US20090017085A1 - Self-supporting films for pharmaceutical and food use - Google Patents

Self-supporting films for pharmaceutical and food use Download PDF

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Publication number
US20090017085A1
US20090017085A1 US10/577,408 US57740804A US2009017085A1 US 20090017085 A1 US20090017085 A1 US 20090017085A1 US 57740804 A US57740804 A US 57740804A US 2009017085 A1 US2009017085 A1 US 2009017085A1
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self
supporting films
group
active principle
films
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US10/577,408
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Francesco Cilurzo
Paola Minghetti
Luisa Montanari
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PHARMAFILM Srl
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PHARMAFILM Srl
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Assigned to PHARMAFILM S.R.L. reassignment PHARMAFILM S.R.L. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: CILURZO, FRANCESCO, MINGHETTI, PAOLA, MONTANARI, LUISA
Publication of US20090017085A1 publication Critical patent/US20090017085A1/en
Priority to US15/218,744 priority Critical patent/US10426725B2/en
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    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
    • A23L29/30—Foods or foodstuffs containing additives; Preparation or treatment thereof containing carbohydrate syrups; containing sugars; containing sugar alcohols, e.g. xylitol; containing starch hydrolysates, e.g. dextrin
    • A23L29/35—Degradation products of starch, e.g. hydrolysates, dextrins; Enzymatically modified starches
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23P—SHAPING OR WORKING OF FOODSTUFFS, NOT FULLY COVERED BY A SINGLE OTHER SUBCLASS
    • A23P20/00—Coating of foodstuffs; Coatings therefor; Making laminated, multi-layered, stuffed or hollow foodstuffs
    • A23P20/20—Making of laminated, multi-layered, stuffed or hollow foodstuffs, e.g. by wrapping in preformed edible dough sheets or in edible food containers
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23P—SHAPING OR WORKING OF FOODSTUFFS, NOT FULLY COVERED BY A SINGLE OTHER SUBCLASS
    • A23P30/00—Shaping or working of foodstuffs characterised by the process or apparatus
    • A23P30/20—Extruding
    • A23P30/25—Co-extrusion of different foodstuffs
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    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
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    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4422—1,4-Dihydropyridines, e.g. nifedipine, nicardipine
    • A—HUMAN NECESSITIES
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    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/485—Morphinan derivatives, e.g. morphine, codeine
    • A—HUMAN NECESSITIES
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    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/5415—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
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    • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • A61K31/5513—1,4-Benzodiazepines, e.g. diazepam or clozapine
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    • A61K31/5517—1,4-Benzodiazepines, e.g. diazepam or clozapine condensed with five-membered rings having nitrogen as a ring hetero atom, e.g. imidazobenzodiazepines, triazolam
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    • 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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
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    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Abstract

Rapidly dissolving self-supporting films for food or pharmaceutical use comprising: a) a filmogenic substance consisting of a maltodextrin; b) a plasticiser; c) an active principle for food or pharmaceutical use, characterised in that said films are free of hydrocolloids.

