WO2013093877A2

WO2013093877A2 - Encapsulation system for controlled release of a bleaching agent

Info

Publication number: WO2013093877A2
Application number: PCT/IB2012/057609
Authority: WO
Inventors: Nigel David Young; Fideline TCHUENBOU
Original assignee: Koninklijke Philips Electronics N.V.
Priority date: 2011-12-23
Filing date: 2012-12-21
Publication date: 2013-06-27
Also published as: WO2013093877A3

Abstract

A bleaching composition (10) includes a plurality of solid microparticles (12). Each microparticle includes a bleaching agent (14) encapsulated in a shell (20) which modifies the release of bleaching agent from the microparticle. The shell includes a hydrophobic material (22) and a release rate modifier (24) in contact therewith.

Description

ENCAPSULATION SYSTEM FOR CONTROLLED RELEASE OF A

BLEACHING AGENT

The following relates to the bleaching arts, and related arts and more specifically concerns a system and method for encapsulation of a whitening agent suitable for whitening teeth and to a composition which includes an encapsulated whitening agent.

Tooth whitening products that are based on hydrogen peroxide and other bleaching agents, such as sodium percarbonate, include toothpastes, peroxide gel strips, whitening solutions, and mouthwashes. The aim is usually to deliver the whitening agent to the teeth in a sufficient amount to effect a color change in the surface of the teeth in an acceptable period of time without causing harm to the user. Some methods rely on using a high concentration for a short time (e.g., 25% hydrogen peroxide for 30 minutes). Others use a much lower concentration for a longer time (e.g., 1-6% hydrogen peroxide for 10-40 hours, either in a single treatment or over several treatments). Care has to be taken when using high concentrations of hydrogen peroxide to avoid damage to soft tissue, such as the gums, and thus such methods are often regulated and are best employed by dental professionals. Peroxide gel strips use lower concentrations of hydrogen peroxide, but entail wearing a plastic strip on the teeth to be treated for an extended period, or inserting fresh strips repeatedly over a long period.

Another problem with hydrogen peroxide is that it rapidly decomposes and becomes ineffective as a bleaching agent. Recently, methods have been proposed for encapsulating carbamide peroxide in shellac to form microspheres. See, Jing Xue and Zhibing Zhang, "Preparation and characterization of calcium- shellac spheres as a carrier of carbamide peroxide," Journal of Microencapsulation 25(8), p. 523 (2008); and Jing Xue and Zhibing Zhang, "Physical, Structural and Mechanical Characterisation of Calcium- Shellac Microspheres as a Carrier of Carbamide Peroxide," Journal of Applied Polymer Science Vol. 113, p. 1619 (2009). The resulting microspheres are suggested as being suitable for combining with a vehicle, such as a toothpaste or gum. However, the shellac- coated microspheres tend to release the hydrogen peroxide fairly slowly, if at all, unless ruptured by application of a significant pressure.

An encapsulation method and a product including encapsulated particles are disclosed which can overcome some of the problems with existing systems.

An advantage of the exemplary encapsulated particles is that a release rate of bleach can be tailored to suit a particular application.

Another advantage of the exemplary encapsulated particles is that rupturing of the particles with applied pressure is not required for release of the bleach.

In accordance with one aspect of the invention, a bleaching composition includes a plurality of solid microparticles. Each microparticle includes a bleaching agent encapsulated in a shell. The shell includes a hydrophobic material and a release rate modifier which modifies the release of bleaching agent from the microparticle.

In accordance with another of the invention, a method of forming a bleaching composition includes encapsulating a bleaching agent with a hydrophobic material and a release rate modifier, at least one of the hydrophobic material and release rate modifier being in molten form, and solidifying the encapsulated bleaching agent to form microparticles in which the bleaching agent forms a core of each microparticle which is surrounded by a shell formed of the hydrophobic material and a release rate modifier.

In accordance with another of the invention, a method for whitening teeth includes applying microparticles to the teeth, the microparticles comprising a bleaching agent encapsulated in a shell, the shell including a hydrophobic material and a release rate modifier which modifies the release of bleaching agent from the microparticles.

The invention may take form in various components and arrangements of components, and in various process operations and arrangements of process operations. The drawings are only for the purpose of illustrating preferred embodiments and are not to be construed as limiting the invention.

FIGURE 1 diagrammatically shows a composition including encapsulated particles in a vehicle in accordance with one embodiment disclosed herein.

FIGURE 2 diagrammatically shows a composition including encapsulated particles in a vehicle in accordance with another embodiment disclosed herein. FIGURE 3 is a flow chart illustrating methods for forming encapsulated particles, optionally in a vehicle, in accordance with embodiments disclosed herein.

FIGURE 4 illustrates an apparatus for forming encapsulated particles in accordance with another embodiment disclosed herein.

FIGURE 5 diagrammatically shows a device for delivery of the encapsulated particles in accordance with another embodiment disclosed herein.

FIGURE 6 graphically shows results of release of hydrogen peroxide from different types of encapsulated particles over time.

While the examples herein refer to dental bleaching, it is to be appreciated that the whitening compositions and encapsulated particles disclosed herein may find use in other applications, such as in laundry detergents, hair products, and the like.

