BRPI0904401A2 - formulation for oral distribution - Google Patents

Abstract

FORMULATION FOR ORAL DISTRIBUTION. The present invention is for the formulation of an oral potion including a mixture of: at least one lipophilic macrocyclic lactone type compound in combination with; at least one hydrophilic anthelmintic compound; characterized by the fact that the compound or compounds of the lipophilic macrocyclic lactone type are mixed with oil, where the oil is characterized by including ricinoleic acid.

Description

Report of the Invention Patent "FORMULATION FOR ORAL DISTRIBUTION"

TECHNICAL FIELD

The invention relates to an oral distribution formulation. More specifically, the invention relates to a formulation comprising a stabilized anthelmintic agent for use in oral formulations.

PREVIOUS TECHNIQUE

Stabilization and delivery of combinations of anthelmintic agents for oral administration have already been considered in the prior art. A wide variety of advantages may be obtained by such combinations and these are discussed in prior art patent reports including WO 00/74489 and WO02 / 09764, incorporated herein by reference.

In particular, WO 00/74489 (NuFarmLt d) describes the stabilization of an agentelipophilic (such as abamectin) on an organic phaseliquid such as oil. The report describes that a levisol-containing aqueous phase can then be added to the organic phase without stability. Lipophilic agents in the organic phase are described as liquid particles or globules suspended in the aqueous phase.

WO 02/09764 (Byron Bassett Ltd) teaches a formulation containing a hydrophilic agent (including Levaisol) together with a lipophilic agent (including various macrocyclic lactone compounds). The formulation is a microemulsion and the lipophilic agent is carried in the oil which is suspended in the hydrophilic agent solution. Important examples in the above formulations use sesame, soybean or canola oils as the preferred carrier substances for the lipophilic agent or agents. It should be appreciated that these oils are simple oils which, according to the inventors' experience, do not solubilize poorly soluble anthelmintic compounds including aabamectin. The prior art solves the problem of insolubility by including solvents such as benzyl alcohol and a bulky organic phase (1-60% w / v).

Oils such as castor oil are not contemplated. Castor oil is a fatty oil extracted from castor seeds. Castor oil is extraordinary in that it consists almost entirely (90%) of unusual unsaturated ricinoleic acid glycerides. Its chemical structure is shown below:

<formula> formula see original document page 3 </formula>

Hydroxy fatty acids such as acids are rarely found in natural oils and no other natural oil has the same purity as castor oil in terms of acyl groups.

Ricinoleic acid is also effective in preventing the growth of numerous species of viruses, bacteria, yeast and mold. It is also toxic, biodegradable and renewable which makes it a useful carrier substance.

WO 00/74489 (NuFarm Ltd) describes various oils that can be used (particularly soybean and canola oils) but does not teach the use of castor oil nor recognize the extraordinary attributes of this oil.

WO 02/09764 (Byron Bassett Ltd) teaches the use of various oils and (in passing) mentions the use of castor oil. Although castor oil is mentioned, no examples are shown showing the use of castor oil nor any teaching on the use of castor oil for improved stability.

NZ534704 (Norbrook) teaches the use of various solvent systems including glycerolformal, polyethylene glycol and / or propylene glycol to help stabilize and distribute mixtures of avermectins and milbemycins.

Achieving a highly stable formulation is desirable as well as meeting other formulation requirements such as dispensing efficacy, prevention of side effects and so on. It should therefore be appreciated that it would be desirable to have a formulation that satisfies all these factors and increases stability over those already known.

It is an object of the present invention to solve the above problems or at least to offer the public a useful choice.

All references, including any patents or patent applications mentioned in this report, are hereby incorporated by reference. None of the references are recognized as prior art. The discussion of references establishes what the authors believe and the applicants reserve the right to dispute the accuracy and appropriateness of the cited documents. It will be clearly understood that, although numerous prior art publications are mentioned in this report, such reference does not constitute acknowledgment of any of these documents. part of the general knowledge common in the art, whether in New Zealand or any other country.

