SI25783A - Three-dimensional printed films as dosage forms - Google Patents

Abstract

The present invention relates to three-dimensionally printed films as dosage forms comprising at least one layer and at least one lipophilic and / or lipophobic active substance. In particular, three-dimensionally printed films are described as dosage forms containing cannabinoids, preferably CBD. The invention further relates to a printable composition, a process for preparing films and their use.

Description

Three - dimensional printed films as dosage forms

FIELD OF THE INVENTION

The present invention relates to three-dimensionally printed films for the delivery of lipophilic and lipophobic active substances, printable mixtures, processes for the production of three-dimensionally printed films and their use. More specifically, the invention discloses three-dimensionally printed films having at least one layer and one active substance.

State of the art

Oral films are a group of flat films that are administered into the oral cavity. They are placed on the ati under the tongue, where they then dissolve. Transmucosal films are absorbed by the body directly through the oral mucosa. The advantage of oral thin film formulations is in their ability to bypass the gastrointestinal tract and obstructions in the gastrointestinal tract until drug absorption, such as first-pass metabolism and degradation of the active ingredient in the stomach. Faster onset of action is possible at lower doses.

An additional advantage for these dosage forms compared to tablets, capsules and other dosage forms that need to be swallowed is that some patient populations have difficulty swallowing, such as children and the elderly. Other advantages are convenient dosing, no water required, no risk of choking, offer the possibility of taste masking, increased stability, availability of a large surface area leading to rapid disintegration in the oral cavity, dose accuracy compared to syrups or oil drops.

In general, commercially available thin films intended for the oral and / or buccal pathway are produced by a solvent casting method, hot melt extrusion, semi-solid casting, solid dispersion extrusion and rolling. In most cases, both the proportion of active substance and the total application of the active substance are limited.

Both lipophilic and lipophobic active substances may be of interest for delivery by oral or any other film. Lipophilic substances should be properly formulated so that they can be delivered by a water-soluble film matrix.

Cannabinoids are typical representatives of lipophilic substances.

Cannabinoid is one in a class of different chemical compounds that act on cannabinoid receptors in cells that alter the release of neurotransmitters in the brain.

Ligands for these receptor proteins include endocannabinoids (produced naturally by animals in the body), phytocannabinoids (found in cannabis and some other plants), and synthetic cannabinoids (artificially produced). The best known cannabinoid is phytocannabinoid tetrahydrocannabinol (THC), the primary psychoactive compound in cannabis. Cannabidiol (CBD) is another important ingredient in the plant. At least 113 different cannabinoids have been isolated from cannabis, showing different effects.

As used herein, “Cannabis” / cannabis includes wild-type Cannabis sativa and its variants, including cannabis chemotypes, which naturally contain very different amounts of individual cannabinoids.

The term cannabinoids as used herein includes, but is not limited to, purified foods and pharmaceutical grade substances that can be obtained by purification from a natural source or by a synthetic route. The formulations according to the invention can be used for the delivery of cannabis plant extracts as well as individual cannabinoids or their synthetic analogues, whether derived from cannabis plants, as well as combinations of cannabinoids. Cannabinoids can be combined with any other lipophilic or lipophobic substance.

Crude plant extracts of cannabinoids, in their concentrated form, are typically viscous oils at room temperature and pressure. These oils contain cannabinoids, plant waxes, plant lipids and sometimes plant pigments such as chlorophyll. These crude plant extracts cause some difficulty in incorporating into orally soluble films when processed as dry, solid, crystalline active ingredients.

Cannabis compounds are usually administered by inhalation of smoke or vapors, ingestion of edible capsules or liquid extracts such as tinctures or oils, or the use of topical solutions and edible films or slices. However, each method of delivery has its drawbacks. For example, current smoking and evaporation systems are unhealthy, inconvenient, and lack adequate dose control.

Oral use of cannabis compounds, like all medicines, is not always a “fast-acting, property that is desirable, for example, in the treatment of acute breakthrough pain. In addition, some pediatric and / or geriatric patients have difficulty taking oral medications due to inability to swallow, nausea, or other gastrointestinal problems. An alternative to solid dosage forms, e.g. liquids, syrups or suspensions often spoil rapidly when exposed to heat or other atmospheric conditions and therefore have a relatively short shelf life. Films or slices containing cannabis extracts are often very sticky, have a bitter taste and thus can contribute to patient non-participation. In addition, conventional thin films or slices often do not contain large amounts of the active ingredient.