With reference to FIGURE 1, a whitening composition 10 includes microparticles 12 which include a bleaching agent 14 embedded in a controlled release carrier material 16. The bleaching agent 14 may form a core 18 of each microparticle 12, with the carrier material 16 encapsulating the core as an outer layer or shell 20 of the microparticle. Microparticles 12 may include more than one particle of bleaching agent 14 forming the core. The illustrated carrier material 16 includes a hydrophobic material 22, serving as a matrix, and a release rate modifier 24 in contact with, e.g., dispersed in, the hydrophobic material 22. The microparticles 12 may be dispersed in vehicle 26, such as a liquid or semisolid, for example, a toothpaste, gum, aqueous liquid, or the like. The composition 10 may be applied to the teeth 28 of a person, to whiten the teeth.

On contact with water 30, e.g., in the oral cavity, on the teeth, or during delivery thereto, the shell 20 becomes more permeable to water, allowing the bleaching agent 14 in the core 18 to escape. For example, pores 32 may form in the shell 20 which extend from an outer surface 34 of the microparticle to the core.

With reference to FIGURE 2, a whitening composition 40 is formed as for the whitening composition 10 of FIGURE 1, except as noted, and where similar elements are accorded the same numbers and new elements are accorded new numbers. The whitening composition 40 includes microparticles 12 which include a bleaching agent 14 embedded in a shell 20 which includes a controlled release carrier material 16. The bleaching agent 14 may form a core 18 of each microparticle 12, with the shell 20 of the microparticle encapsulating the core. The shell 20 includes an outer layer 42 comprising hydrophobic material 22 and a layer 44, intermediate the outer layer and core 18, comprising the release rate modifier 24. The microparticles 12 may be dispersed in vehicle 26, such as a liquid or semisolid, for example, a toothpaste, gum, aqueous liquid, or the like.

As will be appreciated, FIGURES 1 and 2 are intended to be illustrative only and are not intended to be to scale.

In one embodiment, a quantity of the composition 10, 40 is applied to the teeth 28 and maintained in contact with the teeth for sufficient time for the bleaching agent to be released and effect at least a partial whitening of the teeth, such as for example, at least 10 minutes or at least 30 minutes, or several hours, such as 4-12 hours. In one embodiment, the applied composition includes the vehicle 26, e.g., the composition is formulated as a gel, paste, gum, or the like. The vehicle-containing composition 10, 40 may be inserted into a suitably shaped tray which is positioned adjacent the teeth. In other embodiments, the composition is applied with an applicator, such as a brush, piece of foam, or the like. The vehicle 26 may be washed away or otherwise be removed while the microparticles remain adhered to the teeth. The process may be repeated, for example, once a day or less frequently, until a desired color change is effected or to maintain whiteness of the teeth.

In other embodiments, the microparticles 12 are applied to the teeth without a vehicle 26.

In some embodiments, the microparticles 12 may be propelled towards the teeth by a pressurized fluid, which may be gaseous, liquid, vapor, aerosol, mist, or the like, such as water and/or air. For example, an applicator device may be configured to spray the particles in the fluid on the teeth with a velocity sufficient to cause the microparticles 12 to adhere on the teeth and effect whitening.

In other embodiments, the microparticles 12 may be applied to a plastic or other solid carrier material to form a whitening strip which is adhesively adhered to the teeth for several minutes or hours while the bleaching agent is released and whitening of the teeth occurs.

The exemplary microparticles 12 are generally spherical in shape. They can be dry, solid particles of up to 200 micrometers (μηι) in diameter, on average, or up to 100 μιη in diameter. By "solid" it is meant that the particles are solid at ambient temperatures, e.g., solid at a temperature of up to 30°C, at least. By "diameter," it is meant the average dimension, to the extent that the particles are non-spherical. For example, the microparticles 12 can be at least 1 or at least 10 μιη in diameter, on average, and in one embodiment, at least 20 μιη in diameter on average. In some embodiments, the microparticles are up to 50 μιη in diameter, on average. The core 18 may occupy from 1 to 99% of the volume of the microparticle, such as from 10-90%, on average. The shell 20 may be at least 20 nm in thickness, on average, such as at least 0.1 μιη, or at least 1 μιη in thickness, and in some embodiments, up to 40 μιη in thickness, on average. The core 18 may be at least 0.1 μιη in diameter, on average, such as at least 1 μιη in diameter, and in some embodiments, at least 10 μιη, or at least 20 μιη, and can be up to about 100 μιη, in average diameter. In some embodiments, the core may be up to 10 μιη, or up to 20 μιη, or up to 50 μιη in average diameter. In one embodiment, the particles have a core which is up to 15 μιη in average diameter and the microparticles are between 20 and 100 μιη in average diameter. A ratio of a weight of the shell 20 (total carrier material 16) to a weight of the core 18 (total bleaching agent 14) can be for example, from 0.1 :99.9 to 99.9:0.1, or 1 :99 to 99: 1, or 10:90 to 90: 10, or 50:50 to 70:30, such as 60:40.

