EP0804208A1 - Effervescent composition containing iodinated polyvinylpyrrolidone, and use thereof for disinfection - Google Patents

Effervescent composition containing iodinated polyvinylpyrrolidone, and use thereof for disinfection

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Publication number
EP0804208A1
EP0804208A1 EP96902310A EP96902310A EP0804208A1 EP 0804208 A1 EP0804208 A1 EP 0804208A1 EP 96902310 A EP96902310 A EP 96902310A EP 96902310 A EP96902310 A EP 96902310A EP 0804208 A1 EP0804208 A1 EP 0804208A1
Authority
EP
European Patent Office
Prior art keywords
composition according
pvpi
composition
effervescent
polyvinylpyrrolidone
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP96902310A
Other languages
German (de)
French (fr)
Inventor
Jérome Besse
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Galenix Developpement
Original Assignee
Mission SC
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Publication date
Application filed by Mission SC filed Critical Mission SC
Publication of EP0804208A1 publication Critical patent/EP0804208A1/en
Withdrawn legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/74—Synthetic polymeric materials
    • A61K31/785—Polymers containing nitrogen
    • A61K31/787—Polymers containing nitrogen containing heterocyclic rings having nitrogen as a ring hetero atom
    • A61K31/79—Polymers of vinyl pyrrolidone
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N59/00—Biocides, pest repellants or attractants, or plant growth regulators containing elements or inorganic compounds
    • A01N59/12—Iodine, e.g. iodophors; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/58—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
    • A61K9/0007—Effervescent
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders

Definitions

  • Effervescent composition based on iodized polyvinylpyrrolidone and use for disinfection
  • the present invention relates to an effervescent composition based on iodized polyvinylpyrrolidone.
  • Iodine has long been used in various pharmaceutical forms (solution, tincture) for the fine disinfection of small wounds. Despite the good effectiveness of the product, its application is limited because it has a number of side effects.
  • PVPI Iodized polyvinylpyrrolidone
  • PVP polyvinylpyrrolidone
  • iodine contained in the complex is released slowly and gradually.
  • PVPI is characterized by a wide range of applications. The main areas of use are in the field of prophylaxis: - hand disinfection, in particular in surgery,
  • This compound is a broad spectrum antiseptic: - bactericide on all bacteria including chlamydiae and mycoplasmas,
  • PVPI polyvinylpyrrolidone
  • PVPI tablets have already been described, but specifically for mucoadhesive and local use.
  • PVPI tablets have the significant drawback of dissolving very slowly in aqueous media.
  • compositions containing in particular an iodine carrier which can be polyvinylpyrrolidone, an iodide or an iodine compound, an oxidizing agent, an acid and a base in the form of powders. These last two compounds form an effervescent couple.
  • this composition does not include iodized polyvinylpyrrolidone, which is a complex which it is necessary to form before integrating it into a composition.
  • this composition does not contain a disintegrating agent, and therefore is not susceptible to be used to make PVPI solutions extemporaneously, but only to form foams, as indicated in these abstracts.
  • Patent GB-A-2,108,386 (AUCHINCLOSS) describes compositions in dry form containing an iodine source, such as a polyvinylpyrrolidone and iodine complex, a non-reducing acid and a surfactant capable of combine with iodine to form an iodophore.
  • an iodine source such as a polyvinylpyrrolidone and iodine complex
  • a non-reducing acid such as sodium bicarbonate
  • a surfactant capable of combine with iodine to form an iodophore.
  • PCT / GB 90 01 423 discloses a composition comprising an inorganic water-soluble halide, a strong oxidizing agent, which will react with the halide in order to generate hypohalogenic ions, sulfamic acid, and a water-soluble carbonate or bicarbonate in order to produce, in reaction with the acid, an effervescent effect.
  • a disintegrating agent is not mentioned in this application, which preferably relates to chlorine-based tablets.
  • compositions containing PVPI While allowing extemporaneous, reproducible preparation, and easy to use solutions of PVPI.
  • the present invention therefore relates to an effervescent composition for the extemporaneous preparation of PVPI solutions comprising in synergistic amounts:
  • compositions object of the present invention have the advantage of dissolving in less than 10 minutes, and generally in three to five minutes, which allows an extemporaneous preparation of PVPI solution unlike the compositions described in the state of the art. which do not contain a disintegrating agent. They also make it possible to obtain reproducible levels of iodine in solution.
  • effervescent agent and disintegrating agent are meant substances meeting the definitions given by Le Hir in "Pharmacy Abstract Galenic "(Masson Editions; 5th edition).
  • Such a composition advantageously comprises by weight, from 0.1 to 99%, preferably from 10% to 90%, and even more preferably from 20% to 60% of PVPI relative to the total weight of the composition.
  • Said effervescent agent is advantageously a pair comprising on the one hand citric acid and on the other hand carbonic acid, or their derivatives. It can nevertheless be any combination of organic acid / carbonate substances, making it possible to obtain an effervescence.
  • the citric acid derivatives which can be used in such a couple are in particular monosodium citrate, or citric acid monohydrate or anhydrous.
  • a derivative of carbonic acid can be monosodium carbonate.
  • the citric acid and carbonic acid, or their derivatives are advantageously contained in substantially identical amounts.
  • the disintegrating agent may be a substance having a structural similarity to PVPI, in particular a crosslinked polyvinylpyrrolidone (PVP), or a crosslinked carboxymethylcellulose. It can nevertheless be any other substance or mixture of substances having a disintegrating effect as defined above.
  • a composition according to the present invention comprises by weight from 40 to 60% of effervescent agent and from 2 to 10%, preferably from 4 to 6% of disintegrating agent.
