JP2002284703A - Powder pharmaceutical preparation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a drug form capable of facilitating the dissociation of a carrier and drug particles and improving the transfer ratio to mucosal tissues such as bronchus and lungs. SOLUTION: This powder pharmaceutical preparation is obtained by mixing fine particles containing a drug with a sugar alcohol as a carrier having an aerodynamically acceptable particle diameter.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a carrier-based powder formulation, and more specifically, to use a sugar alcohol containing erythritol and / or sorbitol, which are low-hygroscopic and low-adhesive compounds, as a carrier. it relates powder formulation.

[0002]

2. Description of the Related Art Inhalation therapy is used as a method of using respiratory drugs for the treatment of respiratory tract diseases, as well as for the diagnosis of diseases, systemic administration of drugs to the respiratory tract, prevention of illness, and transrespiratory immunity desensitization therapy. . However, in any case, the method for determining the indication of this therapy has not been sufficiently studied, and the development of a corresponding inhalant is being demanded. In applying it as a targeting therapy, it is necessary to consider not only the efficacy of the inhalation agent for the disease but also the method of generating and reaching the drug particles, and the relationship between these and the basic physical properties of the drug. At present, aerosol inhalation therapy is widely used as this type of drug. Actually, bronchodilators, mucolytic agents, antibiotics, antiallergic agents, steroids, vaccines, physiological saline, etc. are used.In the case of these clinical applications, the site of action of inhalants,
Mechanism of action, such as the composition and usage is considered an important factor.

[0003] In recent years the treatment of bronchial asthma and chronic obstructive pulmonary disease, powder inhalers (DryPowder Inhaler, DP
I) has come to the spotlight. Inhalants also include the aforementioned aerosols (quantitative nebulizer, Metered Do
se Inhaler, there is MDI) and nebulizer dosage, these drugs can and has a surface area of about lung the targeted site is comparable to the small intestine, after absorption, such as no first-pass effect It has many excellent properties. It is recognized that the characteristics of general inhalants include 1) rapid onset of drug efficacy, 2) gradual reduction of side effects, 3) administration of small doses, and 4) avoidance of first-pass effects.

[0004] MDI as described above is widely used, although vigorously research still being carried out, since it is necessary to use chlorofluorocarbons as a propellant, environmental problems have been pointed out. Although alternatives to CFCs have been developed to solve this problem, DPIs that do not require CFCs and are more portable are being actively developed. Nebulizer also have a problem that must be stored in a device with the drug in solution, believed Therefore not suitable for unstable drugs, there can be in a stable form drug DPI
Is one of the useful preparations also for long-term stability.

[0005] DPI is classified into capsule type, blister type, reservoir type and the like according to the packaging form. In the case of administration of DPI, an inhalation hole is usually opened in a capsule or the like by a device operation to take out the medicine packaged in these, and the drug is released by the inhalation operation and is administered to a bronchus, a lung, or the like.

[0006] In DPI, there is a close relationship between the particle size of drug particles inhaled by patients and deposition in the respiratory tract [Pharmacia
(1997) Vol. 33, No. 6, there is 98-102], aerodynamic correlation has been observed that what drug particle size are deposited within the trachea and lungs. It is generally known that the optimal size of a drug particle that can reach the bronchial or alveoli site is a particle having an aerodynamic diameter of about 1 to 6 μm [Int. J. Pharm. (1994) 101, 1-13]. Number μm particles reach the lung alveoli, to migrate in the blood is absorbed from efficiently pulmonary mucosa, particularly the particle size is important in the case of expected systemic effects.

However, easily cause aggregation due to various factors if fine particles are also reduced fluidity. Therefore, today a carrier-using formulations that are commonly used in the formulation design of powder inhalers, which is micronized by known techniques a composition comprising an agent is a jet mill and many other reports, the carrier By mixing the particles, a group of particles having a relatively large particle size is obtained, whereby the fluidity is improved, and furthermore, the handling is improved in filling capsules and the like. However carriers are often used in the formulation design is provided in the medical field as reality typically absorb moisture easily, and low dissociation constant of the drug and the carrier has high adhesion to the drug, yet in the device The transfer rate to the lung is low due to the adhesion of the preparation, and the place where the preparation is deposited is in the throat, and in the case of a drug that has a very bad taste for some drugs and has a throat mucous membrane stimulating action, it becomes possible to give a great deal of burden to. The reality is that lower bioavailability can result in higher dosages of the dosage, which can also put more economic burden on the patient. Conventionally, compounds such as lactose have been used as carriers. However, it is difficult to generate a good aerosol for some drugs, the lung coverage is extremely low, and deposition in the throat cannot be avoided. However, it was still insufficient for the development of a formulation for the purpose. Therefore, there is a need for a pharmaceutical design that can solve these problems in medical economics.

