Inhalation particles incorporating a combination of two or more active ingredients

Abstract

Crystalline spherical inhalation particles incorporating a combination of two or more different active ingredients and a process for the preparation thereof. The particles have a narrow particle size distribution, rough surfaces and improved stability. The inhalation particles of the invention are particularly useful in the administration of a combination medicament, e.g. a combination of an anti-inflammatory agent and a bronchodilator, by inhalation in the treatment of asthma and other respiratory disorders.

Description

FIELD OF THE INVENTION[0001]The present invention relates to inhalation particles and inhalation compositions suitable for pulmonary drug delivery and to methods for the preparation thereof. In particular, the present invention relates to inhalation particles incorporating a combination of two or more different active ingredients. The inhalation particles of the invention are particularly useful in the treatment of asthma and other respiratory disorders.BACKGROUND OF THE INVENTION[0002]Inhalation has become the primary route of administration in the treatment of asthma. This is because, besides providing direct access to the lungs, medication delivered through the respiratory tract provides rapid and predictable onset of action and requires lower dosages compared to the oral route.[0003]There have been recent advances in the treatment of asthma resulting from the recognition that asthma is a chronic inflammatory disease. Current asthma drugs can be classified into two classes, namel...

AI Technical Summary

Benefits of technology

[0007]It has now been found that, by using an aerosol flow reactor method, it is possible to prepare uncharged, spherical and crystalline inhalation particles incorporating, in an individual particle, a combination of two or more drugs in a predetermined and constant ratio. The particles provide more controlled delivery of combination medicaments by inhalation, since it is now possible to keep the ratio of the drugs in each dose constant. The particles exhibit improved dispersibility and good stability as a result of their crystalline nature. The particles have a narrow aerodynamic particle size distribution, typically between about 1-5 μm, which is especially suitable for the preparation of compositions for dry powder inhalers. Moreover, particle surfaces are spherical and generally rough, which reduces the force required to break-up the aggregates of the particles or detach the particle from a coarse carrier. Furthermore, the method of the invention provides a high purity product since the product purity only depends on the purity of solution precursors. Moreover, the method is simple and can be easily scaled-up to higher production rates.

Problems solved by technology

One of the drawbacks of anti-inflammatory drugs is that their onset of action is relatively slow.

Therefore, patients often do not recognise any immediate therapeutic effects and tend to stop the medication.

This could cause the inflammation uncontrollable.

However, there are currently debates on the safety of a regular use of β2-agonists as well as efficiency of long-acting β2-agonists.

Also, the short-acting nature of the drug requires more frequent drug administrations, which tend to cause patient compliance problem.

When these combinations are used in dry powder inhalers, the consistency of drug proportion in each dose cannot be easily controlled.

Hence, it is not easy to keep the ratio of the drugs in each dose constant.

The inconsistency of the dose could cause serious problems especially when a very potent drug is delivered in a much higher amount than expected.

However, the method produces amorphous particles, which have stability problems and a high, tendency toward moisture re-absorption, which is undesirable for pharmaceutical particles intended for administration by inhalation.

Furthermore the size and the morphology of the particles obtained are not optimal for pulmonary delivery.

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