WO2010062261A1

WO2010062261A1 - System and method for preparing a controlled releas preparation

Info

Publication number: WO2010062261A1
Application number: PCT/SG2008/000457
Authority: WO
Inventors: Jarupa Viyoch
Original assignee: The Thailand Research Fund; Naresuan University; Axis Ip Holding Pte Ltd
Priority date: 2008-11-29
Filing date: 2008-11-29
Publication date: 2010-06-03

Abstract

A method for preparing a controlled release preparation. The method comprises forming a coating mixture, coating a core with the coating mixture for forming a hydrogel layer over the core. The method further comprises coating the hydrogel layer with hydrophobic polymers to form a hydrophobic layer over the hydrogel layer. The coating mixture if formed by blending an aqueous dispersion of Chitosan with a polysaccharide colloid composition. An active ingredient is added. The coating mixture is coated onto the core by fluidized bed technology. The hydrophobic polymer is also coated onto the hydrogel layer by fluidized bed technology. A system for preparing the controlled release preparation is also provided by the present invention. An exemplary controlled release preparation is also provided by the present invention.

Description

SYSTEM AND METHOD FOR PREPARING A CONTROLLED RELEASE

PREPARATION

Field Of Invention

The present invention relates generally to controlled release preparations. More specifically, the present invention relates to a system and a method for preparing controlled release preparations.

Background

Controlled release preparations, also known as controlled release pellets and controlled release granules, are commonly used for administration of drugs or supplementary nutrients for human beings and animals. For example, a common use for controlled release preparations is for controlled release of active pharmaceutical ingredients after administration of medication. There exist several methods of administering medication, with oral administration being one of the methods.

Oral administration of medication is a widely used method for administering medication. There are various methods for preparing medication for oral administration and pelletization is one of the commonly adopted methods of preparation in the pharmaceutical industry. Pelletization is a process that converts fine particles of active pharmaceutical ingredients or excipients into small, free flowing, spherical or semi- spherical units known as "pellets".

There exist several typically employed techniques, such as spheronization, extrusion, coating pan and layering for pellet preparation. Generally, a pellet comprises three layers, namely, a sugar core or a non-pareil seed, an inner layer of active ingredient and an outer layer of water-insoluble polymer. Controlled release of the active pharmaceutical ingredient contained in the pellet after oral administration is important for achieving optimal effects of the medication. For instance, pellets having the ability to control the release of the active pharmaceutical ingredient facilitate controlled release of the active pharmaceutical ingredient at a desired location, for example at the intestines, after oral administration. The pellet can also provide a controlled rate of release of the active pharmaceutical ingredient over an extended time period. The controlled release property of pellets is important in ensuring, and improving, pharmaceutical efficacy of drugs.

Besides the pharmaceutical .industry, controlled release preparations are also used in the agricultural industry. Controlled release preparations used for agricultural purposes typically facilitate continuous, and controlled rate of, release of pesticidal active ingredients over an extended time period. This enables desired levels of or amount pesticide to be available against target species over the extended period.

Hydrophilic polymers are typically used for coating pellets or granules to thereby effect controlled release of active ingredient contained therewithin. Hydrophilic polymers include cellulose derivatives and acrylate polymers. Recently, the hydrophilic polymer, Chitosan, has been suggested for use in coating pellets or granules for effecting controlled release of active ingredients due to Chitosan' s wide biocompatibility, biodegradability and non-toxicity. However, the tackiness of Chitosan causes extensive agglomeration of pellets or granules during the coating process. Consequently, this increases the occurrence of defects associated with the use of Chitosan and also impairs the yield and quality of the pellets or granules that are coated with Chitosan. As such, little attention has been paid to, and a person skilled in the art is led away from, potential applications of Chitosan as a hydrophilic polymer for the coating of pellets or granules.

Summary

Embodiments of the present invention provide exemplary methods and system for preparing controlled release preparations for addressing the defects of Chitosan for use as a hydrophilic polymer for coating of pellets or granules. In addition, exemplary controlled release preparations are provided by embodiments of the present invention. In accordance with a first aspect of the present invention, there is disclosed a method for preparing a controlled release preparation comprising forming an aqueous dispersion of Chitosan and forming a polysaccharide colloid composition. The method further comprises blending the aqueous dispersion of Chitosan with the polysaccharide colloid composition for forming a coating mixture, the blending of the polysaccharide colloid composition with the aqueous dispersion of Chitosan performed under predetermined conditions for substantially reducing tackiness of Chitosan. In addition, the method comprises coating a predetermined amount of the coating mixture with hydrophobic polymers wherein the hydrophobic polymers forms a hydrophobic layer over at least part of the coating mixture to thereby reduce tackiness of the controlled release preparation.