We recognize that the term 'understand' may, according to jurisdiction, be assigned a unique meaning or an inclusive meaning.

For the purposes of this report, and unless otherwise specified, the term "understand" shall have an inclusive meaning - i.e. it shall be deemed to include not only the components listed therein but also other components or elements not specified. This premise may also be used when the term ^ understood 'orλ comprising' is used with respect to one or more steps in a method or process.

Other aspects and advantages of the present invention will become apparent from the following description which is given by way of example only.

DESCRIPTION OF THE INVENTION

The invention broadly relates to the surprising capabilities and improved stability and solubility in aqueous solutions of a lipophilic macrocyclic agent when mixed with oleage includes ricinoleic acid.

According to one aspect of the present invention we provide an oral potion formulation including a mixture of:

(a) at least one lipophilic lactonamacrocyclic type compound in combination with;

(b) at least one anthelmintichydrophilic compound;

characterized in that the compound or lipophilic macrocyclic lactone type compounds are mixed with oil, where the oil is characterized by including ricinoleic acid.

According to another aspect of the present invention we offer a method for stabilizing and solubilizing at least one lipophilic lactonamacrocyclic type compound in an aqueous solution by the steps of:

(a) mixing the compound or compounds of lipophilic macrocyclic tipolactone with an oil wherein the oil is characterized by including ricinoleic acid;

(b) suspending the mixture from step (a) in aqueous solution.

According to another aspect of the present invention we offer a formulation containing at least one stabilized and solubilized macrocyclical lipophilic lactone-type compound produced by the method substantially as described above.

According to another aspect of the present invention we offer a method for producing an oral potion formulation comprising a mixture of at least one lipophilic lactonamacrocyclic type compound in combination with at least one hydrophilic anthelmintic compound by the steps of:

(a) mixing the lipophilic macrocyclic tipolactone compound or compounds with an oil wherein the oil is characterized by including ricinoleic acid, (b) suspending the mixture of step (a) in aqueous solution including at least one hydrophilic anthiophilic compound.

According to another aspect of the present invention we offer an oral potion formulation including a mixture of at least one lipophilic macrocyclic lactone compound in combination with at least one anthelmintic hydrophilic compound produced by the method substantially as described above.

According to another aspect of the present invention we offer a method for treating a non-human animal of a parasitic infestation by administering to the animal in need of the substantially described oral potion formulation above.

In accordance with another aspect of the present invention we offer the use of a formulation substantially as described above in the manufacture of a medicament for the treatment of a parasitic infestation in an animal.

The inventors have found that when dissolved in castor oil or similar chemical oil, normally insoluble and lipophilic macrocyclic agents can be stabilized and then mixed with aqueous solutions and other hydrophilic active agents. The stability obtained by the use of castor oil or oleosimilar oil is also higher than expected and still meets other formulation requirements such as distribution effectiveness. Further, it is not necessary to add other cosolvents to obtain the desired effects as in prior art methods. Preferably, the formulation is stable when stored for a period of at least 12 months under ambient temperature and humidity conditions. For the purposes of this report, the term 'stable' refers to the chemical stability for at least 12 months (eg within the product's shelf life) of the active agent when stored at or below 25 ° C and ambient humidity and acceptable physical stability. that the composition is substantially homogeneous. As with most oral formulations, suspended actives and excipients may sediment when stored for a certain period of time but the formulation of the present invention may easily be suspended prior to use. In addition, the term stable refers to the formulation which remains at a stationary pH, viscosity and density thus maintaining the desired properties for the oral potion application.

The inventor understands that the compound or lipophilic macrocyclic lactone-like compounds mixed with the oil are suspended in the hydrophilic anthelmintic compound. The inventor further understands that the oil which solubilizes the lipophilic agent dissolves the agent in the micelles of the oily compound and thus 'isolates' the lipophilic agent from the environment.

As will be appreciated by those skilled in the art, an essential advantage of the formulation of the present invention is that lipophilic or poorly soluble agents may be mixed with hydrophilic agents to form combined formulations. Upon dissolution, the lipophilic agent does not mix with the hydrophilic agent or the mixture of the two may result. in unwanted reactions or degradation in agent activity.

