 335, 1058-1059, 1996; UA Liberman, New Eng. J. Med. 335 , 1060-1070, 1996).

Therefore, many formulation studies have been conducted to encapsulate drugs in biodegradable polymers in order to protect such alendronate from the external environment and increase biofilm affinity.

In Korean Patent 648515, a polymer solution prepared by dissolving and dispersing bisphosphonate in an aqueous solution containing a water-soluble polymer and a hydrophilic surfactant is prepared by adding a secondary organic solvent to a primary organic solvent containing a biodegradable polymer and a hydrophobic surfactant. Added to the prepared polymer solution to prepare a primary emulsion solution (W / O), and comprising a bisphosphonate-containing polymer microspheres prepared by dispersing the primary emulsion solution in an external continuous phase, having a sustained effect for treating or preventing bone-related diseases Described are inventions relating to injections. In addition, Korean Patent No. 709015 also describes the invention regarding the polymer microspheres capable of sustained drug release and its preparation method.

In addition, Korean Patent No. 631873 contains alendronic acid or a salt thereof and contains an absorption increasing agent and an absorption increasing auxiliary agent together to increase the bioavailability of the active ingredient by synergistic interaction with each other, thereby improving the treatment of osteoporosis and The invention relates to an alendronic acid preparation with enhanced bioavailability that can be expected to have a prophylactic effect.

In addition, US Pat. Nos. 6350471, 6676965 and EP 1296657 introduce a method of water-insoluble polymer membranes and enteric skin as a way to resolve the effects of alendronate, which is a side effect of acidic esophagitis.

In addition, the present inventors also use alendronate and a cationic material having a reverse charge in Patent Application No. 2008-42957 to form ion-to-compounds to impart fat solubility, and use a specific ratio of a mucoadhesive polymer and an enteric polymer. Multiemulsion methods have been developed to disclose alendronate formulations that can increase bioavailability.

However, the present inventors have attempted to develop an alendronate formulation having a higher bioavailability without producing a complex production process than the alendronate formulation of Patent Application No. 2008-42957, and further improving the bioavailability even without forming an ion-compound compound. The emulsion dry was developed to complete the present invention.

Accordingly, an object of the present invention is to enable the preparation of the W / O / W type emulsion in a simple process by using an aqueous solution of alendronate / chitosan, a polymethacrylate / butanol solution and a polyvinyl alcohol / sodium chloride solution composed of a specific blending ratio The present invention provides a novel alendronate emulsion dried product and a method for preparing the same which can improve the low bioavailability of alendronate and gastrointestinal side effects.

In order to achieve the above object, the present invention is prepared by adding the aqueous solution of (b) in a butanol solution of the following (a) 2: 1 to 3: 1 by volume and emulsified to prepare a W / O emulsion; To the aqueous solution of the following (c) to add the W / O emulsion in a volume ratio of 2: 1 to 10: 3 and emulsified to prepare a W / O / W emulsion; The W / O / W type emulsion was decompressed or concentrated to remove butanol, and the solution of the following (d) was added to the W / O / W type emulsion from which the butanol was removed in a volume ratio of 2: 1 to 5: 1 to uniformity. It provides a process for the preparation of novel alendronate emulsion dried, which is mixed well and dried;

(a) 0.5 to 10 parts by weight of polymethacrylates (polymethacrylates) solution dissolved in 5 to 100 parts by weight of butanol;

(b) a solution in which 0.05-5 parts by weight of alendronate and 0.05-5 parts by weight of chitosan are added to 5-100 parts by weight of water;

(c) a solution of 0.5-2% (w / v) polyvinyl alcohol solution and 0.7-1% (w / v) sodium chloride solution in the same amount; And

(d) 0.5-20% (w / v) aqueous solution of sugars selected from the group consisting of mannitol, lactose and glucose.

In addition, in order to achieve another object, the present invention provides an alendronate emulsion dried product prepared by the above method.

Furthermore, the present invention provides a pharmaceutical composition for preventing and treating bone diseases containing the emulsion dried product as an active ingredient.

Hereinafter, the present invention will be described in detail.

