Modified carrier particles for use in dry powder inhalers

Abstract

The invention relates to carrier particles for use in pharmaceutical compositions for the pulmonary administration of medicaments by means of dry powder inhalers. In particular, the invention relates to a novel technological process for obtaining a carrier modified so as to improve the efficiency of redispersion of active particles and hence increase the respirable fraction. After the treatment of the invention, the surface of said modified carrier particles can also be coated with a suitable additive so as to further improve the respirable fraction.

Description

PRIOR ART[0001] Inhalation anti-asthmatics are widely used in the treatment of reversible airway obstruction, inflammation and hyperresponsiveness.[0002] Presently, the most widely used systems for inhalation therapy are the pressurised metered dose inhalers (MDIs) which use a propellant to expel droplets containing the pharmaceutical product to the respiratory tract.[0003] However, despite their practicality and popularity, MDIs have some disadvantages:[0004] i) droplets leaving the actuator orifice could be large or have an extremely high velocity resulting in extensive oropharyngeal deposition to the detriment of the dose which penetrates into he lungs;[0005] ii) the amount of drug which penetrates the bronchial tree may be further reduced by poor inhalation technique, due to the common difficulty of the patient to synchronise actuation form the device with inspiration;[0006] iii) chlorofluorocarbons (CFCs), such as freons contained as propellants in MDIs, are disadvantageous on ...

AI Technical Summary

Benefits of technology

[0030] It has now been found, and it is the object of the invention, that it is possible to modify the surface properties of the carrier particles and simultaneously modulate their interaction with the micronised drug particles by producing in situ a fine fraction of the carrier itself, without submitting the coarse carrier particles to a milling process but by employing a conventional mixer.

[0031] The use of a mixer, which intrinsically assures milder conditions, allows to modify the surface properties of the carrier particles without significantly changing their sizes, crystalline structure and chemico-physical properties.

[0033] Moreover, hard treatments such as corrasion may moderately reduce the cristallinity of the additives used (Malcolmson R et al. Respiratory Drug Deliv. 1998, VI, 365-367).

[0034] It has been also suprisingly found that, by virtue of the milder operative conditions of the invention, the fraction of fine particles of size larger than 10 .mu.m is poor, as proved by the particle size analysis via laser diffractometry (Malvern). It is well known that only the fine fraction below 10 .mu.m, once redistributed onto the surface of the coarse carrier particles, is indeed responsible for the decrease of the interparticle forces, whereas the fine particles of size larger than 10 .mu.m, contribute to decrease the flowability of the powder.

[0036] By operating according to the process of the present invention, the flow properties of the carrier are not significantly affected, as indicated by the Carr index as well as by the Flodex test. The process of the invention allows therefore to avoid the further separation step of the fine fraction suitable for being mixed with the coarse carrier particles.

[0037] The mixing process of the invention, compared with the milling process as described in WO 95 / 11666, allows to remarkably reduce the time of treatment. In a preferred embodiment of the invention, carriers with suitable properties are indeed obtained after 30 minutes of treatment in a sigma blade mixer whereas, according to WO 95 / 11666, carrier particles should be milled for at least one hour and preferably six hours.

Problems solved by technology

Moreover, hard treatments such as corrasion may moderately reduce the cristallinity of the additives used (Malcolmson R et al.

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