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Feeding chamber, an apparatus and a method for production of doses of dry powder, a method for controlling particle segregation in dry powder during filling

Feeding chamber, an apparatus and a method for production of doses of dry powder, a method for controlling particle segregation in dry powder during filling description/claims

The present invention relates to a method and a device for filling a succession of containers with metered doses of finely divided dry powder, the doses intended for inhalation by means of a dry powder inhaler (DPI).

Dosing of drugs is carried out in a number of different ways in the medical service today. Within health care there is a growing interest in medical products based on administering drugs by inhalation of dry medicament powder directly to the airways and lungs of a patient. Interest focuses often on dry powder inhalers (DPI) because they offer effective, quick and user-friendly delivery of many substances formulated as dry powder doses for treatment of many different disorders. Because onset is faster and the efficacy of inhaled doses often are much higher than e.g. orally administered capsules or tablets, the inhalation doses need only be a fraction of the medicament powder mass in an oral capsule or tablet. Thus, there is an increasing demand for relatively low mass, inhalable, metered medicament doses of dry powder, which require better filling methods and devices for making small and exact inhalation doses with low relative standard deviation (RSD).

Volumetric filling is by far the most common method of producing dry powder doses of medication drugs. Normally in a first step a quantity of powder is introduced into a receptacle of specified volume by gravitation, often aided by mechanical energy in the form of impaction or vibration, or the receptacle may be filled by suction force. Then in a second step, after stripping of possible surplus powder, the receptacle is moved to an emptying position, where the powder is unloaded from the receptacle by gravitation and/or mechanical means into a container such as a blister or capsule etc. A plurality of receptacles may be arranged in a filling tool, which is adapted to a mechanism bringing a plurality of containers, e.g. blisters or capsules, in line with corresponding receptacles so that all metered quantities of powder may be unloaded into the respective containers. The filling tool may be integrated into a filling machine such that the receptacles can be filled and emptied in a more or less continuous, cyclic fashion. Examples of prior art may be studied for instance in publications EP 0 319 131 B1, WO 95/21768, U.S. Pat. No. 6,267,155 B1, U.S. Pat. No. 6,581,650 B2, and DE 202 09 156 U1.

Powders for inhalation need to be finely divided or very porous so that the majority by mass of particles in the powder is between 1 and 5 μm in aerodynamic particle size (AD). Powder particles larger than 5 μm tend not to deposit in the lung when inhaled, but to stick in the mouth and upper airways, where they are medicinally wasted and may even cause adverse side effects. However, finely divided powders are rarely free flowing, but are prone to adhere to all surfaces they come in contact with and the small particles tend to aggregate into lumps. This makes the metering of correct doses more difficult, since the bulk density of the powder may vary considerably from dose to dose even if the bulk density is constant when measured on powder quantities several magnitudes larger than the doses. Metering and filling correct quantities into a dose container is therefore more difficult with low dose masses. However, demand for doses from 5 mg down to 0.1 mg is increasing, putting pressure on the industry to improve methods and devices for metering and filling in the manufacturing stage as well as on dry powder inhalers to improve performance in terms of deaggregation and efficacy. Compacting the powder in the metering receptacle to reduce metering errors can be done, but care must be exercised so that agglomeration is not aggravated and to ensure that the agglomerates may still be de-aggregated by the inhaler.

Furthermore, electrostatic forces, friction forces and van der Waal forces acting on particles become stronger than the gravitation force when particle size diminishes. Medication powders are very susceptible to electrostatic charging during transportation and handling of powders, especially in dry conditions.

There is a need for improvements in methods and devices for precise metering of medicament doses of finely divided powders for inhalation and consistent, reliable filling of doses into suitable containers for use in inhaler devices.

The present invention discloses a method and a device for precise, repeatable metering and filling of finely divided dry powder into a preformed container, the container and its contained dose being adapted for inhalation by means of a DPI.

In a particular embodiment of the disclosed method, a powder feeding chamber, having a powder inlet and a powder outlet, is used as an important intermediate process step for a selected dry powder medicament in making the powder of known quality available to a metering receptacle. A portion of the powder is transferred by a suction method into a metering receptacle of a filling tool, which presents a high finish, low friction, face in which the receptacle is made. After filling, a resulting load of powder in the receptacle is emptied into a dose container by ejection from the receptacle using air pressure.

The feeding chamber is intermittently replenished, preferably by a gravitational arrangement, from a bulk source of the selected powder, in order to keep the quantity of powder in the chamber preferably constant. The feeding chamber holds powder equivalent to a multitude of receptacle loads. The present method is suitable for many dry powders, even those that are finely divided and therefore normally not easy-flowing. The disclosed method is a low enthalpy method, i.e. the energy supplied to the powder in all the steps of filling and metering is very low compared to prior art filling methods. In a particular embodiment of the present invention the powder in the feeding chamber is made to collapse and separated from the walls of the chamber by at least one mechanical member, which preferably moves inside the chamber prior to filling a metering receptacle, such that the body of powder in the chamber is e.g. generally disconnected from the chamber walls. This step is preferably performed immediately before a portion of powder is sucked from the chamber outlet into the receptacle, when the receptacle is lined up with the feeding chamber outlet. A very short and low power suction pulse is sufficient to fill the receptacle with a consistent load of powder repetitively.

In a particular embodiment of the present invention, the feeding chamber outlet is in constant, tight contact with the surface of the filling tool such that particles cannot escape from the powder body in the chamber through the outlet. The filling tool is movable relative the chamber outlet, such that the receptacle may be moved out of contact with the chamber outlet and into a position for emptying the load, although contact is maintained all the time between the chamber outlet and the filling tool. Surprisingly, this relative motion helps to restore the homogeneity of the body of powder in the chamber after filling of a receptacle and the shearing forces, although small, between the powder particles and the filling tool surface even out irregularities in the powder stored in the chamber.

The invention offers the following advantages:

Can be used for producing small doses of dry powder at a high precision and accuracy; Operates according to low enthalpy principle to obtain low particle aggregation; Has low and controllable particle segregation; Provides a relatively constant size gradient of particles during steady state conditions;

Can be used for finely divided particles with low free flowing properties.

• Provisional Patent
• Utility Patent

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