US 2011 0212169A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2011/0212169 A1 Bae et al. (43) Pub. Date: Sep. 1, 2011
(54) METHOD FOR PRODUCING POWDER A63/496 (2006.01) CONTAINING NANOPARTICULATED A63L/439 (2006.01) SPARINGLY SOLUBLE DRUG, POWDER A6II 3L/26 (2006.01) PRODUCED THEREBY AND A63L/92 (2006.01) PHARMACEUTICAL COMPOSITION A6IP 700 (2006.01) CONTAINING SAME (ASAMENDED) A6IP37/06 (2006.01) A6IPI/00 (2006.01) (75) Inventors: Joon-Ho Bae, Gyeonggi-do (KR): A6IP3 L/10 (2006.01) Hyeok Lee, Gyeonggi-do (KR): A6IP3/06 (2006.01) Deok-Ki Hong, Gyeonggi-do (KR): B29B 9/12 (2006.01) Jong-Hwi Lee, Seoul (KR) (52) U.S. Cl. ... 424/451; 424/400; 424/464; 514/254.07; (73) Assignee: Amorepacific Corporation, 514/291; 514/543; 514/568; 264/11 Yongsan-gu (KR) (57) ABSTRACT (21) Appl. No.: 13/127,957 Disclosed are a method for preparing a powder containing a nanoparticulated sparingly soluble drug, a powder prepared (22) PCT Filed: Nov. 10, 2009 thereby, and a pharmaceutical composition containing the same. The disclosed method includes: providing a uniformly (86). PCT No.: dispersed solution of a sparingly soluble drug which is formed into nanoparticles in the presence of a Surface stabi S371 (c)(1), lizer, mixing the uniformly dispersed solution with a water (2), (4) Date: May 5, 2011 soluble dispersant solution; and drying the mixed solution to obtain the powder. (30) Foreign Application Priority Data When the powder containing the nanoparticulated sparingly Nov. 10, 2008 (KR) ...... 102O080111205 soluble drug obtained by the disclosed method is redispersed in an aqueous solution, the sparingly soluble drug Publication Classification retains aparticle size in the nano scale while the solubility and (51) Int. Cl. the dissolution rate of the drug are increased, thereby provid A6 IK 9/14 (2006.01) ing enhanced bioavailability. Consequently, the present dis A6 IK 9/48 (2006.01) closure can be useful in the development of preparations of a A6 IK 9/20 (2006.01) sparingly soluble drug for oral or parenteral administration. Patent Application Publication Sep. 1, 2011 Sheet 1 of 3 US 2011/0212169 A1
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US 2011/0212169 A1 Sep. 1, 2011
METHOD FOR PRODUCING POWDER 0011. The sparingly soluble drug may be at least one CONTAINING NANOPARTICULATED selected, for example, from: a nonsteroidal anti-inflammatory SPARINGLY SOLUBLE DRUG, POWDER drug including acetaminophen, acetylsalicylic acid, ibupro PRODUCED THEREBY AND fen, fenbuprofen, fenoprofen, flurbiprofen, indomethacin, PHARMACEUTICAL COMPOSITION naproxen, etodolac, ketoprofen, dexibuprofen, piroXicam or CONTAINING SAME (ASAMENDED) aceclofenac; an immunosuppressantoratopic dermatitis drug including cyclosporin, tacrolimus, rapamycin, mycopheno TECHNICAL FIELD late or pimecrolimus; a calcium channel blocker including nifedipine, nimodipine, nitrendipine, nilvadipine, felodipine, 0001. The present disclosure relates to a method for pre amlodipine or isradipine; an angiotensin II antagonist includ paring a powder containing a nanoparticulated sparingly ing Valsartan, eprosartan, irbesartan, candesartan, telmisar soluble drug, a powder prepared thereby, and a pharmaceuti tan, olmesartan or losartan; a cholesterol synthesis-inhibiting cal composition containing the same. hypolipidemic agent including atorvastatin, lovastatin, simv astatin, fluvastatin, rosuvastatin or pravastatin; a cholesterol BACKGROUND ART metabolism- and secretion-promoting hypolipidemic agent 0002. A sparingly soluble drug which is poorly soluble in including gemfibrozil, fenofibrate, etofibrate or bezafibrate; water or a pharmaceutical composition containing the same an antidiabetic drug including pioglitaZone, rosiglitaZone or may exhibit low bioavailability upon oral administration metformin; a lipase inhibitor including orlistat; an antifungal since it may be excreted before being absorbed in the gas agent