Preferably, the oil contains approximately 90% ricinoleic acid. More preferably, the oil is castor oil. In preferred embodiments, castor oil used to dissolve a lipophilic agent is relatively viscous and has a high specific gravity compared to most oils. In particular, castor oil is rich in ricinoleic acid. It should be appreciated that while castor oil is a particularly preferred oil, synthetic variant with properties similar to dericin oil can also be used without departing from the scope of the invention.

It is considered that the extraordinary structure of castor oil may help to produce the increased stability observed. More specifically, the inventor understands that ester bonds, double bonds, and castor hydroxyl groups help solubilize the lipophilic agent or agents. In this invention, the remarkable chemical structure of this oil is effective in stabilizing the lipophilic agent and allows it to be mixed with once stabilized hydrophilic solutions.

Preferably, the formulation includes the oil in a ratio of less than 1% w / v of the finished formulation. It should be appreciated by those skilled in the art that this is a low amount of organic phase to achieve the desired effects. In contrast prior art products use more than 1% w / v organic phase and require the use of solvents.

Preferably, the lipophilic macrocyclic lactone-type compound or compounds are a compound or avermectin compounds. More preferably, the lipophilic macrocyclic tipolactone compound or compounds are selected from: abamectin, ivermectin, and combinations thereof.

Preferably, the hydrophilic agent or agents to which the dissolved lipophilic agents may be dispersed using the formulation of the invention include imidotols such as Levaisol HCl.

Preferably, other anthelmintic agents may also be included in the hydrophilic anthelmintic compound. In the preferred embodiments the other anthelmintic agents are selected from: substituted or unsubstituted benzyimidazoles, closantel, praziquantel, and echombinations thereof. Preferably, these agents are suspended in the aqueous solution containing the hydrophilic anthelmintic compound.

Preferably, the lipophilic macrocyclic lactone-type compound or compounds and the hydrophilic anthelmintic compound or compounds in the formulation are included at a sufficient dose to: prevent parasite growth; reduced number of parasites; eliminate parasites; eliminate ingested parasite larvae; reduce the amount of parasite larvae ingested; and combinations of the same.

In preferred embodiments, hypophilic lactonamacrocyclic is included in the formulation at a ratio of approximately 0.05% to 0.2% w / v. In preferred embodiments, the compound or hydrophilic anthelmintic compounds are included in the formulation at a ratio of approximately 2% to 5%. % w / v.

Specific examples are now offered based on the description above.

In one embodiment, the formulation is an oral potion including abamectin dissolved in dericin oil and suspended in an aqueous solution containing levamisol HCl.

In another embodiment, the formulation is an oral composition including abamectin dissolved in castor oil and suspended in an aqueous solution containing Levaisol HCl together with oxfendazolsuspended.

In another embodiment, the formulation is an oral composition including a combination of abamectin dissolved in castor oil and suspended in an aqueous solution containing suspensis comprisivol HCl together with suspended compraziquantel and albendazole.

In another embodiment, the formulation is an oral composition including a combination of castor oil-dissolved abamectin and suspended in aqueous solution containing Levaisol HCl with closantele albendazole.

In another embodiment, the formulation is an oral composition including a combination of ivermectin dissolved in castor oil and suspended in an aqueous solution containing Levaisol HCl together with suspended compraziquantel and albendazole.

Those skilled in the art should also appreciate that producing a desanature formulation is particularly challenging. In addition to the lipophilic versus hydrophilic nature of such combinations, different agents may require very different pH ranges to remain stable. The present invention addresses these pH challenges.

As an example, for a combination of deabamectin and Levamisol HCl, Levamisol HCl is hydrophilic and for better stability it is in an aqueous solution at a pH between 4.0 and 4.5. In contrast, abamectin is stable at higher pH levels (approximately 6.8). By dissolving abamectin in the manner described above, abamectin is 'protected' or 'isolated' from the low pH aqueous medium by the castor oil that carries abamectin.