  • the composition is in the form of powder, granules, or tablets.
  • the present invention may also contain, without being essential, a system buffer at a pH close to 6, in order to limit the degradation of PVPI.
  • a buffering effect is produced by salts such as KH 9 PO4 or by sodium hydroxide.
  • a water-repellent substance can also be contained in the composition, in order to prevent it from being degraded by moisture.
  • Such a water-repellent substance may for example be colloidal silica.
  • the composition according to the invention can also contain one or more surfactants.
  • composition is in the form of granules formed:
  • the present invention also relates to the use of a composition as described above for the disinfection of the skin and mucous membranes.
  • compositions also have the advantage of having an industrial cost price much lower than the cost price of the PVPI. It has been estimated that their cost price is at least 30% lower than that of the solutions.
  • the tablets according to the present invention can be obtained by a process in which the PVPI and the effervescent agent are mixed, then the disintegrating agent and the other constituents of the tablet are introduced.
  • the tablet is then shaped using a tablet press. The whole process must be carried out in a dry place.
  • Granules according to the present invention can be obtained by a process similar to that of tablets, the step of compressing the tablets being replaced by a step of compaction then of granulation, for example on an ERWEKA AR 400 machine.
  • Granules with internal and external phases according to the invention can be obtained by a wet granulation process in which:
  • the internal phase consists of PVPI with possibly a surfactant and an effervescent couple
  • step (3) Add to the mixture of step (2) the previously sieved colloidal silica plus the disintegrant.
  • Humidity 3 g of water per m 3 of dry air, i.e. 20% relative humidity at 20 * C.
  • PVPI PVPI (PVP iodine) 30/06 46.70
  • anhydrous citric acid is replaced, for equivalent weight, by citric acid monohydrate.
  • wetting solution (1) In a suitable container pour the surfactant.
  • step (3) Pour the grain from step (3) in a thin layer on an oven tray.
  • step (5) Granulate the grain of step (5) using an oscillating granulator type ERWEKA AR 400 or equivalent on a grid with a diameter of 800 ⁇ m.
  • step (8) Calibrate the grain obtained in step (7) on an 800 ⁇ m sieve.
  • step (11) Mix 5 minutes at 50 RPM. (12) Introduce the lubricant previously sieved to the mixture of step (11) and mix for 3 minutes.
  • Nonoxymol can be replaced by Cremophor, Tween 80 or any other equivalent surfactant.
  • lactose can be added to the components of this layer.
  • compositions Two types of compositions, one containing a disintegrating agent, crosslinked PVP (polyplasdone XL), and the other devoid of this agent, called respectively GAL 01.16 and GAL 01.17 were produced by direct compression as described in Example 1 .
  • PVP polyplasdone XL

Abstract

An effervescent composition containing synergistic amounts of iodinated polyvinylpyrrolidone, at least one effervescent agent and at least one disintegrating agent. The composition may be powdered, granulated or tabletted.

Description

Composition effervescente à base de polyvinylpyrrolidone iodée et utilisation pour la désinfection Effervescent composition based on iodized polyvinylpyrrolidone and use for disinfection
La présente invention a pour objet une composition effervescente à base de polyvinylpyrrolidone iodée.The present invention relates to an effervescent composition based on iodized polyvinylpyrrolidone.
Elle est en outre relative à l'utilisation de cette composition pour la désinfection.It also relates to the use of this composition for disinfection.
L'iode est utilisée depuis longtemps sous diverses formes pharmaceutiques (solution, teinture) pour la désinfection fine de petites blessures. Malgré la bonne efficacité du produit, son application est limitée car il présente un certain nombre d'effets secondaires.Iodine has long been used in various pharmaceutical forms (solution, tincture) for the fine disinfection of small wounds. Despite the good effectiveness of the product, its application is limited because it has a number of side effects.
La polyvinylpyrrolidone iodée (PVPI) est un complexe de polyvinylpyrrolidone (PVP) et d'iode. En raison de sa complexation avec la molécule de polyvinylpyrrolidone, l'iode contenue dans le complexe est libérée lentement et progressivement.Iodized polyvinylpyrrolidone (PVPI) is a complex of polyvinylpyrrolidone (PVP) and iodine. Due to its complexation with the polyvinylpyrrolidone molecule, the iodine contained in the complex is released slowly and gradually.
La PVPI se caractérise par une vaste étendue d'applications. Les principaux domaines d'emploi relèvent du domaine de la prophylaxie: - désinfection des mains, en particulier en chirurgie,PVPI is characterized by a wide range of applications. The main areas of use are in the field of prophylaxis: - hand disinfection, in particular in surgery,
- antisepsie de la peau et des muqueuses, et de la thérapie: emploi dans les mycoses cutanées, les pyodermies et l'acné,- antisepsis of the skin and mucous membranes, and therapy: use in cutaneous mycoses, pyoderma and acne,
- emploi pour le traitement des vaginites,- use for the treatment of vaginitis,
- traitement des brûlures, du décubitus et des ulcères variqueux.- treatment of burns, decubitus and varicose ulcers.
Ce composé est un antiseptique à large spectre: - bactéricide sur l'ensemble des bactéries y compris chlamydiae et mycoplasmes,This compound is a broad spectrum antiseptic: - bactericide on all bacteria including chlamydiae and mycoplasmas,
- antifongique vis-à-vis des dermatophytes et candidas,- antifungal against dermatophytes and candidas,
- antitrichomonas.- antitrichomonas.