including itraconazole, amphotericin B, terbinafine, trointestinal tract. nystatin, griseofulvin, fluconazole or ketoconazole; a hepato 0003. Furthermore, since it is difficult to be prepared for protective drug including biphenyl dimethyl dicarboxylate, parenteral administration Such as injection, various co-sol silymarin or urSodeoxycholic acid; a gastrointestinal drug vents or Surfactants have to be used, which may cause side including Sofalcone, omeprazole, pantoprazole, famotidine, effects or poor patient compliance. itopride or mesalazine; an antiplateletagent including cilosta 0004 Although there have been attempts to prepare a Zolor clopidogrel; an osteoporosis drug including raloxifene; nanoparticulated sparingly soluble drug in order to improve an antiviral drug including acyclovir, famciclovir, lamivudine solubility in water and bioavailability of the sparingly soluble or oseltamivir; an antibiotic including clarithromycin, cipro drug, it is still difficult to improve bioavailability since the floxacin or cefuroxime; an antiasthmatic or antihistamine nanoparticles tend to aggregate when they are redispersed in drug including pranlukast, budesonide or fexofenadine; a an aqueous Solution. hormone drug including testosterone, prednisolone, estrogen, cortisone, hydrocortisone or dexamethasone; an anticancer drug including paclitaxel, docetaxel, paclitaxel derivatives, DISCLOSURE doxorubicin, adriamycin, daunomycin, camptothecin, etopo Technical Problem side, teniposide or buSulfan; salts thereof, and pharmaceutical derivatives thereof. Specifically, it may be at least one 0005. The present disclosure is directed to providing a selected from naproxen, tacrolimus, Valsartan, simvastatin, method for preparing a powder containing a sparingly soluble fenofibrate, itraconazole, biphenyl dimethyl dicarboxylate, drug, capable of improving solubility in water and bioavail silymarin, Sofalcone, pantoprazole, cilostazol, salts thereof ability of the sparingly soluble drug. and pharmaceutical derivatives thereof. 0006. The present disclosure is also directed to providing 0012 For example, the surface stabilizer may be at least a powder containing a sparingly soluble drug, which is pre one selected from sodium dodecyl sulfate, dioctyl sodium pared by the method. SulfoSuccinate, lecithin, phospholipid, polyoxyethylene Sor 0007. The present disclosure is also directed to providing bitan fatty acid ester, potassium Sorbate, poloxamer, propy a pharmaceutical composition including the powder. lene glycol, methyl cellulose, ethyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, Technical Solution hydroxypropyl methylcellulose, carboxymethyl cellulose, 0008. In one general aspect, the present disclosure pro benzethonium chloride, benzalconium chloride, sorbic acid, vides a method for preparing a powder containing a nanopar potassium Sorbate, benzoic acid, sodium benzoate, propylpa ticulated sparingly soluble drug, including: providing a uni raben, methylparaben, polyvinyl alcohol, polyvinylpyrroli formly dispersed solution of a sparingly soluble drug which is done, alginic acid and sodium alginate. The Surface stabilizer formed into nanoparticles in the presence of a Surface stabi may be used in an amount of about 0.0001-90 wt % based on lizer, mixing the uniformly dispersed solution with a water the weight of the sparingly soluble drug. soluble dispersant solution; and drying the mixed solution to 0013 The uniformly dispersed solution may have an obtain the powder. apparent viscosity ranging from 1 to 100,000 centipoises. 