MXPA97009001A - Pharmaceutical composition prepared by the addition of a savorizing vehicle for a medicame - Google Patents

Abstract

The invention relates to a method for preparing a liquid medicament flavored

Description

PHARMACEUTICAL COMPOSITION PREPARED BY THE ADDITION OF A SAVORIZING VEHICLE FOR A MEDICATION This invention relates to flavoring systems, particularly for flavoring pharmaceutical formulations administered orally. Pharmaceutical formulations for oral administration are often provided in an elaborate liquid form ready to be dispensed by a chemist or pharmacist and consumed by the patient without dilution. Alternatively, said formulations are provided in a concentrated liquid form for reconstitution with a convenient volume of water or other aqueous medium just before ingestion. Additional alternative formulations may be in the form of a dry powder or granules suitable for reconstitution. Many examples of such formulations are known in the art. The active constituents of said formulations and / or the excipients sometimes have an unpleasant taste and therefore a flavoring material is usually included in said formulations. This is particularly the case with pediatric formulations. A problem arises as to taste preferences of such flavorings often varies between patients or groups of patients, such as patients of different nationalities with local taste preferences. For example, a taste that may be acceptable or preferred in one country may be less acceptable in another country, or a taste may be unacceptable for individual pediatric patients while a different flavor may be preferred. The problem of "taste fatigue" may also be experienced. ", given that a patient may tire of repeated doses of the same sabotaged, albeit pleasant, medication sabotaged. Normally pharmaceutical formulations are made as a volume including the sabotagent material. Consequently, any need to prepare alternative sabotaged formulations requires the preparation of amounts of separate volume of sabotaged formulation and the possibility of different individual preferences of adequacy for intensely sabotaged materials which can not be conveniently handled by individual patients in the small amounts in which they are present in a single supply or dose. Therefore, it is convenient to provide a method by which single or individual doses or other small amounts of oral formulations can be easily and individually saboted. In particular, in the case of pediatric formulations it is also convenient to provide any sabotopia system in an attractive and appetizing form In a first aspect the present invention provides a method for preparing a sabotized liquid drug which comprises the addition of a sabotagent vehicle to a medicament The term "saoopzante" means any suitable sabotage means capable of releasing sabotage in a fluid medicament, including dosage means such as a tablet or a capsule containing an aliquot of powder or liquid containing a pharmaceutically acceptable flavoring substance. Alternatively, the sabotating carrier may be a flavoring substance by itself, either in pure form, or preferably in the presence of a pharmaceutically acceptable carrier or excipient. Preferably, the flavoring vehicle is an aliquot of liquid powder containing a pharmaceutically acceptable flavoring substance which is added to the non-flavored medicament, said flavoring being initially contained in a capsule or perfumed bags. Other flavoring vehicles within the scope of the invention include a flavor package, for example a bottle having a cap impregnated with flavor. The bottle is of a suitable size for a treatment method and the patient can be selected from their caps having alternative impregnated flavors. Additional alternatives are oral syringes or dosage cups impregnated with flavoring. An additional flavoring vehicle within the scope of the invention comprises an edible solid substrate in the form of a wafer or thin sheet of a non-toxic material dispersible or soluble in water which dissolves and / or disperses in an aqueous medium. The wafer has a sufficient quantity of an edible flavor substance impregnated in or deposited on its surface., so that the flavoring substance passes in the medium or aqueous solution or dispersion of the substrate therein and imparts a pleasant taste to the liquid material. Preferably the sabopzante vehicle is a capsule or sack each of which contains an aliquot of liquids or saboteurs Other preferred sabotaged vehicles are sabotaged tablets or wafers. More preferably, the sabotaged carrier is a sac or capsule. More preferably, the sabotaged vehicle is a sac or capsule containing a liquid sabotage formulation that is added to the liquid medicament, i.e. the contents of the capsule or bag are added The term "capsule" is understood to mean any container capable of containing a sabopzante The sabopzante inside the capsule can be an aliquot of liquid or powder, preferably the capsule will contain the sabopzante in liquid form said capsules They can be manufactured from any natural synthetic material suitable, for example, polyethylene gelatin In the case of capsules to be added to the medicament, the cap of the capsule is preferably made of a substance that is readily soluble in water or aqueous medium. For example starch. Alternative capsules, which are preferred are those that can contain an aliquot of liquid powder and can be opened by the patient or pharmacist and the content is then added to the formulation. Such capsules include those that have a fragile portion, for example ampoules and the like. The advantage of this type of capsule is that there is no time delay while dissolving the cover of the capsule. By the term "sack" is meant any package capable of containing a flavoring. The bag can be made of any suitable material including paper, plastic or sheet so that it can be opened by the patient or pharmacist and the content is added to the formulation. By the term "liquid medicament" is meant a formulation comprising a drug substance in liquid form for example, a solution, suspension, emulsion or syrup. The liquid medicament can be any pharmaceutical formulation which is in the form of a solution, suspension, emulsion or syrup, including formulations which have been worked up as described above by reconstitution of a concentrate. The saponative substance is dissolved or dispersed in the formulation to impart its flavor to it. In a further aspect of the invention the average dose can be added to a dry or liquid form of medicament before reconstitution dilution. Preferably the flavoring material in tablet, powder or liquid will be of a type that dissolves or disperses rapidly upon contact with the liquid medicament, normally, within a few seconds, or at least a few minutes, so that the flavor passes quickly in the liquid material The amount of flavoring substance may be such that when the sabotant substance passes into the pharmaceutical formulation which includes an ingredient and / or excipients having a strong, unpleasant or otherwise unacceptable flavor, the taste is so masked that the taste of the liquid material becomes pleasant. Preferably the amount of flavoring substance should be sufficient such that the addition of one or more dose means imparts an acceptable taste for an elaborate volume of liquid normally dispensed by the pharmacist sufficient for a method of treating a patient, for example approximately 50 to 600 ml, or it is consumed as unit doses by the patient. The amount of flavoring substance may need to be increased and / or more of the substrates used if the system is intended to be used with a formulation in which the constituents and / or active excipients therein have a particularly strong flavor. The flavoring substance may be any flavoring substance that is acceptable and approved for use with food and / or pharmaceutical formulations. Many times their substance is known. The flavoring substance can be, for example, a natural or artificial flavoring., such as the taste of a fruit, confectionery vegetable. If desired, more than one flavor can be used in a single dose medium. Additionally or alternatively, the flavoring substance may comprise a sweetener, such as sugar, sodium saccharin or aspartate. The dosage means of the invention may contain the flavoring substance in pure form or the flavoring substance itself may be mixed with a suitable pharmaceutical excipient vehicle. In the case of a capsule or sack, the flavoring substance may be present as a solid or a solution, for example, as an aqueous solution. In addition to the flavoring substance, the dosage means may have therein or deposited on their surfaces a coloring substance which is acceptable and approved for use with foods and pharmaceutical formulations. Many substances are known. The coloring substance can be a natural or artificial colorant and can be selected on the basis of being suitable for the flavoring substance, e.g., yellow for a banana flavor or on the basis of a color associated with the supplier, v. gr., a corporate symbol, or associated with a pharmaceutical formulation with which it is intended to be used. The flavoring substance itself can be adequately colored or alternatively the coloring substance can have a suitable flavor, so that a single substance can perform both flavoring and coloring functions. The flavoring means and method of the invention are suitable for use in imparting flavor to pharmaceutical formulations that require or benefit from flavoring to make them more palatable. Said formulations can be of any type, e.g., antibiotics, anti-asthmatic, antitussive analgesic, anti-infiamatory and anti-depressive, etc.