In preferred embodiments, the dissolved agent is formulated for oral administration to an animal.

To help form a suspension suitable for oral administration to an animal, thickening agents or viscosity agents may be used. In one embodiment, the agent or agents include polysaccharides. Specific examples include xanthan gum and carboxymethylcellulose polymers.

Xanthan gum is a material that can produce a large increase in the viscosity of a liquid solution by adding a very small amount of gum of the order of a few percent. Xanthan in particular is a very stable gum over a wide range of temperatures and pH, and is accepted for use in food and pharmaceutical applications.

Carboxymethylcellulose, and in particular, Celloge ™ is a type of high purity polymer used for example in the manufacture of toothpastes to disperse and swell the ingredients in formulations such as toothpaste and thus form a viscous phase. The viscous phase prevents water separation of the different components in the toothpaste and improves storage stability. Carboxymethylcoseis also assists in dispersion upon administration.

Other thickening agents include polyvinylpyrrolidone (PVP) and colloidal silicon dioxide which also acts as dispersing agents.

In other embodiments, the formulation may include pH-adjusting solutions and buffers known in the art to adjust the pH of the aqueous solution to a level that is compatible with water phase agents. In one embodiment, pH adjusting agents include citric acid and / or sodium hydroxide.

Other agents may also be added to the formulation and these include preservatives, wetting agents, solubilizers and other inert carrier substances. Examples include methylparaben, propyl paraben, and polyoxyethylenesorbitan esters such as polysorbate 80 esorbitol.

Agents other than anthelmintic agents are also considered to be added to the formulation. For example, in rural applications, other nutrients such as trace minerals may be added to the formulation to allow the animal to be medicated with pesticides but also to improve animal nutrition.

In one embodiment mineral supplementation may be included in the formulation to provide a source of cobalt, copper, iodine, selenium and zinc.

From the above description it should be appreciated that we provide a formulation for delivery of one or more macrocyclical lipophilic lactone agents in a stable and aqueous form. Formulation has the advantage that it can be further formulated for aqueous oral delivery which is more 'bio-sustainable' and causes less potential side effects when administered. Also, as stabilized lipophilic macrocyclic alactone may be mixed with aqueous solutions, other aqueous phase-soluble hydrophilic agents may also be co-administered in the same formulation. This both increases the efficacy of the product (several parasite spectra can be attacked in one dose) and also saves you the trouble of not having to apply two or more different products. Finally, the method increases the stability of the lipophilic agent in pH ranges outside those normally used to maintain the lipophilic stable agent based on the traditional oils used in such formulations.

BEST MODES FOR CARRYING OUT THE INVENTION

The following are examples showing various embodiments of the present invention and their respective stability measured in terms of asset levels, pH, density and viscosity.

EXAMPLE 1

This formulation refers to a combined oral potion containing the active agents abamectin elevamisol together with a supplemental mineral mixture. This formulation is a formulation intended for administration to sheep.

The compositions used in this example are shown in Table 1.

TABLE 1

<table> table see original document page 15 </column> </row> <table>

The formulation and steps:

1. Charge deionized water.

2. Disperse xanthan gum in propylene glycol and add to dough.

3. Add and dissolve Levaisol HCl in the mass.

4. Dissolve abamectin by heating castor oil to 100 ° C, dissolve abamectin in oil and cool to room temperature and add to dough.

5. Dissolve methyl paraben and propylparaben in polysorbate 80 and add to dough.

6. Dissolve the citric acid and trace elements in water and add to the mass.

7. Add Wacker silica to the batter.

8. Homogenize the solution in massesultant.

9. Dissolve sodium hydroxide in water and adjust mass pH to 4.1-4.4 using sodium hydroxide solution.

10. Make up to volume with water.

The above formulation includes stabilized abamectin dissolved in a dericin oil base which is then combined with an evami sol HCl solution.

Table 2 below shows the stability of the above formulation over a period of 12 months stored at 25 ° C and 60% relative humidity.