In accordance with a second aspect of the present invention, there is disclosed a method for preparing a controlled release preparation comprising forming an aqueous dispersion of Chitosan and forming a polysaccharide colloid composition. The method further comprises blending the aqueous dispersion of Chitosan with the polysaccharide colloid composition for forming a coating mixture, the blending of the polysaccharide colloid composition with the aqueous dispersion of Chitosan performed under predetermined conditions for substantially reducing tackiness of Chitosan. In addition, the method comprises coating a core with a predetermined amount of the coating mixture for forming a first layer over at least part of the core and spraying a predetermined amount of hydrophobic polymer onto the first layer, wherein the hydrophobic polymer forms a second layer over at least part of the first layer to thereby reduce tackiness of the controlled release preparation.

In accordance with a third aspect of the present invention, there is disclosed a method for preparing a controlled release preparation comprising forming an aqueous dispersion of Chitosan and forming a polysaccharide colloid composition. The method further comprises blending the aqueous dispersion of Chitosan with the polysaccharide colloid composition for forming a coating mixture, the blending of the polysaccharide colloid composition with the aqueous dispersion of Chitosan performed under predetermined conditions for substantially reducing tackiness of Chitosan. In addition, the method comprises spraying a predetermined amount of the coating mixture onto a core, wherein the predetermined amount of the coating mixture forms a first layer over at least part of the core.

In accordance with a fourth aspect of the present invention, there is disclosed a system for preparing a controlled release preparation comprising a first module for forming a coating mixture therein, the coating mixture being formed by blending an aqueous dispersion of Chitosan and a polysaccharide colloid composition together, the blending the aqueous dispersion of Chitosan with the polysaccharide colloid being performed under predetermined conditions for substantially reducing tackiness of Chitosan. The system further comprises a second module for facilitating coating of a core with a predetermined amount of the coating mixture, wherein the predetermined amount of the coating mixture forms a first layer over at least part of the core.

In accordance with a fifth aspect of the present invention, there is disclosed a controlled release preparation comprising a predetermined amount of coating mixture, the coating mixture comprising an active ingredient and a blended mixture of an aqueous dispersion of Chitosan and a polysaccharide colloid composition. The controlled release preparation further comprises a hydrophobic layer coating at least part of the predetermined amount of coating mixture, wherein the hydrophobic layer reduces tackiness of the controlled release preparation.

Brief Description Of The Drawings

Exemplary embodiments of the present invention are described hereinafter with reference to the following drawings, in which:

FIG. 1 shows a method flow diagram of an exemplary method for manufacturing a controlled release preparation according to an embodiment of the present invention; FIG. 2 shows a process flow diagram of a process for forming a coating mixture according to a step of the exemplary method of FIG. 1;

FIG. 3 shows a partial cross-sectional view of the controlled release preparation manufactured by the method of FIG. 1 ;

FIG. 4 shows a partial cross-sectional view of the controlled release preparation of FIG. 3 when a hydrophobic layer thereof is ruptured; and

FIG. 5 shows an exemplary system for performing the exemplary method for manufacturing a controlled release preparation of FIG. 1.

Detailed Description

Controlled release preparations are used for administration of drugs or supplementary nutrients for human beings or animals. Hydrophilic polymers are typically used for coating pellets or granules to effect controlled release of active ingredients therewithin. A hydrophilic polymer, Chitosan, has been suggested for use in coating pellets for effecting the controlled release of active ingredients contained therewithin. However, the tackiness of Chitosan can cause agglomeration of pellets during the coating process. This leads to an increased occurrence of coating defects, and consequently impairs the yield and quality of coated pellets. The present invention provides a system and a method for preparing a controlled release preparation for addressing the aforementioned problems.

For purposes of brevity and clarity, the description of the invention is limited hereinafter to applications relating to preparation of controlled release preparations. This however does not preclude various embodiments of the invention from other applications where fundamental principles such as functional, operational and performance characteristics are required. Description of preferred embodiments of the present invention is provided hereinafter with reference to FIG. 1 to FIG. 5, in which like elements are numbered with like reference numerals.