Description

    FIELD OF THE INVENTION
  • The present description relates to rapidly dissolving self-supporting films for pharmaceutical or food use
    • STATE OF THE ART
  • Self-supporting films for pharmaceutical or food use have been known for some time.
  • For example compositions based on edible films are already commercially available. Most of these products use pullulan as the filmogenic component. Pullulan is an expensive ingredient and not easily available. Other materials have been used in place of pullulan. These materials comprise modified starches such as maltodextrin and hydrocolloids such as cellulosic materials, as described for example in US20030053962.
  • However, these films do not present one or more characteristics typical of pullulan such as rapid dissolution, clean mouth feel, clean flavour and ease of manufacture.
  • That these films do not provide a clean mouth sensation is due to the fact that the hydrocolloids tend to gel on contact with saliva.
  • One solution to the aforesaid drawbacks is proposed in WO03/011259 from which is noted that, to obtain properties equivalent to those of pullulan, it is crucial that maltodextrin, smaller quantities of hydrocolloid and, additionally, an inert filler are present simultaneously in the filmogenic composition. In this prior patent, therefore, the hydrocolloid content is reduced by virtue of introducing an inert filler at a concentration between 1 and 30% into the film composition. According to said document, however, the hydrocolloid content cannot be reduced below 10% in that according to this prior patent, as in the preceding US20030053962, the presence of this component in the filmogenic composition appears essential for achieving rapid disintegration of the film.
    • TECHNICAL PROBLEM
  • Therefore the need was felt for a rapidly dissolving edible film which would not pose the problems of known edible films for pharmaceutical or food use.
    • SUMMARY OF THE INVENTION
  • The Applicant has now surprisingly found that self-supporting edible films for food or pharmaceutical use containing maltodextrin as the filmogenic substance can be prepared which dissolve rapidly despite their not containing hydrocolloids.
  • In particular an aspect of the present invention are self-supporting films comprising:
      • a) a filmogenic substance consisting of a maltodextrin,
      • b) a plasticiser
      • c) an active principle for food or pharmaceutical use,
      • characterised in that said films are free of hydrocolloids.
  • In particular, as seen from the tests described below, the self-supporting films of the invention present disintegration times determined in vitro of less than 1 minute, and in vivo actually less than 45 seconds. Moreover, the self-supporting films impart a clean mouth sensation and in addition can be prepared using simple preparation methods, easily achievable with industrial machinery.
  • In this respect a further aspect of the present invention is directed towards various processes for preparing the self-supporting edible films of the present invention.
  • For example, one preparation process for the aforesaid self-supporting film comprises in particular the following steps:
      • i) the maltodextrin, plasticiser and active ingredient for food or therapeutic use are mixed,
      • ii) the mixture derived from the preceding step is extruded in an extruder.
  • Another preparation process according to the present invention comprises in particular the following steps:
      • i) the maltodextrin, plasticiser and active principle for therapeutic or food use are dispersed in a polar solvent,
      • ii) the mixture obtained in the preceding step is rolled onto silicone paper and then dried,
      • iii) the silicone paper is removed from the film obtained in the preceding step.
  • Another preparation process according to the present invention comprises in particular the following steps:
      • i) the maltodextrin, plasticiser and active ingredient for food or therapeutic use are mixed,
      • ii) the mixture was granulated, sieved and mixed with an anti sticking agent
      • iii) the granules were stored at least for 12 h
      • iv) the granules derived from the preceding steps were extruded in an extruder for obtaining the edible film.
    DESCRIPTION OF THE FIGURES
  • Table 1 in FIG. 1 shows formulations used for preparing the films of the present invention as described in example 1.
  • Table 2 in FIG. 2 shows formulations used for preparing the films of the present invention as described in example 2.