La polyvinylpyrrolidone iodée (PVPI) est généralement présentée sous forme de solution. Ce type de formulation présente néanmoins des inconvénients notables, dûs à son manque de conservation, à un prix de fabrication élevé et aux problèmes liés à son stockage et à sa manutention.Iodized polyvinylpyrrolidone (PVPI) is generally presented in the form of a solution. This type of formulation nevertheless has notable drawbacks, due to its lack of conservation, a high manufacturing price and problems related to its storage and handling.
Des comprimés de PVPI ont bien déjà été décrits mais spécifiquement pour l'utilisation mucoadhesive et locale.PVPI tablets have already been described, but specifically for mucoadhesive and local use.
A la connaissance du demandeur, aucune préparation de PVPI permettant la fabrication extemporanée de solutions, sous forme de granules ou de comprimés, ou sous toute autre forme solide, n'a jamais été décrite.To the knowledge of the applicant, no preparation of PVPI allowing the extemporaneous manufacture of solutions, in the form of granules or tablets, or in any other solid form, has never been described.
En effet, en raison du pouvoir liant particulièrement important des PVP, les comprimés de PVPI présentent l'inconvénient notable de se dissoudre très lentement dans des milieux aqueux.Indeed, due to the particularly high binding power of PVP, PVPI tablets have the significant drawback of dissolving very slowly in aqueous media.
Un tel pouvoir liant est un obstacle majeur à l'utilisation de comprimés de PVPI pour la fabrication extemporanée de solutions de ce composé.Such a binding power is a major obstacle to the use of PVPI tablets for the extemporaneous manufacture of solutions of this compound.
Ainsi, les abrégés du brevet JP 63 225 308 (SANYO CHEMICAL INDUSTRIES Ltd.) décrivent des compositions contenant notamment un porteur d'iode, qui peut être de la polyvinylpyrrolidone, un iodure ou un composé d'iode, un agent oxydant, un acide et une base sous forme de poudres. Ces deux derniers composés forment un couple effervescent. Néanmoins cette composition ne comprend pas de polyvinylpyrrolidone iodée, qui est un complexe qu'il est nécessaire de former avant de l'intégrer dans une composition. De plus, cette composition ne contient pas d'agent désintégrant, et de ce fait n'est pas susceptible d'être utilisée pour fabriquer extemporanément des solutions de PVPI, mais seulement pour former les mousses, comme indiqué dans ces abrégés.Thus, the abstracts of patent JP 63 225 308 (SANYO CHEMICAL INDUSTRIES Ltd.) describe compositions containing in particular an iodine carrier, which can be polyvinylpyrrolidone, an iodide or an iodine compound, an oxidizing agent, an acid and a base in the form of powders. These last two compounds form an effervescent couple. However, this composition does not include iodized polyvinylpyrrolidone, which is a complex which it is necessary to form before integrating it into a composition. In addition, this composition does not contain a disintegrating agent, and therefore is not susceptible to be used to make PVPI solutions extemporaneously, but only to form foams, as indicated in these abstracts.
Le brevet GB-A-2 108 386 (AUCHINCLOSS) décrit quant à lui des compositions sous forme sèche contenant une source d'iode, telle qu'un complexe de polyvinylpyrrolidone et d'iode, un acide non réducteur et un agent tensioactif capable de se combiner avec l'iode afin de former un iodophore. Ce brevet ne mentionne pas la présence d'un agent désintégrant, ni même d'un couple effervescent.Patent GB-A-2,108,386 (AUCHINCLOSS) describes compositions in dry form containing an iodine source, such as a polyvinylpyrrolidone and iodine complex, a non-reducing acid and a surfactant capable of combine with iodine to form an iodophore. This patent does not mention the presence of a disintegrating agent, or even of an effervescent couple.
La demande PCT/GB 90 01 423 (AUCHINCLOSS) divulgue une composition comprenant un halogénure inorganique soluble dans l'eau, un agent oxydant fort, qui va réagir avec l'halogénure afin de générer des ions hypohalogéniques, de l'acide sulfamique, et un carbonate ou un bicarbonate soluble dans l'eau afin de produire, en réaction avec l'acide, un effet effervescent. La présence d'un agent désintégrant n'est pas mentionnée dans cette demande, qui concerne préférentiellement des comprimés à base de chlore.PCT / GB 90 01 423 (AUCHINCLOSS) discloses a composition comprising an inorganic water-soluble halide, a strong oxidizing agent, which will react with the halide in order to generate hypohalogenic ions, sulfamic acid, and a water-soluble carbonate or bicarbonate in order to produce, in reaction with the acid, an effervescent effect. The presence of a disintegrating agent is not mentioned in this application, which preferably relates to chlorine-based tablets.
Le brevet US 3 136 692 (STRONG CORB ARNER, INC.) est relatif à des compositions effervescentes contenant de la polyvinylpyrrolidone, un acide organique solide et un agent thérapeutique ou un agent de saveur. La polyvinylpyrrolidone iodée n'est pas citée dans ce brevet, qui ne mentionne pas non plus la présence d'un agent désintégrant.US Patent 3,136,692 (STRONG CORB ARNER, INC.) Relates to effervescent compositions containing polyvinylpyrrolidone, a solid organic acid and a therapeutic agent or a flavoring agent. Iodized polyvinylpyrrolidone is not mentioned in this patent, which also does not mention the presence of a disintegrating agent.
Il ressort donc de l'analyse de l'état de la technique portée à la connaissance du demandeur, qu'aucune des compositions décrite ne permet d'obtenir de manière extemporanée des solutions de polyvinylpyrrolidone iodée.It therefore appears from the analysis of the state of the art brought to the attention of the applicant, that none of the compositions described makes it possible to obtain extemporaneously solutions of iodized polyvinylpyrrolidone.