The core 18 may be partly or entirely formed from the dental bleaching agent 14. For example, at least 10%>, or at least 20%>, or at least 50%>, or at least 80%>, by weight of the core and up to 100% by weight is bleaching agent. Exemplary bleaching agents are solid at ambient conditions and include carbamide peroxide, which is an adduct of urea and hydrogen peroxide (CH₄N₂O-H₂O₂). This material releases hydrogen peroxide on contact with water 30. Other example bleaching agents include alkali metal percarbonates, sodium perborate, potassium persulfate, calcium peroxide, zinc peroxide, magnesium peroxide, strontium peroxide, other hydrogen peroxide complexes, sodium chlorite, combinations thereof, and the like. The term "bleaching agent," herein refers to compounds which are themselves bleaches and to compounds which are bleach precursors, such as carbamide peroxide, which react or decompose to form a bleach.

The microparticles 12 can include the bleaching agent, e.g., carbamide peroxide, at a concentration of at least 5 wt. % or at least 10 wt. %, such as up to about 50 wt. %., or up to about 40 wt. %. For example, at about 20 wt. %. carbamide peroxide, the hydrogen peroxide concentration per particle is about 6 wt. %, which is comparable to whitening strips.

In some embodiments, the core 18 may include additives, such as colorants, preservatives, abrasive materials, emulsifiers, and the like.

The shell 20 provides a moisture-resistant barrier which releases the bleaching agent 14 slowly, on contact of the microparticle 12 with water, thereby providing a controlled release of the bleaching agent. The hydrophobic material 22 of the shell 20 is a water-insoluble and/or hydrophobic material, such as a waxy solid, i.e., is solid at ambient temperature (25°C) and may be a solid at relatively higher temperatures. Exemplary waxes suitable to use as the hydrophobic material include hydrocarbon waxes, such as paraffin wax and the like, which are substantially or entirely free of unsaturation. Exemplary paraffin waxes are higher alkanes and mixtures of higher alkanes of the general formula C„H₂„+2, where typically, 20 < n < 50, and thus have no unsaturation. They are solid at ambient temperatures and melt-processable. The melting point of the waxy solid may be within the range of from 30°C to 100°C. To avoid decomposition of the bleaching agent in the core, the waxy solid may have a melting point of below 80°C, and in one embodiment, below 65°C. Paraffin waxes with a melting point of 40°C-60°C may be used, by way of example. Paraffin wax with a melting point of 53-57°C can be obtained from Sigma- Aldrich. Other paraffin waxes are available with melting points of 45°C, 50-52°C, 53-57°C, and 60°C. The melting point of waxes is determined according to ASTM D87 - 09, "Standard Test Method for Melting Point of Petroleum Wax (Cooling Curve)."

The hydrophobicity of the hydrophobic material can be expressed in terms of its contact angle to water. In one embodiment, the water contact angle is at least 75°, such as at least 85°, and in some embodiments, at least 100°, such as up to 120°. The water contact angle can be determined using a contact angle goniometer, for example. The contact angle can be measured on a flat sheet of wax prepared by spraying the molten wax onto a smooth surface, such as a plastic Petri dish to form a wax layer with thickness of approximately 5 mm. After solidification, the rigid, flat wax layer can be removed from the Petri dish and cut into sheets suitable for contact angle analysis. The contact angle of water in air on the surface of such a sheet can be measured using a goniometer, such as an EasyDrop™ (Kruss, Germany).

of double distilled water in a micro-syringe is dropped on the surface of the sheet placed on a moveable sample stage. The drop is illuminated from one side and the camera on the opposite side records and images the drop. This image is then analyzed by DSA software to calculate the contact angle.

By way of example, two different molecular weights of paraffin wax with melting point of 50-52°C and 53-57°C (Sigma Aldrich, UK) were tested and the measured contact angle was 110.3° ±0.5 and 111.0° ±1, respectively.

The release rate modifier 24 controls the rate of release of the bleaching agent 14 from the microparticles 12. Exemplary release rate modifiers 24 include hydrophilic organic polymers which are capable of hydrogen bonding and that are solid at ambient temperatures (25°C), hydrophilic and/or water soluble powders, and combinations thereof. The release rate modifier 24 is more hydrophilic than the hydrophobic material 22. The release rate modifier may be dispersed in the hydrophobic material. In the case of organic polymers, the release rate modifier 24 may be a material which is insoluble or substantially insoluble in the hydrophobic material 22 such that it forms discrete regions where it is of high concentration in the hydrophobic material (or forms a separate layer 44). The regions may be spaced from each other by the hydrophobic material 22. In the case of hydrophilic and/or water soluble powders as the release rate modifier, the powder may be dispersed throughout the hydrophobic material, or in one embodiment, more highly concentrated near an outer surface thereof. The release rate modifier(s) may be present in the particles 12 at a total concentration of from 0.001 wt. % to 40 wt. %.

