ENCAPSULATED ACTIVE AGENTS, FOR INSTANCE ENCAPSULATED FRAGRANCES AND FLAVOURS, AND PROCESS THEREFOR

Abstract: There is disclosed a controlled release encapsulated active agent, in which an active agent is encapsulated in a continuous coating composition comprising a film former, an enteric compound and a plasticizer for the film former, the coating composition from 10% to 25% by weight of the encapsulated active agent, based on the weight of the active agent plus the coating composition, and the plasticizer com­ prising from 18% to 40% by weight of the film former solids. A process for producing the encapsulated active agent is also disclosed.

Description: This invention relates to encapsulated fragrances and flavours. In particular it relates to the encapsulation of fragrances and flavours which have a controlled rate of release. Specifically it relates to an encapsulation method utilizing as the encapsulating medium a water insoluble film former in conjunction with an enteric composition. Flavours are used as adjunctives in many food and non-food products. Typically, flavours are added to confections, chewing gums and dentifrices. More recently the application of encapsulating techniques has been applied to flavours to prolong, delay, or otherwise enhance the flavour agent's perception by the user of she product containing it. U.S. Patent No. 3,957,964 teaches a dentifrice containing encapsulated flavors wherein various material and synthetic polymers are used as the encapsulating medium for the polymer. Slow release flavours entrapped in edible gels are disclosed for use in chewing gums in U.S. patent 3,920, 849. Similarly, U.S. Patent 3,761,286 teaches the use of encapsulated flavours in chewing gum, toothpaste and foods. The encapsulating medium is a hydroxymethyl methacrylate. Other approaches to the encapsulation of flavours for delayed or sustained release are known to the art. For example, U.S. Patent No. 3,201,353 discloses microinclusion containing flavours in chewing gums. U.S. Patent No. 3,011,949 utilizes liquid sugar for coating solid particles of flavour and uses the dried, pulverized flavour material in chewing gum. Other techniques have utilized gelatin-encapsulated flavors (U.S. Patent No. 2,886,446) and gelatin-concentrated flavors (U.S. Patent No. 2,886,444) for use in chewing gums. In addition to gelatin, the art discloses as encapsulating media gum arabic, ethyl cellulose modified starches, starch hydrolysates, hydrophilic colloids or combinations thereof; see for example U.S. Patent Nos. 3,850,838; 3,930,026; 3,962,463; and 4,316,915. Generally, the teachings relating to hydrophillic colloids describe the absorption of flavors onto hydrocolloids or spray drying the flavors in an aqueous hydrocolloid/flavor matrix. Calcium alginate is disclosed as a coating material for flavor particles in U.S. Patent No. 3,857,964. Other patents which disclose the use of alginates as an encapsulating medium are U.S. Patent Nos. 3,985,913 and 4,238,475. European Patent Application EP-A 40048 discloses a method for preparing calcium alginate fibers which are alleged to be useful in encapsulating flavors. A delayed release sodium fluoride formula encapsulated in a pretreated ethyl cellulose is taught in U.S. Patent No. 4,220,552. The ethyl cellulose is hydrochloric acid treated prior to use. The EP-A 77956 describes microcapsules comprising (i) particles of a core material and (ii) ethylcellulose coating walls deposited on and around said particles of the core material and (iii) an enteric polymer material incorporated into the ethylcellulose coating walls of the microcapsules. According to one aspect of the present invention, there is provided an encapsulated active agent, in which an active agent is encapsulated in a continuous coating composition comprising a water-insoluble film former, an enteric compound and a plasticizer for the film former, the coating composition comprising from 10% to 25% by weight of the encapsulated active agent, based on the weight of the active agent plus the coating composition, the plasticizer comprising from 18% to 40% by weight of the film former solids, and the weight ratio of the film former to enteric compound being in the range from 5:1 to 0.5:1. Another aspect of the present invention provides a process for producing a controlled release encapsulated active agent, which process comprises encapsulating the active agent in a coating composition comprising a water-insoluble film former, an enteric compound and a plasticizer for the film former, the coating composition comprising from 10% to 25% by weight of the encapsulated active agent, based on the weight of active agent plus coating composition, the plasticizer comprising from 10% to 40% by weight of the film former solids, the weight ratio of the film former to enteric compound being in the range from 5:1 to 0.5:1. It has surprisingly been found that a fragrance or flavour agent having a controlled release rate can be prepared by encapsulating the fragrance or flavouring agent in the specified coating composition. The enteric compound is water-soluble