On notera en outre que ces compositions de l'état de la technique ne permettent pas d'obtenir de manière reproductible des solutions de PVPI présentant des taux d'iode libres déterminés. Ceci est particulièrement vrai pour le brevet japonais qui associe dans des mousses de la PVP libre et de l'iode libre, et qui n'utilise pas un complexe déjà formé de PVPI.It will also be noted that these prior art compositions do not make it possible to obtain reproducibly PVPI solutions with determined free iodine levels. This is particularly true for the Japanese patent which combines in free foams PVP and free iodine, and which does not use a complex already formed of PVPI.
Le demandeur s'est donc attaché à mettre au point des compositions contenant de la PVPI tout en permettant une préparation extemporanée, reproductible, et facile à mettre en oeuvre de solutions de PVPI.The applicant has therefore endeavored to develop compositions containing PVPI while allowing extemporaneous, reproducible preparation, and easy to use solutions of PVPI.
Il a trouvé que l'association de la PVPI, d'agents effervescents et d'agents désintégrants, sous forme de granules ou de comprimés, se conserve durablement et permet d'obtenir rapidement une solution de PVPI par mise en contact de cette association avec un milieu aqueux.He found that the combination of PVPI, effervescent agents and disintegrating agents, in the form of granules or tablets, is durable and allows a rapid solution of PVPI to be obtained by contacting this association with an aqueous medium.
La présente invention a donc pour objet une composition effervescente pour la préparation extemporanée de solutions de PVPI comprenant en quantités synergiques:The present invention therefore relates to an effervescent composition for the extemporaneous preparation of PVPI solutions comprising in synergistic amounts:
- de la polyvinylpyrrolidone (PVPI)- polyvinylpyrrolidone (PVPI)
- au moins un agent effervescent, et- at least one effervescent agent, and
- au moins un agent désintégrant. Les compositions objet de la présente invention présentent l'avantage de se dissoudre en moins de 10 minutes, et généralement en trois à cinq minutes, ce qui permet une préparation extemporanée de solution de PVPI à la différence des compositions décrites dans l'état de la technique qui ne contiennent pas d'agent désintégrant. Elles permettent de plus d'obtenir des taux d'iode en solution reproductibles.- at least one disintegrating agent. The compositions object of the present invention have the advantage of dissolving in less than 10 minutes, and generally in three to five minutes, which allows an extemporaneous preparation of PVPI solution unlike the compositions described in the state of the art. which do not contain a disintegrating agent. They also make it possible to obtain reproducible levels of iodine in solution.
On entend par agent effervescent et agent désintégrant des substances répondant aux définitions données par Le Hir dans "Abrégé de Pharmacie Galénique" (Editions Masson; 5ème édition).By effervescent agent and disintegrating agent is meant substances meeting the definitions given by Le Hir in "Pharmacy Abstract Galenic "(Masson Editions; 5th edition).
Une telle composition comprend avantageusement en poids, de 0,1 à 99 %, préférentiellement de 10% à 90%, et encore plus préférentiellement de 20% à 60% de PVPI par rapport au poids total de la composition.Such a composition advantageously comprises by weight, from 0.1 to 99%, preferably from 10% to 90%, and even more preferably from 20% to 60% of PVPI relative to the total weight of the composition.
Ledit agent effervescent est avantageusement un couple comprenant d'une part de l'acide citrique et d'autre part de l'acide carbonique, ou leurs dérivés. Il peut néanmoins être toute association de substances acide organique/carbonate, permettant d'obtenir une effervescence. Les dérivés de l'acide citrique pouvant être utilisés dans un tel couple sont en particulier le citrate monosodique, ou l'acide citrique monohydraté ou anhydre. Un dérivé de l'acide carbonique peut être le carbonate monosodique.Said effervescent agent is advantageously a pair comprising on the one hand citric acid and on the other hand carbonic acid, or their derivatives. It can nevertheless be any combination of organic acid / carbonate substances, making it possible to obtain an effervescence. The citric acid derivatives which can be used in such a couple are in particular monosodium citrate, or citric acid monohydrate or anhydrous. A derivative of carbonic acid can be monosodium carbonate.
L'acide citrique et l'acide carbonique, ou leurs dérivés, se trouvent avantageusement contenus en quantités sensiblement identiques. L'agent désintégrant peut quant à lui être une substance présentant une similarité de structure avec la PVPI, a notamment une polyvinylpyrrolidone (PVP) réticulée, ou une carboxyméthylcellulose réticulée. Il peut néanmoins être toute autre substance ou mélange de substances présentant un effet désintégrant tel que défini ci-dessus.The citric acid and carbonic acid, or their derivatives, are advantageously contained in substantially identical amounts. As for the disintegrating agent, it may be a substance having a structural similarity to PVPI, in particular a crosslinked polyvinylpyrrolidone (PVP), or a crosslinked carboxymethylcellulose. It can nevertheless be any other substance or mixture of substances having a disintegrating effect as defined above.
Avantageusement, une composition selon la présente invention comprend en poids de 40 à 60% d'agent effervescent et de 2 à 10%, préférentiellement de 4 à 6 % d'agent désintégrant.Advantageously, a composition according to the present invention comprises by weight from 40 to 60% of effervescent agent and from 2 to 10%, preferably from 4 to 6% of disintegrating agent.
De manière préférentielle, la composition se présente sous la forme de poudre, de granules, ou de comprimés.Preferably, the composition is in the form of powder, granules, or tablets.