An exemplary method 100 for manufacturing a controlled release preparation 10, for example a controlled release pellet or controlled release granule as shown in FIG. 1 is provided according to an embodiment of the present invention.

The exemplary method 100 comprises a first step 110 of forming a coating mixture and a second step 120 of coating a core 20 with the coating mixture. The coating of the core 20 in the step 120 results in formation of a hydrogel layer 30 over the core 20. The method 100 further comprises a third step 130 of coating the hydrogel layer 30 with a hydrophobic layer 40.

The step 110 of the exemplary method 100 utilizes a process 200 for forming the coating mixture. The process 200 for forming the coating mixture is shown in FIG. 2. In the step 210 of the process 200, a predetermined amount of a hydrophilic composition or hydrophilic substance is provided. For purposes of the present invention, the hydrophilic composition provided in the step 210 is Chitosan. Chitosan is preferably provided in a powder form.

Chitosan is a linear polysaccharide comprising randomly distributed β-(l-4)-linked D- glucosamine and N-acetyl-D-glucosamine. Generally, Chitosan is manufactured commercially manufactured by a deactylation of Chitin, which is a main structural element in exoskeleton of crustaceans. Degree of deactylation of commercially manufactured Chitosan is typically in the range of 60% to 100%. The amino group of Chitosan gives Chitosan a pKa value of approximately 6.5 and therefore, Chitosan is positively charged and soluble in acidic or neutral solutions. Chitosan is also non-toxic and bio-degradable, thereby making it suitale for use as an element or component for the coating of the controlled release preparation 10. In a step 220, Chitosan is dispersed in deionised water for obtaining an aqueous dispersion of Chitosan. Aqueous acid is preferably added during dispersion of Chitosan in the deionised water. Examples of the aqueous acid include, but is not limited to, lactic, citric, glycolic, formic, acetic, adipic, malic, malonic, propionic, pyruvic, succinic, nitric and hydrochloric acids. The addition of the aqueous acid enables adjustment of pH of the aqueous dispersion of Chitosan as required using techniques known to a person skilled in the art. Preferably, the pH value of the aqueous dispersion of Chitosan is adjusted to substantially between pH 3 and pH 4.

In a step 230, a predetermined amount of polysaccharide is provided. Preferably, the polysaccharide is provided in a powder form. The polysaccharide is for example starch. Starch is a complex carbohydrate comprising of a number of glucose monosaccharide units joined together by glycosidic bonds and has a chemical formula of (C₆Hi oOsV Starch may be obtained from various sources including, but not limited to, corn, rice and tapioca. It will be appreciated by a person skilled in the art that other polysaccharides may be used instead of starch.

In a step 240, polysaccharide colloids are formed from the predetermined amount of polysaccharide. To form polysaccharide colloids, the polysaccharide is first dispersed in deionised water. The dispersed polysaccharide is then heated and agitated for gelatinizing and forming the polysaccharide colloids. The steps 210 and 220, and the steps 230 and 240, may be performed either simultaneously or sequentially.

The steps 210 to 240 results in the formation of the aqueous dispersion of Chitosan and the polysaccharide colloids. The aqueous dispersion of Chitosan is then mixed with the polysaccharide colloids in a step 250 for forming a Chitosan-polysaccharide mixture. More specifically, the aqueous dispersion of Chitosan is blended with the polysaccharide colloids in a predetermined ratio by weight in the step 250 for forming a Chitosan- polysaccharide mixture. The blending of the aqueous dispersion of Chitosan with the polysaccharide colloids is preferably performed under specified predetermined conditions, for example at predetermined temperatures, speeds and pressures.

The blending of the aqueous dispersion of Chitosan with the polysaccharide colloids preferably facilitates flocculation of Chitosan for aiding the formation of the Chitosan- polysaccharide mixture. Preferably the blending of the aqueous dispersion of Chitosan with the polysaccharide colloids reduces tackiness of Chitosan. Further preferably, the specified predetermined conditions are selected for enhancing at least one of yield and quality of the controlled release preparation 10 being manufactured.