Particularly, suitable formulations are those routinely administered to pediatric patients, in particular antibiotic, anti-asthmatic, antitussive, and analgesic formulations Particularly preferred are those formulations containing the anti-asthmatic compound 4-oxo-8- [4- (4-phen? lbutox?) benzo? lam? no] -2- (tetrazol-5-? l) -4H-1-benzopranol or a pharmaceutically acceptable salt thereof, ie the compound having the Pranlukast INN Other preferred formulations with those containing antibiotics such as amoxicillin. Normally in use, the non-sabotaged bulk pharmaceutical formulations can be prepared in a central source and packaged in individual containers each of which contains a sufficient supply for a method of treating a patient, is said, one or more unit doses Each of said packages may be supplied with one or more of the dose means described above in one or more flavors that are dapta to the patient's preference Either the pharmacist or the patient can add one or more dose means of the invention to achieve an acceptable taste. In the case where the patients personally add the dosage means, capsules, tablets are generally preferred, sacks or wafers since they are easier and safer to handle The liquid formulation can be a formulation prepared by the reconstitution by the user of a dry powder, granules or a dispersible or water soluble tablet with water or an aqueous medium The sabopzante system can introduced into the formulation after reconstitution, v gr, in a unit dose prepared in a drinking container Alternatively the sabopzante system can be added to the powder or granules before reconstitution before the water or aqueous medium is added, v.gr ., to a volume container of powder or granules containing several unit doses of the formulation. Alternatively, the flavoring system may be introduced into the formulation at the same time as the water or aqueous medium. In this last mode, the volume can be reconstituted and the flavoring system will then impart its flavor to the liquid of elaborated volume. In another aspect, the invention provides a device comprising a method of liquid medicament, or a concentrate for the same, together with one or more dose means containing flavorant. In a further aspect, the invention provides a pharmaceutical composition prepared by the addition of a flavoring-containing dose means for a medicament. The problem of liquid flavors to be drunk is not confined to pharmaceutical formulations. Many beverages, e.g., milk-based beverages, may be flavored by the addition of solid flavorings, e.g., compact tablets or powders or granules in sacks or other containers, or capsules. For example, GB 1176087 describes effervescent sweetening tablets, EP 0124663 discloses compacting sweeteners and flavoring tablets, EP 0082460 describes flavoring capsules. These known products result in the problem of relative inconvenience and there is a need for a more convenient alternative and / or an alternative that provides other novel benefits.