The present disclosure provides three-dimensionally printed film compositions containing THC and / or CBD, optionally in the form of a cannabis extract, and methods of making and using the same for treating a disease or disorder in a subject.

THC and CBD are highly hydrophobic, which poses a challenge for formulating mixtures suitable for convenient administration to human and animal subjects. Therefore, there is a need for stable and suitable dosage forms of THC and CBD.

U.S. Pat. No. 10,092,611 discloses a process for obtaining cannabis plant extract and pharmaceutical dosage forms (oral thin films, transdermal patches) containing the extract.

U.S. 2017/0290870 discloses an oral thin film comprising a matrix and an active agent, e.g. extracted substance derived from cannabis or hemp evenly dispersed in the matrix. The film contains 1% to 70% by weight of active ingredient in the film.

U.S. 2016/0051510 discloses U.S. 2011/0276522 discloses orally soluble films that include botanical extract.

WO 2018/094037 discloses oral thin films containing cannabidiol-containing plant extracts and processes for their preparation. The present disclosure provides compositions containing cannabidiol, optionally in the form of a cannabis extract, and methods of making and using the same for treating a disease or disorder in a subject. Generally, a viscous solution comprising cannabidiol is prepared and the viscous solution is passed through a casting machine. The extruded films are then dried or heated to evaporate excess solvent.

In general, commercially available and other prior art thin films intended for the oral and / or buccal route are produced by conventional film-forming processes, such as e.g. solvent casting method hot melting, semi-solid casting, extrusion and solid dispersion rolling.

Dose uniformity is a common problem of thin films prepared by conventional methods. In addition, the special physical and mechanical properties for film processing e.g. tensile strength.

Therefore, there is a need to prepare a film formulation by a simple process.

Advantages of the present invention:

A customized film formulation can be produced, in terms of dosage and taste. An unlimited combination of active substances and layers is possible, also useful for high doses and large amounts of active substance (‘load’). Extremely simplified industrial process that does not require special physical and mechanical properties in the processing of the film and therefore allows a simplified composition.

Summary of the invention

The present disclosure presents three-dimensionally printed films for the delivery of lipophilic and lipophobic active substances, processes for their use. Preferably, it represents three-dimensionally printed films containing cannabis compounds, most preferably THC and CBD. The disclosure further provides printable compositions that allow for a defined printing process.

Detailed description of the invention

A first aspect of the present invention is directed to three-dimensionally printed films comprising at least one layer containing a lipophilic and / or lipophobic active substance. Depending on the needs, additional layers containing the same or different active substance may be present.

The lipophilic and lipophobic active substance can be selected from the group of drugs, e.g. analgesics, muscle relaxants, antihistamines, decongestants, anti-inflammatory drugs, antibiotics, antiviral drugs, psychotherapeutics, hormones, cardiovascular agents, vitamins, minerals, steroids; food medicines, vaccines, diagnostics.

As used herein, an active substance means any substance that provides a pharmacological activity or other direct effect in diagnosing, curing, alleviating, treating or preventing a disease or affecting the structure or any function of the human or animal body. Therefore, the active substance as used herein is intended but limited for use in the fields of human and veterinary medicine, diagnostic, nutritional, nutritional supplements, medical devices, cosmetic products.

Preferably, the active substance is selected from cannabinoids.

As used herein, the term cannabinoid refers to a chemical substance that exhibits direct or indirect activity at the cannabinoid receptor. The cannabinoid substance may be a crude botanical extract of cannabinoids in the form of an emulsion free of waxes and oils, oils, pastes, liquids, resins or crystals, purified isolated individual cannabinoids of various purities, synthetic cannabinoids and their derivatives, CBD, THC, their derivatives or any combination of cannabinoids . Among the most important cannabinoid substances are THC and CBD. Preferably, the film may contain THC and / or CBD in all ratios.

When the active substance is CBD, it may be present in a purity of at least 90% and up to about 100%, with little or no trace of THC. When the active substance is THC, it may be present in a purity of at least 90% and up to about 100%, with little or no trace of CBD. The active substance may be present in the film in an amount of from about 1% to about 70% by weight.