[0008]

An object of the present invention is to develop a drug form which facilitates dissociation of a carrier and drug particles and improves the rate of transfer to mucosal tissues such as bronchi and lungs. Yes, this prevents accumulation in mucosal tissue and suppresses local irritation.

[0009]

Means for Solving the Problems The inventors of the present invention have conducted intensive studies in order to solve the above-mentioned problems, and as a result, after producing fine particles containing a drug by a pulverizer such as a jet mill, containing the obtained drug. By mixing the fine particles with a low-hygroscopic and low-adhesive compound such as erythritol as a carrier, we succeeded in preventing the occurrence of a strong bond between the drug and the carrier,
The present invention has been completed. Furthermore, at this time, by using erythritol as an excipient, it was possible to obtain various further synergistic effects.

That is, the present invention provides the following (1) to (7)
I will provide a. (1) A powder preparation obtained by mixing fine particles containing a drug with a sugar alcohol as a carrier having an aerodynamically acceptable particle size. (2) a sugar alcohol is erythritol and / or sorbitol, powder formulation according to (1). (3) powder formulation are inhalants or nasal preparations, powder formulation according to claim 1 or 2. (4) The powder preparation according to any one of the above (1) to (3), wherein the particle size of the carrier is in the range of 10 to 200 µm. (5) The above (1) to (1), wherein the fine particles further contain an excipient.
Powder formulation according to any one of (4). (6) The powder preparation according to the above (5), wherein the excipient is erythritol. (7) The ratio of the fine particles to the carrier is 1: 100 to 10: 1
The powder preparation according to any one of the above (1) to (6), wherein

[0011]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail. [1] Drug The drug used in the present invention is not particularly limited, and includes drugs used as medicaments or used in the future. Drugs include those that can be obtained in powder form and those that can be processed into powder form by processing such as grinding. The shape and particle size of the drug that can be used in the present invention are not particularly limited, but the present invention can be used effectively when the drug has self-aggregation ability due to intermolecular interaction. As a drug having a self-aggregating ability by intermolecular interaction, for example, glucagon [J. Biol. Chem.
984) 259, 7031-7], FGF [Biochem. J. (1999) 341, 61
3-20], growth hormone [Biochemistry (1993) 32, 1555-6
2], endothelin [Pept. Res. (1992) 5, 97-101], calcitonin [Biochem. Biophys. Res. Commun. (1998) 2
45, 344-8], insulin [Int. J. Pharm. (1999) 191,
51-64] glucagon-like peptide -1 [Pharmaceutical Res
earch (1998) 15, 254-62]. Further, particularly preferably in the present invention, the agent is intended for very dose is very small, it is difficult that uniform mixing for preparation. For example, but not limited to, a series of angiotensin converting enzyme inhibitors, LH-RH, ACTH, Caerulein, CCK, salmon calcitonin, EG
F, G-CSF, GM-CSF, oxytocin, neurotensin,
Ghrelin, PTH, PTHrP, somatostatin, V
IP, PACAP, vasopressin, enkephalin, endorphin, dynorphin, substance P, β-NGF, T
GF-β, erythropoietin, interferon α, β, or γ, interleukin, tumor necrosis factor, GHRF, c-
The present invention can be used for immunosuppressants such as GRP, ANP, CRF, secretin, and cyclosporin, and for a series of serine proteases such as α-MSH, thrombin and plasmin, or derivatives containing agonists and antagonists thereof. Also, it is possible to utilize the present invention formulated as direct administration of pulmonary diseases such as lung, lung pneumothorax.

Although peptides and proteins are very expensive, they have been shown to aggregate under specific conditions including high concentration conditions. For example, calcitonin described above has a concentration of 50 mg / mL or more. Self-aggregation at concentrations has been observed. Hydrogen bonds, hydrophobic interactions and many other interactions are observed in the group of peptidic and proteinaceous compounds, and it has been pointed out that physicochemical denaturation such as aggregation or sedimentation can occur during production. It is also possible to prevent them beforehand.