  • FIG. 3 shows a graph of the in vivo bioavailability of the film of the present invention prepared as described in example 2 and containing paracetamol (formulation 6 in table 2), and by way of a syrup (Tachipirina syrup), where the y-axis shows paracetamol concentration expressed in gg/ml whereas the x-axis shows time in minutes.
    •  DETAILED DESCRIPTION OF THE INVENTION
  • The maltodextrin used in the self-supporting film of the present invention has a dextrose content of less than 50 equivalents, preferably between 11 and 40.
  • The plasticiser used in the self-supporting films of the present invention is preferably chosen from the group consisting of polyalcohols, citric acid esters, sebacic acid esters or their mixtures. Propylene glycol, glycerine, sorbitol, maltitol or their relative mixtures are particularly preferred.
  • The active principle for food use is preferably an active principle with a refreshing action on the breath and indicated for oral hygiene, preferably eugenol and menthol or an active principle suitable for nutritional supplementation, preferably mineral salts chosen from those normally used for such purposes or one or more vitamins, the vitamin being ascorbic acid in a particularly preferred embodiment. The active principle for therapeutic use can be a principle with an essentially topical activity for the oral cavity chosen from antibacterial, antimycotic, antiviral agents or disinfectants of the oral cavity, or can be an active principle with an essentially systemic action chosen from the class consisting of anti-inflammatory, analgesic, antipsychotic, hypnotic, anxiolytic, antihypertensive, myorelaxant, antimigraine, antiparkinsonian, antiemetic, antihistaminic, beta blocking and antiasthmatic agents.
  • The active principles contained in said films are preferably chosen from the class consisting of: Piroxicam, Ketoprofen, Sodium diclofenac, Tramadol hydrochloride, Morphine, Nifedipine, Diazepam, Lorazepam, Alprazolam, Bromazepam, Triazolam, Lormetazepam, Zolpidem, Paracetamol, Selegiline, Atenolol, Salbutamol, Sumatriptan, Clozapine, Cetirizine, Ondansetron, Fentanyl and their pharmaceutically acceptable salts.
  • The self-supporting films of the present invention contain maltodextrin in concentrations preferably between 40 and 80% by weight, plasticiser in concentrations between 15 and 55% by weight and active principle for food or pharmaceutical use in quantities between 0.05 and 30% by weight on the total weight of said film, and can possibly contain other excipients chosen from antisticking agents such as microcrystalline cellulose, colloidal silica or talc, sweeteners, flavourings, colouring agents, preservatives, acidity regulating systems or mixtures thereof.
  • In the process for preparing edible self-supporting films by extrusion, a further aspect of the present invention, the extrusion step (ii) is preferably conducted at a temperature between 60 and 120° C. in a single screw extruder. In the second preparation process, a further aspect of the present invention, the polar solvent used in step (i) is preferably chosen from water, water-miscible solvents or relative mixtures. In accordance with a particularly preferred embodiment the solvent consists of water or a mixture of water and ethanol. The temperature of said step, when a mixture of the aforesaid solvents are used, is preferably between 60 and 105° C.
  • The self-supporting films of the present invention can be prepared using other methods such as by compacting the filmogenic formulation by the ultrasound technique.
  • Some examples of formulations for the self-supporting films of the present invention, some processes for preparing said self-supporting films, as well as in vitro and in vivo disintegration tests conducted on films obtained with some of the illustrated formulations are given by way of non limiting examples.
    • EXAMPLE 1 Films Prepared by Extrusion Preparation Method
  • The components of the formulations given in table 1 of FIG. 1 are mixed and extruded with a single screw extruder at a temperature of 105° C.
    • Disintegration Assay
  • The test was undertaken in accordance with the method in the European Pharmacopoeia 5.01 Ed., 2.9.1. Disintegration of tablets and capsules (01/2005:20901)
  • Purified water maintained at 37° C. was used as the medium. The result is the average of 3 determinations ±standard deviation. The results are given in table 3.
  • TABLE 3
    Disintegration time
    Form. Disintegration time
    no. (in seconds)
    2 50 ± 4
    5 54 ± 4
    6 40 ± 1
    8 30 ± 1
    11 32 ± 2
    17 19 ± 1