in solutions at a pH of 5.50 or greater. The preferred film former is ethylcellulose, and the preferred enteric compound is an acrylic polymer. The coating can be applied from an emulsion of the coating material by spray coating in a fluidized bed of the material to be encapsulated. Generally, flavours and fragrances in foods, chewing gums, denture compositions and so forth, are oils. These flavour or fragrance oils can be converted to a dry state by preparing compositions known in the art as spray dried flavours or fragrances. Spray dried flavours and fragrances are prepared by dissolving in water a solid carrier for the flavour or fragrance oils. The oil is then added to the aqueous solution of carrier with high shear mixing in order to disperse the oil. The dispersion of oil in carrier solution is then spray dried. Any water soluble edible composition may be utilized as the carrier. Generally, however, the carrier is maltodextrin. The spray dried flavour or fragrance can comprise up to about 30% by weight of flavour or fragrance oil based on carrier plus oils. The spray dried flavours or fragrances preferably comprise 15% to 25% flavour or fragrance oil. The term "flavouring agent" as used in the specification means a solid, particulate, water-soluble composition having incorporated therein a flavour oil. The preferred method of incorporating the flavour oil into the flavouring agent is by the afore-described spray drying technique. The preparation of preparation of spray dried flavours is well known in the art and does not form a part of this invention. Generally, spray dried flavours and fragrances are of a fine particle size. While it is possible to utilize such fine particle size flavouring agents or fragrance, it is preferred that the flavoring agent or fragrance, have a particle size of from 0.33 to 0.84 mm (20 mesh to about 50 mesh (U.S. Standard stainless steel mesh)); preferably the mesh size is -20 + 50. The appropriate particle size range can be selected by sieving through a 0.84 mm (20 mesh) screen and utilizing material which collects on a 0.33 mm (50 mesh) screen. At particle sizes substantially smaller than 0.33 mm (50 mesh) the particles have too large a surface area and encapsulation becomes uneconomical because of the high surface area of the particle, resulting in the use of large quantities of encapsulating material. Particles of greater than 0.84 mm (20 mesh) create problems in the feeder of tableting machines for denture cleansing compositions. In order to achieve the flavour or fragrance release rates desired in the practice of this invention the encapsulating coating composition comprises from 10% to 25% by weight based on the total weight of encapsulated flavouring agent or fragrance, preferably 15% to 20% by weight. Below 10% by weight of coating the release rate will be too fast. Above 25% by weight of coating the release rate will be too slow for practical use in denture cleansing compositions. In the practice of this invention the coating composition in a carrier vehicle is sprayed into the inlet stream of a fluidized bed in which the flavouring agent or fragrance particles are fluidized. The coating can be applied either from a solution or an emulsion. Preferably, water based emulsions are utilized to avoid health and fire hazards as well as recovery problems associated with the use of organic solvent solutions. The solids content of the vehicle used for the coating can be 8% to 30% by weight based on the total weight of vehicle plus coating material, preferably 10% to 25% by weight, more preferably 15% to 20% by weight. Below 8% solids inordinately long process times are required to apply coatings of a suitable thickness. At higher solids contents, that is in excess of 30% by weight, the solution or emulsion is too viscous and coating operations may show polymer incompatabilities and are therefor not uniform. The plasticizer is required in the coating composition in order to ensure good film forming characteristic. Excessive amounts of plasticizer result in stickiness of the coating and agglomeration of coated particles. Too low a level of plasticizer results in discontinuous coatings with, as a consequence, immediate release of flavouring agent or fragrance in the solution in which it is used. While the preferred range of plasticizer will depend on the specific film forming material utilized, generally from 18% to 40% by weight based on the film former solids is used, preferably 20% to 30% (w/w). It should be noted that reference to coating weight includes film former, plasticizers and adjunctives which may be included in the coating formulation . The type of plasticizer used will depend on the selection of the film former. Specific plasticizers are normally recommended by the film former supplier; and no advantage is seen in deviating from those recommendations. Where the film former is ethylcellulose the preferred plasticizer is dibutyl sebacate. Triethyl citrate can also be used. The film former must not be water-soluble. Since, the pH of denture cleansing compositions is usually at least 7.0 and preferably 7.5 to 