The amount of active substance that can be used in the films of the present invention depends on the dose required to provide the desired amount of active substance. In case the active substance is CBD, CBD represents from about 1% by weight of the film to about 70% by weight of the film. If the active substance is THC, THC represents from about 1% by weight to about 70% by weight of the film.

The film of the present invention includes at least one film-forming polymer. The film-forming polymers can be selected from the group consisting of pullulan, hydroxypropyl methyl cellulose (HPMC), hydroxyethyl cellulose, hydroxypropyl cellulose, polyvinyl pyrrolidone (PVP), carboxymethyl cellulose, polyvinyl alcohol (PVA), sodium alginate, polyethylene xanthan gum, tragacanth gum, guar gum, acacia gum, arabic gum, polyacrylic acid, methyl methacrylate copolymer, carboxy vinyl polymer, amylose, high amylose starch, hydroxypropylated high amylose starch, dextrin, pectan, chitin, chitin, chitin gelatin, zein, gluten, soy protein isolate, whey protein isolate, casein. The polymers can be used alone or in combination.

The preferred film-forming polymer is PVP, in amounts ranging from about 3% to about 40% by weight of the film, preferably from about 8% to 35% by weight of the film. PVP can be used in combination with HPMC and PVA.

The film of the present invention further comprises a plasticizer. Said plasticizer comprises one or more: polyols, glycols, acetines, carboxylic acids and carboxylic acid esters. More specifically, said optional plasticizer comprises one or more of: polyethylene glycol, glycerol, triacetin, citric acid and triethyl citrate. Optionally, said plasticizer or plasticizers are present in an amount of from about 0.5% by weight to about 20% by weight of the solid film. More specifically, said optional plasticizer or plasticizers are present in an amount of from about 2% by weight to about 15% by weight of the solid film.

The film of the invention may further comprise a disintegrant selected from croscarmellose sodium, sodium starch glycolate, polyvinylpyrrolidone, carboxymethylcellulose, hydroxypropylmethylcellulose, alginate, mannitol, glucose, derivatives thereof, and combinations or similar disintegrants thereof. The disintegrant is present in an amount of from about 3% to about 45% by weight, preferably from about 8% to about 30% by weight.

The film of the present invention may further comprise a surfactant or surfactant. The surfactant can be selected from sodium lauryl sulfate, poloxamers, sorbitan esters, polysorbates (PEGylate sorbitan (a derivative of sorbitol, esterified with a fatty acid), sorbitans, stearic acid, their derivatives and combinations thereof. Preferably, Poloxamer 407 and Polysorbate are selected as surfactants.

A suitable amount of surfactant is in the range of about 1% to 35% by weight, Preferably from about 8 to about 25% by weight.

The film of the present invention may further comprise a mucoadhesive agent. Suitable mucoadhesive agents include e.g. carboxymethyl cellulose, polyvinyl alcohol, polyvinyl pyrrolidone (povidone), sodium aiginate, methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, polyethylene glycols, carbopoles, polycarbophils, carboxyvinyl copolymers, alkyl polypropyl alkyl gum, karaya gum, ethylene vinyl acetate, dimethylpolysiloxanes, polyoxyalkylene block copolymers, pectin, chitosan, carrageenan, xanthan gum, gelan gum, locust bean gum and hydroxyethylmethacrylate copolymers.

The film of the present invention further comprises flavor masking agents, flavors, sweeteners and colorants.

The films described here can be of any thickness. The size and shape depend on the intended use. The thickness of one layer can range from 50 μ to 1000 μ, preferably from 80 μ to 300 μ. The thickness of multilayer films can be from 80 μ to 5000 μ.

The film of the invention may be formulated for immediate or controlled release and may be administered, but not limited to, as a sublingual, buccal, flowable dosage form.

The composition of the present invention may be formulated as a mono or multi-dosage form, potentially with a score line.

The film described here allows for high dosing accuracy.

Another object of the present invention are three-dimensionally printed films comprising at least one layer comprising a cannabinoid substance.

Cannabinoid substances can be combined with any other lipophilic or lipophobic substance. Depending on the needs, additional layers containing the same or different active substance may be present.

A further object of the invention are three-dimensionally printed films comprising at least one layer comprising CBD as active substance. CBD can be natural or synthetic, present in the form of oil, wax, crystals, resin, powder or paste.