The present invention is to prepare a W / O / W type alendronate emulsion by using an aqueous solution of alendronate / chitosan, polymethacrylate / butanol and polyvinyl alcohol / sodium chloride solution, and then drying it to prevent and treat bone diseases Is to use.

In this case, incorporating chitosan into the drug water phase allendronate in the primary W / O emulsion, electrostatically neutralizes the anion of the allendronate, imparting retention in the body, improving absorption in the small intestine, and absorbing it from the digestive tract. This is because it increases the amount.

In addition, the organic phase of the primary W / O-type emulsions uses eudragit of polymethacrylate, an enteric polymer that dissolves above pH 6, to reduce the side effects of alendronate drugs that exhibit esophagitis and gastrointestinal ulcers. It is preferable. At this time, in order to increase the emulsification efficiency, it is preferable to use n-butanol rather than organic solvents such as acetone, ethanol, methanol, and the like which are frequently used.

A polyvinyl alcohol / sodium chloride aqueous solution is then used in the water phase of the secondary W / O / W type multiple emulsion to provide stability and the desired solidify of the emulsion. This serves to facilitate the stability and workability of the pharmaceutical formulation.

The preparation method of the alendronate emulsion dried product according to the present invention will be described in more detail by processes.

First step: preparing a solution for preparing the alendronate emulsion

(A) Preparation of polymethacrylate / butanol solution (organic phase)

0.5-10 parts by weight of polymethacrylates are added to 5-100 parts by weight of butanol and dissolved uniformly. It is based on 0.5 to 10 parts by weight of polymethacrylate. Butanol is less than 5 parts by weight, but polymethacrylate is not sufficiently dissolved. If it is used in excess of 100 parts by weight, butanol is removed when drying the W / O / W type emulsion. Since it is difficult to carry out, it is preferable to use it within the use range mentioned above.

At this time, the polymethacrylate in the present invention is to use an enteric base selected from the group consisting of Eudragit L 100, Eudragit L 12,5, Eudragit L 100-55 and Eudragit L 30D-55. desirable.

(B) Alendronate / Chitosan Aqueous Solution

0.05 to 5 parts by weight of alendronate and 0.05 to 5 parts by weight of chitosan are added to 5 to 100 parts by weight of water and dissolved uniformly. The use of the alendronate and chitosan in the range of 1: 100 to 100: 1 based on the weight of the chitosan to the efficacy of the alendronate appears, it is preferable to use the same amount to maximize the efficacy. In this case, it is preferable to dissolve the alendronate and chitosan in water of 20 to 100 times on a mixed weight basis in the formation of a W / O type emulsion of the drug water phase and the Eudragit organic phase. In addition, chitosan is the most excellent in the use of high molecular weight chitosan (10,000 ~ 40,000) molecular weight chitosan (molecular weight range is not limited to the embodiment) and improved bioavailability and electrostatic neutralization.

(C) Manufacture of polyvinyl alcohol / sodium chloride solution (water phase)

It is prepared by mixing the same amount of 0.5-2% (w / v) polyvinyl alcohol aqueous solution and 0.7-1% (w / v) sodium chloride aqueous solution. At this time, polyvinyl alcohol is used as a reemulsification and sodium chloride solidifies the suspension state of the emulsion, so that the originalization can be obtained solid, polyvinyl alcohol in the aqueous polyvinyl alcohol solution is 0.5% (w Using less than / v)% or more than 2% (w / v) results in poor W / O / W emulsion formation efficiency and less than 0.7% (w / v) or 1% (w) of sodium chloride in aqueous sodium chloride solution. When used in excess of / v), the solidification reaction is lowered or the salt concentration is high, and thus it is preferably used within the above-mentioned range of use.

(D) Preparation of sugar solution

A 0.5-20% (w / v) aqueous solution of sugar selected from the group consisting of mannitol, lactose and glucose is prepared. In the present invention, the sugar is used as an emulsion stabilizer, because the sugar protects the emulsion and inhibits aggregation of the emulsion during the process of freezing, sublimation, dehydration of the water during freeze-drying. At this time, in the present invention, when the sugar of less than 0.5% (w / v) is used, the above-described effect is insignificant, and if it is used in excess of 20% (w / v), the drying of the emulsion is hindered, therefore, within the above-mentioned range of use It is preferable to use.