    In vivo Dissolution Assay
  • Three 4 cm2 samples of the formulation under examination were administered to 6 healthy volunteers. The test consists of retaining the film sample in the mouth, and determining the time needed to sense its disappearance.
  • The test was conducted on formulations no. 2, 5, 17 (table 1).
  • In each case dissolution time was less than a minute.
    • EXAMPLE 2 Films Prepared by Spreading and Evaporation of the Solvent Preparation Method
  • The components of the formulations given in table 2 of FIG. 2 are dispersed in the mixture of solvents, given in the same table, and maintained at 80° C. The mixture, maintained at the same temperature, is rolled onto silicon paper and dried.
    • Disintegration Assay
  • The test was undertaken in accordance with the method in the European Pharmacopoeia 5.01 Ed., 2.9.1. Disintegration of tablets and capsules (01/2005:20901)
  • Purified water maintained at 37° C. was used as the medium. The result is the average of 3 determinations ±standard deviation.
  • The results are given in table 4
  • TABLE 4
    Disintegration time
    Form. Disintegration time
    no. (in seconds)
    4 27 ± 4
    5 36 ± 4
    6 50 ± 3
    7 37 ± 8
    13 32 ± 2

    In vivo dissolution assay
  • A 4 cm2 sample of the formulation under examination was administered to each of 6 healthy volunteers. The test consists of retaining the film sample in the mouth, and determining the time needed to sense its disappearance.
  • The test was conducted on formulations no. 3, 6, 13 (table 1).
  • In each case dissolution time was less than 45 seconds.
  • Determination of in vivo Bioavailability
  • The object of this pilot study was to evaluate the absorption and pharmacokinetic profile after a single administration of 50 mg paracetamol carried by Formula 6 (table 2) and by a commercial syrup containing paracetamol (Tachipirina syrup) in 3 healthy volunteers aged between 23 and 24 years. The experiment was conducted as a crossover with a 15 day wash-out period.
  • With the aim of evaluating the pharmacokinetic profiles of the two formulations, saliva and blood samples were taken before application and at 10 min, 20 min, 45 min, 1 h, 2 h, 3 h, 4 h, 6 h after administration. Paracetamol was determined in the saliva.
  • The salivary concentrations of paracetamol determined in saliva after administration of the syrup and of the rapidly disintegrating film overlap completely as shown in FIG. 3.
    • EXAMPLE 3 Films Prepared by Granulation and Extrusion
  • Film composition
    Formulation Formulation Formulation Formulation
    A B C D
    Components (% m/m) (% m/m) (% m/m) (% m/m)
    Maltodextrin 71 47 70 71.4
    (DE 11)
    Glycerol 16 — 16 16.5
    Menthol 1 — — —
    Microcrystal- 12 10 12 12
    line cellulose
    Paracetamol — 21 — —
    Ondansetron — — 2 —
    Fentanyl — — — 0.1
    Propylene — 20 — —
    Glycol
    Sodium citrate — 2 — —
    • Preparation Method
  • The components, with the exception of the microcrystalline cellulose, were mixed into a sigma blade mixer; the time of mixing was 1 hour for formulation B and 30 minutes for formulation A, C and D.
  • The mixture was transferred in an oscillating granulator and microcrystalline cellulose was added as antisticking agent. The granules are stored for at least 12 hours at ambient temperature and then sieved.
  • The granules were extruded with a single screw extruder. The extruder temperatures were set in the range 85-130° C.
    • Disintegration Test
  • The test was undertaken in accordance with the method in the European Pharmacopoeia 5.01 Ed., 2.9.1. Disintegration of tablets and capsules (01/2005:20901)
  • Purified water maintained at 37° C. was used as the medium. The results were the average of 3 determinations ±standard deviation.
  • The disintegration times were less of 45 sec for all the formulations.
  • In vivo Dissolution Assay
  • Three 4 cm2 samples of the formulation A were administered to 6 healthy volunteers. The test consists of retaining the film sample in the mouth, and determining the time needed to sense its disappearance.
  • In each case dissolution time was less than 15 sec.

Claims (27)