La présente invention peut aussi contenir, sans pour autant que celui-ci soit essentiel, un système tampon à un pH proche de 6, afin de limiter la dégradation de la PVPI. Avantageusement, un tel effet tampon est réalisé par des sels tels que KH9PO4 ou par l'hydroxyde de sodium. Une substance hydrofuge peut aussi être contenue dans la composition, afin d'éviter que celle- ci ne soit dégradée par l'humidité. Une telle substance hydrofuge peut être par exemple de la silice colloïdale. La composition selon l'invention peut aussi contenir un ou plusieurs agents tensioactifs.The present invention may also contain, without being essential, a system buffer at a pH close to 6, in order to limit the degradation of PVPI. Advantageously, such a buffering effect is produced by salts such as KH 9 PO4 or by sodium hydroxide. A water-repellent substance can also be contained in the composition, in order to prevent it from being degraded by moisture. Such a water-repellent substance may for example be colloidal silica. The composition according to the invention can also contain one or more surfactants.
De manière avantageuse, ladite composition est mise sous forme de granules formés:Advantageously, said composition is in the form of granules formed:
* d'une phase interne comprenant du PVPI et un couple effervescent ,* an internal phase comprising PVPI and an effervescent couple,
* d'une phase externe comprenant un désintégrant et un lubrifiant.* an external phase comprising a disintegrant and a lubricant.
La présente invention est en outre relative à l'utilisation d'une composition telle que décrite ci- dessus pour la désinfection de la peau et des muqueuses.The present invention also relates to the use of a composition as described above for the disinfection of the skin and mucous membranes.
Elle peut notamment être utilisée, une fois remise en solution, dans: des solutions dermiques, gynécologiques, moussantes ou pour gargarismes,It can in particular be used, once redissolved, in: dermal, gynecological, foaming or gargle solutions,
- des compresses imprégnées,- impregnated compresses,
- des pansements humides,- wet dressings,
- des pommades.- ointments.
Elles présentent, outre des avantages économiques, des avantages pratiques indéniables puisqu'elles facilitent le transport et la manutention de la PVPI.They present, in addition to economic advantages, undeniable practical advantages since they facilitate the transport and handling of PVPI.
Ces compositions présentent d'autre part l'avantage de présenter un prix de revient industriel très inférieur au prix de revient des solutions de PVPI. Il a été estimé que leur prix de revient est inférieur au moins de 30% à celui des solutions.These compositions also have the advantage of having an industrial cost price much lower than the cost price of the PVPI. It has been estimated that their cost price is at least 30% lower than that of the solutions.
Les comprimés selon la présente invention peuvent être obtenus par un procédé dans lequel on mélange la PVPI et l'agent effervescent, puis on introduit l'agent désintégrant et les autres constituants du comprimé.The tablets according to the present invention can be obtained by a process in which the PVPI and the effervescent agent are mixed, then the disintegrating agent and the other constituents of the tablet are introduced.
Le comprimé est alors mis en forme à l'aide d'une comprimeuse. L'ensemble du procédé doit être effectué à l'abri de l'humidité.The tablet is then shaped using a tablet press. The whole process must be carried out in a dry place.
Des granules selon la présente invention peuvent être obtenus par un procédé similaire à celui des comprimés, l'étape de compression des comprimés étant remplacée par une étape de compaction puis de granulation, par exemple sur une machine ERWEKA AR 400.Granules according to the present invention can be obtained by a process similar to that of tablets, the step of compressing the tablets being replaced by a step of compaction then of granulation, for example on an ERWEKA AR 400 machine.
Des granules avec phases interne et externe selon l'invention peuvent être obtenus par un procédé de granulation humide dans lequel:Granules with internal and external phases according to the invention can be obtained by a wet granulation process in which:
- la phase interne est constituée de PVPI avec éventuellement un tensio-actif et un couple effervescent,- the internal phase consists of PVPI with possibly a surfactant and an effervescent couple,
- l'ensemble est mouillé avec de l'eau, - on sèche le grain obtenu, et- the whole is wetted with water, - the grain obtained is dried, and
- on ajoute la phase externe comprenant les autres constituants de la composition.- adding the external phase comprising the other constituents of the composition.
L'homme du métier pourra se référer à l'ouvrage général: "Abrégé de Pharmacie Galénique" - Le Hir- Editions Masson, pour la mise en oeuvre de la présente invention, et particulièrement pour la préparation des compositions objet de la présente invention.A person skilled in the art may refer to the general work: "Abrégé de Pharmacie Galènes" - Le Hir- Editions Masson, for the implementation of the present invention, and in particular for the preparation of the compositions which are the subject of the present invention.
La présente invention est illustrée sans pour autant être limitée par les exemples qui suivent : EXEMPLE 1- Préparation de comprimés selon l'invention.The present invention is illustrated without however being limited by the following examples: EXAMPLE 1 Preparation of tablets according to the invention.
MélanσeMelanσe
(1) Introduire dans un mélangeur TURBULA ou équivalent la PVPI plus l'agent effervescent. (2) Mélanger 10 minutes à 50 RPM.(1) Introduce the PVPI plus the effervescent agent into a TURBULA mixer or equivalent. (2) Mix 10 minutes at 50 RPM.
(3) Additionner au mélange de l'étape (2) la silice colloïdale préalablement tamisée plus le désintégrant.(3) Add to the mixture of step (2) the previously sieved colloidal silica plus the disintegrant.
(4) Mélanger 5 minutes à 50 RPM. (5) Introduire le lubrifiant (PEG 6000 ou équivalent) au mélange de l'étape (4) et mélanger pendant 3 minutes.(4) Mix 5 minutes at 50 RPM. (5) Add the lubricant (PEG 6000 or equivalent) to the mixture of step (4) and mix for 3 minutes.