The present formulation design is also effective for steroids and β-stimulants which do not have a desired systemic action, or drugs which are desired to have a local action in the bronchus. It can be used for many drugs for which home treatment is desired as an effective administration method. It is widely available as a non-peptide proteinaceous drug, specifically anti-inflammatory steroid or non-steroidal anti-inflammatory agents, analgesics, anti-inflammatory agents, sedatives, treating depression agents, antitussive expectorants, antihistamines, antiallergic agents, antiemetics , Sleeping pills, vitamins, sex steroid hormones, antineoplastics, antiarrhythmics, hypertensives, anxiolytics, psychotropics, antiulcers, inotropics, analgesics, bronchodilators, obesity treatments, Examples include antiplatelet aggregating drugs, diabetes drugs, muscle relaxants, migraine drugs, antirheumatic drugs, and the like, and these can be used alone or in combination.

[2] Excipient In the present invention, it is often advantageous to use a drug together with an excipient to form fine particles containing the drug. This is because it is difficult to uniformly mix the carrier and the fine particles when preparing a preparation having an extremely low drug content. It is also possible to inhibit aggregation due to the interaction between drugs, but this is not limited as long as the drug amount is relatively large and the aggregation is low. As used herein, the term “fine particles” refers to fine particles of a drug or fine particles of a drug and an excipient.

[0015] Usually, excipients powders, increase of the solid preparation such as tablets, diluted, fill, which is added for the purpose of complement form, greatly affects the release characteristics of the agent, the the selection or change Note require. In the present invention, excipients are effective to increase drug solubility and / or reduce self-aggregation ability. Therefore, a water-soluble excipient is preferable as the excipient. In the present invention, excipients, commonly used starches, lactose, glucose, sucrose, crystalline cellulose, calcium sulfate, calcium carbonate, talc, titanium oxide and the like are used. There, and may also be used, which is expected to some extent metabolism. Other, erythritol, trehalose, sucrose, methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, carmellose sodium, pullulan, dextrin, gum arabic, agar, gelatin, tragacanth, sodium alginate, polyvinylpyrrolidone, polyvinyl alcohol, fatty acids such as stearic acid or a salt thereof, may be used, such as waxes.

In the powder preparation according to the present invention, a particularly preferred excipient is erythritol. The use of erythritol as an excipient, dissociation of fine particles and a carrier comprising an agent becomes easier. This is believed to be useful effect obtained by improving the properties of the whole fine particles by the nature of the low adhesion of erythritol.

[3] Carrier In the present invention, the carrier is used to prevent agglomeration of the drug until the administration of the powder formulation, and at the time of administration, to separate efficiently at the time of inhalation operation using an inhaler to enhance absorption efficiency. use. When using carrier DPI formulation design, drug is reliably released from the capsule or device, it is desirable that the drug is separated with high probability from the support surface, it is necessary to formulations designed with full consideration. Prevention of fluidity and drug aggregation of formulation in use of the carrier, such as the propriety of dose increase or decrease is important. Therefore, toxicity and physicochemical stability, as well as easiness and workability in handling, are required as selection criteria for the carrier.In the present invention, erythritol and sugar alcohols containing sorbitol are used as carriers. For example, compounds having low hygroscopicity and low adhesion can be used. Other sugar alcohols, for example xylitol, mannitol, maltitol, reduced palatinose, and lactitol, and the like, without limitation in the present invention. Carriers that can be used in the powder formulations of the present invention are those that have an aerodynamically acceptable particle size. Specifically, the particle size of the carrier is in the range of 10 to 200 [mu] m.

A particularly preferred carrier in the present invention is erythritol. The dissociation of erythritol from the drug is extremely easy, and as a result, it is possible to present a high target tissue transfer rate, and the accumulation in the throat is small, and thus the burden felt by the user on the taste quality of the contained drug. There is reduced. Although so that the carrier remains in the throat in the formulation design, of concern at that time is a foreign body sensation caused by this product. However, erythritol is very soluble, and its effect is such that it is used for orally disintegrating tablets (Japanese Patent Application Laid-Open No. 09-316006). It is possible to eliminate it. To further enhance the tissue penetration rate of the formulation, it is possible to lower than the other pharmaceutical formulations The drug content in the formulation, economic burden this is by inducing a reduction in the manufacturing cost of the patient it is possible to reduce the. In addition, the high sweetness of this compound
Although the highest among many sugar alcohol it is 75 and the erythritol is 100, thereby it is possible to improve the taste of the deposited formulation at the throat. The taste improvement is not only due to the sweetness of mere erythritol can be expected further effect by bitterness-masking effect that is observed in the compound (JP 10-306038). In addition, it is considered that the present compound which does not cause the Maillard reaction prevents the deterioration of the preparation such as coloring and the like, and the appearance of the preparation is less likely to be impaired. Inhaled preparations are often developed not for in-hospital treatments but rather for home medical treatment. Because of their necessity, they can be applied to diabetes drugs, but erythritol has an energy value (kcal / 100 g)
Is almost zero and has very little effect on blood sugar levels, so that it can be used continuously for a long period of time against this disease. Further, in the administration of inhalation, it is falling into whether anxiety preparations are really laid, in case of inhalation of erythritol there is a clear cool feel, confirm the effect of the formulation by inhalation the perceived coolness it is possible to.