According to a preferred embodiment, the three-dimensionally printed film according to the invention comprises, with respect to the total weight of the film, (A) CBD oil: 10-47% by weight (B) PVP: 10-35% by weight (C) HPMC: 2-20% by weight % (D) Surfactant: 5-20% by weight (E) Mannitol: 2-20% by weight (F) Optional additional excipients

According to a preferred embodiment, the three-dimensionally printed film according to the invention comprises, with respect to the total weight of the film, (A) CBD oil: 10-47% by weight (B) PVP: 10-35% by weight (C) HPMC: 2-20% by weight % (D) Glycerol: 3-15% by weight (E) Poloxamer407: 5-20% by weight (F) Mannitol: 2-20% by weight (G) Edible color 5-25% by weight (H) Menthol aroma: 0.5 - 5% by weight% (I) Optional additional excipients

Solvents used in the preparation of the printable mixture in the form of a liquid printing paste:

Water - solvent: 20 - 80% by weight on non-volatile components

Ethanol - solvent: 200 - 400% by weight on non-volatile components

The solvents may be predominantly selected from protic and aprotic polar groups.

Edible color has the following composition: glucose syrup, sucrose, lemon, saffron, gel-forming agent - carrageenan, acids - lactic acid, color E133, acetic acid, Na-lactate, preservative - potassium sorbate,

The appropriate dose depends on the disease being treated. The dose may vary from about 2 mg to about 150 mg.

Furthermore, another object of the invention is a printable composition which forms a typical paste consistency and allows a defined printing process.

The printing composition / printable mixture comprises:

A. Active substance, 10-47% by weight,

B. At least one film-forming polymer, 10 - 35% by weight,

C. At least one disintegrant, 5-25% by weight,

D. Surfactant, 5-20% by weight,

E. Plasticizer, 3-15% by weight,

F. Ethanol, 200 to 400% by weight, on non-volatile ingredients,

G. Water, 20 - 80% by weight, on non-volatile ingredients,

H. Optional additional excipients and solvents.

Composition ranges for non-volatile ingredients are defined for solvent-free composition.

The printable composition is suitable for three-dimensional printing of films according to the invention.

A further object of the invention is a printable CBD composition comprising:

A. CBD oil, 10-47% by weight,

B. PVP, 10-35% by weight,

C. HPMC, 2 - 20% by weight,

D. Surfactant, 5-20% by weight,

E. Glycerol, 3-15% by weight,

F. Mannitol, 2 to 20% by weight,

G. Ethanol 200 - 400% by weight on non-volatile ingredients,

H. Water 20 - 80% by weight on non-volatile ingredients,

I. Optional additional excipients and solvents.

Composition ranges for non-volatile ingredients are defined for solvent-free composition.

A further object of the invention is a process for preparing a three-dimensional printing film according to the present invention.

The method includes the following steps:

a) preparation of a printable mixture,

b) three-dimensional printing,

c) drying the film.

The thin film according to the invention is made by a three-dimensional (3D) printing process. Suitable 3D printing techniques include FDM techniques (fused deposition modeling, hot melt extrusion), dosing valve method, jetting and air / pulse pulse technology, and combinations thereof.

.FDM (hot melt extrusion)

The filament of the corresponding polymer is extruded through a preheated nozzle. The printing mixture is heated twice, first during filament preparation and second during 3D printing. The process temperature is equal to or higher than the melting point of the polymer.

2. 3D printing with dosing valves

Loading of the film material is achieved by spray valves for liquid or paste, where different types of valves can be used. Pressure or mechanically activated valves (“pinch”, “spool”, needle or diaphragm valves) load material stored in a pressurized chamber or by gravity supply to the loading needle. When the valve is open, the material flows to the printing surface.

The valve is mounted on a mechanical actuator (linear base, robotic arm or similar) that moves according to a computer program. The program determines the format.

3. Jetting

The high-resolution (INK JET) printhead loads the print liquid onto the print surface at room temperature, either higher or lower, depending on the properties of the liquid. The print head is powered by the printer driver. After printing the liquid on the printing surface, the final shape is achieved with elevated temperature or UV light (polymerization).

4. Air / pulse technology

Dosing valves are not used to load printed material onto the printed area. The dosing of the printing paste through the printing nozzle is controlled by the air (gas) pressure in the dosing chamber.

Layers of material can be deposited via any of the described methods to form a 3D printed structure.

The preferred printing device for three-dimensional printing of the rapid release dosage form is the needle dosing type with a pneumatic dosing valve.