0009. The water-soluble dispersant may be at least one 0014. In another general aspect, the present disclosure Selected from carageenan, gelatin, agar, alginic acid, arabi provides a powder containing a nanoparticulated sparingly noxylan gum, f-glucan, guar gum, arabia gum, locust bean soluble drug, comprising: a sparingly soluble drug which is gum, pectin, starch, Xanthan gum, casein, glucomannan, formed into nanoparticles in the presence of a Surface stabi cyclodextrin, methylcellulose, chitosan, Xyloglucan and glu lizer; and a water-soluble dispersant; when the powder is ten. Specifically, it may be carageenan. redispersed in an aqueous solution, 10 to 90% of the particles 0010. The water-soluble dispersant solution may have a based on a particle size normal distribution curve have a concentration of about 0.1-5 wt %, and the water-soluble particle size ranging from 10 to 1,000 nm. Specifically, the 10 dispersant Solution may be used in an amount of about 0.01 to 90% of the particles may have a particle size of about 10 to 0.1 wt % based on the weight of the sparingly soluble drug. 400 nm based on the particle size normal distribution curve. US 2011/0212169 A1 Sep. 1, 2011
0015. In another general aspect, the present disclosure dipine or isradipine; an angiotensin II antagonist including provides a pharmaceutical composition comprising the pow Valsartan, eprosartan, irbesartan, candesartan, telmisartan, der containing the nanoparticulated sparingly soluble drug. olmesartan or losartan; a cholesterol synthesis-inhibiting 0016 A formulation of the pharmaceutical composition hypolipidemic agent including atorvastatin, lovastatin, simv may be granule, powder, syrup, liquid, Suspension, tablet, astatin, fluvastatin, rosuvastatin or pravastatin; a cholesterol capsule, troche or pill for oral administration, or transdermal metabolism- and secretion-promoting hypolipidemic agent agent, lotion, ophthalmic ointment, ointment, plaster, cata including gemfibrozil, fenofibrate, etofibrate or bezafibrate; plasm, cream, paste, Suspension, liquid, injection or Supposi an antidiabetic drug including pioglitaZone, rosiglitaZone or tory for parenteral administration. metformin; a lipase inhibitor including orlistat; an antifungal agent including itraconazole, amphotericin B, terbinafine, Advantageous Effects nystatin, griseofulvin, fluconazole or ketoconazole; a hepato protective drug including biphenyl dimethyl dicarboxylate, 0017. When the powder containing the nanoparticulated silymarin or urSodeoxycholic acid; a gastrointestinal drug sparingly soluble drug obtained by the method according to including Sofalcone, omeprazole, pantoprazole, famotidine, the present disclosure is redispersed in an aqueous solution, itopride or mesalazine; an antiplateletagent including cilosta the sparingly soluble drug retains a particle size in the nano Zolor clopidogrel; an osteoporosis drug including raloxifene; scale while the solubility and the dissolution rate of the drug an antiviral drug including acyclovir, famciclovir, lamivudine are increased, thereby providing enhanced bioavailability. or oseltamivir; an antibiotic including clarithromycin, cipro Consequently, the present disclosure can be useful in the floxacin or cefuroxime; an antiasthmatic or antihistamine development of preparations of a sparingly soluble drug for drug including pranlukast, budesonide or fexofenadine; a oral or parenteral administration. hormone drug including testosterone, prednisolone, estrogen, cortisone, hydrocortisone or dexamethasone; an anticancer DESCRIPTION OF DRAWINGS drug including paclitaxel, docetaxel, paclitaxel derivatives, 0018 FIG. 1 shows particle size distribution of the pow doxorubicin, adriamycin, daunomycin, camptothecin, etopo ders containing the drug prepared in Example 1 when redis side, teniposide or buSulfan; therapeutically equivalent salts persed in an aqueous solution, depending on the concentra thereof; and pharmaceutical derivatives thereof. tion of a carageenan Solution; 0026 Specifically, the sparingly soluble drug may be at 0019 FIGS. 2a and 2b show electron microscopic images least one selected from naproxen, tacrolimus, Valsartan, sim of the powders containing the drug prepared in Example 1 vastatin, fenofibrate, itraconazole, biphenyl dimethyl