The preparation using the present compound has extremely low hygroscopicity compared to the preparation using a lactose carrier, and it is considered that it can be used clinically regardless of the climate. The ratio of the fine particles to the carrier according to the invention is 1: 100
10: is preferably 1 range. If the number of fine particles is larger than this range, the uniformity of the content may be impaired, and if the number of carriers is large, there is a risk that some drugs may lose pharmacological activity.

[0020] [4] for the production of fine particles including mixing and grinding step medicament drug and excipients is first necessary micronized drug or drug and excipient. When a drug and an excipient are contained, a step of mixing and pulverizing the drug and the excipient is included. The pulverization is performed, for example, by pulverizing a dry product obtained by freeze-drying a drug or a solution or suspension of a drug and an excipient. Alternatively, the drug or drug and excipient may be mixed directly ground and by aerodynamic grinder. The method for producing the fine particles according to the present invention is not particularly limited, and a method commonly used by those skilled in the art can be appropriately used. Examples of such a method include a spray-dry method for converting a solution state into a powder and a method using a supercritical fluid. The former is a technique that has been used since ancient times, the latter is one of the relatively new concept has become in recent years to obtain particular attention. For the preparation of drug particles using supercritical fluid, PCA method (precipitation wi
th compressed antisolvent), rapid expan
sion of supercritical fluid solutions (RESS) and GA
There are the S method (gas antisolvent) and the like, but the PCA method has recently attracted attention. In this method, a drug is dissolved in dimethyl sulfoxide (DMSO) and sprayed into supercritical CO ₂ to produce a fine powder. Even proteins can be used in this method, for example Winter
s and colleagues target P for lysozyme, trypsin, and insulin.
Fine particle powder (15 μm) is prepared by the CA method [J. P.
harm. Sci. (1996) 85, 586]. Which method is used to produce the fine particles according to the present invention can be appropriately determined depending on the types of the drug and the excipient, the final particle size, and the like.

In the present invention, although the crushing of the drug or drug and excipient conventional drying milling can be used,
In particular, it is preferable to use an aerodynamic crusher. Specifically, as a general dry pulverizer, a device for efficiently pulverizing a small amount such as a mortar or a ball mill for a laboratory is widely used. Rolling ball mills, centrifugal ball mills, vibrating ball mills, and planetary ball mills are known as ball mills, and these can be pulverized based on principles such as grinding, rotation, vibration, and impact. For industrial use, there are many apparatuses for efficiently pulverizing a large amount of raw materials, such as a medium stirring mill, a high-speed rotary grinding / impact mill, and a jet mill. High-speed rotary grinding mills include disc mills and roller mills. High-speed rotary impact mills include milling by shearing force in addition to rotary impact such as a cutter mill (knife mill), hammer mill (atomizer), pin mill, and screen mill. There is something to do. Many jet mills mainly perform pulverization by impact, and the types include the most orthodox particle-particle collision type, particle-collision plate collision type, and nozzle suction type (blowing) type. This grinding process, micronized drug or drug and excipient, easily separated from the carrier after administration, fine particles such as can reach the target site of bronchial or pulmonary 胞等 is obtained.

[0022] [5] carrier and fine particles mixing process obtained above mixing and grinding step of fine particles, then mixed with a carrier, so as to form a stable complex until administration. For mixing the carrier and the fine particles, a generally known mixer can be used. There are mainly a batch type and a continuous type, and the batch type further includes two types, a rotary type and a fixed type. Rotary types include horizontal cylindrical mixers, V-type mixers, double-cone type mixers, and cubic mixers. Fixed types include screw-type (vertical and horizontal) mixers, rotating screw-type mixers, and ribbons. There are type (vertical, horizontal) mixers. The continuous type is also divided into two types, a rotary type and a fixed type. The rotary type is a horizontal cylindrical mixer, a horizontal conical mixer, and the fixed type is a screw type (vertical and horizontal) mixer, a ribbon type (vertical, horizontal) mixers, rotary disc type mixers are known. In addition, medium-stirring type mill, high speed milling, impact milling, mixing method and using aerodynamic grinder such as a jet mill, using a bag made of properties equivalent to nylon property or even by stirring It is possible to make a homogeneous mixed preparation.