Second Process: First W / O Type Alendronate Emulsion Manufacturing Process

(A) (1) Alendronate / chitosan aqueous solution is added and emulsified to the eudragit / butanol solution of the first step to prepare a primary W / O emulsion.

At this time, it is preferable to emulsify the mixture of the Eudragit / butanol solution and the Alendronate / chitosan solution in a volume ratio of 2: 1 to 3: 1 to efficiently form a W / O emulsion.

Third Process: Secondary W / O / W Type Alendronate Multiple Emulsion Manufacturing Process

The W / O type emulsion of the second step is added to the polyvinyl alcohol / sodium chloride aqueous solution of (C) of the first step and emulsified to prepare a W / O / W type emulsion.

At this time, it is preferable to emulsify the polyvinyl alcohol / sodium chloride aqueous solution and the W / O type emulsion in a volume ratio of 2: 1 to 10: 3 to efficiently form a W / O / W type emulsion.

4th process: organic solvent removal process

The butanol is removed by depressurizing or concentrating the W / O / W type emulsion of the third step.

5th process: drying process

To the W / O / W type emulsion from which the butanol of the fourth step is removed, an aqueous solution of sugar (d) of the first step is added, mixed uniformly, and dried.

At this time, it is preferable to mix and dry the W / O / W type emulsion from which butanol has been removed and the aqueous solution of sugar in a volume ratio of 2: 1 to 5: 1 in order to efficiently exhibit the emulsion stabilization effect of the aqueous solution of sugar, and the drying is an emulsion. It is preferable to carry out freeze drying in terms of the efficiency of the dry matter.

The bone disease used in the present invention is a metabolic bone disease, and refers to osteoporosis, Paget's disease, rickets disease, osteomalacia, nephrotic dystrophy, hyperparathyroidism and hypothyroidism of the renal convertor. This is because alendronate is well known for its prophylactic and therapeutic effects on the aforementioned bone diseases.

In addition, it is preferable that the content of the alendronate emulsion dried prepared according to the present invention is in the unit dosage form of 1 to 70 mg based on the alendronic acid, as is generally known. This is because it is the effective concentration of the previous alendronate formulation.

As described above, the present invention enables the preparation of a W / O / W type emulsion in a simple process by using an aqueous solution of alendronate / chitosan, a polymethacrylate / butanol solution and an aqueous solution of polyvinyl alcohol / sodium chloride, which are composed of a specific blending ratio. In addition, it is possible to provide a new allenronate formulation that can improve the problems such as low bioavailability of the alendronate and a decrease in the absorption rate in the gastrointestinal tract.

Hereinafter, the present invention will be described in more detail with reference to Examples. However, these examples are for illustrative purposes only, and the scope of the present invention is not limited to these examples.

Example 1

1. Butanol solution of polymethacrylate

5 g of Eudragit L100-55 was added to 100 ml of n-butanol (specific gravity: 0.811), and dissolved by stirring at room temperature for 30 minutes to prepare a polymethacrylate butanol solution of the present invention.

2. Alendronate / chitosan aqueous solution

0.5 g of Alendronate sodium hydrate was added to 50 ml of distilled water (specific gravity: 1), stirred for 30 minutes at 65 W 5 ° C, and dissolved. Then, 0.5 g of chitosan (MW 10,000 or more) was added and stirred for 20 minutes to dissolve. Chitosan aqueous solution was prepared.

3. Polyvinyl alcohol / sodium chloride solution

250 ml of 1% (w / v) polyvinyl alcohol solution and 250 ml of 0.9% (w / v) sodium chloride solution were mixed to prepare a polyvinyl alcohol / sodium chloride aqueous solution of the present invention.

4. Aqueous sugar solution

100 ml of 10% (w / v) D-mannitol aqueous solution was prepared.