In a step 260, an active ingredient 50 is introduced or added to the Chitosan- polysaccharide mixture to produce a coating mixture. More specifically, the active ingredient 50 is dispersed or dissolved in the blended Chitosan-polysaccharide mixture to obtain the coating mixture. The active ingredient 50 is for example a pharmacologically active composition or a pesticidal active composition. A person skilled in the art will appreciate that other active ingredients may be introduced to the Chitosan-polysaccharide mixture, both singularly and in combination, for producing the coating mixture. The coating mixture is preferably stirred at room temperature for a predetermined period of time before being subsequently utilized.

As previously mentioned, the method 100 for manufacturing the controlled release preparation 10 further comprises a step 120 of coating the core 20 with the coating mixture.

Preferably, fluidized bed technology or fluidized bed technique is used in the step 120 for spraying a predetermined amount of the coating mixture onto the core 20 to thereby coat the core 20. The coating of the core 20 with the coating mixture results in the formation of the hydrogel layer 30 (also known as a first layer) over the core 20. The core 20 is for example, a non-pareil seed, which may be described as an inert sugar sphere that can be used as a carrier for active ingredients. Fluidized bed technology

Fluidized bed technology is typically used in industry for mixing a medium comprising solid particulate substances with liquids or gases. A fluidized bed is formed when a quantity of the medium comprising the solid particulate substance is placed under appropriate conditions to cause the medium comprising solid particulate substances to behave as a fluid. This is typically achieved by an introduction of pressurized fluid through the medium. The introduction of pressurized fluid through the medium enables the medium to have properties and characteristic of fluids (i.e. fluidization of the medium).

The fluidized bed can be considered to be an inhomogenous mixture of solid particles and fluid, which can be represented by a single bulk density. The fluidized bed exhibits fluid properties expected of Archimedes' principle. An object with higher density than the fluidized bed will sink when placed therein, whereas an object with a lower density will float. Two common types of fluidized beds are stationary beds and circulating beds.

Fluidized beds enable high levels of contact between the solid particulate substance and the liquid or gas. In addition, fluidized beds enable high intermixing of the medium comprising the solid particulate substance and the liquid or gas. Fluidized bed technology is useful for interface modification, for example coating of solid items.

Spraying conditions of the coating mixture onto the core 20 can be determined, and varied, as required.

An exemplary set of spraying conditions is provided below: Inlet temperature: 60⁰C

Feeding rate: substantially four to five grams per minute

Air pressure: substantially two bars

Product temperature: substantially 40⁰C to 50⁰C The exemplary set of spraying conditions provided above is preferably selected for enhancing speed of formation and quality of the hydrogel layer 30 surrounding the core 20. Preferably, approximately three hundred to six hundred grams of the coating mixture is sprayed or is required for the coating of each core 20.

The amount of coating mixture sprayed onto each core 20 can be varied as required for correspondingly varying a thickness of the hydrogel layer 30. The thickness of the hydrogel layer 30 preferably determines rate of release of the active ingredient 50 by the manufactured controlled release preparation 10.

The amount or quantity of the coating mixture, in combination with the exemplary set of spraying conditions, enables the formation of controlled release preparations 10, more specifically controlled release pellets, having sizes substantially within the range of 20 to 60 mesh (i.e. 250 to 850 μm).

The step 120 of the method 100 results in coating of the core 20 with the hydrogel layer 30, the hydrogel layer 30 comprising the Chitosan-polysaccharide mixture and the active ingredient 50.

In the step 130, the hydrogel layer 30 is then coated with the hydrophobic layer 40 (also known as a second layer) to thereby form the controlled release preparation 10 or controlled release pellet. Preferably, fluidized bed technology or fluidized bed technique is used in the step 130 for spraying a predetermined amount of hydrophobic polymers onto the hydrogel layer 30 to thereby coat the hydrogel layer 30.

Hydrophobic polymers include, but are not limited to, polymethacrylates. Examples of polymethacrylates include Eudragit L30 D-55 and ethyl cellulose.

An exemplary set of spraying conditions for spraying the hydrophobic polymer onto the hydrogel layer 30 is provided as follows: Inlet temperature: 60⁰C

Feeding rate: substantially four to five grams per minute

Air pressure: substantially two bar

Product temperature: substantially 40⁰C to 50⁰C

The exemplary set of spraying conditions for spraying the hydrophobic polymer onto the hydrogel layer 30 described above may be varied as required for varying properties or characteristics of the hydrophobic layer. Preferably, substantially six hundred grams of the hydrophobic polymer is sprayed onto the hydrogel layer 30 of each core 20.