In the case of hydrophilic and/or water soluble powders as release agents, these may be present in the microparticles 12 in a total concentration of from 0.001 wt. % to 30 wt. %, such as 0.1- 20 wt. %, or 1.0 to 10 wt. %. Examples of hydrophilic powders include anhydrous inorganic particles, such as silicon dioxide, e.g., hydrophilic silica and silica nanopowders. Exemplary water-soluble powders include water-soluble acids and salts thereof, such as anhydrous phosphate salts, e.g., sodium polyphosphate, sodium tripolyphosphate, sodium pyrophosphate; anhydrous citric acid and salts thereof, such as alkali metals salts, e.g., sodium citrate; anhydrous sodium sulfate, anhydrous magnesium salts, such as magnesium sulfate and magnesium chloride. Combinations of such release agents may be employed. The hydrophilic and/or water soluble powders remain solid during formation of the shell. The hydrophilic and/or water soluble powders, such as silica, may have an average particle size of, for example, 1-100 nanometers (nm), e.g., 5-20 nm, and a surface area of, for example 50-400 m²/g. Hydrophilic fumed silica, for example, may be obtained under the tradename AEROSIL™ from Evonik Industries with a specific surface area (measured by the BET method) in the range of 90-300 m²/g. As an example, AEROSIL™ 200 has a specific surface area of 200 m²/g.

When hydrophilic organic polymers are used as release rate modifiers 24, these may be present in the microparticles 12 at a total concentration of from 0.5 wt. % to 40 wt. %., e.g., 1-35 wt. %, or 10-30 wt. %. The hydrophilic organic polymers may be liquefied during formation of the shell. In one embodiment, the hydrophilic polymer has a melting point of at least 30°C or at least 40°C, such as up to 80°C. The hydrophilic polymer can have a weight average molecular weight of at least 300. Examples of suitable hydrophilic organic polymers include polyalkylene glycols, such as polyethylene glycol and polypropylene glycol, and esters thereof, polyamide compounds (e.g., polyvinylpyrrolidone), poly( vinyl acetate), poly( vinyl alcohol), poly(acrylic acid), polyacrylamide, polyoxylglycerides, such as lauroyl, oleoyl, and stearoyl polyoxylglycerides, which are mixtures of monoesters, diesters, and triesiers of glycerol and monoesters and diesters of polyethylene glycols (e.g., lauroyl macrogolglycerides, such as GELUCIRE™ 44/14, available from Gattefosse, which has a melting point of 44°C and an HLB of 14), and ethylene oxide derivatives thereof, poloxamers, which are triblock copolymers having a central hydrophobic block of poly(propylene oxide) and two side blocks of poly(ethylene oxide) (e.g., poloxamer 188, which has a melting point 52°C), and derivatives thereof, and mixtures thereof.

Exemplary polyethylene glycols (PEG) suitable for the release rate modifier may have a weight average molecular weight of from 300 daltons to 50,000 daltons, such as about 600-35000, or 1000 to 5,000 daltons. Such materials are commercially available as PEG 1000 (melting point 37-40°C), PEG 1500 (melting point 44-48°C), PEG 2000 (melting point 49-52°C), and the like. A combination of polyethylene glycols having different molecular weights may be employed to tailor the release rate. For example a mixture may be formed by combining, e.g., in a ratio of from 1 : 10 to 10: 1, a polyethylene glycol having a molecular weight of about 500-1200 (on average), such as PEG 1000, with a polyethylene glycol having a molecular weight of at least 1500 or at least 1800 (on average), such as PEG 1500 or PEG 2000. In one embodiment, a combination of PEGs with average molecular weight ranging from 300 daltons to 50,000 daltons may be mixed on appropriate amounts to provide a mixture which is liquid at a temperature of 35-70°C, such as 45-60°C. For example, PEG with an average molecular weight of 20,000 and PEG 1500 have melting points of 60-65°C and 44-48°C, respectively, and a mixture of PEG 1500 and PEG 20,000 may be liquid at about 55°C, depending on the ratio.

In the case of hydrophilic organic polymers, such as PEG, the discrete regions (FIG. 1) in which the polymer is localized may have an average size of, for example, at least 0.1 or at least 0.5 nm, and can be up to 100 nm, or up to 20 nm, e.g., 0.5-5 nm. For example, the hydrodynamic radius of glycerol is 0.3 nm and that of PEG 1000, PEG 2000 and PEG 4000 is approximately 0.9, 1.4 and 1.9 nm, respectively.

A ratio of hydrophobic material 22 to the release rate modifier 24 in the microparticles may be from 1 :99 to 99: 1, expressed by weight, such as from 2:98 to 98:2, or from 10:90 to 90: 10, or from 15:85 to 85: 15. The ratio can be at least 30:70, or at least 40:60, or at least 60:40. For example, in the case of polymers, such as PEG, the ratio of hydrophobic material to release rate modifier may be about 60:40 or about 50:50. For hydrophilic and/or water soluble powders, the ratio of hydrophobic material to the release rate modifier may be higher, such as at least 85: 15, or at least 90: 10.

The microparticles generally have a low water content, such as less than 5 wt. %, or less than 1 wt. %, or less than 0.2 wt. % of the microparticles is made up of water (free and bound).

In some embodiments, the release rate modifier 24 increases the rate of release of the bleaching agent, as compared with the hydrophobic material 22 alone. For example, the amount of bleaching agent released from the microparticles with the exemplary release rate modifier 24 (e.g., expressed as weight of hydrogen peroxide), may be at least 10% greater or at least 50% greater, over an initial period of two hours, than for the equivalent microparticles formed without the release rate modifier 24, when exposed to the same aqueous conditions (e.g., a buffered release medium, at a temperature of 30-40°C, e.g., as discussed in the Example below). By "equivalent microparticles," it is meant the microparticles are identically formed except that no release rate modifier is employed. In some embodiments, the release rate modifier 24 may provide the exemplary microparticles 12 with a more uniform rate of release of hydrogen peroxide than equivalent microparticles formed without the release rate modifier 24, when exposed to the same aqueous conditions (e.g., buffered release medium at a temperature of 30-40°C). For example, the initial release rate (expressed as wt. of hydrogen peroxide/hr), over about two hours, may be, on average, less than that of equivalent microparticles without the release rate modifier and may be on average, higher than that of equivalent microparticles in the subsequent two hour period.