dicar when redispersed in the aqueous solution, when the concen boxylate, silymarin, Sofalcone, pantoprazole, cilostazol, salts tration of the carageenan solution is 0.1 wt % (2a) and 2 wt % thereof, and pharmaceutical derivatives thereof. (2b); and 0027. The particle size of the sparingly soluble drug used 0020 FIGS. 3a and 3b show atomic force microscopic in the step 1 is not particularly restricted. For example, the (AFM) images of the powders containing the drug prepared in sparingly soluble drug may be pretreated using a commonly Example 5 when redispersed in an aqueous solution, when the employed milling method Such as fragmentation or air jet concentration of the carageenan solution is 0.5 wt % (3a) and milling to form particles having an average particle size of 1 wt % (3b). less than 100 um, before conducting the step 1. 0028. The surface stabilizer serves to prevent aggregation MODE FOR INVENTION of the sparingly soluble drug particles. It can be any of phar 0021 Hereinafter, the embodiments of the present disclo maceutically acceptable organic or inorganic compounds sure will be described in detail. which are physically miscible with the sparingly soluble drug 0022. Step 1: Provision of Uniformly Dispersed Solution and the water-soluble dispersant but do not chemically react Containing Sparingly Soluble Drug them. 0023. In the step 1, an active ingredient, i.e. a sparingly 0029 Representative examples may include sodium dode soluble drug, is mixed with a surface stabilizer. Then, the cyl sulfate (SDS or SLS), dioctyl sodium sulfosuccinate, resulting mixture is ground and dispersed uniformly. lecithin, phospholipid, polyoxyethylene Sorbitan fatty acid 0024. In the present disclosure, the sparingly soluble drug ester (e.g., Tween), potassium Sorbate, poloxamer, propylene used as the active ingredient is not particularly restricted, but glycol, methyl cellulose, ethyl cellulose, hydroxymethyl cel may be an organic material which is sparingly soluble in a lulose, hydroxyethyl cellulose, hydroxypropyl cellulose, liquid dispersant. The liquid dispersant may be water or an hydroxypropyl methylcellulose, carboxymethyl cellulose, aqueous solution. Alternatively, it may be an alcohol oran oil. benzethonium chloride, benzalconium chloride, sorbic acid, “Sparingly soluble' as used herein means a solubility of 30 potassium Sorbate, benzoic acid, sodium benzoate, propylpa mg/mL or less, specifically, 10 mg/mL or less, more specifi raben, methylparaben, polyvinyl alcohol, polyvinylpyrroli cally, 0.1 mg/mL or less, in a liquid dispersant at room tem done, alginic acid, Sodium alginate, and a mixture thereof. perature. Specifically, it may be at least one selected from hydroxypro 0025 Specific examples of the sparingly soluble drug may pyl cellulose and poloxamer. include: a nonsteroidal anti-inflammatory drug including 0030. In the present disclosure, the surface stabilizer may acetaminophen, acetylsalicylic acid, ibuprofen, fenbuprofen, be used in an amount of 0.0001-90 wt %, specifically 0.01-50 fenoprofen, flurbiprofen, indomethacin, naproxen, etodolac, wt %, more specifically 0.1-20 wt %, based on the weight of ketoprofen, dexibuprofen, piroxicam or aceclofenac; an the sparingly soluble drug. immunosuppressant or atopic dermatitis drug including 0031 When grinding the mixture of the sparingly soluble cyclosporin, tacrolimus, rapamycin, mycophenolate orpime drug and the Surface stabilizer, water, an aqueous Solution or crolimus; a calcium channel blocker including nifedipine, a buffer solution may be used as a solvent. The solvent may nimodipine, nitrendipine, nilvadipine, felodipine, amlo contain an alcohol in an amount of less than 50% depending US 2011/0212169 A1 Sep. 1, 2011 on the properties of the sparingly soluble drug. The alcohol ing the sparingly soluble drug according to the present dis that may be employed in the present disclosure includes closure may include significantly decreased amount of an methyl alcohol, ethyl alcohol, propyl alcohol, etc., and a excipient and thus may improve patient compliance. mixture thereof. 