1. Self-supporting films comprising:
a) a filmogenic substance consisting of a maltodextrin,
b) a plasticiser,
c) an active ingredient for food or pharmaceutical use, wherein said films are free from hydrocolloids.
2. Self-supporting films as claimed in claim 1, wherein the maltodextrin (a) has a dextrose content of less than 50 expressed in equivalents.
3. Self-supporting films as claimed in claim 2 wherein said 1o dextrose content is between 11 and 40.
4. Self-supporting films as claimed in claims 1, wherein the plasticiser is selected from the group consisting of polyalcohols, citric acid esters, sebacic acid esters or their mixtures.
5. Self-supporting films as claimed in claims 1, wherein the plasticiser is selected from the group consisting of propylene glycol, glycerine, sorbitol, maltitol and their relative mixtures.
6. Self-supporting films as claimed in claims 1, wherein the active principle for food use is an active principle with a breath freshening action and/or indicated for oral hygiene or an active principle suitable for nutritional supplementation.
7. Self-supporting films as claimed in claim 6, wherein said active principle for food use is selected from the group consisting of menthol and eugenol.
8. Self-supporting films as claimed in claim 6 wherein said active principle suitable for nutritional supplementation is selected from the group consisting of mineral salts normally used for such purpose and vitamins.
9. Self-supporting films as claimed in claim 8 wherein the vitamin is ascorbic acid.
10. Self-supporting films as claimed in claims 1, wherein said active principle for therapeutic use is selected from the group consisting of active principles with essentially lo topical activity.
11. Self-supporting films as claimed in claim 10, wherein said active principle is selected from the group consisting of antibacterial, antimycotic, antiviral agents and disinfectants of the oral cavity.
12. Self-supporting films as claimed in claims 1 wherein the active principle for therapeutic use is selected from the group consisting of active principles with essentially systemic activity.
13. Self-supporting films as claimed in claim 12, wherein said active principle with essentially systemic activity is selected from the group consisting of anti-inflammatory, analgesic, antipsychotic, hypnotic, anxiolytic, antihypertensive, myorelaxant, antimigraine, antiparkinsonian, antiemetic, antihistaminic, beta blocking and antiasthmatic agents.
14. Self-supporting films as claimed in claim 1, wherein said principle is selected from the group consisting of: Piroxicam, Ketoprofen, Sodium diclofenac, Tramadol hydrochloride, Morphine, Nifedipine, Diazepam, Lorazepam, Alprazolam, Bromazepam, Triazolam, Lormetazepam, Zolpidem, Paracetamol, Selegiline, Atenolol, Salbutamol, Sumatriptan, Clozapine, Cetirizine, Ondansetron, Fentanyl and their pharmaceutically acceptable salts.
15. Self-supporting films as claimed in claim 14, containing maltodextrin at concentrations between 40 and 80% by weight, plasticiser in concentrations between 15 and 55% by weight and the active principle for food or pharmaceutical use in a quantity between 0.05% and 30% by weight on the total weight of said film.
16. Self-supporting films as claimed in claims 1, containing other excipients selected from the group consisting of anticaking agents, sweeteners, flavourings, colouring agents, preservatives, acidity regulating systems and mixtures thereof.
17. Self-supporting films as claimed in claim 16, wherein said antisticking agents are selected from the group consisting of microcrystalline cellulose, colloidal silica and talc.
18. Process for preparing self-supporting films claimed in claim 1, comprising the following steps:
i) mixing the maltodextrin, plasticiser and active principle for food or therapeutic use,
ii) extruding the mixture coming from the preceding step .
19. Process as claimed in claim 18, wherein the extrusion step (ii) is preferably conducted at a temperature between 60 and 120° C.
20. Process as claimed in claim 18, conducted in a single screw extruder.
21. Process for preparing self-supporting films claimed in claim 1, comprising the following steps:
i) dispersing the maltodextrin, plasticiser and the active principle for therapeutic or food use in a polar solvent at a temperature between 60 and 105° C.,
ii) rolling the mixture obtained in the preceding step onto a silicone paper and drying it,
iii) removing the silicone paper from the film obtained in the preceding step.
22. The process as claimed in claim 21, wherein the polar solvent used in step (i) is selected from the group consisting of water, a water miscible solvent and mixtures thereof.
23. Process as claimed in claim 22, wherein said solvent consists of water and a water-ethanol mixture.
24. Process as claimed in claim 23, wherein the temperature of steps (i) and (ii) is between 60 and 105° C.
25. Process for preparing self-supporting films claimed in claim 1, comprising the following steps:
i) mixing the maltodextrin, plasticiser and active ingredient for food or therapeutic use,
ii) granulating and sieving the mixture and mixing it with an anti sticking agent,
iii) storing the granules at least for 12 h,
iv) extruding the granules coming from the preceding step thereby obtaining the edible film.
26. Process as claimed in claim 25, wherein the extrusion step (ii) is conducted at a temperature between 70 and 140° C.
27. (canceled)
US10/577,408 2003-10-27 2004-10-27 Self-supporting films for pharmaceutical and food use Abandoned US20090017085A1 (en)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012053006A3 (en) * 2010-10-18 2012-08-02 Panacea Biotec Ltd Improved oral fast dissolving films comprising combination of polymers and method of preparation thereof
US20150231065A1 (en) * 2012-09-28 2015-08-20 Pharmafilm S.R.L. Orodispersible films having quick dissolution times for therapeutic and food use
US9993558B2 (en) 2004-10-01 2018-06-12 Ramscor, Inc. Sustained release eye drop formulations
US10028965B2 (en) 2013-05-24 2018-07-24 Icon Bioscience, Inc. Use of sustained release dexamethasone in post-cataract surgery inflammation
US10226450B2 (en) * 2014-09-25 2019-03-12 Shilpa Medicare Limited Pharmaceutical film composition

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AR051397A1 (en) * 2004-10-21 2007-01-10 Novartis Ag PHARMACEUTICAL COMPOSITION
HUE038022T4 (en) * 2006-10-02 2023-02-28 Spepharm Ag Non-mucoadhesive film dosage forms
CN102892815B (en) * 2010-03-26 2016-05-18 陶氏环球技术有限责任公司 The film of melt extrusion
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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4222973A (en) * 1978-07-10 1980-09-16 The Mead Corporation Process for producing casting release paper and product
US20030068378A1 (en) * 1999-01-21 2003-04-10 Lavipharm Laboratories Inc. Compositions and methods for mucosal delivery
US20040028732A1 (en) * 2000-07-04 2004-02-12 Falkenhausen Christian Von Rapidly-decomposing administrable form for releasing active ingredients in the oral cavity or in bodily cavities
US20040096569A1 (en) * 2002-11-15 2004-05-20 Barkalow David G. Edible film products and methods of making same
US20050118217A1 (en) * 2003-10-24 2005-06-02 Barnhart Scott D. Rapidly disintegrating films for delivery of pharmaceutical of cosmetic agents

