DE202004021099U1 - Medical product useful to e.g. treat asthma, comprises a dry powder medicament dose (comprising fine particle dose of tiotropium and at least one dry excipient) loaded into a container for use in a dry powder inhaler - Google Patents

Abstract

Medical product (A) comprises a dry powder medicament dose (I) loaded into a container for use in a dry powder inhaler, where (I) comprises a fine particle dose of tiotropium (II) and at least one dry excipient (III) present in the form of finely divided particles; the container comprises a dry and high barrier seal; and (I) in the container is adapted for either volumetric or electric field dose forming methods. Independent claims are also included for: (1) a device (B) comprising a dry powder inhaler and (A); and (2) a kit comprising a dry powder inhaler and (A), where the container is separate from the dry powder inhaler and the container is adapted for insertion into the dry powder inhaler. ACTIVITY : Antiasthmatic; Respiratory-Gen. MECHANISM OF ACTION : None given.

Description

technical area

The The present invention relates to a medical product comprising inhalable doses of tiotropium, which are in a moisture-proof, dry container and, in particular, a metered dry powder medicament dose from tiotropium bromide for administration by a dry powder inhaler suitable is.

State of technology

asthma and chronic obstructive pulmonary disease (COPD) more than 30 million people in the US. More than 100,000 deaths each Year become these states attributed. A hindrance to the airflow through the lungs is the main feature of each of these tracheal diseases and the used Medication in the treatment is often similar.

The Chronic Obstructive Pulmonary Disease (COPD) is a common one chronic lung disease, which includes chronic bronchitis and Includes emphysema. The reasons the COPD are not complete known. Experience shows that the most important cause of chronic Bronchitis and emphysema is cigarette smoking. air pollution and occupational burdens can also play a role, especially in connection with cigarette smoking. Inheritance caused also some emphysema cases, due to an alpha-antitrypsin deficiency.

The Administration of asthma medications through an oral inhalation route is now very much in the center, because of the advantages offered how fast and predictable start of operation, cost effectiveness and higher Degree of comfort for the user. Dry powder inhalers (DPI) are used as an administration tool compared to other inhalers particularly interesting, due the flexibility that offer them in relation to the nominal dose range, i. H. the amount the active substance administered in a single inhalation can be.

anticholinergics, z. As tiotropium, especially tiotropium bromide, are effective bronchodilator Agents. These drugs have a relatively fast onset Effect and a long duration of action, especially tiotropium bromide, which can be active for up to 24 hours. Reduce anticholinergics the vagus cholinergic smooth muscle tone, what is the most reversible component of COPD. anticholinergics have shown that they have relatively minor side effects in clinical Examinations, dry mouth and constipation are maybe the most common Symptoms. As it is common It is very difficult to properly diagnose and diagnose asthma and COPD because both disorders are common can be present It is beneficial to patients who have a temporary or permanent bronchial Narrowing that causes shortness of breath suffer with a low but effective dose of a long-acting Anticholinergic, preferably with tiotropium bromide, because of the low side effects.

Tiotropium bromide is the preferred anticholinergic because of its high potency and long duration of action. However, it is difficult to formulate dry powdered tiotropium to provide acceptable dose efficiency performance when using prior art DPIs. The efficiency of a dose depends largely on the delivery of a stable and high particulate matter dosage (FSD) from the dry powder inhaler. The FSD is the inhalable dose level from the dry powder inhaler with an aerodynamic particle size below 5 microns. Thus, when inhaling a dose of dry drug powder, it is important to obtain in the mass a high level of fine particle content (FPF) of particles having an aerodynamic size preferably below 5 μm in the inhaled air. The majority of the larger particles (> 5 μm) do not follow the air flow into the many branches of the respiratory tract, but remain stuck in the throat and upper respiratory tract, where the drug may not exert its intended effect, but instead may be harmful to the user , It is also important to keep the dosage as accurate as possible for the user and to maintain stable efficiency over time, and that the dosage of the drug during normal storage does not deteriorate. For example, Boehringer Ingelheim KG (BI) tiotropium bromide sells under the brand name Spiriva ^®. Surprisingly, we have found in a recent study of inhalability of Spiriva ^®, that the Spiriva ^® / HandiHaler ^® system from BI for administration of doses contained in gelatin capsules comprising, by inhalation poor performance and a short in-use stability.