Typical 3D printing process parameters:

Air pressure 0.5-10 bar

Needle speed XY 0-110 mm / s

ID (inside diameter) of the printer nozzle 0.2 -1.2 mm

Any other type of valve can be used, e.g. extrusion type or piston driven type.

Useful solvents include alcohols, preferably ethanol, water, aprotic solvents, e.g. acetonitrile, acetone, isopropanol. The preferred solvent is a combination of ethanol and water in a ratio of from 0 to 100 v / v, preferably from 5 to 20% v / v.

The liquid printing paste must have the appropriate viscosity.

In particular, the inventors shall submit the following points:

A three-dimensionally printed film comprising at least one layer comprising a lipophilic and / or lipophobic active substance.

A film according to item 1, wherein the active substance is selected from the group of cannabinoids.

3. The film according to points 1 and 2, wherein the active ingredient is a crude botanical extract of cannabinoids.

4. The film of points 1 and 2, wherein the lipophilic substance is THC.

The film according to items 1 and 2, wherein the lipophilic substance is CBD.

The film according to items 1 and 2, wherein the lipophilic active ingredient is a mixture of THC and CBD in any ratio.

7. The film according to items 1 and 6, wherein the amount of THC is less than 0.2% by weight.

A film according to points 1 and 4, wherein the THC is in the form of an oil, wax, oil, crystals, resin, powder or paste.

The film according to items 1 and 5, wherein the CBD is in the form of an oil, wax, crystal, resin, powder or paste.

lO. Film referred to in points 1 and 5, containing:

(A) CBD oil: 10-47% by weight (B) PVP: 10 - 35% by weight (C) HPMC: 2-20% by weight (D) Surfactant: 5-20% by weight (E) Mannitol: 2-20% by weight % (F) Optional additional excipients

11. Film referred to in points 1 and 5, containing:

(A) CBD oil: 10-47% by weight (B) PVP: 10-35% by weight (C) HPMC: 2-20% by weight (D) Glycerol: 3-15% by weight (E) Poloxamer 407:% by weight 5 -20 (F) Mannitol: 2-20% by weight (G) Edible color 5-25% by weight (H) Aroma flavor: 0.5 - 5% by weight (I) Optional excipients.

The film of claim 1, wherein the layer comprises an additional lipophilic or lipophobic active substance.

13. A film according to item 1, comprising one or more additional layers.

14. The film of points 1 and 13, wherein the additional layer comprises an additional active substance.

15. The film according to items 1 and 14, wherein the additional active ingredient is selected from drugs, nutraceuticals, vaccines, diagnostics, food, food supplements, medical devices and cosmetics.

A film according to any one of the preceding claims, wherein the at least one layer further comprises a film-forming agent selected from the group consisting of pullulan, hydroxypropylmethyl cellulose (HPMC), hydroxyethyl cellulose, hydroxypropyl cellulose, polyvinyl pyrrolidone (PVP), carboxymethyl cellulose, polyvinyl alcohol (PVA), sodium alginate, polyethylene glycol, xanthan gum, tragacanth gum, guar gum, acacia gum, arabic gum, polyacrylic acid, methyl methacrylate copolymer, carboxy vinyl high amorphous amyropylose amyloxy , dextrin, pectin, chitin, chitosan, levan, elsinan, collagen, gelatin, zein, gluten, soy protein isolate, whey protein isolate, casein.

17. The film of item 16, wherein the film-forming polymer is polyvinyl pyrrolidone.

The film of claim 16, wherein the film-forming polymer is polyvinyl pyrrolidone in combination with hydroxypropylmethyl cellulose.

19. The film of claim 16, wherein the film-forming polymer is polyvinyl pyrrolidone in combination with polyvinyl alcohol.

A film according to any one of the preceding claims, wherein the amount of film-forming agent is from 3% to 40% by weight, preferably from 8% to 35% by weight of the film.

The film of any one of the preceding claims, wherein the at least one layer further comprises a disintegrant selected from the group consisting of croscarmellose sodium, sodium starch glycolate, insoluble polyvinyl pyrrolidone, hydroxypropylmethylcellulose, carboxymethylcellulose, gluginate, combinate, mannitol, mannitol, mannitol, mannitol, mannitol .

22. The film of claim 21, wherein the disintegrant is present in an amount of from 3% to 45% by weight, preferably from 8% to 30% by weight.