11.0, for example, 9.0 to 10.0, the film former must not be solubilized by basic solutins. While the film former must be water-insoluble it must be permeable with respect to water. Preferably the film former is swelled by water. The preferred film former is ethylcellulose. A class of polymeric compounds used in the preparation of pharmaceutical capsules is known as enteric coatings. They are so called because they dissolve in the intestinal fluids which have a relatively high pH as compared to the very acidic stomach fluids in which the coatings are insoluble. As used in the specification and claims the term "enteric composition" means a polymer or compound which is normally water-insoluble but is rendered water soluble at pH's of 5.5 or greater. Preferably a pH of at least 7.0 is required to solubilize the enteric compositions of this invention. Typical of enteric compositions are copolymers of acrylic acetate and vinyl alcohol the ratio of acetate to alcohol groups is 1:1. The structure of these polymers is : where R is an alkyl group of 1 to 10 carbon atoms. Preferably R is a C₁-C₄ alkyl radical. Other enteric compositions include polyvinylbutyrate and polyvinylphthalate. Enteric compositions are incorporated into the film former coating in order to control the rate of release of flavouring agent or fragrance. The weight ratio of film former to enteric compound is 5:1 to 0.5:1, preferably 1.5:1 to 1:1. At a weight ratio of greater than 5:1 there is insufficient enteric compound in the film and the rate of flavour release is too slow. At a ratio of less than 0.5:1.0 the rate of release of flavour is too rapid and approaches that of where no coating is used. A particularly preferred film former suitable for use in the process of this invention is ethylcellulose when utilizing as the plasticizer dibutyl sebacate. Both the ethyl cellulose emulsion and acrylic latex dispersion are available commercially at a 30% (w/w) solids content. A plasticizer for ethylcellulose, dibutyl sebacate, is available as a 100% (w/w) active material. Spray dried flavors and fragrances are generally available as fine powders, that is less than 149 micrometers (100 mesh). In order to utilize these products it is preferred that they be granulated to provide particles in the 0.33 to 0.84 mm (20 to 50 mesh) range. Methods of granulation are well known in the art. The particular method used in the practice of this invention utilizes a rotary mixer wherein an ethanol/water (75/25 v/v) solution is added into the powder mix and blended until a uniformly wet granulation develops. The method of granulation is not critical. In the practice of this invention 5% to 15% by weight of methylcellulose is added to the spray dried flavor as a granulation aid. Preferably 8% to 12% of methycellulose based on the weight of methylcellulose plus spray dried flavor is used. In preparing the granulation 50 to 70 grams of an ethanol/water solution (75/25 v/v) per 100 grams of flavouring agent are added into the flavouring agent mix. The granulated material is then wet sceened through a 0.84 mm (20 mesh) screen, oven dried and re-sieved. All material passing through a 0.84 mm (20 mesh) screen and collected on a 0.33 mm (50 mesh) screen is reserved and the remainder is discarded or subsequently used in the granulation of fines. The flavour oils which can be incorporated into the spray dried flavor to form the flavouring agent of this invention include the well known flavour oils utilized in processed foods, gums and confectionary compositions. Both synthetic and natural flavour oils derived from plants, leaves, flowers, fruits and so forth and combinations thereof may be utilized in the practice of this invention. Illustrative, non-limiting examples of these flavourings include spearmint oil, cinnamon oil, oil of wintergreen (methylsalicylate) and peppermint oils. Synthetic and natural fruit flavours are also useful including citrus oils, for example, lemon, orange, lime and grapefruit; fruit essences including apple, strawberry, cherry, pineapple, and the various flavourings such as aldehydes and esters including cinnamyl acetate, cinnamaldehyde, citral diethyl acetal, dihydrocarvyl acetate, eugenyl formate, and p-methylamisol. Generally, any flavouring such as those described in Chemicals Used in Food Processing , pub. 1274 by the National Academy of Sciences, pages 49-53 and 63-258 may be used. Fragrances generally comprise natural and synthetic oils which give off a characteristic pleasant odour. Illustrative non-limiting examples of fragrances of this invention are spearmint, peppermint and cloves. The term "fragrance agent" as used in the specification and claims means the fragrance oils in a spray dried particulate form as heretofore described. The encapsulated flavouring agent and fragrances of this invention may be used advantageously in denture cleansing compositions, chewing gums, denture adhesives, processed foods and confectionaries. The amount of flavouring agent, or fragrance agents employed is normally a matter of preference and will be determined by such factors as flavour, or fragrance