Thus, there is a need for an improvement in a medicinal product containing inhaled dry powder doses of tiotropium bromide, e.g. B. Spiriva ^®, and suitable adapted inhaler devices for the purpose of administration.

Summary

The The present invention discloses a medical product for use in the treatment of respiratory diseases and includes a measured Dose of a dry powder formulation of tiotropium, directly in a moisture-proof, dry container that acts as a dry one Highest protection against Moisture works, filled and is sealed in this. The container itself does not give water which affect the tiotropium powder inside could. Thus, the container gives no water to the dose and entry of moisture from Outside in the container is thereby prevented.

The Tiotropium dose is also intended for inhalation and is the container so dry and dense that the dose efficiency when dispensing unaffected by moisture is.

In a further aspect of the invention, there is disclosed a type of inhaler comprising at least one sealed, moisture-proof, dry container with a dose of tiotropium, e.g. B. Spiriva ^® , and deliver this dose with a stable FSD over the expected life of the product.

In In another aspect of the invention, tiotropium may include at least an additional pharmaceutically active ingredient are mixed or formulated, with the goal of combining tiotropium with other medicines which are used in the treatment of respiratory diseases. The present invention encompasses such an application of tiotropium in a combination with drugs that are sealed directly into a moisture-proof, dry container used in a DPI is filled where the combination is suitable for inhalation by the user is.

Short description of drawings

The Invention, together with further objects and advantages thereof, is best understood by reference to the following detailed Description in conjunction with the attached drawings, in which

1 is a plot of the results of tests S1 to S5 and HBS1 to HBS3;

2 in plan view and side views, a first embodiment of a dose that is stored on a dose bed, and represents a maximum protection seal; and

3 in plan view and side views represents a second embodiment of a dose on a dose bed and a maximum protection seal.

Precise description

Tiotropium is a new, important anticholinergic substance for the treatment of asthma and COPD, but tiotropium is known in the industry to have problems with maintaining stability in use due to its sensitivity to moisture. This fact is also documented in the report "College Ter Beoordeling Van Geneesmiddelen's Medicines Evaluation Board; Public Assessment Report; Spiriva ^® 18 μg, inhalation powder in hard capsules; RVG 26191 '(2002-05-21) on page 6/28 under "Product Development and Finished Product", which states a very short stability in the use of the product Spiriva ^® (9 days) and a fragility of the capsule in the blister packaging and a very low FSD: "about 3 μg" reported.

Details about one Inhalation equipment with inhalable powder of tiotropium and the use of an inhaler for the administration of tiotropium can also in the international publication WO 03/084502 A1 are studied. Details about tiotropium compounds, Drugs based on such compounds, the application of Compounds and processes for the preparation of compounds can be found in the European Patent Application 0 418 716 B1.