In some embodiments, the exemplary microparticles 12 formed with the release rate modifier 24 release at least 10%, or at least 20%, or at least 30% by weight of the total amount of bleaching agent (expressed in terms of hydrogen peroxide) that they contain over a period of 12 hours after contact with the teeth or aqueous medium at 30°-40°C. In some embodiments, the exemplary microparticles formed with the release rate modifier 24 release less than 40%>, or at less than 30%>, or less than 25% by weight of the bleaching agent (expressed in terms of hydrogen peroxide), over a period of 4 hours after contact with the teeth or with an aqueous medium at 30°-40°C.

As will be appreciated from the foregoing, the amount and type of release rate modifier can be selected to tailor the release rate according to the desired application. For example, if the microparticles are to remain in contact with the teeth for a period of several hours, a slower release rate may be more desirable than when the microparticles 12 are to be more quickly removed.

In one embodiment, the shell may further include an emulsifier, dispersed in the hydrophobic material. Exemplary nonionic surfactants suitable as emulsifiers include fatty acids, polyol fatty acid esters, such as polyglyceroi esters, fatty alcohol polyglycol ethers, alkylphenol polyglycol ethers, fatty acid polyglycol esters, fatty acid amide polyglycol ethers, fatty amine polyglycol ethers, alkoxylated triglycerides, mixed ethers and mixed formals, optionally partly oxidized alk(en)yl oligoglycosides or glucuronic acid derivatives, fatty acid-N-alkyl glucamides, protein hydrolyzates (particularly wheat-based vegetable products), sugar esters, sorbitan esters, polysorbates, amine oxides and combinations thereof. As examples of suitable emulsifiers, nonionic surfactants with a low hydrophile-lipophile balance (HLB) may be used. The HLB may be from 2-5. Surfactants that are able to form micelles are able to improve the stability of hydrogen peroxide. Examples of these emulsifiers include C12-C24 fatty acids, such as lauric acid (CI 2), myristic acid (C14), palmitic acid (C16), stearic acid (C18), oleic acid (C18), linoleic acid (CI 8), and mixtures thereof. Such fatty acid emulsifiers can be obtained from Sigma- Aldrich under the tradename SPAN™, such as SPAN™ 60, which has an HLB of 4.7, SPAN™ 65, with an HLB of 2.1, SPAN™ 80, with an HLB of 4.3. Exemplary polyglycerol esters include polyglycerol polyricinoleate (PGPR), which has an HLB of 3, and is available from Evronik Industries, Essen Germany, or Danisco. A blend of surfactants having a high HLB and low HLB value may be used.

The emulsifier may be present in the microparticles at a concentration of at least

0.001 wt. %, such as at least 0.1 wt. %, or at least 1 wt. %, and can be present at up to 5 wt. % or up to 10 wt. %, e.g., about 2 wt. %.

Release rate modifiers and emulsifiers may be suitably selected such that they do not adversely affect the stability of the bleaching agent, e.g., of hydrogen peroxide.

Mechanisms by which the release rate is controlled by the release rate modifier are proposed by way of example. In one embodiment, the release rate modifier 24 dissolves in water, leaving pores 30 in the shell where the release rate modifier was previously located. In other embodiments, the release rate modifier attracts and/or absorbs water, increasing in volume and causing a localized disruption in the integrity of the shell.

For example, in the case of a wax/PEG mixture as the encapsulation medium, the wax is hydrophobic, repelling water, while the solid PEG is hydrophilic, attracting water. The release rate can be engineered by varying the ratio of these components. When water is present, it is attracted to hydrophilic regions on the surface of the microsphere (FIG. 1) that are defined by the regions of PEG release rate modifier, or to the layer 44, through small cracks in the layer 42 (FIG. 2). The PEG region becomes the site of a pore as water swells the PEG. When a pore penetrates to the carbamide peroxide core, the core releases hydrogen peroxide when it gets wet.

The emulsifier present may also affect the release rate.

A method for optimizing a release rate of the bleaching agent from the particles may include formulating sets of microparticles, each set having a different ratio of hydrophobic material to release rate modifier and testing the sets of microparticles to determine the release rates or amount of bleaching agent released in a selected time period. The method can further include selecting an optimal ratio of hydrophobic material to release rate modifier, based on the results of the tests, for example, to provide a desired release rate of the bleaching agent. Similar tests may be performed with combinations of release rate modifiers and/or emulsifiers, such as different combinations of PEG molecular weight, and selecting a combination of release rate modifiers to identify an optimal combination of release rate modifiers for optimizing a release rate of the bleaching agent. Various combinations of these tests are also contemplated.