Example 2

Eudragit 5g, n-butanol 100ml, Alendronate 5g, chitosan 5g, distilled water 50ml, 150ml of 1% polyvinyl alcohol solution and 150ml of 0.9% sodium chloride solution and 5% of D-mannitol in the same manner as in Example 1 Using 5 ml, a solution for preparing an alendronate emulsion according to the present invention was prepared.

Example 3

In the same manner as in Example 1, 0.5 g of Eudragit, 10 ml of n-butanol, 0.05 g of Alendronate, 0.05 g of chitosan, 5 ml of distilled water, 25 ml of 1% polyvinyl alcohol solution and 25 ml of 0.9% sodium chloride solution and 5% of D Using 5 ml of mannitol, a solution for preparing an alendronate emulsion according to the invention was prepared.

Example 4

The aqueous solution of Example 1-2 was slowly added to the butanol solution of Example 1-1 at 2: 1 to 3: 1 by volume and emulsified at 7,500 rpm for 10 minutes with a homogenizer at room temperature to prepare a W / O emulsion. The W / O type emulsion was slowly added to the aqueous solution of Example 1-3 at a volume ratio of 2: 1 to 10: 3 and emulsified at 7,500 rpm for 45 minutes with a homogenizer at room temperature to form a W / O / W emulsion. Prepared.

The W / O / W type emulsion was concentrated under reduced pressure at 50 ° C. of 80-100 mmhg with a rotary evaporator to remove butanol, and then the W / O / W type emulsion was removed. A solution of 1-4 was added at a volume ratio of 2: 1 to 5: 1, mixed uniformly, and lyophilized to prepare an alendronate emulsion dried product of the present invention. This was named N168.

Example 5

Using the solution of Example 2 in the same manner as in Example 4, to prepare the dried alendronate emulsion of the present invention. This was named N169.

Example 6

Using the solution of Example 3 in the same manner as in Example 4, to prepare the dried alendronate emulsion of the present invention. This was named N173 (or C116).

Example 7: refine

100 parts by weight of microcrystalline cellulose for direct hitting, 300 parts by weight of lactose, 27 parts by weight of sodium gluconate, and 3 parts by weight of magnesium stearate were added to the total 500 parts by weight including the dried Alendronate emulsion prepared in Example 6, followed by hardness. Tablets were made such that 9 Kp.

Experimental Example

1. Physical Properties

Alendronate content, yield, encapsulation rate, average particle size, zeta potential of each sample prepared in Examples 5 and 6 were measured. At this time, the content, yield and loading rate of the alendronate were analyzed using HPLC, and the analysis was performed as follows.

HPLC method

For liquid chromatography analysis of the encapsulation rate, prepare a test solution of 0.1 M sodium citrate (pH 7.65), 0.1 M sodium borate, Fmoc chloride first, and then take 13 mg of alendronate, add 50 ml of 0.1 M sodium citrate, and shake it slowly for 30 minutes. The mixture was mixed with 100 ml, and 6 ml of this solution was added, 0.1 M sodium citrate was added, and the filtrate was adjusted to 25 ml. Subsequently, an appropriate amount of this solution was taken and 0.1M sodium borate was added to contain 62.4 ug to 156 ug of alendronate. 4 ml of Fmoc chloride was added and mixed for 30 seconds, and left at room temperature for 25 minutes. Then, 25 ml of dimethylene chloride was added and shaken for 30 seconds, followed by centrifugation at 1500 rpm for 10 minutes to obtain a supernatant. The sample was injected at a flow rate of 1.5 ml / min using a column to be analyzed at a wavelength of 266 nm.

The results are shown in Table 1 below.

content(%) yield(%) Inclusion Rate (%) Zeta Potential (mV) Particle size (nm) N169 20.5 84.2 96.3 2.26 380 N173 2.7 87.9 52.2 4.94 475.6

In addition, each sample was fixed on a metal plate and filled with argon gas, which is an inert gas, and then subjected to a pretreatment process of coating with a thin gold foil. The surface was observed by Scanning Electron Microscopy (SEM).

The results are shown in FIG. 2A shows a picture of N169 and FIG. 2B shows a picture of N173.