In view of the above information that was given in the quoted report a test program for the physical stability of the product Spiriva ^® in terms of the compatibility of the formulation placed together with the components of the device, in accordance with the guidelines of the Food and Drug Administration (FDA) Guidance for Industry; Metered Dose Inhaler (MDI) and Dry Powder Inhaler (DPI) Drug Products; Chemistry, Manufacturing, and Controls Documentation ", page 37/62" Drug product stability ", lines 1209 to 1355. In" Guidance for Industry; Stability Testing of Drug Substances and Drug Products; DRAFT GUIDANCE; Container / Closure, pages 35 and 36/110, lines 1127-1187, the FDA states: "Stability data should be developed for the drug in any type of direct container or packaging for marketing, advertising or bulk storage were proposed. The possibility of interaction between the drug and the container or package and the potential introduction of extractants into the formulations of the drug product during storage should be assessed during the container / package qualification studies using sensitive and quantitative methods active drug substance or major drug carrier of the drug product through interaction with the container / package or constituent components of the drug delivery device is generally rated as part of the stability protocol This is usually achieved by testing these important drug product components, as well as monitoring various important parameters (e.g. pH, shelf life, efficacy) Excessive loss of a component or alteration of a parameter will cause the drug product to become the applicable n specifications can not meet. " According to the FDA publication "Guidance for Industry; Stability Testing of Drug Substances and Drug Products' was a three-week test program under accelerated conditions (40 ± 2 ° C / 75 ± 5 RH) for the container packaging of the product Spiriva ^® , in this case the capsule and blister pack and the impact of the capsule and the blister pack on the FSD, set up and tested.

Carrying out of Testing

Spiriva ^® powder formulation in bulk form and Spiriva ^® capsules from the local pharmacy were added to the laboratory together with the HandiHaler ^® . The laboratory was set up to perform in vitro tests according to European Pharmacopoeia (EP) and US Pharmacopoeia (USP) using two Andersen cascade impactors. All analytical work was then performed according to the normalized procedures for physical tests and determinations for aerosols, metered dose inhalers and dry powder inhalers described in Pharmacopoeias (e.g., USP 2002 <601>) using a high performance liquid chromatograph system (HPLC ) of the prior art.

Spiriva ^® tests

Test S1

Aerodynamic fine particle fraction of metered and delivered dose out of Handihaler ^® using Spiriva ^® a -Formulation of loose powder filled into originator capsules during relative humidity below 10%. The test was performed with 4 kPa pressure drop over the HandiHaler ^® at room temperature and laboratory ambient conditions.

Test S2

Aerodynamic fine particle fraction of metered and delivered dose from the HandiHaler ^® using commercially available Spiriva ^® capsules purchased from our local pharmacy. The test was performed with 4 kPa pressure drop over the HandiHaler ^® at room temperature and laboratory ambient conditions.

Test S3

A stability test in the use of the aerodynamic fine particle fraction of metered and delivered dose from the HandiHaler ^® using commercially available Spiriva ^® capsules purchased from our local pharmacy. From the blister pack with 5 capsules one capsule was removed and the remaining 4 capsules were stored for 4 days at 40 ° C and 75% relative humidity. The blister pack containing the 4 capsules was then placed in an exicator for 2 hours before the tests were performed. The test was performed with 4 kPa pressure drop over the HandiHaler ^® at room temperature and laboratory ambient conditions.

Test S4

A stability test in the use of the aerodynamic fine particle fraction of metered and delivered dose from the Han ^® diHaler using commercially available Spiriva ^® capsules purchased from our local pharmacy. From the blister pack with 5 capsules one capsule was removed and the remaining 4 capsules were stored for 13 days at 40 ° C and 75% relative humidity. The blister pack containing the 4 capsules was then placed in an exicator for 2 hours before the tests were performed. The test was performed with 4 kPa pressure drop over the HandiHaler ^® at room temperature and laboratory ambient conditions.

Test S5

A stability test in the use of the aerodynamic fine particle fraction of metered and delivered dose from the HandiHaler ^® using commercially available Spiriva ^® capsules purchased from our local pharmacy. From the blister pack with 5 capsules, one capsule was removed and the remaining 4 capsules were stored for 21 days at 40 ° C and 75% relative humidity. The blister pack containing the 4 capsules was then placed in an exicator for 2 hours before the tests were performed. The test was performed with 4 kPa pressure drop over the HandiHaler ^® at room temperature and laboratory ambient conditions.

