GB2118945A

GB2118945A - Microporous powders charged with active substances

Info

Publication number: GB2118945A
Application number: GB8310812A
Authority: GB
Inventors: Christoph Josefiak
Original assignee: Akzo NV
Current assignee: Akzo NV
Priority date: 1982-04-23
Filing date: 1983-04-21
Publication date: 1983-11-09
Also published as: JPS58198533A; DE3215211A1; FR2525492A1; GB2118945B; GB8310812D0

Abstract

Microporous powder charged with an active substance for the controlled release thereof, is made by spraying into a gas a homogeneous solution of a polymer, an active substance and, optionally, an inert liquid. The microporous powder may comprise a thermoplastic polymer charged with the active substance and may have a porosity of from 60 to 80%, an outer skin of the thermoplastic polymer having a thickness of from 0.1 to 1 mu m and an opening content of from 2 to 20%, the openings in the outer skin having a diameter of up to 1 mu m. The microporous powders are particularly suitable for the controlled release of active substances over a prolonged period.

Description

SPECIFICATION Microporous powders charged with active substances and production thereof This invention relates to microporous powders charged with active substances and to a process for the production thereof; more particularly, it relates to such powders for the controlled release of the active substances.

Processes for the production of porous and microporous powder-like or granule-like particles have long been known. Processes for the production of fine microporous particles containing certain active substances are also known.

Thus, synthetic resin foams which may be used for soil improvement purposes are described in KUNSTSTOFFE, Vol. 55, No. 5, 1965, pages 389 to 390. The foams in question are flake-like polystyrene particles ranging in size from 4 to 12 mm or urea/formaldehyde foams. These particles are capable of loosening soil and also of adsorbing water to a certain extent and releasing it again at a later stage when the soil dries out through lack of rain, so that they act as a drainage medium and are able to regulate the water balance of the soil, particularly in dry regions.

However, such particles are not suitable for charging ab, initio with active substances which are subsequently released under control into the surrounding environment.

DE-OS No. 1,694,713 also described open-cell particulate foams which are intended to act as embedding media or supports for various active agents. However, there is no indication in this specification of a process for advantageously producing particles charged with active substances which are suitable for the controlled long-term release of those active substances.

DE-AS No. 2,035,601 describes microcellular polymer particles which have a particle size ranging from a maximum of 500 Mm to a minimum of 0.02 ssm and which comprise at least one void, preferably several voids, having an average diameter of at least 200 ssm. These known polymer particles are also not particularly suitable for the controlled long-term release of active substances.

Also, NL-OS No. 75/00873 describes an antistatic agent for polyolefins which may be ground into granules or powders. However, the particles described in this specification are not particularly suitable for controlled long-term release in the proper sense, instead they are added to other polymer compositions as a so called master batch and are intended to improve the distribution of the antistatic agent in the polymer to which antistatic properties are to be imparted.

It is also known that powders or porous granules containing an active substance may be provided with an impregnating agent. Thus, European Patent No. 5302, for example, describes a process in which granules are charged with an active substance and in which a polyurethane skin intended to seal off the pore is formed by chemical reaction. This process is complicated and laborious.

Although several microporous powders suitable for taking up and releasing active substances are known, there is still a need for microporous powders with which it is possible to release active substances to the surrounding environment under control over a prolonged period. There is also a need for an improved, economic and simple process for producing microporous powders of this type.

Accordingly, an object of the present invention is to provide a microporous powder which is charged with one or more active substances and which uniformiy releases the active substance(s) under control over a prolonged period.

Another object of the present invention is to provide microporous powders which may be charged with large quantities of active substance and which, by virtue of the particular structure thereof, do not initially release a large quantity of active substance, even when it is initially present in a high concentration, and subsequently fall off rapidly in releasing the active substance.

Another object of the present invention is to provide a process by which it is possible readily and economically to obtain microporous powders of the abovementioned type.

A further object of the present invention is to provide microporous powders and a process for the production thereof wherein, for the purpose of improving long-term release, the microporous powder does not have a secondary membrane of another material.

According to the present invention, these objects are achieved by microporous powders of a thermoplastic polymer charged with active substance for controlled release thereof, characterized by a porosity of from 60 to 80%, an outer skin of the thermoplastic polymer having a thickness of from 0.1 to 1 ,um and an opening content of from 2 to 20%, the openings in the outer surface having a diameter of up to 1 ym.

According to the present invention, these microporous powders charged with one or more active substances for the controlled release thereof are produced by a process which is characterized in that a homogeneous solution of a polymer and of an active substance which optionally contains an additional inert liquid is sprayed into a gas. It is preferred to use a poreforming active substance. Where an inert liquid is additionally used, this liquid may itself be poreforming.