0040 Step 3: Obtainment of Powder 0032. In the present disclosure, an aqueous solution con 0041. In the step 3, the mixed dispersion solution obtained taining the sparingly soluble drug and the Surface stabilizer is in the step 2 is dried by a commonly employed process to mixed and ground using mechanical energy to reduce the obtain powder. particle size of the sparingly soluble drug and homogenize the 0042. By evaporating water from the mixed dispersion dispersion. Solution through freeze drying, vacuum drying or hot air 0033. The grinding may be conducted by a commonly employed method, for example, by a wet grinding process drying, the powder of the present disclosure may be obtained. using a dispersion mill such as a ball mill, an oscillating mill, 0043. The powder obtained in accordance with the present a bead mill, etc., an ultrasonic irradiation process, a shearing disclosure retains the original particle size in the nano scale force grinding process, or the like. The processing tempera when the powder is redispersed in an aqueous solution Such as ture and processing time may be adjusted appropriately water or a buffer solution, and 10 to 90% of the particles based according to the kind of the sparingly soluble drug and onaparticle size normal distribution curve have aparticle size mechanical properties thereof. For example, the grinding of 10 to 1,000 nm, specifically 10 to 400 nm. may be conducted at room temperature, and the grinding time 0044 Since the powder prepared according to the present may be varied according to mechanical means and processing disclosure, in which the sparingly soluble drug, the Surface conditions. For example, ball milling may be conducted for 3 stabilizer and the water-soluble dispersant solution are uni days or longer when a low shear energy is used, and it may be formly mixed, stably retains the original particle size in the finished in several hours when a high shear energy is nano scale when redispersed in water oran aqueous solution, employed. it exhibits enhanced bioavailability without side effects 0034. The sparingly soluble drug may be formed into caused by impurities. The powder prepared according to the nanoparticles by the grinding. That is to say, the sparingly present disclosure may retain the particle size in the nano soluble drug may be ground Such that it exhibits a particle size scale at room temperature for 6 months or longer when redis distribution of 10 to 1,000 nm, specifically 10 to 400 nm, for persed in an aqueous solution, without aggregation. 10 to 90% of the drug particles determined based on a particle 0045. Furthermore, it can be stored easily since it is in size normal distribution curve. powder form, and it may be useful in the development of 0035. The uniformly dispersed solution obtained in the preparations for oral or parenteral administration. step 1 has an apparent viscosity ranging from 1 to 100,000 0046. The present disclosure further provides a pharma centipoises, specifically 10-50,000 centipoises, more specifi ceutical composition comprising the powder prepared cally 500-10,000 centipoises. As the processing time of the according to the present disclosure together with a commonly step 1 is longer, the particle size of the sparingly soluble drug employed pharmaceutically acceptable carrier. A formulation becomes Smaller and more uniform. of the pharmaceutical composition may be granule, powder, 0036 Step 2: Mixing of Uniformly Dispersed Solution syrup, liquid, Suspension, tablet, capsule, troche or pill for Containing Drug with Water-Soluble Dispersant Solution oral administration, or transdermal agent, lotion, ophthalmic 0037. In the step 2 of the present disclosure, the uniformly ointment, ointment, plaster, cataplasm, cream, paste, Suspen