Tests of maximum protection sealing

Test HBS1

A stability test in use of the aerodynamic fine particle fraction introduced of metered and delivered dose out of Handihaler ^® using Spiriva ^® -Rezeptur of loose powder, at a relative humidity below 10% into containers, which act as a high barrier seal, in this case aluminum foils from Alcan Singen , Germany, and then sealed absolutely tight. The aluminum containers were put in an exicator for 2 hours before the Spiriva ^® -Pulverformulierung was filled from the aluminum containers into the originator capsules at a relative humidity below 10%. The test was performed with 4 kPa pressure drop over the HandiHaler ^® at room temperature and laboratory ambient conditions.

Test HBS2

A stability test in use of the aerodynamic fine particle fraction introduced of metered and delivered dose out of Handihaler ^® using Spiriva ^® formulation from bulk powder, at a relative humidity below 10% into containers, which act as a high barrier seal, in this case aluminum foils from Alcan Singen , Germany, and then sealed absolutely tight. The sealed aluminum containers were stored for 7 days at 40 ° C and 75% relative humidity in climatic chambers. The aluminum containers were put in an exicator for 2 hours before the Spiriva ^® -Pulverformulierung was filled from the aluminum containers into the originator capsules at a relative humidity below 10 degrees. The test was performed with 4 kPa pressure drop over the HandiHaler ^® at room temperature and laboratory ambient conditions.

Test HBS3

A stability test in use of the aerodynamic fine particle fraction introduced of metered and delivered dose out of Handihaler ^® using Spiriva ® formulation from bulk powder, at a relative humidity below 10% into containers, which act as a high barrier seal, in this case aluminum foils from Alcan Singen , German, and then sealed absolutely tight. The sealed aluminum containers were stored for 14 days at 40 ° C and 75% relative humidity in climatic chambers. The aluminum containers were put in an exicator for 2 hours before the Spiriva ^® -Pulverformulierung was filled from the aluminum containers into the originator capsules at a relative humidity below 10%. The test was performed with 4 kPa pressure drop over the HandiHaler ^® at room temperature and laboratory ambient conditions.

Tests for dry powder inhaler C-haler

A test was also conducted outside the stability test program to test our own Inha to evaluate the so-called C-haler lator, in comparison with the HandiHaler ^® using a tiotropium formulation. The C-haler cartridge used high barrier seals made out of aluminum foils from Alcan Singen, Germany and the containers were volumetrically with 5 mg of the Spiriva ^® powder formulation filled in loose form. The test was carried out using a 4 kPa pressure drop across the C-haler at room temperature and laboratory ambient conditions. The Anderseninger's test results were calculated on the basis of a fraction of fine particles based on the delivered dose as well as the metered dose and converted into FSD values. The results are shown in Table 1 below.

The results of tests S1-5 and HBS1-3 are in 1 shown graphically. The Y-axis is designated '% of the FSD of the Spiriva ^® commercially available. "This relates to the FPD out of the HandiHaler ^®, where 100% is the FPD from a fresh sample from the pharmacy.

Table 1. Inhaled particulate matter (FSD) <5 μm in%

Conclusion from the tests performed with Spiriva ^®

Surprisingly, we have found in our tests and concluded that tiotropium is extremely sensitive to moisture and that conventional packaging in gelatin capsules used for a majority of respiratory products seriously affects FSD. The results indicate that there is a need for a dry, moisture-proof, top-seal that surrounds the tiotropium formulation to maintain the original level of fines. Not so surprising in the light of these findings is that we have also found that the tiotropium formulation must also be properly protected during use if a further reduction in FSD is to be avoided. Removing the gelatin capsule has an unexpected, strong, positive effect on the performance of the Spiriva ^® formulation.