The film of any one of the preceding claims, wherein the at least one layer further comprises a surfactant selected from the group consisting of sodium lauryl sulfate, poloxamers, sorbitan esters, polysorbates, sorbitans, stearic acid, derivatives thereof, and combinations thereof.

24. The film of item 23, wherein the amount of surfactant is from 1% to 35% by weight, preferably from 8% to 25% by weight.

25. The film of items 23 and 24, wherein the surfactant is selected from Poloxamer 407 and Polysorbate.

A film according to any one of the preceding claims, wherein the plasticizer / plasticizer is selected from the group consisting of polyols, glycols, acetines, carboxylic acid and carboxylic acid esters.

27. The film of item 26, wherein the plasticizer / plasticizer is selected from polyethylene glycol, glycerol, triacetin, citric acid, and triethyl citrate.

28. The film according to items 26 and 27, wherein the amount of plasticizer is from 0.5% to 20% by weight, preferably from 2% to 15% by weight.

29. A film according to any one of the preceding claims, wherein the film is prepared by a process comprising the following steps:

a) preparation of a printable mixture;

b) three-dimensional printing of the film; in

c) drying the film.

30. A printable mixture comprising the following ingredients:

A. Active substance, 10-47% by weight,

B. At least one film-forming polymer, 10-35% by weight,

C. At least one disintegrant, 5-25% by weight,

D. Surfactant, 5-20% by weight,

E. Plasticizer, 3-15% by weight, (F) Ethanol, 200 - 400% by weight on non-volatile components, (G) Water, 20 - 80 wt. % by weight on non-volatile components, (H) Optionally additional excipients, the composition ranges for non-volatile components being defined for the solvent-free composition.

31. Printable mixture containing the following ingredients:

(A) CBD oil, 10-47% by weight, (B) PVP, 10-35% by weight, (C) HPMC, 2 - 20% by weight, (D) Surfactant, 5-20% by weight, (E) Glycerol, 3-15% by weight, (F) Mannitol, 2-20% by weight, (G) Ethanol 200 - 400% by weight based on non-volatile ingredients, (H) Water 20 - 80% by weight based on non-volatile ingredients,

Optional additional excipients, the composition ranges for non-volatile components being defined for the solvent-free composition.

32. A method of preparing a three-dimensionally printed film comprising the steps

a) preparation of a printable mixture;

b) three-dimensional film printing; in

c) drying the film.

33. The method of item 32, wherein the dosing valve technique is used in a three-dimensional printing step.

34. The method of points 32 and 33, wherein the film is printed with a dosing needle type with a pneumatic dosing valve.

35. The method of item 32, wherein the FDM (fused deposition modeling) process is used in the three-dimensional printing step.

36. The method of item 32, wherein the ink jett three-dimensional printing process is used.

37. The method of item 32, wherein three-dimensional air / pulse printing technology is used.

38. The method of item 32, wherein the film is dried for 1 to 2 hours at 30 ° to 50 ° C.

39. Film according to point 1 for use as a medicament.

40. Film according to points 1 and 5 for use as a food supplement.

41. Film according to points 1, 5 and 40 for use in adults with a daily intake of CBD up to 130 mg.

42. A film according to point 1 for use in adults and children, containing at least CBD and THC as active substances.

43. Film according to item 1 for use in diagnostic purposes.

44. Film according to point 1 for use as a vaccine.

45. Foil according to point 1 for use as a medical device.

46. Film according to point 1 for use as a cosmetic product.

47. Use of a cannabinoid for the preparation of a three-dimensionally printed film according to point 1.

48. Three-dimensional printed film containing the following ingredients:

(J) CBD oil: 10-47% by weight (K) PVP: 10-35% by weight (L) HPMC: 2-20% by weight (M) Glycerol: 3-15% by weight (N) Poloxamer407: 5-20% by weight % (O) Mannitol: 2-20% by weight (P) Edible color 5 - 25% by weight (Q) Flavor aroma: 0.5 - 5% by weight (R) Optional additional excipients.

49. The film according to item 1, wherein the active substance is selected from drugs, nutraceuticals, vaccines, diagnostics, food, food supplements, medical devices, cosmetics.