Exemplary methods of forming the composition 10, 40 are illustrated in FIGURE 3. The method begins at SI 00. At SI 02, the hydrophobic material is melted. At SI 04, separately or with S102, the release agent may be melted (e.g., in the case of PEG). At SI 06 the hydrophobic material and release agent may be combined, if not already combined in SI 02. A molten mixture of the hydrophobic material and release rate modifier may be formed, for example, by heating the hydrophobic material, and optionally the release rate modifier and emulsifier, to a sufficient temperature to melt at least the hydrophobic material. The components may be stirred to disperse the release rate modifier throughout the hydrophobic material to form a shell material. At SI 08, the bleaching agent may be coated with the shell material. The bleaching agent is incorporated into the molten mixture, for example, by combining solid particles of bleaching agent with the molten mixture. The molten mixture is separated into solid microparticles (SI 10), for example, by spraying the mixture into a coolant, such as carbon dioxide, or dissolving the mixture in liquefied carbon dioxide and quickly releasing the pressure, or spraying the mixture onto a cooled surface. Optionally, at SI 12, the solid microparticles are combined with a vehicle 26, such as a liquid or a semisolid vehicle. The method ends at SI 14.

In another embodiment, suited to forming the composition 40, the method proceeds from SI 04 to SI 16, where the bleaching agent, e.g., in particulate form, is coated with a layer 42 of the molten release agent, and, thereafter, at SI 18, by a layer 44 of the hydrophobic material. The method then proceeds to SI 10. As will be appreciated, steps SI 16 and SI 18 may be reversed and/or repeated one or more times.

The microparticles can be formed by a variety of methods including spray cooling, precipitation, and the like. Spray cooling/chilling methods can be used where the molten hydrophobic material containing the core material is sprayed into a cold chamber or onto a cooled surface and allowed to solidify. For example, small particles of carbamide peroxide, or other bleaching agent, are combined with a molten mixture of wax and release rate modifier, e.g., PEG. The mixture is sprayed through a nozzle into a fluid at a sufficiently low temperature to solidify the mixture as microparticles. For example, carbon dioxide at low temperature may be used as the cooling fluid.

FIGURE 4 schematically illustrates an exemplary apparatus 50 for forming the microparticles 12. A first reservoir 52 holds the bleaching agent, e.g., a solution of the bleaching agent in a suitable solvent, such as carbamide peroxide dissolved in glycerol, or carbamide peroxide powder dispersed in a liquid. The contents of the first reservoir 52 may be agitated with an agitator 54, such as a vibrator, stirrer, rotation device, or the like. A second reservoir 56 holds the carrier material, e.g., a mixture of molten wax and PEG. A nozzle assembly 58 includes an inner nozzle tube 60, connected with the first reservoir 52, and a concentric outer tube 62, connected with the second reservoir 56. A jet of bleach agent (e.g., pressurized by a pump or the like), exits the first nozzle tube 60 into a concentric annular jet of molten carrier material from the second nozzle tube. The nozzle assembly 58 terminates in a chilled vessel 64, which is optionally fed with a coolant, such as carbon dioxide at low temperature and optionally under pressure, through a feed tube 66. The molten carrier solidifies upon exiting the annular jet. The release rate modifier may be present in the inner and/or the outer jet. In another embodiment, the particles 12 may be formed on contact with a chilled surface.

In other embodiments, C0₂ at low temperature and optionally under pressure, is used to encapsulate the bleaching agent in PEG or other polymer as first coat 44, and then a thin layer 42 of wax is applied to avoid rapid dissolution (as in the composition 40 shown in FIG. 2).

Other methods for forming encapsulated particles which may be used herein are disclosed, for example, in U.S. Patent No. 4,919,841, to Kamel, et al. (deposition and annealing of wax coated particles), U.S. Pat. Nos. 4,078,099, 4,136,052 and 4,327,151, all to Mazzola (spray methods), EP 0 132 184 to Scotte (spraying encapsulant onto bleach in a mixer), U.S. Pat. Nos. 3,015,128, 3,310,612 and 3,389,194 to Somerville, et al. (concentric tube with rotary head), U.S. Pat. No. 3,943,063 to Morishita, et al. (core dispersed in film forming polymer solution), U.S. Pat. No. 3,856,699 to Miyano, et al. (crushed, wax- covered core particles are heated in an aqueous medium), U.S. Pat. No. 3,847,830 to Williams, et al. (peroxygen compounds are held in a fluidized bed and enveloping agent is molten hot prior to spraying onto the peroxygen particles), and EP 0 337 523 (spray drying methods). Other encapsulation techniques are disclosed in MICROENCAPSULATION: Methods and Industrial Applications, Edited by Benita and Simon (Marcel Dekker, Inc., 1996).

The exemplary microparticles 12 loaded, for example, with carbamide peroxide 14 are able to provide slow and sustained release of hydrogen peroxide for teeth whitening.

The exemplary microparticles may be formulated as a composition 10 for home use or for use by a dental professional. For example, they may be employed in professional treatments where high concentrations of bleaching agent are released in a short period of time, by tailoring the concentration of the release rate agent appropriately. Since the hydrogen peroxide release is local to the teeth, the microparticles may be used without soft tissue isolation. Alternatively, the microparticles may be used for home treatments. For example, a whitening composition may be applied, and the hydrogen peroxide released slowly and locally over an extended period.