As can be seen, minimal changes in active agent concentration, pH, nadensity and viscosity were observed.

TABLE 2

<table> table see original document page 16 </column> </row> <table> <table> table see original document page 17 </column> </row> <table>

EXAMPLE 2

This formulation refers to a combined oral potion containing the active agents oxfendazole, Levaisole and Abamectin together with a mineral supplement mixture. The compositions used in this example are shown in Table 3.

TABLE 3

<table> table see original document page 17 </column> </row> <table> <table> table see original document page 18 </column> </row> <table>

The formulation is prepared by the following steps:

1. Charge deionized water. Add and dissolve the plasdone K25 with mixing.

2. Dissolve methyl paraben and propylparaben in polysorbate 80. Disperse gomaxanthan and add to dough.

3. Add and dissolve Levaisol HCl in the mass.

4. Suspend oxfendazole in the dough

5. · Dissolve abamectin by heating castor oil to 100 ° C, dissolve abamectin in oil and cool to room temperature and add to dough.

6. Dissolve the citric acid and trace elements in water and add to the mass.

7. Add Wacker silica to the batter.

8. Homogenize the solution in massesultant.

9. Dissolve sodium hydroxide in water and adjust mass pH to 4.1 to 4.4 using sodium hydroxide solution.

10. Make up to volume with water.

The above formulation includes stabilized abamectin dissolved in a dericin oil base which is then combined with a suspended oxfendazole containing delevamisol HCl solution.

Table 4 below shows the stability over a 12 month period for the formulation of delevamisol, abamectin and oxfendazole described above when stored at 25 ° C and 60% relative humidity. As can be seen, minimal changes in active agent concentration, pH , nadensity and viscosity.

TABLE 4

<table> table see original document page 19 </column> </row> <table>

EXAMPLE 3

This formulation refers to a combined oral potion containing the active agents praquiquant1, albendazole, Levaisole and Abamectin together with a mineral supplement mixture. The compositions used in this example are shown in Table 5.

TABLE 5

<table> table see original document page 19 </column> </row> <table> <table> table see original document page 20 </column> </row> <table>

The formulation is prepared by the following steps:

1. Charge deionized water. Add and dissolve K25 plasdone with mixing.

2. Dissolve methyl paraben and propylparaben in polysorbate 80. Disperse gomaxanthan and add to dough.

3. Add and dissolve Levaisol HCl in the mass

4. Add sorbitol to dough.

5. Suspend pra z i quant e1 and albendazole in the mass

6. Dissolve the abamectin by heating castor oil to 100 ° C, dissolve the abamectin in the oil and cool to room temperature and add to the mass.

7. Dissolve the citric acid and trace elements in water and add to the mass.

8. Add Wacker silica to the batter.

9. Add the plasdone K25 to the dough.

10. Dissolve sodium hydroxide in water and adjust mass pH to 4.0-4.4 using sodium hydroxide solution.

11. Make up to volume with water.

The above formulation includes stabilized abamectin dissolved in a dericin oil base which is then combined with a delevamisol HCl solution containing suspended albendazole and praziquantels.

Table 6 below shows the stability over a 12 month period for the formulation of delevamisol, abamectin, albendazole and praziquantelima when stored at 25 ° C and 60% relative humidity. As can be seen, minimal changes in active agent concentration, pH, density and viscosity were observed.

TABLE 6

<table> table see original document page 21 </column> </row> <table> <table> table see original document page 22 </column> </row> <table>

EXAMPLE 4

This formulation refers to a combined oral potion containing the active agents Levaisol, Albendazole, Closantel and Abamectin together with a mineral supplement mixture. The compositions used in this example are shown in Table 7.

TABLE 7

<table> table see original document page 22 </column> </row> <table> <table> table see original document page 23 </column> </row> <table>

The formulation is prepared by the following steps:

1. Charge deionized water. Add and dissolve K25 plasdone with mixing.

2. Dissolve methyl paraben and propylparaben in 80.xanthan polysorbate and add to dough.

3. Add and dissolve Levaisol HCl in the mass.

4. Suspend closantel and albendazole in the dough.

5. Dissolve abamectin by heating castor oil to 100 ° C, dissolve abamectin in oil and cool to room temperature and add to dough.