The tests carried out show that the moisture content of the gelatin capsule, the FPD out of the HandiHaler ^® with approximately 50% from the time of loading the dose into a capsule until the point in time when the product reaches the market, is reduced. When loading Spiriva ^® cans into dry containers made of materials that have the highest barrier properties, and then storing the filled containers at 40 ° C and 75% relative humidity before the Spiriva ^® cans are filled into the manufacturer capsules and the same tests using the HandiHaler ^® as previously performed, no change in particulate matter (PFD) was detected, even after long periods of time. However, the Spiriva ^® FSD in gelatin capsules continues to decrease during the product 's period of use and FSD has been shown to decrease by a further 20% after 5 days' storage at 40 ° C and 75% RH in use in the Stability Test Moisture barrier in the opened blister secondary packaging. Table 1 shows that our C-haler own, the high barrier container used has an improved by 2.6 times performance than HandiHaler ^® with respect to FPD based on metered dose.

State of technology

Measured doses of the Spiriva powder formulation are today filled into gelatin capsules at the manufacturer's site. A gelatin capsule typically contains 13 to 14% by weight of water in the dosage forming step, and after the capsules have been filled, they are dried in a special process to minimize the water content. A number of dried capsules are then placed in a standard blister pack. Details of suitable capsule materials and methods of manufacture of the prior art Technology can be found in the German patent application DE 101 26 924 A1 to be studied. The remaining small amount of water in the capsule material after drying is thus trapped in the blister pack and some water is released into the trapped air, increasing the relative humidity in the air.

The Balance between the trapped air in the packaging and the gelatin capsule generates a relative humidity within the blister pack, which is the FSD of the tiotropium powder the dry powder inhaler adversely affected.

It is interesting to note that the vast majority of dry powder formulations of many types of medicaments are not severely affected by the trapped moisture in the capsule material or by normal variations in the relative humidity of the ambient air. Surprisingly, our research has shown that tiotropium is very different. Tiotropium powder is very much affected by very small amounts of water, so it tends to stick to the wall surfaces and accumulate. Through some mechanisms, the FSD will decrease over time. Since the capsules are only used as a convenient, mechanical carriers of Spiriva ^® doses, a solution to the moisture problem, the capsules would be not to use, but the doses directly into containers, consisting of a dry packaging material with hochabdichtenden seal properties during dry Environmental conditions, preferably below 10% relative humidity to fill.

The The present invention discloses a dry, moisture-proof, directly filled and sealed containers, comprising a measured dose of tiotropium powder or a pharmaceutically acceptable salt, enantiomer, racemate, hydrate, Solvats, including Mixtures thereof, and in particular tiotropium bromide, optional further comprising excipients. The term "tiotropium" in this document is a generic term for all active forms thereof, including pharmaceutically acceptable salts, Enantiomers, racemates, hydrates, solvates or mixtures thereof and can also drug carrier for any Purposes included. The container uses dry maximum protection seals, the impermeable across from Moisture and other contaminants are, and may be in a dry powder inhaler be used or the container may be designed to be part of an inhaler device is.

By "dry" it is meant that the walls of the container are formed of selected materials so that the walls, especially the inner wall of the container, can not release water which could interfere with the tiotropium powder in the dose, thus decreasing the FSD. As a logical consequence, the structure and materials of the container should not be selected from those described in the German publication DE 101 26 924 A1 were proposed.

"Highest protection seal" means a dry one Packaging design or material or combinations of materials. A maximum protection seal is characterized in that it has a high barrier to moisture and that the seal itself is "dry", i.e. it can not produce measurable quantities at the expense of the powder. A maximum protection seal can be used for Example of one or more layers of materials, i. technical polymers, aluminum or other metals, glass, silicon oxide, which together make up the highest protection seal represent.

A "high sealing Container "is a mechanical Construction to a dose of z. B. Tiotropium record and to enclose. The high-sealing container is using the maximum protection seals, which the walls of the container represent, built.

"Directly filled "means that the metered dose of tiotropium is filled directly into the highly-sealed container, d. H. without the dose first z. B. in a gelatin capsule to fül len, and then enclose from one or more main containers (Capsules) in a secondary packaging made of one material with maximum protection seal.