[0023] [6] powder formulations of the present invention obtained in route above process, pulmonary administration, by transmucosal administration, such as nasal administration, can be administered to a subject. Specifically, where the route of administration is pulmonary administration, it can be administered using any inhaler used in the art. Spin inhalers,
Ihera, FlowCaps, jet Heller, Diskhaler, rotor Hastings Ra, inspired Ys, may be to use the device for inhalation transpulmonary such in-halation Eight and quantitative sprayer or the like, but is not limited thereto.

[0024]

EXAMPLES cited examples the invention will now be described more specifically, but the present invention is not limited thereto. [Example 1] Preparation of powders of various compounds All of the compounds were pulverized by the same method using an aerodynamic crusher. Grinding conditions Equipment used: AO-Jet Mill (Seishin company) Raw material supply method: Auto feeder Supply air pressure: 6.0 kg / cm ² G Grinding air pressure: 6.5 kg / cm ² G Dust collection method: Outlet bug (polyethylene) Te, glucagon, salmon calcitonin, lactose diluent or erythritol dilutions of insulin, or theophylline, to prepare a pulverized tranilast, the average particle size of about 70 [mu] m erythritol carrier or lactose carrier, (average particle size of about 50 [mu] m) It was mixed with uncharged bag Te
([Micronized material] / [325M] = 0.4). Each yields about 5-7
Was split.

Example 2 Release Characteristics of Glucagon Formulation The glucagon formulation prepared in Example 1 was subjected to a U-cascade impactor as an artificial airway and lung model.
Analysis was performed according to the method described in the SP, and the dispersibility and tissue reach of various samples were examined. The cascade impactor is a stack of eight stages and a final filter, combined with a current meter and a suction pump. The basic method USP No. 2000 "Physical Test
s and Determinations / Aerosols "Medium" Multistage Casc
ade Impactor Apparatus "was applied technique described. The specific method is as follows.

Cascade impactor analysis method apparatus: Under-Sensampler (AN-200, manufactured by Shibata Chemical) Pump flow rate: 28.3 L / min Specimen: Glucagon lactose dilution + lactose carrier Glucagon lactose dilution + erythritol carrier Glucagon erythritol dilution + lactose carrier glucagon erythritol dilutions + erythritol carrier filled with these formulations a day station two items capsules were analyzed using the following devices. Device used: Jet Heller (Unisia Jex Inc.)

[0027] was quantified glucagon amount trapped in each stage in the HPLC analysis condition cascade impactor analyzed by HPLC under conditions shown below. Column: TOSO ODS-120 T (Tosoh) Detector: RF-535 (Shimadzu) Pump: LC-10 AD (Shimadzu) Excitation wavelength: 280 nm Fluorescence detection wavelength: 346 nm Mobile phase flow rate: 1.0 mL / min Mobile phase _{: 35% CH 3 CN aq (} 0.1% TFA acidified) column oven temperature: room temperature

The results of analysis by the cascade impactor are shown in FIG. 1 (the line graph shows the percentage of the collected amount at each stage relative to the total amount of glucagon in the preparation). Referring to FIG. 1, it can be seen that the amount of collected glucagon is higher when erythritol is used as an excipient or carrier than when lactose is used as a carrier and excipient. Furthermore, when erythritol is used as a carrier and an excipient, it is found that the amount of collected glucagon is highest. These results clearly show the usefulness of the erythritol carrier and also show that the use of erythritol as an excipient further improves its formulation characteristics. Notably it corresponds to the throat in this model Stag
Trapped amount of e 0 (particle size 11 [mu] m or more) is that has decreased clearly by erythritol used, thereby local irritation that may occur by the accumulation and drug in the throat local is suppressed. Table 1 shows the transfer rate of the glucagon preparation to the lung in this model.

[0029]

[Table 1]

[0030] As apparent from the results in Table 1, the difference really clear pulmonary delivery ratio in lactose carrier and erythritol carrier using the formulation was confirmed. This is further confirmed in the use of erythritol excipients as well as carriers.
When erythritol was used as both the carrier and the excipient, good results far exceeding the respective figures were obtained.
These results confirmed the usefulness of using erythritol as a carrier and the synergistic effect of using erythritol as an excipient.