One particular advantageous embodiment of the process according to the present invention is characterized by the use of a homogeneous solution of a polymer and of an active substance that form a binary system which, in its liquid aggregate state, comprises a region of complete miscibility and a region having a miscibility gap, the solution which has a temperature above the separation temperature being sprayed into a gas which has a temperature below the separation temperature.

The inert liquid may be a non-solvent for the polymer used. From 20 to 70% of active substance and from 30 to 80% of inert liquid are preferably used for forming the solution. Such compositions are particularly advantageous in cases where the active substance itself is not pore-forming.

In another particularly advantageous embodiment of the process according to the present invention, the powders are rinsed after spraying.

Polyamide-6, inter, alia, is a particularly suitable polymer, y-butyrolactone being particularly suitable for use as the additional inert liquid.

Thermoplastic polymers which may advantageously be used for the purposes of the present invention are mentioned in DE-OS No.

2,737,745. This specification also mentions a large number of active substances to which it frequently refers as functional liquids which may be processed together with the thermoplastic polymers to form a microporous powder according to the present invention. Thus, as mentioned on page 89, paragraph 2 and page 90, paragraph 1 of DE-OS No. 2,737,745, it is possible according to the present invention to use functional liquids, for example, which act as animal repellents, fragrance donors, insecticides, medicaments, deodorants, pesticides and perfumes.

The Examples and Tables of the abovementioned specification exemplify numerous functional liquids together with suitable polymers and reference may be made thereto.

The polymer used and the active substance preferably form a system which, in its liquid aggregate state, comprises a region of complete miscibility and a region having a miscibility gap. A solution present as a single, liquid phase is sprayed. This means that the solution must have a temperature above the separation temperature of the system.

The solution is sprayed into a gas which has a temperature below the separation temperature.

Below the separation temperature, the system becomes a two-phase system, i.e. in general two liquid phases are initially formed alongside one another.

It is of particular advantage to spray the homogeneous solution into a gas at room temperature.

Air may be used as that gas, although it is also possible to use other gases, such as nitrogen or noble gases.

It is particularly advantageous if the systems used have a miscibility gap in the liquid aggregate state. In this way, the microporous powders develop a particularly favourable pore or micropore structure. In addition to the active substance, one or more inert liquids may be used.

In this case, the inert liquid, the active substance and the polymer should again form a homogeneous solution.

By adding a suitable inert liquid, polymer/active substance systems which do not have a miscibility gap in the liquid aggregate state may be changed into a system which has a miscibility gap in the liquid aggregate state. Thus, a system having a miscibility gap may actually be formed in the first instance by addition of the inert liquid; alternatively, it is even possible to enlarge the miscibility gap, so that interesting effects are obtained.

By selecting the temperature difference between the temperature of the solution to be sprayed and the temperature of the gas into which the solution is sprayed, it is possible to vary the properties of the powder. In particular, the particulate form of the powder and the nature of the power volume, for example may be controlled by the choice of temperature. In cases where the temperature difference is relatively slight, the particulate form of the resulting powders assumes a more spherical character.

It is advantageous for the difference in temperature between the solution and the gas to be as large as possible. Accordingly, it is preferred to spray the solution into a gas which is at room temperature.

On solidification, the powder accumulates in a more or less irregular form, depending on the cooling conditions. In many cases, it is still covered externally by a film of active substance, so that a certain tackiness may be developed.

However, this tackiness is not so intense as to render separation of the individual particles impossible. On the contrary, the powder obtained in this way may generally be split up very easily into its individual particles, for example by dispersion into another liquid or even mechanically.

It is particularly advantageous for the powder to be subjected to a rinsing treatment after solidification, which gives particularly free-flowing particles that may be handled in the same way as dry powders, granules or granulates. Rinsing is carried out by a brief, simple treatment with a suitable solvent or cleaning agent, such as an alcohol.

The viscosity of the solution to be sprayed may be varied within wide limits although it is advantageous for the viscosity to amount to no more than 5 Pa.s. A viscosity of this order may be adjusted by correspondingly adjusting the polymer concentration, by the choice of the molecular weight of the polymer, by the temperature and also by the choice of the active substance and of the additional liquid optionally used.

It is self-evident that the viscosity of the solution to be sprayed is adjusted before spraying to an appropriate value which, in many cases, is also governed by the spraying process, for example by the choice of the spraying nozzle, the gas used and the temperature of the gas.

The polymers used are, in particular, low molecular weight polymers having a molecular weight of up to 40,000 Daltons.

In cases where inert liquids are additionally used, it is particularly preferred to use liquids of the type mentioned in U.K. Patent Application No.

83 03773. Above all, the edible oils and edible fats mentioned therein are particularly suitable for numerous applications because they are non-toxic, harmless substances which are required for a variety of different purposes.