• Verwendung eines Heißsiegellacks, durch Druck und Wärme;
• Verwendung von Wärme und Druck, um die Materialen zu verschmelzen;
• Ultraschallschweißen der sich berührenden Materialien.

The high-density containers to be filled with tiotropium should preferably be made of aluminum foils approved for direct contact with pharmaceutical products. Aluminum foils, which work well in this context, are usually made of engineering polymers coated with aluminum foil to give the film the proper mechanical properties to prevent tearing of the aluminum foil during molding. The sealing of the molded containers is normally carried out using a thinner cover sheet of pure aluminum or coated aluminum and polymer. The container and the cover sheets are then sealed together, using at least one of several possible methods, for example:

• Use of a heat sealing lacquer, by pressure and heat;
• Using heat and pressure to fuse the materials;
• Ultrasonic welding of contacting materials.

tiotropium in its pure form is a very powerful drug and will therefore usually diluted before making the dose by using it physiologically acceptable excipients, z. As lactose, in a selected relationship or selected conditions dilute In order to form a preferred method of forming or filling a Dose to fit. Details about Inhalable powders containing tiotropium in admixture with excipients, Powder manufacturing process, use of powder and capsules for powder can in the international publication WO 02/30389 A1 are studied.

In In another aspect of the invention, tiotropium may be with one or more mixed or formulated with several pharmacologically active ingredients with a goal to combine tiotropium with other medicines, which are used in a treatment of respiratory diseases. The present invention comprises such an application of tiotropium, if a combination of tiotropium and other medicines in stored in a dry, moisture-proof, highly sealing container and sealed, the container for insertion into a DPI is intended for inhalation by the user. Examples of interesting Combinations of substances together with tiotropium can be inhaled Steroids, nicotinamide derivatives, beta-agonists, beta-mimetics, antihistamines, adenosine A2A receptors, Be PDE4 inhibitors, dopamine D2 receptor agonists.

One sealed, dry, high-density container of the invention, directly filled with a formulation of tiotropium may be in the form of a Be blister pack or he can z. B. a flat dose bed or a molded cavity in an aluminum foil or cast one Cavity of a polymeric material comprising a high barrier film against entry of moisture use, z. B. aluminum or a combination of aluminum and polymer materials. The sealed, dry, high-sealing containers may form part of an inhaler device or it may be a separate part for insertion into an inhaler device intended for the administration of doses.

An inhaler providing prolonged delivery of a dose during the course of a single inhalation is a preferred embodiment of an inhaler for the delivery of the tiotropium powder formulation, e.g. B. Spiriva ^®. An air razor method as described in our publication US 2003/0192539 A1 is preferably used in the inhaler to efficiently and gradually nebulize the dose when delivered to the user. Surprisingly enough, an application performs an inhaler for a prolonged delivery and using the Air-razor method on a dose of tiotropium in a Spiriva ^® -Rezeptur to a FSD, which is at least twice as high as that of the HandiHaler ^® of the prior art.

Summarized For example, the invention discloses a medical product for use in the treatment of respiratory diseases and includes a measured Dose of a tiotropium dry powder formulation, directly into a container filled and sealed there, with the container as a dry maximum protection seal serves to increase the application and entry of moisture into the tiotropium powder to prevent. The tiotropium dose is also suitable for inhalation and the container is so dense that the effectiveness of the dose when given is not affected by moisture. In another Aspect of the invention, an inhaler type is shown, at least a sealed, moisture-proof container of a tiotropium dose can absorb the dose with a constant particulate matter over the expected life of the product.