(6) Stocker le mélange dans un récipient à l'abri de l'humidité. Compression(6) Store the mixture in a container protected from humidity. Compression
(7) Equiper la machine à comprimer de poinçons de diamètre 20 mm.(7) Equip the tableting machine with 20 mm diameter punches.
(8) Effectuer la compression.(8) Perform compression.
(9) Contrôler l'humidité absolue, le poids, la dureté des comprimés en cours de fabrication.(9) Control the absolute humidity, the weight, the hardness of the tablets during manufacture.
Conditions opératoires optimales.Optimal operating conditions.
Humidité: 3 g d'eau par m3 d'air sec soit 20% d'humidité relative à 20*C.Humidity: 3 g of water per m 3 of dry air, i.e. 20% relative humidity at 20 * C.
Ce procédé permet d'obtenir les comprimés suivants:This process makes it possible to obtain the following tablets:
FORMULE GAL 01-10GAL FORMULA 01-10
Quantité % (en poids)Quantity% (by weight)
PVPI (PVP iodine) 30/06 46,70PVPI (PVP iodine) 30/06 46.70
Acide citrique anhydre agent 20,45 Carbonate monosodique effervescent 24,55Anhydrous citric acid agent 20.45 Effervescent monosodium carbonate 24.55
PVP réticulée 5Crosslinked PVP 5
(Polyplasdone XL)(Polyplasdone XL)
Polyéthylène glycol 6000 (PEG) 3Polyethylene glycol 6000 (PEG) 3
(micronisé) Silice colloïdale (Aérosil R 972) 0,3(micronized) Colloidal silica (Aerosil R 972) 0.3
Poids théorique 2,14 gTheoretical weight 2.14 g
FORMULE GAL-O1-08FORM GAL-O1-08
Dans cette formule, l'acide citrique anhydre est remplacé, à poids équivalent, par de l'acide citrique monohydraté.In this formula, anhydrous citric acid is replaced, for equivalent weight, by citric acid monohydrate.
Ces deux formules permettent d'obtenir une dissolution totale du comprimé en 5 minutes (GAL 01- 10) et 6 minutes 30 secondes (GAL 01-08) respectivement. EXEMPLE 2-These two formulas allow total dissolution of the tablet in 5 minutes (GAL 01-10) and 6 minutes 30 seconds (GAL 01-08) respectively. EXAMPLE 2-
Préparation de granules selon l'invention par granulation humide.Preparation of granules according to the invention by wet granulation.
Solution de mouillage (1) Dans un récipient adapté verser le tensioactif.Wetting solution (1) In a suitable container pour the surfactant.
(2) Brancher l'agitateur équipé d'une défloculeuse ou équivalent, vitesse: 50 RPM.(2) Connect the agitator equipped with a deflocculator or equivalent, speed: 50 RPM.
(3) Verser la quantité d'eau nécessaire pour arriver au volume.(3) Pour the amount of water necessary to reach the volume.
(4) Arrêter l'agitation, à l'instant où le tensioactif est entièrement solubilisé.(4) Stop the agitation, at the moment when the surfactant is completely dissolved.
Mouillage de la PVPIPVPI wetting
(1) Introduire la PVPI dans un mélangeur planétaire équipé d'une lyre ou équivalent.(1) Introduce the PVPI in a planetary mixer equipped with a lyre or equivalent.
(2) Positionner l'interrupteur du mélangeur sur vitesse 1.(2) Set the mixer switch to speed 1.
(3) Verser la quantité de solution de mouillage avec ou sans le tensioactif (Poids/poids) puis compléter avec de l'eau la granulation jusqu'à obtention d'un grain satisfaisant.(3) Add the amount of fountain solution with or without the surfactant (Weight / weight) then complete the granulation with water until a satisfactory grain is obtained.
(4) Verser le grain de l'étape (3) en couche fine sur un plateau d'étuve.(4) Pour the grain from step (3) in a thin layer on an oven tray.
(5) Sécher le grain pendant 7 heures au maximum à 60'C. (6) Contrôler la perte à la dessication du grain de l'étape (5) (inférieure à 1%).(5) Dry the grain for a maximum of 7 hours at 60 ° C. (6) Check the loss on drying of the grain from step (5) (less than 1%).
GranulationGranulation
(7) Granuler le grain de l'étape (5) à l'aide d'un granuleur oscillant type ERWEKA AR 400 ou équivalent sur une grille de diamètre 800 μm.(7) Granulate the grain of step (5) using an oscillating granulator type ERWEKA AR 400 or equivalent on a grid with a diameter of 800 μm.
(8) Calibrer le grain obtenu à l'étape (7) sur un tamis de 800 μm.(8) Calibrate the grain obtained in step (7) on an 800 μm sieve.
Mélange final (9) Verser le mélange de l'étape (8) dans un mélangeur type Turbula ou équivalent.Final mixture (9) Pour the mixture from step (8) into a Turbula type mixer or equivalent.
(10) Additionner les excipients de la phase externe excepté le lubrifiant.(10) Add the excipients of the external phase except the lubricant.
(11) Mélanger 5 minutes à 50 RPM. (12) Introduire le lubrifiant préalablement tamisé au mélange de l'étape (11) et mélanger pendant 3 minutes.(11) Mix 5 minutes at 50 RPM. (12) Introduce the lubricant previously sieved to the mixture of step (11) and mix for 3 minutes.
CompressionCompression
(13) Equiper la machine à comprimer du poinçon du diamètre 20 mm.(13) Equip the tableting machine with the 20 mm diameter punch.