dispersed solution containing drug obtained in the step 1 is Sion, liquid, injection or Suppository for parenteral adminis mixed with the water-soluble dispersant solution for aiding in tration. dispersion by Stirring for several minutes to several hours so 0047. The examples and experiments will now be as to prevent aggregation of the drug during drying, maintain described. The following examples and experiments are for the particle size of the drug in the nano Scale even in the illustrative purposes only and not intended to limit the scope powderstate, and retain the particle size in the nano Scale even of the present disclosure. when redispersed in an aqueous solution. 0038. The water-soluble dispersant used in the present Example 1 disclosure may be a polymer material that dissolves well and is viscous in water, and is unharmful to the human body. Particle Size Variation of Drug Depending on Con Representative examples may include polysaccharides Such centration of Water-Soluble Dispersant Solution. In as carageenan, gelatin, agar, alginic acid, arabinoxylan gum, order to observe particle size variation of a drug f-glucan, guar gum, arabia gum, locust bean gum, pectin, depending on the concentration of a water-soluble Starch, Xanthan gum, casein, glucomannan, cyclodextrin, dispersant solution, naproxen (TCI Chem) was used methylcellulose, chitosan, Xyloglucan and gluten, etc. These as a sparingly soluble drug and a carageenan solution may be used alone or in combination. Specifically, carag was used as the water-soluble dispersant Solution. eenan, gelatin oralginic acid, etc. may be used among them. Most specifically, carageenan may be used. The water 0048 Specifically, hydroxypropyl cellulose (hereinafter soluble dispersant solution may have a concentration of 0.1-5 HPC, 0.33 g) and distilled water (22.67 g) were added to wt %, specifically 2-5 wt %. naproxen (2 g), and the mixture was wet ground at room 0039. The water-soluble dispersant solution may be used temperature for 5 days using Micro Jet Mill System (JE in an amount of 0.01-0.1 wt % based on the weight of the Powder, Korea). The resulting slurry mixture was mixed with sparingly soluble drug. Since the water-soluble dispersant a carageenan solution of the same amount. At this time, the Solution is capable of preventing aggregation of the sparingly concentration of the carageenan Solution was varied at 5,3,2, soluble drug and maintaining the particle size of the drug in 1, 0.5, 0.1 and 0 wt %. When the concentration was 0 wt %, the nano Scale even with a small amount, the powder contain distilled water was added instead of the carageenan solution. US 2011/0212169 A1 Sep. 1, 2011
The resulting mixture was frozen in a refrigerator and freeze dried for 24 hours using a freeze drier to obtain the desired TABLE 2 powder. Carageenan Average particle 0049. Each powder (0.01 g) was redispersed in distilled concentration (wt %) size (Lm) water (5 mL) and particle size was measured. The result is 3 0.23 (+0.06) shown in FIG.1. Electron microscopic images of the powders 2 0.21 (+0.06) when the concentration of the carageenan Solution was 0.1 wt 1 0.26 (+0.06) % and 2 wt % are shown in FIGS. 2a and 2b, respectively. The O.S 0.36 (+0.71) O (Comparative 22.2 (+16.1) redispersion was conducted by lightly shaking the mixture Example 2) with a hand. The particle size was measured under aqueous condition using a laser scattering particle size analyzer (LA 910, Horiba, Japan) (Mie & Fraunhofer, relative refraction 0055 As seen from Table 2, when the carageenan concen index=1). The resolving power of the ultrasonic disperser tration was 0 wt % (Comparative Example 2), the drug par used for the particle size measurement was 40 W (39 kHz), ticle size increased as compared to when freeze drying was and the speed of stirring and circulation was 340 mL/min. The performed (Comparative Example 1). In contrast, when cara particle size measurement was made after performing ultra geenan was used, the nano-scale particle size was retained Sonic dispersion for 1 minute. after the redispersion. 0050. When the slurry mixture obtained after the wet 0056