6. Dissolve the citric acid and trace elements in water and add to the mass.

7. Add Wacker silica to the batter.

8. Add K25 plasdone to the dough.

9. Mix the solution in massesultant.

10. Dissolve sodium hydroxide in water and adjust mass pH to 4.1-4.4 using sodium hydroxide solution.

11. Make up to volume with water.

The above formulation includes stabilized abamectin dissolved in a dericin oil base which is then combined with a delevamisol HCl solution containing albendazole and suspended closantels.

Table 8 below shows the stability over a 12 month period for a formulation of Levaisol, Abamectin, Albendazole and Closantel when stored at 25 ° C and 60% relative humidity. As can be seen, minimal changes in active agent concentration, pH, nadensity and viscosity were observed.

TABLE 8

<table> table see original document page 24 </column> </row> <table> <table> table see original document page 25 </column> </row> <table>

EXAMPLE 5

This formulation refers to a combined oral potion containing the active agents albendazole, Levaisol, praziquantel and ivermectin together with a mineral supplement mixture.

The compositions used in this example are shown in Table 9.

TABLE 9

<table> table see original document page 25 </column> </row> <table> <table> table see original document page 26 </column> </row> <table>

The formulation prepared by the following steps:

1. Charge 15L of deionized water.

2. Add and dissolve Cellogen 7A with mixing,

3. Add and dissolve Levamisol HCL with mixing.

4. Add and suspend Praziquantel and Albendazole with silverson mixture.

5. In a separate container, heat the castor oil to 70 ° C - 80 ° C and dissolve the Ivermectin. Cool to room temperature and add to the mass with mixing.

6. Add and dissolve the Plasdone K25 with mixing.

7. In a separate container, pre-dissolve omethyl paraben and propyl paraben in Polysorbate 80.

8. Add 4.5L of deionized water, asylum Wacker, 70% pre-dissolved Step Ieo Sorbitol Polysorbate 80 with desilverson mixture.

9. Add and dissolve citric acid, sodium oselenate and cobalt edetate with mixing.

10. In a separate container dissolve sodium hydroxide in 1.5L of deionized water.

11. Adjust pH to 4.0 - 4.4 using the sodium hydroxide solution from step 10.

12. Make up to volume with deionized water and mix for 1 hour.

The above formulation includes stabilized ivermectin dissolved in a dericin oil base which is then combined with a delevamisol HCl solution containing suspended albendazole and praziquantels.

Table 10 below shows the stability over a period of 27 months for the formulation of delevamisol, ivermectin, albendazole and closantel described above when stored at 25 ° C and 60% relative humidity. As can be seen, minimal changes in active agent concentration, pH, density and viscosity were observed.

TABLE 10

<table> table see original document page 27 </column> </row> <table> <table> table see original document page 28 </column> </row> <table>

It will be appreciated from the above description that the formulation of the present invention provides a stabilized lactocyclic lactonamacrine such as abamectin eivermectin dissolved in castor oil, and which may be mixed in an aqueous solution including other hydrophilic agents such as Levaisol HCl. The formulation is stable at room temperature.

Aspects of the present invention have been described by way of example only and it should be appreciated that modifications and additions may be made thereto without departing from its scope in the appended claims.

