Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Modified carrier particles for use in dry powder inhalers

a carrier particle and dry powder technology, applied in the direction of woodworking apparatus, pharmaceutical delivery mechanism, granular delivery, etc., can solve the problems of moderate reduction of the crystallinity of the additives used, hard treatment,

Inactive Publication Date: 2004-01-15
CHIESI FARM SPA
View PDF7 Cites 6 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Modified carrier particles for use in dry powder inhalers
  • Modified carrier particles for use in dry powder inhalers
  • Modified carrier particles for use in dry powder inhalers

Examples

Experimental program
Comparison scheme
Effect test

example 2

Preparation of a Salbutamol Base / Lactose Binary Mixture

[0067] Analogously to what described in example 1, a mixture containing micronised salbutamol base as active ingredient in a ratio of 200 .mu.g to 24 mg total mixture was prepared.

[0068] The poured and tapped densities and the flowability characteristics were determined as described in example 1. The dry powder for inhalation was loaded in a Pulvinal.RTM. inhaler and the aerosol performances were determined as described in example 1.

[0069] The results are reported in Table 3 in comparison with a similar preparation obtained by mixing the active ingredient with .alpha.-lactose monohydrate lactose 90-150 .mu.m not pre-treated in a mixer (standard preparation).

3TABLE 3 Preparation of Example 2 Standard preparation Technological parameters Apparent Density (g / mL) Poured 0.71 0.74 Tapped 0.78 0.83 Flodex test (.0. 4 mm) 4 4 Flow Rate through .0. 4 mm (g / min) 72 --Carr Index (%) 9 11 TSI test Mean weight (mg) 22.2 (1.7) 25.2 (3.3) Emi...

example 3

Preparation of a BDP / Lactose / Magnesium Stearate Ternary Mixture

[0072] The powder carrier was prepared according to Example 1 a) by mixing .alpha.-lactose monohydrate for 30 minutes in a sigma blade mixer. Afterwards lactose was mixed with 0.25% by weight of magnesium stearate in a Turbula mixer for two hours. Finally the dry powder for inhalation was prepared by mixing an amount of micronised beclomethasone dipropionate corresponding to a dose of 200 .mu.g and the carrier (lactose+magnesium stearate) for 30 minutes in a Turbula rotting mixer at 32 rpm.

[0073] The poured and tapped densities, the flowability characteristics as well as the aerosol performances were determined as described in example 1.

[0074] The results are reported in Table 4 in comparison with a standard formulation obtained by mixing 200 .mu.g of micronised BDP with a carrier powder consisting of 99.75% by weight of .alpha.-lactose monohydrate 90-150 .mu.g not pre-treated in a mixer, and 0.25% by weight of magnesium...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
mean aerodynamic diameteraaaaaaaaaa
mean aerodynamic diameteraaaaaaaaaa
mean diameteraaaaaaaaaa
Login to View More

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 ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(United States)
IPC IPC(8): A61K9/00A61K9/14A61K9/16A61K9/72
CPCA61K9/145A61K9/0075
Inventor MUSA, ROSSELLABILZI, ROBERTOVENTURA, PAOLOCHIESI, PAOLO
Owner CHIESI FARM SPA
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com