Method for the production of commercial nanoparticle and micro particle powders

Abstract

The present invention relates to methods for producing nanoparticle and microparticle powders of a biologically active material which have improved powder handling properties making the powders suitable for commercial use using dry milling processes as well as compositions comprising such materials, medicaments produced using said biologically active materials in particulate form and/or compositions, and to methods of treatment of an animal, including man, using a therapeutically effective amount of said biologically active materials administered by way of said medicaments.

Description

FIELD OF THE INVENTION[0001]The present invention relates to methods for producing nanoparticle and microparticle powders of a biologically active material using dry milling processes, as well as compositions comprising such materials, medicaments produced using said biologically active materials in particulate form and / or compositions, and to methods of treatment of an animal, including man, using a therapeutically effective amount of said biologically active materials administered by way of said medicaments. Compositions of the present invention have unexpectedly improved powder handling properties relative to compositions made by conventional techniques, making them advantageous for use in commercial applications.BACKGROUND[0002]Poor bioavailability is a significant problem encountered in the development of compositions in the therapeutic, cosmetic, agricultural and food industries, particularly those materials containing a biologically active material that is poorly soluble in w...

AI Technical Summary

Benefits of technology

[0026]Preferably, the powder handling characteristics of the biologically active material produced by this invention are superior to the powder handling characteristics of a biologically active material with the same, similar or larger particle size manufactured using a conventional process. Preferably, the biologically active material subject to this invention has superior product flow characteristic compared to the product flow characteristic of a biologically active material with the same, similar or larger particle size manufactured using a conventional process. Preferably, the biologically active material subject to this invention has a lower static charge compared to the static charge of a biologically active material with the same, similar or larger particle size manufactured using a conventional process. Preferably, the biologically active material subject to this invention has a lower cohesiveness profile compared to the cohesiveness profile of a biologically active material with the same, similar or larger particle size manufactured using a conventional process. Preferably, the biologically active material subject to this invention has a lower propensity for aggregation compared to the propensity for aggregation of a biologically active material with the same, similar or larger particle size manufactured using a conventional process. Preferably, the biologically active material subject to this invention has a lower propensity for adherence to other materials compared to the propensity for adherence of a biologically active material with the same, similar or larger particle size manufactured using a conventional process. Preferably, the biologically active material subject to this invention has increased uniformity compared to a biologically active material with the same, similar or larger particle size manufactured using a conventional process. Preferably, the biologically active material subject to this invention has reduced levels of dust compared to a biologically active material with the same, similar or larger particle size manufactured using a conventional process. Preferably, the biologically active material subject to this invention has improved rheology compared to a biologically active material with the same, similar or larger particle size manufactured using a conventional process. Preferably, the biologically active material subject to this invention has reduced segregation compared to a biologically active material with the same, similar or larger particle size manufactured using a conventional process. Preferably, the biologically active material subject to this invention has increased bulk density or tapped bulk density compared to a biologically active material with the same, similar or larger particle size manufactured using a conventional process. Preferably, the biologically active material subject to this invention has superior powder flow as defined by the Hausner ratio or Carr's index compared to a biologically active material with the same, similar or larger particle size manufactured using a conventional process. Preferably, the biologically active material subject to this invention has lower compressibility compared to a biologically active material with the same, similar or larger particle size manufactured using a conventional process. Preferably, the biologically active material subject to this invention has increased permeability compared to a biologically active material with the same, similar or larger particle size manufactured using a conventional process. Preferably, the biologically active material subject to this invention has a higher minium ignition energy compared to a biologically active material with the same, similar or larger particle size manufactured using a conventional process. Preferably, the biologically active material subject to this invention has higher hopper flow rates compared to a biologically active material with the same, similar or larger particle size manufactured using a conventional process. Preferably, the biologically active material subject to this invention has smaller critical orifice diameter compared to a biologically active material with the same, similar or larger particle size manufactured using a conventional process. Preferably, the biologically active material subject to this invention has smaller angle of repose compared to a biologically active material with the same, similar or larger particle size manufactured using a conventional process. Preferably, the biologically active material subject to this invention has smaller dynamic angle of repose compared to a biologically active material with the same, similar or larger particle size manufactured using a conventional process.

Problems solved by technology

Poor bioavailability is a significant problem encountered in the development of compositions in the therapeutic, cosmetic, agricultural and food industries, particularly those materials containing a biologically active material that is poorly soluble in water at physiological pH.

In addition, poorly soluble active agents tend to be disfavored or even unsafe for intravenous administration due to the risk of particles of agent blocking blood flow through capillaries.

The wet milling process, however, is prone to contamination, thereby leading to a bias in the pharmaceutical art against wet milling.

Many of these approaches commonly convert a drug into an amorphous state, which generally leads to a higher dissolution rate.

However, formulation approaches that result in the production of amorphous material are not common in commercial formulations due to concerns relating to stability and the potential for material to re-crystallize.

These techniques for preparing such pharmaceutical compositions tend to be complex.

By way of example, a principal technical difficulty encountered with emulsion polymerization is the removal of contaminants, such as unreacted monomers or initiators (which may have undesirable levels of toxicity), at the end of the manufacturing process.

However, these techniques suffer from a number of disadvantages including at least the inability to produce sufficiently small particles such as those obtained by milling, and the presence of co-solvents and / or contaminants such as toxic monomers which are difficult to remove, leading to expensive manufacturing processes.

Many of the technologies discussed above require the particles to be produced in a liquid suspension such that expensive and complicated further processing is needed to make common dry formulations such as tablets.

Some technologies such as micronization do produce material in a dry form, but the particles have inherently high cohesiveness and high static charge.

This leads to poor product flow and high aggregation properties.

The product fails to flow smoothly into containers (such as capsules) and aggregates significantly when poured.

It also adheres significantly to process equipment and containers, thus resulting in a significant loss of product.

One solution adopted by the prior art is to bind the material to a carrier product or to dissolve the material in a solution to improve product handling, but these steps add to the overall expense of any process.

Firstly, the nanoparticles produced by the Fukami process are sticky and difficult to handle.

Secondly, to overcome this problem the particles had to be dispersed in water and spray coated onto a carrier particle.

The spray coating process, which uses significant amounts of energy, is expensive and adds to the overall cost of the manufacturing.

One limitation of many of the prior art processes is that they are not suitable for commercial scale.

A component of this sub optimal bioavailability is also likely due to the poor water solubility of this drug.

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