Claims (48)

1. Formulation for Oral Distribution CHARACTERIZED as an oral potion formulation including a mixture of: (a) at least one lipophilic lactonamacrocyclic type compound in combination with (b) at least one anthelmintichydrophilic compound; macrocyclical lipophilic lactone type compounds are mixed with oil, where the oil is characterized by including ricinoleic acid. A formulation according to claim 1 wherein the formulation is stable when stored for a period of at least 12 months under ambient temperature and humidity conditions. A formulation according to claim 1 or claim 2 wherein the oil-lipophilic macrocyclic lactone-like compound or compounds are suspended in the hydrophilic anthelmintic compound. Formulation according to any one of the above claims wherein the oil contains approximately 90% by weight of acidic kinetic acid. Formulation according to any of the above CHARACTERIZED claims where the oil is castor oil. Formulation according to any one of the above CHARACTERIZED claims wherein the oil is included to a ratio less than 1% by weight of the finished formulation. Formulation according to any one of the above claims wherein the compound or macrocyclical lipophilic lactone type compounds are selected from: abamectin, ivermectin, and combinations thereof. A formulation according to any one of the above claims wherein the hydrophilic antihelminthic compound is Levaisol HCl. Formulation according to any one of the above claims wherein the compound or macrophilic macrocyclic lactone type compounds and the hydrophilic anthelmintic compound or compounds in the formulation are included at a dose sufficient to: prevent parasite growth; reduce the number of parasites; eliminate parasites; eliminate ingested parasitic larvae; reduce the amount of parasite larvae ingested; and combinations thereof. A formulation according to any one of the above claims wherein the hypophilic lactonamacrocyclic is included in the formulation at a ratio of approximately 0.05% to 0.2% w / v. Formulation according to any one of the above claims wherein the compound or hydrophilic anthelmintic compounds are included in the formulation at a ratio of approximately 2% to 5% w / v. A formulation according to any one of the above claims wherein the hydrophilic anthelmintic compound also includes other anthelmintic agents. A formulation according to claim 12 wherein the other agents are selected from: substituted or unsubstituted benzamide, closantel, praziquantel, and combinations thereof. Formulation according to any one of the above claims wherein the formulation also includes selected xanthan gum-emodifying thickeners, carboxymethylcellulose polymers, polyvinylpyrrolidone, colloidal silicon dioxide and combinations thereof. Formulation according to any one of the above claims wherein the formulation also includes pH adjusting agents including citric acid, sodium hydroxide and combinations thereof. Formulation according to any one of the above claims wherein the formulation also includes preservatives, wetting agents, solubilizers and other inert carrier substances selected from: methylparaben, propyl paraben, polyoxyethylene sorbitanesters including polysorbate 80, sorbitol, echombinations thereof. Formulation for Oral Distribution CHARACTERIZED for being an oral potion formulation including abamectin dissolved in castor oil and suspended in an aqueous solution containing LevaisolHCl. Formulation for Oral Distribution CHARACTERIZED for being an oral potion formulation including abamectin dissolved in castor oil and suspended in an aqueous solution containing LevaisolHCl together with suspended oxfendazole. 19. Oral Distribution FormulationCARACTERIZED as an oral potion formulation including a combination of abamectin dissolved in castor oil and suspended in an aqueous solution containing Levamisol HCl together with suspended ζanthanel and albendazole. 20. Formulation for Oral Distribution CHARACTERIZED as an oral potion formulation including a combination of abamectin dissolved in castor oil and suspended in an aqueous solution containing Levaisol HCl with closantel ealbendazole. 21. Oral Distribution FormulationCARACTERIZED as an oral potion formulation including a combination of ivermectin dissolved in castor oil and suspended in an aqueous solution containing Levaisol HCl together with suspended compraziquantel and albendazole. 22. Formulation for Oral Delivery CHARACTERIZED for being an oral potion formulation including a mixture of at least one lipophilic macrocyclic lactone type compound in combination with castor oil, substantially as described above and with reference to the Examples. 