type and the strength desired. In general, 0.05% to 3.5% by weight of encapsulated flavouring agent based on the overall composition is used, preferably 0.5 to 2.5% by weight, more preferably 0.7% to 1.2% by weight. The fragrance agent is utilized in the same proportions set forth above for the flavouring agents. The method of encapsulation utilized in the practice of this invention is well known to those skilled in the art and can be accomplished with an Aeromatic STREA coater using known techniques. Those skilled in the art will recognize that the objective is to produce a dry, non-tacky coated product, and, therefore, will appreciate what process parameters are required to achieve that end. The coating is applied by spraying a solution or emulsion comprising the film former composition into the air inlet stream of a fluidized bed comprising the particles to be coated. To ensure evaporation of the vehicle the inlet air temperature should be about 20°C to about 70°C preferably about 40°C to about 65°C. Sufficient air flow is required to fluidize the particles to be coated so that a "boiling bed" condition exists. The flow rate will depend on the bed height and particle density. As those skilled in the fluidzation art will recognize, the flow rate must be sufficient so that the pressure drop through the bed exceeds the bed weight per unit area. However, excessive flow rates are to be avoided to minimize attrition of particles in the air stream. The bed diameter of the equipment utilized in the reduction to practice of this invention is 112 mm (4 1/2 inches), and bed heights of 50 to 200 mm (2 to 8 inches) were used. A flow rate of 20 m³/hr. to 80 m³/hr. has been found to be adequate. Preferably flow rates of 25 m³/hr. to 70 m³/hr. are used, more preferably the fluidization flow rate is 30 m³/hr. to 50 m³/hr. The encapsulation process of this invention is more readily appreciated by reference to the following examples. All parts and percentages in the examples as well as in other parts of the description and claims are by weight unless otherwise specified. EXAMPLE I GRANULATION A 90/10 (w/w) blend of hydroxypropyl methylcellulose and spray dried peppermint fragrance agent was prepared and charged into the rotary mixer (approximately 0.2 Kg.). A granulating fluid comprising 75/25 ethanol/ water (v/v) was added at about 65g. per 100 g. of fragrance agent. When all of the fluid had been added, the uniformly wet granulation was discharged and passed through a 0.84 mm (20 mesh) screen. The particles were then dried at 60°C in a forced draft oven for about 15 minutes. The dried particles were again sieved and all material which passed through 0.84 mm mesh (20 mesh) and was retained on a 0.33 mm (50 mesh) screen was resieved for use in coating. EXAMPLE II ENCAPSULATION PROCESS The granulated spray dried fragrance of Example I was coated with a plasticized film of ethylcellulose and acrylic polymer using an Aeromatic STREA-1 coater. The air inlet temperature was about 60°C and the air flow rate was 32 m³/hr. The coating solution comprising the film former (ethylcellulose), enteric composition (acrylic polymer) and plasticizer (dibutyl sebacate) was sprayed into the inlet a stream at about 2 to 3 ml/min. After addition of the coating solution the product was dried in the unit for about 15 minutes at 60°C. The theoretical coating weight on the particles was 15.28% based on the weight of fragrance agent plus coating. Approximately 0.200 Kg of charge (spray dried fragrance) was used requiring approximately 36 grams of coating material (about 200.00 gms. of coating solution). The coating solution had the following formulation: The talc served to minimize particle to particle adhesion. The solution was prepared using a high shear blade mixer. EXAMPLE III DENTURE CLEANSING COMPOSITION A denture cleansing tablet was prepared utilizing the encapsulated fragrance prepared in Example II. The tablet composition was as follows: In the above denture cleansing composition the potassium monopersulfate and sodium perborate act as bleaching agents. The EDTA and sodium tripolyphosphate are sequestering agents used to maintain a solution of the composition clear. The sodium carbonate acts to buffer the pH of the cleansing solution to about 7.2 7.5. The sodium sulfate is a filler and the bicarbonate and citric acid act as effervescent agents to break up the tablet and generate a stirring action in the solution. The foregoing denture cleansing composition is merely illustrative of the denture cleansers in which the encapsulated fragrance of this invention can be utilized. The encapsulated fragrance is suitable for use in any denture cleanser composition whether in tablet or granule form. When the above described tablet was added to 120 ml. of water at 45°C, fragrance began to be released at about 3 minutes. Maximum fragrance was detected at about 6 minutes, and the total duration of the fragrance odor was about 15 minutes. By contrast when unencapsulated fragrance is used the odour dissipates in about 3 to 5 minutes. It is within the scope of this invention to utilize both