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19512252C2 (en) * 1995-03-31 2000-05-31 Fraunhofer Ges Forschung Process for the production of films from starch and films produced by this process
IT1303753B1 (en) * 1998-11-13 2001-02-23 Ct Lab Farm Srl ORAL ADMINISTRABLE PHARMACEUTICAL COMPOSITIONS CONTAINING A RESISTANT COATING BASED ON ACRYLIC POLYMERS.
US6660292B2 (en) 2001-06-19 2003-12-09 Hf Flavoring Technology Llp Rapidly disintegrating flavored film for precooked foods
WO2003011259A1 (en) 2001-07-30 2003-02-13 Wm. Wrigley Jr. Company Improved edible film formulations containing maltodextrin
US6656493B2 (en) * 2001-07-30 2003-12-02 Wm. Wrigley Jr. Company Edible film formulations containing maltodextrin
AU2003260091A1 (en) * 2002-08-27 2004-03-19 Wm. Wrigley Jr. Company Breath freshening and oral cleansing product using carvacrol
US7232577B2 (en) * 2002-10-21 2007-06-19 L. Perrigo Company Readily dispersible dietary fiber composition
US8007852B2 (en) * 2002-11-18 2011-08-30 Olam West Coast, Inc. Method for production of frozen vegetables or fruits
US8012505B2 (en) * 2003-02-28 2011-09-06 Alk-Abello A/S Dosage form having a saccharide matrix
CA2520383C (en) * 2003-03-26 2013-12-17 The Procter & Gamble Company Rapidly dissolving edible film compositions with improved film strength and stability

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4222973A (en) * 1978-07-10 1980-09-16 The Mead Corporation Process for producing casting release paper and product
US20030068378A1 (en) * 1999-01-21 2003-04-10 Lavipharm Laboratories Inc. Compositions and methods for mucosal delivery
US20040028732A1 (en) * 2000-07-04 2004-02-12 Falkenhausen Christian Von Rapidly-decomposing administrable form for releasing active ingredients in the oral cavity or in bodily cavities
US20040096569A1 (en) * 2002-11-15 2004-05-20 Barkalow David G. Edible film products and methods of making same
US20050118217A1 (en) * 2003-10-24 2005-06-02 Barnhart Scott D. Rapidly disintegrating films for delivery of pharmaceutical of cosmetic agents

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Definition of "self-supporting" from the Free Dictionary, accessed from the internet on June 26, 2013 from the site: http://www.thefreedictionary.com/self-supporting). *

Cited By (8)

* Cited by examiner, † Cited by third party
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US9993558B2 (en) 2004-10-01 2018-06-12 Ramscor, Inc. Sustained release eye drop formulations
US10744202B2 (en) 2004-10-01 2020-08-18 Ramscor, Inc. Sustained release eye drop formulations
WO2012053006A3 (en) * 2010-10-18 2012-08-02 Panacea Biotec Ltd Improved oral fast dissolving films comprising combination of polymers and method of preparation thereof
US20150231065A1 (en) * 2012-09-28 2015-08-20 Pharmafilm S.R.L. Orodispersible films having quick dissolution times for therapeutic and food use
CN104884041A (en) * 2012-09-28 2015-09-02 法玛费尔姆有限责任公司 Orodispersible films having quick dissolution times for therapeutic and food use
US11123287B2 (en) * 2012-09-28 2021-09-21 Pharmafilm S.R.L. Orodispersible films having quick dissolution times for therapeutic and food use
US10028965B2 (en) 2013-05-24 2018-07-24 Icon Bioscience, Inc. Use of sustained release dexamethasone in post-cataract surgery inflammation
US10226450B2 (en) * 2014-09-25 2019-03-12 Shilpa Medicare Limited Pharmaceutical film composition

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ATE397920T1 (en) 2008-07-15
EP1689374B1 (en) 2008-06-11
DK1689374T3 (en) 2008-10-13
US20170035692A1 (en) 2017-02-09
DE602004014404D1 (en) 2008-07-24
ITMI20032087A1 (en) 2005-04-28
US10426725B2 (en) 2019-10-01
EP1689374A1 (en) 2006-08-16
WO2005039543A1 (en) 2005-05-06

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