23. Formulation for Oral Distribution CHARACTERIZED as a method for stabilizing and solubilizing at least one lipophilic lactonamacrocyclic type compound in an aqueous solution by the steps of: (a) mixing the lipophilic macrocyclic tipolactone compound or compounds with an oil wherein the oil is characterized by including acid (b) suspending the mixture from step (a) in aqueous solution. A method according to claim 23 wherein the mixture resulting from step (b) is stable when stored for a period of at least 12 months under ambient temperature and humidity conditions. A method according to claim 23 or claim 24 wherein the oil contains approximately 90% by weight of acid. A method according to any one of claims 23 to 25 wherein the oil is oleodicin. A formulation according to any one of claims 23 to 26 wherein the oil is included at a rate of less than 1% by weight of the finished formulation. A method according to any one of claims 23 to 27 wherein the macrocyclic lactophilic compound or lactone-like compounds are selected from abamectin, ivermectin, and combinations thereof. A method according to any one of claims 23 to 28 wherein the macrocyclic lactophilic compound or lactone-like compounds are included at a dose sufficient to: prevent the growth of parasites; reduced number of parasites; eliminate parasites; eliminate ingested parasite larvae; reduce the amount of parasite larvae ingested; and combinations of the same. A method according to any one of claims 23 to 29 wherein the hypophilic lactonamacrocyclic is included in the formulation at a ratio of approximately 0.05% to 0.2% w / v. A method according to any one of claims 23 to 30 wherein the aqueous solution also includes other anthelmintic agents. A method according to claim 31 wherein the other agents are selected from: Levaisol HCl, substituted or unsubstituted benzimidazoles, closantel, praziquantel, and combinations thereof. 33. Formulation for Oral Distribution CHARACTERIZED as a method for stabilizing and solubilizing at least one lipophilic lactonaraacrocyclic type compound in an aqueous solution substantially as described above and with reference to the Examples. Formulation for Oral Delivery A formulation comprising at least one stabilized and solubilized macrocyclic lactone-type compound produced by the method according to any one of claims 23 to 32. 35. Formulation for Oral DistributionCharacterized as a method for producing an oral potion formulation including a mixture of at least one macrocyclic lactophilic lactone type compound in combination with at least one hydrophilic anthelmintic compound by the steps of: (a) mixing the compound or compounds of the lipophilic macrocyclic typolactone with an oil wherein the oil is characterized by including ricinoleic acid, (b) suspending the mixture of step (a) in an aqueous solution including at least one hydrophilic anthelmintic compound. A method according to claim 35 wherein the mixture resulting from step (b) is stable when stored for a period of at least 12 months under ambient temperature and humidity conditions. A method according to claim 35 or claim 36 wherein the oil contains approximately 90% by weight of acid. A method according to any one of claims 35 to 37 wherein the oil is castor oil. A method according to any one of claims 35 to 38 wherein the oil is included at a rate of less than 1% by weight of the finished formulation. A method according to any one of claims 35 to 39 wherein the macrocyclic lactophilic compound or lactone-like compounds are selected from: abamectin, ivermectin, and combinations thereof. A method according to any one of claims 35 to 40 wherein the macrocyclic lipophilic compound or lactone-like compounds are included at a sufficient dose to: prevent parasite growth; reduced number of parasites; eliminate parasites; eliminate ingested parasite larvae; reduce the amount of parasite larvae ingested; and combinations of the same. A method according to any one of claims 35 to 41 wherein the hypophilic lactonamacrocyclic is included in the formulation at a ratio of approximately 0.05% to 0.2% w / v. A method according to any one of claims 35 to 42 wherein the aqueous solution also includes other anthelmintic agents. A method according to claim 43 wherein the other agents are selected from: Levaisol HCl, substituted or unsubstituted benzyimidazoles, closantel, primer1, and combinations thereof. 45. Formulation for Oral Delivery A method for producing an oral composition including a mixture of at least one lipophilic macrocyclic lactone-type compound in combination with at least one substantially described hydrophilic anthelmintic compound with reference to the Examples. Formulation for Oral Delivery A composition which is an oral potion formulation including a mixture of at least one lipophilic macrocyclic lactone type compound in combination with at least one anthelmintic hydrophilic compound produced by the method according to any one of claims 35 to 44. Formulation for Oral Delivery A method for treating a parasitic infestation in a non-human animal by administering to the animal in need thereof the oral potion formulation according to any one of claims 1 to 21. Formulation for Oral Distribution CHARACTERIZED by the use of the formulation according to any one of claims 1 to 21 in the manufacture of a medicament for treating a parasitic infestation in an animal.