(14) Effectuer la compression.(14) Perform compression.
(15) Contrôler le poids, la dureté des comprimés en cours de fabrication.(15) Check the weight and hardness of the tablets during manufacture.
Matériel de compression FROGERAIS type 0A- Alternative.Compression material FROGERAIS type 0A- Alternative.
Ce procédé permet d'obtenir les granules suivants dont les compositions sont données dans le tableau I ci-après.This process makes it possible to obtain the following granules, the compositions of which are given in Table I below.
Ces granules permettent d'obtenir une dissolution du comprimé en respectivement 7 minutes ( GAL 02.11 et GAL 02-13), moins de 5 minutes (GAL 02- 14), et 3 minutes 30 sec. (GAL 02-15 et GAL 02-16).These granules make it possible to obtain a dissolution of the tablet in respectively 7 minutes (GAL 02.11 and GAL 02-13), less than 5 minutes (GAL 02-14), and 3 minutes 30 sec. (GAL 02-15 and GAL 02-16).
Dans ce procédé le Nonoxymol peut être remplacé par du Crémophor, du Tween 80 ou tout autre tensio- actif équivalent. Afin de faciliter l'écoulement lors de la formation de la couche externe, on peut rajouter du lactose aux composants de cette couche. EXEMPLE 3: Influence de la présence d'un agent désintégrant.In this process, Nonoxymol can be replaced by Cremophor, Tween 80 or any other equivalent surfactant. In order to facilitate the flow during the formation of the outer layer, lactose can be added to the components of this layer. EXAMPLE 3 Influence of the Presence of a Disintegrating Agent.
Deux types de compositions l'une contenant un agent désintégrant, de la PVP réticulée (polyplasdone XL), et l'autre dépourvue de cet agent, appelées respectivement GAL 01.16 et GAL 01.17 ont été fabriquées par compression directe comme décrit dans l'exemple 1.Two types of compositions, one containing a disintegrating agent, crosslinked PVP (polyplasdone XL), and the other devoid of this agent, called respectively GAL 01.16 and GAL 01.17 were produced by direct compression as described in Example 1 .
Les temps d'effervescence de comprimés de 20 mm dans 10 ml d'eau ont été ensuite testés.The effervescence times of 20 mm tablets in 10 ml of water were then tested.
Il ressort du tableau II que les comprimés GAL 01.16 se dissolvent en environ 4 min., alors que les comprimés dépourvus d'agent désintégrant GAL 01.17 ne sont toujours pas dissous après 24 heures.It appears from Table II that the GAL 01.16 tablets dissolve in approximately 4 min., While the tablets lacking GAL 01.17 disintegrating agent are still not dissolved after 24 hours.
Ceci montre clairement la nécessité de la présence de l'agent désintégrant et l'effet qui en résulte. This clearly shows the necessity of the presence of the disintegrating agent and the effect which results therefrom.
TABLEAU I Composition des granules obtenus selon l'exemple 2TABLE I Composition of the granules obtained according to Example 2
Poids en % FORMULATIONSWeight in% FORMULATIONS
Couche interne GAL 02.11 GAL 02.13 GAL 02.14 GAL 02.15 GAL 02.16Inner layer GAL 02.11 GAL 02.13 GAL 02.14 GAL 02.15 GAL 02.16
PVPI 30/06 46,7 41,3 21,6 35,05 30,28 tensioactif 0,94 0,49 0,7 0,6 (Nonoxynol, solution à 20%)PVPI 30/06 46.7 41.3 21.6 35.05 30.28 surfactant 0.94 0.49 0.7 0.6 (Nonoxynol, 20% solution)
KH2P04 (solution à 0,8 0,69 0,2 N)KH 2 P0 4 (0.8 0.69 0.2 N solution)
NaOH (solution à 0,2 N) 0,147 0,127NaOH (0.2 N solution) 0.147 0.127
Carbonate monosodique 24,53Monosodium carbonate 24.53
Acide citrique anhydre 20,45Anhydrous citric acid 20.45
PEG6OO0 micronisé 3 PEG6OO0 micronized 3
TABLEAU II TABLE II
GAL 01 .16 GAL 01.17GAL 01 .16 GAL 01.17
PVPI 30/06 36 ,7 38,6PVPI 30/06 36, 7 38.6
Citrate monosodique 30 ,81 33,5Sodium citrate 30, 81 33.5
Carbonate monosodique 24 ,19 26,31Monosodium carbonate 24, 19 26.31
Polyplasdone XL 5 -Polyplasdone XL 5 -
Aérosil R 972 0,3 0,33Aerosil R 972 0.3 0.33
Benzoate de sodium 3 3,26Sodium benzoate 3 3.26
Dose de PVPI par comprimé 750 mg 750 mgPVPI dose per tablet 750 mg 750 mg
Poids théorique des 2,044g 2,049g comprimés (20 mm)Theoretical weight of the 2,044g 2,049g tablets (20 mm)
Temps de désintégration 4 min > 24 h (10 ml) Decay time 4 min> 24 h (10 ml)

Claims

REVENDICATIONS
1. Composition effervescente pour la préparation extemporanée de solutions de polyvinylpyrrolidone iodée comprenant en quantités synergiques:1. Effervescent composition for the extemporaneous preparation of iodized polyvinylpyrrolidone solutions comprising in synergistic amounts:
- de la polyvinylpyrrolidone iodée (PVPI)- iodized polyvinylpyrrolidone (PVPI)
- au moins un agent effervescent, et- at least one effervescent agent, and
- au moins un agent désintégrant.- at least one disintegrating agent.