0068. As seen from Table 7, the nano-scale particle size TABLE 5 was retained after the redispersion for the different drugs when the carageenan Solution was used as the water-soluble Dispersant Freeze drying dispersant solution. concentration (wt %) Gelatin 5 0.16 (+0.05) 1. A method for preparing a powder containing a nanopar 3 0.13 (+0.06) ticulated sparingly soluble drug, comprising: 2 0.16 (+0.08) providing a uniformly dispersed solution of a sparingly 1 0.45 (+0.89) soluble drug which is formed into nanoparticles in the presence of a Surface stabilizer; 0062. As seen from Tables 4 and 5, when the gelatin or mixing the uniformly dispersed solution with a water alginic acid solution was used as the water-soluble dispersant Soluble dispersant solution; and Solution, the nano-scale particle size was retained after the drying the mixed solution to obtain the powder. redispersion for the different drying methods. 2. The method according to claim 1, wherein the water soluble dispersant is at least one selected from carageenan, Example 4 gelatin, agar, alginic acid, arabinoxylan gum, f-glucan, guar gum, arabia gum, locust bean gum, pectin, starch, Xanthan Particle Size Variation of Drug Depending on Drug gum, casein, glucomannan, cyclodextrin, methylcellulose, Concentration chitosan, Xyloglucan and gluten. 0063 Powders were prepared in the same manner as in 3. The method according to claim 2, wherein the water Example 1, except for increasing the concentration of soluble dispersant is carageenan. naproxen to 16 wt % and changing the carageenan concen 4. The method according to claim 1, wherein the water tration to 1 and 0.5 wt %. soluble dispersant solution has a concentration of 0.1-5 wt %. 0064. The obtained powders were redispersed in distilled 5. The method according to claim 1, wherein the water water and drug particle size was measured in the same manner soluble dispersant solution is used in an amount of 0.01-0.1 as in Example 1. The result is given in Table 6. wt % based on the weight of the sparingly soluble drug. 6. The method according to claim 1, wherein the sparingly TABLE 6 soluble drug is at least one selected from: a nonsteroidal anti-inflammatory drug including acetaminophen, acetylsali Carageenan Average particle cylic acid, ibuprofen, fenbuprofen, flurbiprofen, indometha concentration (wt %) size (Lm) cin, naproxen, etodolac, ketoprofen, dexibuprofen, piroxicam 1 0.22 (+0.07) or aceclofenac; an immunosuppressant or atopic dermatitis O.S 0.56 (+1.20) drug including cyclosporin, tacrolimus, rapamycin, myco phenolate or pimecrolimus; a calcium channel blocker 0065. As seen from Table 6, the nano-scale particle size including nifedipine, nimodipine, nitrendipine, nilvadipine, was retained after the redispersion even when the drug con felodipine, amlodipine or isradipine; an angiotensin II centration was increased. Furthermore, the redispersed dried antagonist including Valsartan, eprosartan, irbesartan, cande nanoparticle powders were observed by atomic force micros Sartan, telmisartan, olmesartan or losartan; a cholesterol Syn copy (AFM). As seen from FIGS. 3a and 3b, the nano-scale thesis-inhibiting hypolipidemic agent including atorvastatin, particle size was retained after the redispersion. lovastatin, simvastatin, fluvastatin, rosuvastatin or pravasta tin, a cholesterol metabolism- and secretion-promoting hypo Example 5 lipidemic agent including gemfibrozil, fenofibrate, etofibrate or beZafibrate; an antidiabetic drug including pioglitaZone, Particle Size Variation of Drug Depending on Kind rosiglitaZone or metformin; a lipase inhibitor including orl of Drug istat; an antifungal agent including itraconazole, amphoteri cin