The steps 110 to 130 of the method 100 results in the manufacture of the controlled release preparation 10, which comprises the core 20 as the innermost layer, the hydrogel layer 30 surrounding the core 20 and the hydrophobic layer 40 surrounding the hydrogel layer 30. A partial cross-sectional view of the controlled release preparation 10 is shown in FIG. 3.

The controlled release preparation 10 can also be referred to as the controlled release pellet or the controlled release granule. Size, or diameter, of the controlled release pellet or the controlled release granule can be varied by varying the amounts of coating mixture and the hydrophobic polymer sprayed onto the core 20 and the hydrogel layer 30 respectively.

Controlled release preparations are important in the pharmaceutical industry for controlling rate of release of active ingredients, more specifically pharmaceutical compositions or drugs, within the body of a human or animal. Ability to control rate of release of the pharmaceutical compositions or drugs enhances pharmaceutical efficacy of the pharmaceutical compositions or drugs. In addition, controlled release preparations can also aid control of location at which the pharmaceutical compositions or drugs are released within the body. Furthermore, controlled release preparations enable control of time periods of release of the pharmaceutical compositions or drugs therefrom. Similarly, controlled release preparations can be used for agricultural purposes to allow a controlled rate of release of pesticidal active ingredients over a predetermined time period. This enables desired levels of pesticide to be available against target species over the predetermined time period.

Release of the active ingredient 50 depends on several factors, including thickness and composition of the hydrogel layer 30 and the hydrophobic layer 40. During initiation of release, the hydrogel layer 30 absorbs a fluid or a medium. Absorption of the fluid causes the swelling of the hydrogel layer 30. Rate of absorption of the fluid by the hydrogel layer 30 is at least partially dependent on the composition and thickness of the hydrogel layer 30. In addition, the extent, rate and characteristics of the swelling are also at least partially dependent on the polysaccharide used and the thickness of the hydrogel layer 30.

Active substance or compositions present in the hydrogel layer 30 dissolves in the fluid or medium that has been absorbed by the hydrogel layer 30. The swelling of the hydrogel layer 30 ruptures or causes the disintegration of the hydrophobic layer 40. A partial cross- sectional view of the controlled release preparation 10 comprising a ruptured hydrophobic layer 40 is shown in FIG. 4. The rupturing of the hydrophobic layer 40 results in release of the active ingredient 50 from the controlled release preparation 10 by a process of diffusion from the hydrogel layer 30 into the fluid surrounding the controlled release preparation 10.

Alternatively, the hydrophobic layer 40 is able to withstand pressure applied thereto by the swelling of the hydrogel layer 30, and therefore does not rupture. Accordingly, pressure built up within the hydrogel layer 30 causes the active ingredient 50 to permeate and diffuse through the hydrophobic layer 40 into the fluid surrounding the controlled release preparation 10.

Rate of diffusion of the active ingredient 50 from the hydrogel layer 30 into the fluid surrounding the controlled release preparation 10 is controlled. Preferably, the rate of diffusion of the active ingredient 50 is at least partially dependent on the structure, thickness and composition of the hydrogel layer 30. Alternatively, the rate of diffusion of the active ingredient 50 is at least partially dependent on the structure, thickness and composition of both the hydrophobic layer 40 and the hydrogel layer 30.

It will be understood by a person skilled in the art in light of the foregoing disclosure that the structure, composition and thickness of the hydrophobic layer 40 can be altered for withstanding different pressures applied thereto by the swelling of the hydrogel layer 30. For example, the spraying conditions of the hydrophobic polymer onto the hydrogel layer 30 can be varied for varying at least one of the structure, composition and thickness of the hydrophobic layer 40.

Example 1: Controlled Release Preparation Comprising Curcuminiod as Active Ingredient

Curcuma longa is a Zingiberaceae species, which is typically found in tropical regions of the world, for example Thailand. Curcuminoids are extracted from Curcuma longa. Curcuminoids belong to the family of polyphenols and are known to be effective antioxidants. Curcuminoids are able to conjugate with free radicals, especially peroxyl radicals, to thereby inhibit lipid peroxidation and DNA degradation. Accordingly, controlled release preparations or controlled release granules comprising Curcuminoids as the active ingredient have been developed for use as a component of poultry feed, for example chicken feed.