According to a further aspect of the invention, a flavoring system for flavoring a drinkable liquid material comprises a solid edible substrate in the form of a wafer or thin sheet of a non-toxic dispersible or water soluble material which dissolves and / or dispersed in an aqueous medium to produce a drinkable solution or suspension, the substrate having a sufficient amount of an edible flavoring substance impregnated in or deposited on its surface so that the flavoring substance passes into the aqueous medium in solution or dispersion of the substrate in it and imparts a pleasant taste to the liquid material. The drinkable liquid can be a pharmaceutical oral formulation as described above or preferably a beverage such as a milk-based beverage. The edible solid substrate is preferably pharmaceutically acceptable and must be made from a material that dissolves or disperses rapidly in contact with the liquid material. Said moment is generally adequate if the flavoring system is used to impart flavor to a liquid pharmaceutical formulation after it is made from a concentrate, or a drink for short-term consumption. Suitable materials for said substrate are known, for example, fibrous or compact particulate edible materials such as carbohydrates, for example, polysaccharides such as materials based on starch and cellulose. As an example of said material is the rice paper, which disintegrates easily and disperses in water or other aqueous medium to form a pleasant dispersion. Suitably, the flavoring system of the invention can be made by the process of applying the flavoring substance to a pre-processed substrate, v., A solid absorbent substrate. The substrate may suitably have the shape of a small wafer, typically 0.5 to 2 mm thick and usually 1-5 cm wide. The wafers can be provided individually or separately attached, for example, in the form of a strip or sheet of individual wafers bound by weak ligatures, for example, the wafer being misaligned by lines thinned or punched through a strip or sheet in some way Continuous In said single sheet strip, the wafers may be the same flavoring substance or the individual objects may differ in the nature of their sabotating substance. The wafers can have a particular shape to suit the preferences of individual patients or markets. For example, the wafers can be simple geometric shapes such as square rectangles, circle, triangle, hexagons, etc. Alternatively, the wafers can have shapes that are suggestive of the sabopzante substance, v gr, in a form that represents a fruit, etc. Alternatively, the wafers may have a shape related to a trademark and another symbol associated with the supplier Alternatively, particularly for pediatric patients, the wafer may have a shape that is nice for children, such as a novel character, etc. The substrate may additionally be embossed in some appropriate manner, for example, for decoration, to provide a relief symbol such as a symbol associated with the supplier or a pharmaceutical formulation with which it should be used or with Braille text to help the partially blind people. The flavoring substance may be impregnated in or deposited on its surface by known techniques. For example, the flavoring substance can be mixed with the fibers or particles before they are compacted, or alternatively the substrate can be processed first, then the flavoring substance can be impregnated into or deposited thereon, for example as a liquid, which can be the pure flavoring substance itself or a solution or solvent thereof, v. gr. , in a volatile solvent that can be water. Appropriate techniques for accomplishing this will be apparent to those skilled in the art. The amount of flavoring substance impregnated in or deposited on the substrate will depend on the nature of the flavoring substance and the application to which the flavoring system will be placed. Suitably, the amount of flavoring substance should be sufficient such that the addition of one or more of the substrates imparts an acceptable taste to an adequate volume of the processed liquid. Additionally or alternatively, the substrate may have a symbol printed thereon, for example, a symbol representing the flavoring substance, such as a representation of a fruit, etc. Said additional symbol or alternatively may be associated with the supplier, for example, a trademark or with a pharmaceutical formulation with which it is intended to be used. Additionally or alternatively, the substrate may have printed on the same text that contains information for the user. If such material is printed on the substrate, then the ink used must be an ink substance which is acceptable and approved for use with food and pharmaceutical formulations. The ink itself may contain all or at least part of the flavoring substance., so that the sabotating substance and said symbol can be deposited on the substrate in a single operation. In one form of the invention, suitable for flavor-based milk drinks that at least initially have an empty surface, the colorant may be such that if the wafer is deposited on the upper surface of the gap, the solution or dispersion of the wafer will has a color symbol as described above can leave a colored image in the shape of the symbol on the hollow side This can have an attractive effect. Therefore, as an alternative aspect of this invention, a method for imparting a flavor to a liquid pharmaceutical formulation for drinking is provided, which comprises the step of introducing into the liquid formulation a sabopzante system comprising an edible solid substrate which is dissolved and / or dispersed in an aqueous medium to produce a solution or dispersion for drinking, the substrate having a sufficient amount of an edible flavoring substance impregnated in or deposited on its surface so that the flavoring substance passes into the aqueous medium in solution or dispersion of the substrate therein and imparts a pleasant flavor to the formulation. The invention also provides a method for imparting a flavor to a liquid material for drinking by introducing a flavoring substance into the liquid material by means of a flavoring system as described above. The invention also provides the use of a flavoring system as described above for the importation of a flavor into a liquid drinking material. The invention also provides a flavoring system as described above provided for the purpose of imparting a flavor to a liquid material for drinking. The invention also provides one or more flavoring systems as described above provided in combination with one or more unit doses of an oral pharmaceutical formulation or a concentrate for reconstitution with an aqueous medium in an oral pharmaceutical formulation. The invention will now be described by way of example only with reference to the appended figures which are representative of the invention only and is not intended to limit the generality of this description.