2. Efficacy Experiment

end. in vivo

In order to demonstrate the efficacy of improving the bioavailability of the dried alendronate emulsion prepared according to the present invention, a method of analyzing urine using rats was used.

In the urine analysis method, after the oral administration of the alendronate sample was left for 24 hours while freely supplying water and feeding in the metabolic cage, the urine collected in the metabolic cage was analyzed to compare the absorption of the alendronate in the body.

As a result, as shown in FIG. 3, C116 (same as N173) has the highest bioavailability due to the highest absorption rate in the body (C113 to 115, C103, 104, P8 and F50 are completely different from N173). Manufacturing method, which is prepared by the method of the alendronate formulation described in Patent Application No. 2008-42957)

I. in vitro

Cell permeability experiments using monolayer epithelial cells using CaCo-2 cells were performed to analyze the relative permeability coefficient ( P app) relative to the conventional formulation and to compare it with bioavailability. At this time, metoprolol was used as a positive control drug, atenolol was used as a negative control drug, and the control drug was a F (alendronate sodium) formulation and a main ingredient material sold by D Company.

As a result, it was found that the dried alendronate emulsion according to the present invention showed superior drug permeation efficacy compared to the reference drug.

In addition, in accordance with the Comparative Dissolution Test of the Korea Food and Drug Administration Notice No. 2006-26, the device was tested for dissolution for 120 minutes with water (900 ml) at 50 rpm in accordance with the 2nd method (paddle method). , Company D's F formulation showed a dissolution rate of 100% at about 10 minutes, whereas N173 prepared according to the present invention showed a dissolution rate of about 50% at 20 minutes and a dissolution rate of 100% after 60 minutes. It could be confirmed (not shown).

As a result, in case of the F formulation, the drug is rapidly eluted, which is likely to cause gastrointestinal damage. However, the emulsion dried product of the present invention is delayed by 100% or more by 50% by the influence of Eudragit, an enteric coating base, and thus the esophagus and gastrointestinal tract. It is thought that the side effects of drug effects of alendronate can be minimized during the treatment.

1 is a schematic diagram briefly showing a process for producing an alendronate emulsion dried product according to the present invention.

2A and 2B show SEM images of an alendronate emulsion dried according to an embodiment of the present invention.

Figure 3 is a graph showing the body uptake of the alendronate emulsion dried in accordance with the present invention through the urine collection test of rats.

Claims (5)

To the butanol solution of (a), an aqueous solution of (b) was added 2: 1 to 3: 1 by volume and emulsified to prepare a W / O emulsion; To the aqueous solution of the following (c) to add the W / O emulsion in a volume ratio of 2: 1 to 10: 3 and emulsified to prepare a W / O / W emulsion; The W / O / W type emulsion was decompressed or concentrated to remove butanol, and the solution of the following (d) was added to the W / O / W type emulsion from which the butanol was removed in a volume ratio of 2: 1 to 5: 1 to uniformity. A method for preparing a novel alendronate emulsion dried product, characterized in that the mixing is carried out and drying it; (a) 0.5 to 10 parts by weight of polymethacrylates (polymethacrylates) solution dissolved in 5 to 100 parts by weight of butanol; (b) a solution in which 0.05-5 parts by weight of alendronate and 0.05-5 parts by weight of chitosan are added to 5-100 parts by weight of water; (c) a solution of 0.5-2% (w / v) polyvinyl alcohol solution and 0.7-1% (w / v) sodium chloride solution in the same amount; And (d) 0.5-20% (w / v) aqueous solution of sugar selected from the group consisting of mannitol, lactose and glucose. The method of claim 1, wherein the polymethacrylate is an enteric base selected from the group consisting of Eudragit L 100, Eudragit L 12,5, Eudragit L 100-55 and Eudragit L 30D-55. A process for producing a novel Alendronate emulsion dried product. The method of claim 1, wherein the chitosan has a molecular weight of 10,000 or more. Alendronate emulsion dried prepared by the method of claims 1 to 3. A pharmaceutical composition for preventing and treating bone diseases, comprising the dried substance of claim 4 as an active ingredient.

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