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

[0190]Without wishing to be bound by theory, it is believed that the physical degradation (including but not limited to particle size reduction) of the millable grinding matrix affords the advantage of the invention, by acting as a more effective diluent than grinding matrix of a larger particle size. Again, as will be described subsequently, a highly advantageous aspect of the present invention is that certain grinding matrixes appropriate for use in the method of the invention are also appropriate for use in a medicament. The present invention encompasses methods for the production of a medicament incorporating both the biologically active material and the grinding matrix or in some cases the biologically active material and a portion of the grinding matrix, medicaments so produced, and methods of treatment of an animal, including man, using a therapeutically effective amount of said biologically active materials by way of said medicaments.

[0191]Analogously, as will be described subsequently, a highly advantageous aspect of the present invention is that certain grinding matrixes appropriate for use in the method of the invention are also appropriate for use in a carrier for an agricultural chemical, such as a pesticide, fungicide, or herbicide. The present invention encompasses methods for the production of an agricultural chemical composition incorporating both the biologically active material in particulate form and the grinding matrix, or in some cases the biologically active material, and a portion of the grinding matrix, and agricultural chemical compositions so produced. The medicament may include only the biologically active material together with the milled grinding matrix or, more preferably, the biologically active material and milled grinding matrix may be combined with one or more pharmaceutically acceptable carriers, as well as any desired excipients or other like agents commonly used in the preparation of medicaments.

[0192]Analogously, the agricultural chemical composition may include only the biologically active material together with the milled grinding matrix or, more preferably, the biologically active materials and milled grinding matrix may be combined with one or more carriers, as well as any desired excipients or other like agents commonly used in the preparation of agricultural chemical compositions.

[0193]In one particular form of the invention, the grinding matrix is both appropriate for use in a medicament and readily separable from the biologically active material by methods not dependent on particle size. Such grinding matrixes are described in the following

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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