The exemplary composition 10, 40 may include other components, such as abrasive polishing agents, for example, silicas, aluminas, phosphates, orthophosphates, polymetaphosphates, beta calcium pyrophosphate, and calcium carbonate; anti-plaque agents, for example, stannous salts, copper salts, strontium salts and magnesium salts; anti- staining compounds, for example silicone polymers; anti-caries agents, for example, calcium glycerylphosphate and sodium trimetaphosphate; plant extracts; and mixtures thereof, flavorings, and the like. These components may be incorporated in the microparticles or separately added.

FIGURE 5 illustrates an example microparticle delivery device 70 which may be used for whitening teeth. A capsule 72 containing a unit dose of the microparticles 12 is received in a receptacle 74 of the device, which may be located in a body 76 or in a nozzle 78 of the device 70. A fluid source, which in the exemplary device includes a source 80 of a liquid, such as water, and a source 82 of a gas, such as air under pressure, supplies fluid to the capsule 72. The pressurized fluid ejects the microparticles into a stream of the fluid 84 that exits the nozzle 78. A user can cause the device to pulse the spray on the teeth, by pressing a button 84. The same or a separate button may be used for inserting a capsule 72 into the receptacle. The capsule 72 may be stored in a tray 86 until needed. In other embodiments, the microparticles may be delivered from a multi-dose container, e.g., in small bursts. Example devices which may be adapted to deliver the spray of microparticles in a fluid are disclosed, for example, in U.S. Pub. Nos. 2009/0305187; 2010/003520; 2010/0273125; 2010/0273126; 2010/0273127; 2010/0217671; 2011/0207078; 2011/0244418; and WO 2010/055435.

While the exemplary microparticles are particularly suited to tooth whitening, it is to be appreciated that they may find use in other bleaching applications.

The following examples, which are not intended to limit the scope of the invention, demonstrate how the release rate can be tailored using different release rate modifiers.

EXAMPLES

Reagents

The following reagents were obtained:

As a whitening agent, carbamide peroxide was obtained from Sigma (15-17% active oxygen basis, 04078, Fluka). The particle size distribution of the carbamide peroxide in this material is relatively broad with particle size ranging from 200 to 2000 μιη and the majority of crystals being around 800 μιη. Smaller particles would be expected to be more effective for this application.

As a carrier material, paraffin wax (melting point 53-57°C) was supplied by Sigma,

UK.

The following release rate modifiers were obtained:

Polyethylene glycols with different molecular weight (PEG1500 and PEG2000) were obtained from Sigma, UK.

Colloidal silicone dioxide AEROSIL™ 200, a fumed silica having an average particle size of about 12 nm and a moisture content (measured according to DIN 55921) of less than 1%, was supplied by Evronik Industries, Essen Germany.

Anhydrous sodium tripolyphosphate (STPP) was supplied by Sigma and particles less than 40 μιη were used after sieving through screens of 40 μιη. As a processing aid (emulsifier), polyglycerol polyricinoleate (PGPR) was supplied by Palsgaard, Sweden.

Production of hydrogen peroxide-loaded microparticles

Microparticles loaded with carbamide peroxide (CP) were prepared by spray cooling/congealing. Micro-carriers (CP) were prepared according to Table 1. The release rate modifiers were used in the following amounts:

Formula A: Control- no release rate modifier.

Formula B: PEG1500 at 29.4 wt. % of the microparticles.

Formula C: PEG2000 at 29.4 wt. % of the microparticles.

Formula D: AEROSIL™ 200 at 2 wt. % of the microparticles

Formula E: Sodium tripolyphosphate (STPP)- anhydrous powder, at 2 wt. % of the microparticles.

A ratio of carrier (everything but CP) to carbamide peroxide, by weight, was 3 :2 for all formulations.

The carrier material was heated in a jacketed beaker at a temperature of 5°-10°C above its melting point and the release rate agent added. For example, 58.8 g of paraffin wax was allowed to melt at 65°C and 2 g of PGPR, AEROSIL™ or STPP was added to the molten wax while stirring at 700 rpm for 3 min. 39.2 g of CP were then added to the mixture whilst stirring for another 3 min and the obtained suspension was loaded into a preheated 1 mL syringe to avoid solidification of the suspension in the syringe orifice. The molten suspension in the syringe, used to simulate a nozzle, was allowed to drop on a cold glass plate placed above an ice tray. The solid pastille-like capsules were then scraped from the plate with a spatula and stored in tightly closed plastic containers at 4°C.

The particles were all solid at room temperature and also at 37°C in PBS buffer. When a mixture of paraffin wax and PEG was used as a carrier, they were melted separately. The emulsifier (PGPR) was added to the paraffin wax after the melting step. CP was added to the molten paraffin containing the PGPR, followed by PEG while stirring, under the same conditions as above.

The encapsulation efficiency (% EE) can be calculated as follows: The mass of hydrogen peroxide recovered is determined after its extraction from the capsule using HPLC grade isopropanol as a solvent. The extract is filtered with a hydrophilic polyethersulfone filter unit (Millex-GP, 0.22 μιη) and the quantity of hydrogen peroxide determined spectrophotometrically at 351 nm. PEG was found to improve encapsulation efficiency.