The gas into which the solution is sprayed in accordance with the present invention may be under normal atmospheric pressure. However, it is also possible, although not generally necessary, to work under reduced pressure.

It was particularly surprising to find that it is possible in accordance with the present invention to produce microporous powders charged with active substance which are capable of releasing the active substance under control, i.e. uniformly, over a prolonged period.

The present invention may be applied to a wide variety of applications and, in addition to the applications mentioned above, may also be used, inter alia, for the prolonged release of hormones, a variety of medicaments for veterinary and human medicine, in forestry and agriculture.

Another advantage resides in the fact that the spraying operation may be carried out very easily using conventional nozzles known from process technology of the type described, for example, in Ullmanns Enzyklopadie Der Technischen Chemie, Vol. 1,3rd Edition, 1951, pages 728 to 731, or Ullmanns Enzyklopadie Der Technischen Chemie, Vol II, 4th Edition, 1972, pages 254 to 258.

Production of the microporous powders charged with active substances may be carried out very easily and economically. To this end, for example, a solution is prepared from a polymer, such as polyamide-6, an active substance, such as methyl nonyl ketone, and y-butyrolactone as inert pore-forming agent by heating, optionally with stirring. In this connection, it is preferred to prepare a solution which has a maximum viscosity of 5 Pa.s.

Spraying into air or gas is an extremely simple operation which does not involve technical problems.

In addition to the nozzles mentioned in Ullmanns Enzyklopadie, other suitable nozzles are the nozzles known from the production of hollow fibres. In these so-called two-bore nozzles, the internal bore may be used for ejecting the solution; a hot gas under pressure may be passed through the outer, annular opening, the spraying effect being improved in a particular way.

It was particularly surprising to find that the powders produced in accordance with the present invention contain a large number of inner, effective voids in which the active substance is stored and, in addition have a relatively uninterrupted surface which ensures that the active substance is released to the surrounding environment in constant, precisely measured quantities over a prolonged period. In this way, an outstanding long-term effect is obtained.

The surface or rather the skin of the powder formed in accordance with the present invention is relatively uninterrupted so that the active substance is not released prematurely and in excessive concentrations at the beginning of the release process, but does contain sufficient openings to enable the active substance to emerge from the powder charged with active substance.

The present invention is illustrated by the following Examples: Example 1 A solution of 10% of polyamide-6 (solution viscosity 2.5), 80% of y-butyrolactone and 10% of methyl nonyl ketone (active substance) was prepared at approximately 1 9000 and sprayed with compressed air at 2000C through a twobore nozzle into a relatively large collecting vessel at room temperature. The resulting powder had a pore volume of 62%, as determined by mercury porosimetry after extraction of the powder.

Example 2 A solution of 10% of polypropylene, 27% of castor oil and 63% of isopropyl myristate is sprayed into air at approximately 2500C. The polypropylene powder formed has a pore volume of approximately 70%.

A conventional hollow filament nozzle with diameters of 1.5,0.9 and 0.65 mm was used in both Examples.

Claims

1. A process for the production of a microporous powder charged with an active substance for the controlled release thereof, which comprises spraying into a gas a homogeneous solution of a polymer an active substance and, optionally, an inert liquid.

2. A process as claimed in claim 1, wherein a pore-forming active substance is used.

3. A process as claimed in claim 1 or claim 2, wherein a pore-forming inert liquid is used.

4. A process as claimed in any of claims 1 to 3, wherein a homogeneous solution of a polymer and an active substance that form a binary system which, in its liquid aggregate state, comprises a region of complete miscibility and a region having a miscibility gap, is used and the solution having a temperature above the separation temperature is sprayed into a gas having a temperature below the separation temperature.

5. A process as claimed in any of claims 1 to 4, wherein an inert liquid which is a non-solvent for the polymer is used.

6. A process as claimed in any of claims 1 to 5, wherein a solution containing from 20 to 70% of active substance and from 30 to 80% of inert liquid is used.

7. A process as claimed in any of claims 1 to 6, wherein the powder is rinsed after spraying.

8. A process as claimed in any of claims 1 to 7, wherein a poiyamide-6 is used as the polymer.

9. A process as claimed in claim 8, wherein ybutyrolactone is used as the inert liquid.

10. A process as claimed in claim 1 substantially as herein described with particular reference to the Examples.

11. A microporous powder which comprises a thermoplastic polymer charged with an active substance for the controlled release thereof, which has a porosity of from 60 to 80%, an outer skin of the thermoplastic polymer having a thickness of from 0.1 to 1 ,um and an opening content of from 2 to 20%, the openings in the outer skin having a diameter of up to 1 ym.

12. A powder as claimed in claim 11 substantially as herein described with particular reference to the Examples.