To manufacture the controlled release granule, substantially 0.5 grams to 1.5 grams of Chitosan is dispersed in sixty-five grams of deionised water. Aqueous acid is then added when required to the Chitosan dispersion for adjusting the pH value thereof to substantially pH 6.5. Substantially 0.5 grams to 1.5 grains of starch is also dispersed in twenty-five grams of deionised water. The starch dispersion is heated and agitated for gelatinizing and forming starch colloids.

The Chitosan dispersion is then blended with the dispersion of starch colloids. More specifically, the Chitosan dispersion and the dispersion of starch colloids are blended in a ratio (by weight) of a range between and including 1 :3 and 3:1. The blending of starch colloids with the Chitosan dispersion is important for reducing inherent tackiness of Chitosan.

A predetermined amount of Curcuminoids is added to the blended mixture of Chitosan dispersion and starch colloids to form a coating mixture. Fluidized bed technology is then utilized for coating a core, for example a non-pareil seed, with the coating mixture. A predetermined amount of coating mixture is sprayed onto the core using the fluidized bed technology forms a hydrogel layer surrounding the core. The predetermined amount of coating mixture is substantially between 300 grams and 600 grams.

The hydrogel layer is then coated with polymer Eudragit® L30 D-55 to thereby form a hydrophobic layer around the hydrogel layer. Coating of the hydrogel layer is performed by spraying a predetermined amount of Eudragit® L30 D-55 using the fluidized bed technology. The coating of hydrogel layer with Eudragit® L30 D-55 protects the controlled release granule from unwanted moisture absorption to thereby aid prevention of degradation of Curcuminoids within the controlled release granule. For example, the coating of the hydrogel layer with Eudragit® L30 D-55 facilitates protection of Curcuminoids from light degradation.

The amount of coating mixture used for coating the core, and the amount of Eudragit® L30 D-55 used for coating the hydrogel layer, can be varied for varying thickness of the hydrogel layer and the hydrophobic layer respectively. Each of the thickness of the hydrogel layer and the hydrophobic layer partially determines rate of release of Curcuminoids from the controlled release granule.

In addition, the amount of coating mixture used for coating the core, and the amount of Eudragit® L30 D-55 used for coating the hydrogel layer is selected for forming controlled release granules of a size between 250 μm and 850 μm, comprising Curcuminoids of a concentration of substantially 6 mg per gram of the controlled release granule.

A stability study was performed on the formed controlled release granule for determining rate of release of the Curcuminoids from the controlled release granule. It was found that at the following conditions:

Temperature: 50 ⁰C, and

Relative Humidity: 75%, the amount of Curcuminoids in each granule decreases by substantially 20 % within a time period of one month and substantially 60% within a time period of 4 months.

The hydrogel layer, which comprises of Chitosan and starch, is capable of absorbing moisture or humidity. The relative amounts of Chitosan and starch of the Hydrogel layer can be varied for varying the moisture absorbing capacity of the controlled release granule.

The controlled release granule comprising Curcuminoids as described above enables controlled release of Curcuminoids in the body of poultry when consumed thereby. Curcuminoids released within the body of poultry serve as anti-oxidants for enhancing at least one of growth, health and meat-quality of the poultry. An exemplary system 300 as shown in FIG. 5 is also provided by an embodiment of the present invention. The system 300 comprises at least one of mechanisms, modules, devices, components or means for implementing the method 100 described above.

The system 300 comprises a first module 310 or device for forming or making the coating mixture. More specifically, the first module 310 performs or enabling the steps 210 to 250 of the process 200. Preferably, the first module 310 comprises a blender 320 that is shaped and configured for blending the aqueous dispersion of Chitosan with the polysaccharide colloids. Further preferably, the first module comprises a controller 330 couplable to the blender 320 for controlling operation of the blender 320. Preferably, the system 300 enables the blending of the aqueous dispersion of Chitosan with the polysaccharide colloids to occur at predetermined set conditions, for example at predetermined temperatures, speeds or pressures.

The system 300 further comprises a second module 340 for performing the step 120 of the method 100. The second module 340 effects the coating of the core 20 with the coating mixture. The second module 340 comprises a first holding vessel 350 for enabling formation of the fluidized bed therein. The second module 340 preferably comprises control mechanisms 360 couplable to the first holding vessel 350 for enabling setting and varying of the spraying conditions for the coating mixture onto the core 20.