Example 3 Release Characteristics of Insulin Preparation The dispersibility and tissue reach of various samples of the insulin preparation prepared in Example 1 were examined using a cascade impactor, which is an artificial airway and lung model. Specimen: Insulin lactose diluent + lactose carrier Insulin lactose diluent + erythritol carrier Both preparations were filled in JP No. 2 capsule and analyzed using a jet spatula.

[0032] was quantified glucagon amount trapped in each stage in the HPLC analysis condition cascade impactor analyzed by HPLC under conditions shown below. Column used: TOSO ODS-120 T (Tosoh) Detector: SPD-10A (Shimadzu) Pump: LC-10 AD (Shimadzu) Detection wavelength: 220 nm Mobile phase flow rate: 1.0 mL / min Mobile phase: 34% CH ₃ CN aq (0.1% TFA acidified) Column oven temperature: room temperature

The result of studies under the above conditions, the drug delivery ratio to the lungs and bronchi were calculated as shown in Table 2. As is clear from the results in Table 2, when erythritol was used as a carrier, a significantly higher lung / bronchi reach rate was achieved as compared with the case where lactose was used as a carrier, and erythritol was useful as a carrier. Indicated.

[0034]

[Table 2]

Example 4 Release Characteristics of Salmon Calcitonin Preparation The dispersibility and tissue reach of various samples of the salmon calcitonin preparation prepared in Example 1 were examined using a cascade impactor as an artificial airway and lung model. . Specimens was performed salmon calcitonin lactose diluent + lactose carrier salmon calcitonin lactose dilutions + erythritol carrier Both formulations day station using a jet Heller filled into two items capsules analysis. The amounts of salmon calcitonin preparations collected at each stage were measured, and the drug arrival rates to the lungs and bronchi were calculated. The results in Table 3 were obtained. Example 3
Similarly to the results obtained in Example 2, when erythritol was used as a carrier, a high lung / bronchi reach rate was achieved, and the usefulness of the erythritol carrier was demonstrated for salmon calcitonin.

[0036]

[Table 3]

Example 5 Release Characteristics of Tranilast Preparation A tranilast preparation prepared in Example 1 without using an excipient was prepared using a cascade impactor, which is an artificial airway and lung model, as in Examples 2 to 4. The dispersibility and tissue reach of various samples were examined. Sample: tranilast pulverized + lactose carrier tranilast pulverized + filled erythritol carrier both formulations in Japanese Pharmacopoeia two items capsules were analyzed using a jet Heller. When the amount of the tranilast preparation collected at each stage was measured, the drug delivery rate to the lungs and bronchi was calculated as shown in Table 4.

[0038]

[Table 4]

[0039] From the results shown in Table 4, whereas the lactose carrier is somewhat lower target tissue arrival rate, it can be seen that the improved target tissue arrival rate is remarkable when using erythritol carrier.

[0040]

According to the present invention, the use of a sugar alcohol containing erythritol or sorbitol, which is a low-hygroscopic and low-adhesion compound, as a carrier facilitates dissociation between the fine particles containing the drug and the carrier. Tissue selectivity,
Properties of the powder preparation such as bioavailability can be improved.

[Brief description of the drawings]

FIG. 1 shows the results of cascade impactor analysis of glucagon formulations.

 ────────────────────────────────────────────────── ─── Continuing on the front page (72) Kazuhisa Kashimoto 1-2-2 Kubogaoka, Moriya-machi, Kitasoma-gun, Ibaraki Pref.

Claims (7)

[Claims] 1. A powder preparation obtained by mixing fine particles containing a drug with a sugar alcohol as a carrier having an aerodynamically acceptable particle size. 2. The method according to claim 1, wherein the sugar alcohol is erythritol and / or
Or sorbitol, powder formulation according to claim 1. 3. A powder formulation is a inhalants or nasal preparations, powder formulation according to claim 1 or 2. 4. The powder preparation according to claim 1, wherein the particle size of the carrier is in the range of 10 to 200 μm. 5. The powder formulation according to claim 1, wherein the fine particles further comprise an excipient. 6. The powder formulation according to claim 5, wherein the excipient is erythritol. 7. ratio of fine particles and the carrier are 1: 100
The powder formulation according to any one of claims 1 to 6, which is in the range of 10: 1.