Figure 1 shows a perspective view of a flavoring system of the invention in the form of a circular wafer. Figure 2 shows a view of a flavor system of the invention in the form of a strip of rectangular wafers. Figure 3 shows a view of a flavor system of the invention in the form of a sheet of rectangular wafers. Referring to Figure 1, a flavoring system comprises a circular wafer (11) of rice paper, about 1 mm thick and about 3 cm in diameter. The wafer (11) is impregnated with a lemon / lime flavoring substance corresponding to approximately 28 mg of dry lemon flavor and 1.4 mg of dry lime flavor. The wafer (11) is printed with a symbol of a lemon (12) in yellow and with the phrase (13), (14), (15) that respectively establishes the flavor, the supplier and its intended use, that is, as a flavoring system for a 500 mg oral amoxicillin suspension. The wafer (11) is also graded in relief with Braille letters (16) indicating the nature of the wafer. Although all printing (12-15) and embossing (16) is shown in Figure 1 because it is located on one side of the wafer (11), some attempt to be located on the opposite side and some of the prints and / or engraved in relief shown from below could be omitted. Referring to Figure 2, a flavoring system comprises a strip (21) of rice paper, about 1 mm thick, divided by perforated lines (22) through the strip (21) into individual rectangular wafers (23), each of which is approximately 2.5 square cm. The entire strip is impregnated with a lemon / lime flavoring substance so that each wafer of Figure 2 contains enough of the flavor substance to impart a desired intensity of flavor to a unit oral dose of a pharmaceutical formulation when in a volume of wafer suitable for drinking. Each wafer (23) also has a symbol, phrase and relieved engraving (not shown) as on the wafer of Figure 1. The wafers (23A) can easily separate the strip (21) in the perforated lines (22). Referring to Figure 3, a flavoring system comprises a sheet (31) of rice paper, divided by a grid pattern of perforated lines (32) which delineate individual rectangular wafers (33). The sheet (31) is approximately 1 mm thick, and the individual wafers (33) each are approximately 2.5 square cm. Each wafer (33) has printed on it a symbol (34A, 34B) in a colored ink which also includes a flavoring substance. The alternate rows of the wafers (33) are printed with symbols (34A, 34B) which include a different flavoring substance and the symbol (34A, 34B) is selected so that it is appropriate for the flavoring substance, for example, a symbol of an orange indicating an orange flavoring substance. Each wafer (33) may also have the sentence and embossed (not shown) as shown in Figure 1. The wafers (33A) may be easily separated from the sheet in the perforated lines (32). In use, to a pharmaceutical formulation in liquid form, for example made by the reconstitution of a dry tablet or granulated formulation of a sack in approximately 100 ml of water for oral administration, one or more of the individual wafers (11, 23A, 33A), whether of the same flavor or different flavors to suit the individual taste preference. The wafer (11, 23A, 33A) disintegrates in the liquid formulation and its dissolution and / or dispersion can be rushed by the agitation of the liquid. Upon disintegration of the wafer (11, 23A, 33A) the flavoring substance is dispersed or dissolved in the formulation, thus imparting its flavor to the formulation. Example 1 A reconstitutable formulation containing 250 mg of the antibiotic amoxicillin can be made palatable by the use of 28 mg of dried lemon flavor plus 1.4 mg of dry lime flavor plus 2.5 mg of sodium saccharin. These amounts of flavoring substance can be easily impregnated in or deposited on the surface of a wafer as described herein. Example 2 A flavoring granule soluble in water, for example, a carbohydrate or granule based on sugar, can be initiated on one or more flavoring components, for example, 1, 2 or 3 orange flavors or mixtures thereof. If required, a sweetening or coloring agent may be added. Suitable amounts of the resulting mixture can be filled into bags or capsules using standard filler equipment.