The system 300 further comprises a third module 370 for performing the step 130 of the method 100. The third module 370 effects the coating of the hydrogel layer 30 over the hydrophobic layer 40. The third module 370 comprises a second holding vessel 380 for formation of the fluidized bed therein to thereby enable spraying of the hydrophobic polymer for coating the hydrogel layer 30. The third module 370 preferably comprises control mechanisms 390 coupled to the second holding vessel 380 for setting and varying of the spraying conditions for the hydrophobic polymer onto the hydrogel layer 30. It will be understood by a person skilled in the art that the second module and the third module may be combined into a single module, apparatus or device capable of performing the functions of both the second module and the third module. It will also be understood by a person skilled in the art that operation of any one of more of the mechanism, modules, components or means of the system 300 may be either software controlled or mechanically or manually controlled.

In the foregoing manner, an exemplary method and an exemplary system for preparing a controlled release preparation are described according to embodiments of the present invention. Although only embodiments of the present invention are disclosed, the invention is not to be limited to the specific forms or arrangements of parts so described and it will be apparent to one skilled in the art in view of this disclosure that numerous changes and/or modifications can be made without departing from the scope and spirit of the invention.

Claims

1. A method for preparing a controlled release preparation comprising: forming an aqueous dispersion of Chitosan; forming a polysaccharide colloid composition; blending the aqueous dispersion of Chitosan with the polysaccharide colloid composition for forming a coating mixture, the blending of the polysaccharide colloid composition with the aqueous dispersion of Chitosan performed under predetermined conditions for substantially reducing tackiness of Chitosan; and coating a predetermined amount of the coating mixture with hydrophobic polymers, wherein the hydrophobic polymers forms a hydrophobic layer over at least part of the coating mixture to thereby reduce tackiness of the controlled release preparation.

2. The method as in claim 1 , further comprising: spraying the coating mixture onto a core for forming a first layer over at least part of the core.

3. The method as in claim 1, wherein the spraying of the coating mixture onto the core is effected by fluidized bed technology, use of fluidized bed technology facilitating at least one of determination and control of spraying conditions of the coating mixture onto the core.

4. The method as in claim 3, wherein spraying conditions of the coating mixture onto the core are having an inlet temperature of substantially 60⁰C, a product temperature of substantially 40⁰C to 50⁰C, a feeding rate of substantially 4 to 5 grams per minute, and an air pressure of substantially 2 bar.

5. The method as in claim 1 , wherein the hydrophobic polymers are sprayed onto the coating mixture by fluidized bed technology to thereby control the formation of the hydrophobic layer.

6. The method as in claim 1 , further comprising: adding a predetermined amount of active ingredient to the coating mixture.

7. The method as in claim 6, wherein the active composition is one of a pharmacologically active substance and a pesticidal active substance.

8. The method as in claim 1 , further comprising: providing a predetermined amount of Chitosan; dispersing the provided predetermined amount of Chitosan in deionised water to thereby form the aqueous dispersion of Chitosan; and adjusting the pH of the aqueous dispersion of Chitosan by adding a predetermined amount of acid.

9. The method as in claim 1 , further comprising: dispersing a predetermined amount of polysaccharide in deionised water; heating and agitating the predetermined amount of polysaccharide in deionised water to thereby form the polysaccharide colloid composition.

10. The method as in claim 1, wherein the aqueous dispersion of Chitosan is blended with the polysaccharide colloid composition in a predetermined ratio by weight of substantially between and including 1:3 and 3:1.

11. The method as in any one of the preceding claims, wherein the polysaccharide is starch.

13. The method as in any of the preceding claims, wherein the hydrophobic polymers are polymethacrylate.

14. A method for preparing a controlled release preparation comprising: forming an aqueous dispersion of Chitosan; forming a polysaccharide colloid composition; blending the aqueous dispersion of Chitosan with the polysaccharide colloid composition for forming a coating mixture, the blending of the polysaccharide colloid composition with the aqueous dispersion of Chitosan performed under predetermined conditions for substantially reducing tackiness of Chitosan; coating a core with a predetermined amount of the coating mixture for forming a first layer over at least part of the core; and spraying a predetermined amount of hydrophobic polymer onto the first layer, wherein the hydrophobic polymer forms a second layer over at least part of the first layer to thereby reduce tackiness of the controlled release preparation.

15. The method as in claim 14, wherein the predetermined amount of the coating mixture is sprayed onto the core by fluidized bed technology, use of fluidized bed technology facilitating at least one of determination and control of conditions for spraying the predetermined amount of the coating mixture onto the core.