B, terbinafine, nystatin, griseofulvin, fluconazole or keto 0066 Powders were prepared in the same manner as in conazole; a hepatoprotective drug including biphenyl Example 1, except for using itraconazole (Pacific Pharma), dimethyl dicarboxylate, silymarin or urSodeoxycholic acid; a tacrolimus (Pacific Pharma), fenofibrate (Sigma) and sofal gastrointestinal drug including Sofalcone, omeprazole, pan cone (DaeHee Chemical) and changing the carageenan con toprazole, famotidine, itopride or mesalazine; an antiplatelet centration to 5 wt %. agent including cilostazol or clopidogrel, an osteoporosis 0067. The obtained powders were redispersed in distilled drug including raloxifene; an antiviral drug including acyclo water and drug particle size was measured in the same manner Vir, famciclovir, lamivudine or oseltamivir; an antibiotic as in Example 1. The result is given in Table 7. including clarithromycin, ciprofloxacin or cefuroxime; an antiasthmatic or antihistamine agent including pranlukast, TABLE 7 budesonide or feXofenadine; a hormone drug including test osterone, prednisolone, estrogen, cortisone, hydrocortisone Average particle or dexamethasone; an anticancer drug including paclitaxel, Drugs size (Lm) docetaxel, paclitaxel derivatives, doxorubicin, adriamycin, Itraconazole 0.11 (+0.06) daunomycin, camptothecin, etoposide, teniposide or busul Tacrolimus 0.16 (+0.09) Fenofibrate 0.16 (+0.09) fan; salts thereof; and pharmaceutical derivatives thereof. Sofalcone 0.32 (+0.11) 7. The method according to claim 6, wherein the sparingly soluble drug is at least one selected from naproxen, tacroli mus, Valsartan, simvastatin, fenofibrate, itraconazole, biphe US 2011/0212169 A1 Sep. 1, 2011 nyl dimethyl dicarboxylate, silymarin, Sofalcone, pantopra a sparingly soluble drug which is formed into nanoparticles Zole, cilostaZol, salts thereof and pharmaceutical derivatives in the presence of a Surface stabilizer, and thereof. a water-soluble dispersant, 8. The method according to claim 1, wherein the surface wherein 10 to 90% of the particles based on a particle size stabilizer is at least one selected from sodium dodecyl sulfate, normal distribution curve have a particle size ranging dioctyl sodium Sulfo Succinate, lecithin, phospholipid, poly from 10 to 1,000 nm when the powder is redispersed in oxyethylene Sorbitan fatty acid ester, potassium Sorbate, an aqueous solution. poloxamer, propylene glycol, methyl cellulose, ethyl cellu 12. The powder according to claim 11, wherein 10 to 90% lose, hydroxymethyl cellulose, hydroxyethyl cellulose, of the particles based on the particle size normal distribution hydroxypropyl cellulose, hydroxypropyl methylcellulose, curve have a particle size ranging from 10 to 400 nm when the carboxymethyl cellulose, benzethonium chloride, benzalco powder is redispersed in the aqueous solution. nium chloride, Sorbic acid, potassium Sorbate, benzoic acid, 13. A pharmaceutical composition comprising the powder Sodium benzoate, propylparaben, methylparaben, polyvinyl of claim 11 together with a pharmaceutically acceptable car alcohol, polyvinylpyrrolidone, alginic acid, and Sodium algi rier. nate. 14. The pharmaceutical composition according to claim 9. The method according to claim 1, wherein the surface 13, wherein the formulation of pharmaceutical composition stabilizer is used in an amount of 0.0001-90 wt % based on the is granule, powder, syrup, liquid, Suspension, tablet, capsule, weight of the sparingly soluble drug. troche or pill for oral administration; or transdermal agent, 10. The method according to claim 1, wherein the uni lotion, ophthalmic ointment, ointment, plaster, cataplasm, formly dispersed solution has an apparent viscosity ranging cream, paste, Suspension, liquid, injection or suppository for from 1 to 100,000 centipoises. parenteral administration. 11. A powder containing a nanoparticulated sparingly soluble drug, comprising: c c c c c