Table 1 : Composition of different formulations of hydrogen peroxide- loaded

microparticles with a theoretical Η?0? content of 12 % (w/w).

CP= carbamide peroxide; STPP=anhydrous sodium tripolyphosphate; PGPR= polyglycerol polyricino leate

Hydrogen peroxide (Η?0?) release study

An Η₂0₂ release study was performed with 0.5 g of each of the CP-loaded microparticles of Formulations A-E in a release medium (Phosphate Buffered Saline (PBS), pH 7.4 at 37°C) designed to mimic the release of hydrogen peroxide from the particles when contacting the teeth of a user with the composition. The microparticles were dispersed in 20 mL of the release medium, placed in an orbital shaker at 150 rpm. lmL of aliquots were withdrawn at predetermined times, suitably diluted with the release medium, and the amount of H₂0₂ quantified spectrophotometrically at 351 nm. The withdrawn volume was immediately replaced with an equivalent volume of the fresh medium maintained at the same temperature. FIGURE 6 shows the hydrogen peroxide release profiles from the different microparticles. As can be seen, the release rate can be tailored by using different release agents.

Each of the documents referred to above is incorporated herein by reference.

Except in the Examples, or where otherwise explicitly indicated, all numerical quantities in this description specifying amounts of materials, reaction conditions, molecular weights, number of carbon atoms, and the like, are to be understood as modified by the word "about." Unless otherwise indicated, each chemical or composition referred to herein should be interpreted as being a commercial grade material which may contain the isomers, by-products, derivatives, and other such materials which are normally understood to be present in the commercial grade. It is to be understood that the upper and lower amount, range, and ratio limits set forth herein may be independently combined. Similarly, the ranges and amounts for each element of the invention may be used together with ranges or amounts for any of the other elements. As used herein any member of a genus (or list) may be excluded from the claims.

The invention has been described with reference to the preferred embodiments. Obviously, modifications and alterations will occur to others upon reading and understanding the preceding detailed description. It is intended that the invention be construed as including all such modifications and alterations insofar as they come within the scope of the appended claims or the equivalents thereof.

Claims

CLAIMS: Having described the preferred embodiments, the invention is now claimed to be:

1. A bleaching composition (10, 40) comprising:

a plurality of solid microparticles (12), each microparticle comprising a bleaching agent (14) encapsulated in a shell (20), the shell comprising:

a hydrophobic material (22), and

a release rate modifier (24), which modifies the release of bleaching agent from the microparticle.

2. The composition of claim 1, wherein the microparticles in the composition have an average diameter of less than 100 μιη.

3. The composition of either of claims 1-2, wherein the bleaching agent comprises carbamide peroxide.

4. The composition of any one of claims 1-3, wherein the hydrophobic material comprises a waxy solid.

5. The composition of claim 4, wherein the waxy solid comprises paraffin wax.

6. The composition of any one of claims 1-5, wherein the release rate modifier comprises a hydrophilic or water soluble material.

7. The composition of any one of claims 1-6, wherein the release rate modifier is selected from the group consisting of polyethylene glycol, silica, water-soluble alkali metal salts, and combinations thereof.

8. The composition (10) of any one of claims 1-7, wherein the release rate modifier forms discrete regions dispersed in the hydrophobic material.

9. The composition (40) of any one of claims 1-8, wherein the shell includes a layer (42) of the hydrophobic material and a layer (44) of the release rate modifier which spaces the core from the layer of the hydrophobic material.

10. The composition of any one of claims 1-9, wherein a ratio of hydrophobic material: release rate modifier is from 90: 10 to 10:90.

11. The composition of claim 10, wherein a ratio of hydrophobic material: release rate modifier is at least 40:60.

12. The composition of any one of claims 1-11, wherein the shell (20) further comprises an emulsifier.

13. The composition of any one of claims 1-12, further comprising a vehicle (26), and wherein the microparticles are dispersed in the vehicle.

14. A method for whitening teeth comprising applying the composition (10, 40) of any one of claims 1-13 to the teeth (28).

15. A method of forming a bleaching composition comprising:

encapsulating a bleaching agent (14) with a hydrophobic material (22) and a release rate modifier (24), at least one of the hydrophobic material and release rate modifier being in molten form; and

solidifying the encapsulated bleaching agent to form microparticles (12) in which the bleaching agent forms a core (18) of each microparticle which is surrounded by a shell (20) of the hydrophobic material and a release rate modifier.

16. The method of claim 15, further comprising combining the microparticles with a vehicle (25).

17. A method for whitening teeth comprising: applying microparticles (12) to the teeth, the microparticles comprising a bleaching agent (14) encapsulated in a shell (20), the shell comprising:

a hydrophobic material (22), and

a release rate modifier (24), dispersed in hydrophobic material, which modifies the release of bleaching agent from the microparticles.

18. The method of claim 17, wherein the applying includes applying the microparticles in a vehicle (26) to the teeth.

19. The method of claim 17 or claim 18, wherein the hydrophobic material comprises paraffin wax.

20. The method of any one of claims 17-19, wherein the release rate modifier is selected from the group consisting of polyethylene glycol, silica, water-soluble alkali metal salts, and combinations thereof.