Claims (45)

A medical product comprising a dry powder dosage Tiotropium filled directly into a container, characterized that a dry maximum protection seal the container forming; the highest protection seal of the container prevents ingress of moisture, the original fine particle content the powder dose is maintained, and the dry powder dose in the container to Administration by a dry powder inhaler. A medical product according to claim 1, characterized in that the administration of the dry by inhalation of a dry powder inhaler providing a prolonged dose delivery. Medical product according to claim 1, characterized that the tiotropium substance consists of one or more physiological acceptable salts of tiotropium. Medical product according to claim 1, characterized a containing drug carrier is lactose. Medical product according to claim 1, characterized molded or flat aluminum foils, optionally with polymers coated, the top dry seal form. Medical product according to claim 1, characterized that a cavity formed of a selected poly mermaterial is going to the container High barrier seal properties the container represent, confer. Medical product according to claim 1, characterized that a cavity made of a polymer material together with a maximum protection seal, the container is molded to it with high sealing sealing properties to provide. Medical product according to claim 1, characterized that the container is part of a dry powder inhaler. Medical product according to claim 1, characterized that the container a separate part suitable for insertion into a dry powder inhaler. Medical product according to claim 1, characterized that the container a separate part comprising a main part suitable for insertion in a dry powder inhaler, and a secondary part containing the Main body in a moisture-proof packaging surrounds. Medical product according to claim 1, characterized that the medical product is for use in the treatment is thought of respiratory diseases. A pharmaceutical composition comprising tiotropium or a physiologically acceptable salt thereof and a physiological one acceptable excipients, characterized in that the composition directly into a dry, moisture-proof packaging or a dry, high-density container filled and in this is sealed to the original fine particle content to maintain the composition. Pharmaceutical composition according to claim 12, characterized in that the administration of the combination of Dry powder dose by inhalation from a dry powder inhaler, the one extended Dose delivery is performed. Pharmaceutical composition according to claim 12, characterized in that the tiotropium is one or more physiologically includes acceptable salts of tiotropium. Pharmaceutical composition according to claim 12, characterized in that a containing excipient comprises lactose is. Pharmaceutical composition according to claim 12, characterized in that molded or flat aluminum foils, Optionally coated with polymers that are dry, moisture-proof Form packing or dry, high-sealing container. Pharmaceutical composition according to claim 12, characterized in that one formed from a polymer material Cavity with high sealing sealing properties the dry, moisture-proof packaging or the dry, high-sealing container forms. A pharmaceutical composition according to claim 12, characterized in that a cavity formed of a polymer material together with a maximum barrier seal forms the dry, moisture-proof package or the dry, high-density container, thereby reducing the packaging or the container is given maximum protection sealing properties. Pharmaceutical composition according to claim 12, characterized in that the dry, moisture-proof packaging or the dry, high-density container part of a dry powder inhaler represents. Pharmaceutical composition according to claim 12, characterized in that the dry, moisture-proof packaging or the dry, high-density container is a separate part, suitable for insertion in a dry powder inhaler. Pharmaceutical composition according to claim 12, characterized in that the dry, moisture-proof packaging or the dry, high-density container is a separate part, comprising a main packaging suitable for insertion into a Dry powder inhaler, and a moisture-proof secondary packaging or a secondary container, which surround the main packaging. Pharmaceutical composition according to claim 12, characterized in that the pharmaceutical composition intended for use in the treatment of respiratory disease is. Medical product, including tiotropium and separately or together with at least one additional active pharmaceutical Component and optionally comprising excipients in a medical Dry powder combination dose directly into a container filled is, characterized in that a dry maximum protection seal the container forming; the highest protection seal of the container prevents ingress of moisture, the original fine particle content the combination dose is maintained, the combination dose to Administration by a dry powder inhaler, and of the at least one extra active pharmaceutical ingredient from the following group of Substances selected inhaled steroids, nicotinamide derivatives, beta-agonists, beta-mimetics, antihistamines, adenosine A2A receptors, PDE4 inhibitors, dopamine D2 receptor