16. A method for preparing a controlled release preparation comprising: forming an aqueous dispersion of Chitosan; forming a polysaccharide colloid composition; blending the aqueous dispersion of Chitosan with the polysaccharide colloid composition for forming a coating mixture, the blending of the polysaccharide colloid composition with the aqueous dispersion of Chitosan performed under predetermined conditions for substantially reducing tackiness of

Chitosan; and spraying a predetermined amount of the coating mixture onto a core, wherein the predetermined amount of the coating mixture forms a first layer over at least part of the core.

17. The method as in claim 16, further comprising: spraying a predetermined amount of hydrophobic polymer onto the first layer for forming a second layer over at least part of the first layer, wherein the second layer facilitates reduction of tackiness of the controlled release preparation.

18. The method as in claim 17, wherein the spraying of at least one of the coating mixture and the hydrophobic polymer is by fluidized bed technology, use of fluidized bed technology facilitating at least one of determination and control of conditions for the spraying of the at least one of the coating mixture and the hydrophobic polymer.

19. A system for preparing a controlled release preparation comprising: a first module for forming a coating mixture therein, the coating mixture being formed by blending an aqueous dispersion of Chitosan and a polysaccharide colloid composition together, the blending the aqueous dispersion of Chitosan with the polysaccharide colloid being performed under predetermined conditions for substantially reducing tackiness of Chitosan; and a second module for facilitating coating of a core with a predetermined amount of the coating mixture, wherein the predetermined amount of the coating mixture forms a first layer over at least part of the core.

20. The system as in claim 19, further comprising: a third module for facilitating coating of the first layer with hydrophobic polymers, wherein the hydrophobic polymers forms a second layer over at least part of the first layer to thereby reduce tackiness of the controlled release preparation.

21. The system as in claim 19, the second module comprising: a fluidized bed mechanism for spraying the coating mixture onto the core for forming the first layer over the at least part of the core; and a controller coupled to the fluidized bed mechanism for at least one of setting and controlling spraying conditions of the coating mixture onto the core.

22. The system as in claim 21, wherein the spraying conditions for spraying the coating mixture onto the core are having an inlet temperature of substantially 60⁰C, a product temperature of substantially 40⁰C to 50⁰C, a feeding rate of substantially 4 to 5 grams per minute, and an air pressure of substantially 2 bar.

23. The system as in claim 20, the third module comprising: a fluidized bed mechanism for spraying the hydrophobic polymers onto the first layer; and a controller coupled to the fluidized bed mechanism for at least one of setting and controlling spraying conditions of the hydrophobic polymers onto the first layer.

24. The system as in claim 19, the first module further comprising: a first disperser for dispersing a predetermined amount of Chitosan in deionised water for forming the aqueous dispersion of Chitosan, wherein pH value of the aqueous dispersion of Chitosan is adjustable by adding aqueous acid thereto.

25. The system as in claim 24, the first module further comprising: a second disperser for dispersing a predetermined amount of polysaccharide in deionised water; and a heating and agitating element for heating and agitating the predetermined amount of polysaccharide in deionised water to thereby obtain the polysaccharide colloid composition.

26. The system as in claim 19, wherein the aqueous dispersion of Chitosan is blended with the polysaccharide colloid composition in a predetermined ratio by weight of substantially between and including 1 :3 and 3:1.

27. The system as in any of claims 19 to 26, wherein the polysaccharide is starch.

28. The system as in claim 19, wherein the coating mixture comprises an active ingredient added thereto, the active composition being one of a pharmacologically active substance and a pesticidal active substance.

29. The system as in any of claims 19 to 28, wherein the hydrophobic substance is a polymethacrylate.

30. A controlled release preparation comprising: a predetermined amount of coating mixture, the coating mixture comprising an active ingredient and a blended mixture of an aqueous dispersion of Chitosan and a polysaccharide colloid composition; and a hydrophobic layer coating at least part of the predetermined amount of coating mixture, wherein the hydrophobic layer reduces tackiness of the controlled release preparation.

31. The controlled release preparation of claim 30, further comprising: a core, the predetermined amount of coating mixture forming a first layer over at least part of the core.

32. The controlled release preparation as in claim 30, wherein at least one of the first layer and the hydrophobic layer is formed by fluidized bed technology.