conventional unencapsulated fragrances and the encapsulated fragrance of this invention in the same composition in order to have both instant release of fragrance as well as a delayed release of fragrance over the entire denture cleansing cycle (about 12 to 15 min.). Similarly, where a flavouring agent is encapsulated by the process of this invention it may be utilized in conjunction with an unencapsulated flavoring for use, for example, in chewing gum. The term "chewing gum" as used in the specification and claims means both bubble gum and adult chewing gum. Chewing gum compositions are well known in the art and generally comprise a gum base which is an uncured elastomeric polymer, a sweetener and various adjunctives including, flavourings, softeners and emulsifiers. The term "denture" as used in the specification and claims means false teeth, dental bridges and other similar orthodontic devices. The term "denture cleansing composition" as used in the specification and claims means a solid tableted or granulated cleansing agent which is utilized in a water solution to clean dentures. Denture cleansing compositions are well known in the art and generally comprise a bleaching agent, effervescent compounds, a buffer to maintain pH at about 7.0 to about 11.0, preferably about 7.5 to 9.5; a sequestering agent to hold metal compounds, for example magnesium and heavy metals, in solution in order to ensure that the denture cleansing solution is clear and other adjunctives such as flavourings, coloring agents and binders. Chewing gum compositions and denture cleansing compositions per se do not form a part of this invention unless they have incorporated therein the encapsulating flavouring agents and/or fragrance agents of this invention. The term "controlled release" as used in the specification and claims means release of flavour or fragrance gradually over a period of time rather than instantaneous release after the passage of a period of time. The term "active agent" as used in the specification and claims means the flavouring agents and fragrance agents which are encapsulated by the process of this invention.

Claims: An encapsulated active agent, in which an active agent is encapsulated in a continuous coating composition comprising a water-insoluble film former, an enteric compound and a plasticizer for the film former, the coating composition comprising from 10% to 25% by weight of the encapsulated active agent, based on the weight of the active agent plus the coating composition, the plasticizer comprising from 18% to 40% by weight of the film former solids, and the weight ratio of the film former to enteric compound being in the range from 5:1 to 0.5:1. An encapsulated active agent according to claim 1, wherein the film former is ethylcellulose and the plasticizer is dibutyl sebacate. An encapsulated active agent according to claim 1 or 2, wherein the enteric compound is an acrylic polymer. An encapsulated active compound according to claim 1, 2 or 3, wherein the weight ratio is in the range from 1.5:1 to 1:1. An encapsulated active compound according to any preceding claim, wherein the coating composition comprises from 15% to 20% by weight of the encapsulated active agent. An encapsulated active agent according to any preceding claim, wherein the plasticizer comprises from 20% to 30% by weight of the film former solids. An encapsulated active agent according to any preceding claim, wherein the active agent has a particle size in the range from 0.33 to 0.84 mm (20 mesh to 50 mesh (U.S. standard stainless steel mesh)). An encapsulated active agent according to any preceding claim, wherein the active agent is a flavouring agent. An encapsulated active agent according to any one of claims 1 to 7, wherein the active agent is a fragrance agent. A denture cleansing composition which includes, as a fragrance, the encapsulated fragrance agent as claimed in claim 9. A chewing gum composition which includes, as a flavouring, the encapsulated flavouring agent as claimed in claim 8. A process for producing a controlled release encapsulated active agent, which process comprises encapsulating the active agent in a coating composition comprising a water-insoluble film former, an enteric compound and a plasticizer for the film former, the coating composition comprising from 10% to 25% by weight of the encapsulated active agent, based on the weight of active agent plus coating composition, the plasticizer comprising from 10% to 40% by weight of the film former solids, the weight ratio of the film former to enteric compound being in the range from 5:1 to 0.5:1. A process according to claim 12, wherein the coating composition is applied by spray coating a coating solution or a coating emulsion of the coating composition onto the active agent. A process according to claim 13, wherein the coating solution or coating emulsion contains from 8 to 30% (w/w) of coating composition, based on the weight of emulsion or solution.

Inventors: SCHOBEL, ALEXANDER M.
Applicants: WARNER-LAMBERT COMPANY
Application year: 1984
Main classification: B01J13
IPC codes: A61K8, A23G4, A61Q11