agonists. Medical product according to claim 23, characterized characterized in that the administration of the dry powder dose by Inhalation of a dry powder inhaler, which prolonged dose delivery provides, performed becomes. Medical product according to claim 23, characterized in that the tiotropium substance consists of one or more physiologically acceptable salts of tiotropium. Medical product according to claim 23, characterized characterized in that a containing excipient comprises lactose is. Medical product according to claim 23, characterized characterized in that formed or flat aluminum foils, optional coated with polymers that form top dry seal. Medical product according to claim 23, characterized characterized in that a cavity of a selected polymer material is shaped to the container High barrier seal properties the container represent, confer. Medical product according to claim 23, characterized characterized in that one of a polymer material together with a High barrier seal shaped cavity the container represents to him with high sealing sealing properties to provide. Medical product according to claim 23, characterized characterized in that the container is part of a dry powder inhaler. Medical product according to claim 23, characterized characterized in that the container a separate part suitable for insertion into a dry powder inhaler. Medical product according to claim 23, characterized characterized in that the container a separate part comprising a main part suitable for insertion in a dry powder inhaler, and a secondary part containing the Main body in a moisture-proof packaging surrounds. Medical product according to claim 23, characterized in that the medicinal product is to be used with the treatment of respiratory diseases. A pharmaceutical composition comprising tiotropium or a physiologically acceptable salt thereof and separated or together with at least one active pharmaceutical ingredient, optionally comprising physiologically acceptable excipients in a Dry powder combination dose characterized in that the dry powder combination dose directly into a dry, moisture-proof packaging or a dry, high-sealing container filled and sealed in these to the original fine particle content (FPF) to maintain the composition; the at least one active pharmaceutical ingredient from the following group of Substances selected in halodable steroids, nicotinamide derivatives, beta-agonists, beta-mimetics, Antihistamines, adenosine A2A receptors, PDE4 inhibitors, dopamine D2 receptor agonists. A pharmaceutical composition according to claim 34, characterized in that the administration of the dry powder combination dose by inhalation from a dry powder inhaler providing a prolonged dose delivery provides, performed becomes. A pharmaceutical composition according to claim 34, characterized in that the tiotropium one or more physiological includes acceptable salts of tiotropium. A pharmaceutical composition according to claim 34, characterized in that a containing excipient comprises lactose is. A pharmaceutical composition according to claim 34, characterized in that molded or flat aluminum foils, Optionally coated with polymers that are dry, moisture-proof Form packing or dry, high-sealing container. A pharmaceutical composition according to claim 34, characterized in that one formed from a polymer material Cavity with high sealing sealing properties the dry, moisture-proof packaging or the dry, high-sealing container forms. A pharmaceutical composition according to claim 34, characterized in that one composed of a polymer material with a maximum protection seal Molded cavity the dry, moisture-proof packaging or forming the dry, high-sealing container, thereby reducing the packaging or the container High barrier seal properties be lent. A pharmaceutical composition according to claim 34, characterized in that the dry, moisture-proof packaging or the dry, high-density container part of a dry powder inhaler represents. A pharmaceutical composition according to claim 34, characterized in that the dry, moisture-proof packaging or the dry, high-density container is a separate part, suitable for insertion in a dry powder inhaler. A pharmaceutical composition according to claim 34, characterized in that the dry, moisture-proof packaging or the dry, high-density container is a separate part, comprising a main packaging suitable for insertion into a Dry powder inhaler, and a moisture-proof secondary packaging or a secondary container, which surround the main packaging. A pharmaceutical composition according to claim 34, characterized in that the pharmaceutical composition intended for use in the treatment of respiratory disease is. A medical product comprising a dry powder dose of tiotropium filled directly into a container suitable for administration by a dry powder inhaler, wherein a dry, moisture-proof protective seal forms the container; the moisture-proof protective seal of the container prevents moisture from entering the powder dose, thereby maintaining the original fine particle fraction of the powder dose for at least seven days, and an administered microparticle dose of tiotropium of the medical product is generally independent of Ver Changes in ambient humidity conditions.