2. Composition selon la revendication 1, caractérisée en ce que la composition comprend en poids de 0,1 à 99%, préférentiellement de 10 à 90%, et encore plus préférentiellement de 20 à 60 % de PVPI par rapport au poids total de la composition.2. Composition according to claim 1, characterized in that the composition comprises by weight from 0.1 to 99%, preferably from 10 to 90%, and even more preferably from 20 to 60% of PVPI relative to the total weight of the composition.
3. Composition selon l'une des revendications 1 ou 2 caractérisée en ce que ledit agent effervescent est un couple comprenant d'une part de l'acide citrique et d'autre part de l'acide carbonique, ou leurs dérivés.3. Composition according to one of claims 1 or 2 characterized in that said effervescent agent is a pair comprising on the one hand citric acid and on the other hand carbonic acid, or their derivatives.
4. Composition selon la revendication 3, caractérisée en ce qu'elle contient sensiblement les mêmes quantités molaires d'acides citrique et carbonique, ou de leurs dérivés.4. Composition according to claim 3, characterized in that it contains substantially the same molar amounts of citric and carbonic acids, or their derivatives.
5. Composition selon l'une des revendications 1 à 4, caractérisée en ce que l'agent désintégrant est une polyvinylpyrrolidone réticulée.5. Composition according to one of claims 1 to 4, characterized in that the disintegrating agent is a crosslinked polyvinylpyrrolidone.
6. Composition selon l'une des revendications 1 à 4, caractérisée en ce que l'agent désintégrant est une carboxyméthylcellulose réticulée.6. Composition according to one of claims 1 to 4, characterized in that the disintegrating agent is a crosslinked carboxymethylcellulose.
7. Composition selon l'une des revendications 1 à 6, caractérisée en ce qu'elle contient un système tampon à un pH proche de 6.7. Composition according to one of claims 1 to 6, characterized in that it contains a buffer system at a pH close to 6.
8. Composition selon la revendication 7, caractérisée en ce que l'effet tampon est réalisé par KH2P04 et NaOH. 8. Composition according to claim 7, characterized in that the buffering effect is produced by KH 2 P0 4 and NaOH.
9. Composition selon l'une des revendications 1 à 8, caractérisée en ce qu'elle contient une substance hydrofuge.9. Composition according to one of claims 1 to 8, characterized in that it contains a water-repellent substance.
10. Composition selon l'une des revendications 1 à 9, caractérisée en ce qu'elle se présente sous la forme de poudre, de granules ou de comprimé.10. Composition according to one of claims 1 to 9, characterized in that it is in the form of powder, granules or tablet.
11. Utilisation d'une composition selon l'une des revendications 1 à 11 pour la désinfection de la peau et des muqueuses. 11. Use of a composition according to one of claims 1 to 11 for the disinfection of the skin and mucous membranes.
EP96902310A 1995-01-30 1996-01-30 Effervescent composition containing iodinated polyvinylpyrrolidone, and use thereof for disinfection Withdrawn EP0804208A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
FR9501047A FR2729858B1 (en) 1995-01-30 1995-01-30 EFFERVESCENT COMPOSITION BASED ON IODIZED POLYVINYLPYRROLIDONE AND USE FOR DISINFECTION
FR9501047 1995-01-30
PCT/FR1996/000157 WO1996023510A1 (en) 1995-01-30 1996-01-30 Effervescent composition containing iodinated polyvinylpyrrolidone, and use thereof for disinfection

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EP0872544A1 (en) * 1997-04-14 1998-10-21 The Procter & Gamble Company Dry effervescent granules and granular compositions comprising the same
US6974590B2 (en) 1998-03-27 2005-12-13 Cima Labs Inc. Sublingual buccal effervescent
US20030091629A1 (en) 1998-03-27 2003-05-15 Cima Labs Inc. Sublingual buccal effervescent
US7147873B2 (en) * 2002-01-16 2006-12-12 3M Innovative Properties Company Antiseptic compositions and methods
WO2005065317A2 (en) 2003-12-31 2005-07-21 Cima Labs Inc. Effervescent oral fentanyl dosage form
BRPI0418228B8 (en) 2003-12-31 2021-05-25 Cima Labs Inc dosage form, and method of preparing a tablet for buccal, gingival or sublingual administration of fentanyl
WO2005065318A2 (en) 2003-12-31 2005-07-21 Cima Labs Inc. Effervescent oral opiate dosage form
US20060246027A1 (en) * 2005-05-02 2006-11-02 Tanner Paul R Personal care composition
FR2900795B1 (en) * 2006-05-15 2011-04-29 Solutio Lab DETERGENT FORMULATION AND DISINFECTANT IN DIVIDED SOLID FORM CONTAINING AS ACTIVE INGREDIENT A PVP IODEE / POTASSIUM IODIDE ASSOCIATION
WO2011089584A1 (en) * 2010-01-25 2011-07-28 Modi-Mundipharma Pvt. Ltd Process for the preparation of a granular oral composition
WO2016015691A1 (en) 2014-07-30 2016-02-04 Albert SARKESSYAN A pharmaceutical composition having antibacterial and virucidal effects
JP6955784B2 (en) * 2017-07-04 2021-10-27 フルケム リミテッドＦｌｕｃｈｅｍ Ｌｔｄ An antiviral and antibacterial composition for eyes, oral cavity, nasal cavity or inhalation containing a solid composition containing an iodo agent and sodium chloride having improved water solubility and an aqueous solution thereof.
IT202100003764A1 (en) * 2021-02-18 2022-08-18 Diego Zito BIOCIDAL DETERGENT

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FR2729858B1 (en) 1997-04-18
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