Claims (16)

1. CLAIMS 1. A method for preparing a flavored liquid medicament which comprises the addition of a flavoring vehicle to a medicament.
2. 2. The method according to claim 1, wherein the flavoring vehicle is a capsule.
3. 3. The method according to claim 1, wherein the flavoring vehicle is a flavor aliquot in pure form or in the presence of a pharmaceutically acceptable carrier or excipient.
4. 4. The method according to claim 3, wherein the flavor is contained in a capsule or bag.
5. 5. The method according to claim 3 or 4, wherein the flavor is in liquid form.
6. 6. The method according to any of the claims 1 to 5, in which the medicament is a solution, suspension, emulsion or syrup.
7. 7. The method according to any of claims 1 to 6, wherein the medicament is an antibiotic, antiasthmatic, antitussive or analgesic drug.
8. 8. The method according to any of claims 1 to 6, wherein the medicament is a 4-oxo-8- [4- (4-phenylbutoxy) benzoylamino] -2- (tetrazoi-5-ii) -4H -1-benzopyran or a pharmaceutically acceptable sai thereof.
9. 9. A kit comprising a liquid medicament method, or a concentrate thereof, together with one or more flavoring vehicles.
10. 10. A kit according to claim 9, wherein the flavoring vehicle is an aliquot of flavor in pure form or in the presence of a pharmaceutically acceptable carrier or excipient thereof.
11. 11. A kit according to claim 10, wherein the flavor is contained in a capsule or bag.
12. 12. A pharmaceutical composition prepared by the addition of a flavor vehicle containing flavor for a medicament.
13. 13. A pharmaceutical composition according to claim 12, wherein the medicament is 4-oxo-8- [4- (4-phenylbutoxy) benzoylamino] -2- (tetrazol-5-yl) -4H-1-benzopyran or a pharmaceutically acceptable salt thereof.
14. 14. A pharmaceutical composition according to claim 8, wherein the medicament is amoxicillin.
15. 15. A flavoring system for flavoring a liquid material for drinking, which comprises a solid edible substrate in the form of a wafer or thin sheet of a non-toxic dispersible or water soluble material which dissolves and / or disperses in a aqueous medium to produce a solution or suspension for drinking, the substrate having a sufficient quantity of an edible flavoring substance impregnated in or deposited on its surface so that the flavoring substance passes into the aqueous medium in solution or dispersion of the substrate therein; imparts a pleasant taste to the liquid material.
16. 16. A method for imparting a taste to a liquid material for drinking, which comprises the step of introducing into the liquid formulation a flavoring system comprising a solid edible substrate which is dissolved and / or dispersed in an aqueous medium to produce a solution or suspension for drinking, the substrate having a sufficient amount of an edible flavoring substance impregnated in or deposited on its surface so that the flavoring substance passes into the aqueous medium in solution or dispersion of the substrate therein and imparts a pleasant taste to the formulation.