The present invention is illustrated by the following non-limiting examples:

Examples:

Example 1:

Preparation of three-dimensionally printed film

Ingredient mass % wt Function CBD oil 0.3 g 24% Active substance polyvinyl pyrrolidone (PVP) 0.3 g 24% Film forming polymer Polyvinyl alcohol (PVA) 0.3 g 24% Film forming polymer Stevia 0.15 g 12 Sweetener Glucose 0.05 g 4 Disintegrant Glycerol 0.1 g 8 Plasticizer Polysorbate 0.05 g 4 Surfactant 1.25 g 100 Ethanol 3.5 ml Water 1.0 ml

Dissolve PVA and sugars in water. PVP, CBD oil and polysorbate were dissolved in ethanol. The resulting mixtures were mixed to obtain a homogeneous paste, primed for 3D printing.

These sample films were 3D printed with a dosing needle type with a pneumatic dosing valve.

Parameters:

Air pressure: 5 bar

Needle speed XY: 40 mm / s

ID (inside diameter) of the printer nozzle: 0.8 mm

After printing, the films were dried at 50 ° C for 1 hour.

Claims (34)

Patent claims A three-dimensionally printed film as a dosage form comprising at least one layer comprising a lipophilic and / or lipophobic active substance. The film of claim 1, wherein the active ingredient is selected from the group consisting of cannabinoids. The film according to claims 1 and 2, wherein the active ingredient is a crude botanical extract of cannabinoids. The film of claims 1 and 2, wherein the lipophilic substance is THC. The film of claims 1 and 2, wherein the lipophilic substance is CBD. The film of claims 1 and 2, wherein the lipophilic active substance is a mixture of THC and CBD in any ratio. The film of claims 1 and 5, wherein the CBD is in the form of an oil, wax, crystal, resin, powder or paste. A film according to claims 1 and 5, comprising: a) CBD oil: 10-47% by weight b) PVP: 10-35% by weight c) HPMC: 2-20% by weight d) Surfactant: 5-20% by weight e) Mannitol: 2-20% by weight f) Optional additional excipients Film according to claims 1 and 5, comprising: a) CBD oil: 10-47% by weight b) PVP: 10-35% by weight c) HPMC: 2-20% by weight d) Glycerol: 3-15% by weight e) Poloxamer407: 5-20% by weight 1) Mannitol: 2-20% by weight g) Edible color 5-25% by weight h) Flavor aroma: 0.5 - 5% by weight i) Optional additional excipients. The film of claim 1, wherein the layer comprises an additional lipophilic or lipophobic active substance. The film of claim 1, comprising one or more additional layers. The film according to claims 1 and 10, wherein the additional active substance is selected from drugs, nutraceuticals, vaccines, diagnostic agents, food, food supplements, medical devices, cosmetics. The film of any one of the preceding claims, wherein the at least one layer further comprises a film-forming agent selected from the group consisting of pullulan, hydroxypropylmethyl cellulose (HPMC), hydroxyethyl cellulose, hydroxypropyl cellulose, polyvinyl pyrrolidone (PVP), carboxymethyl cellulose. , polyvinyl alcohol (PVA), sodium alginate, polyethylene glycol, xanthan gum, tragacanth gum, guar gum, acacia gum, arabic gum, polyacrylic acid, methyl methacrylate copolymer, carboxy vinyl polymer, amylose, high amylose starch hydroxy starch hydro , pectin, chitin, chitosan, levan, elsinan, collagen, gelatin, zein, gluten, soy protein isolate, whey protein isolate, casein. The film of claim 13, wherein the film-forming polymer is polyvinyl pyrrolidone. The film of claim 13, wherein the film-forming polymer is polyvinyl pyrrolidone in combination with hydroxypropylmethyl cellulose. A film according to any one of the preceding claims, wherein the amount of film-forming agent is from 3% to 40% by weight, preferably from 8% to 35% by weight of the film. The film of any one of the preceding claims, wherein the at least one layer further comprises a disintegrant selected from the group consisting of croscarmellose sodium, sodium starch glycolate, polyvinyl pyrrolidone, hydroxypropylmethylcellulose, carboxymethylcellulose, alginate, mannitol, their combination and glucose. The film of claim 17, wherein the disintegrant is present in an amount of from 3% to 45% by weight, preferably from 8% to 30% by weight. The film of any one of the preceding claims, wherein the at least one layer further comprises a surfactant selected from the group consisting of sodium lauryl sulfate, poloxamers, sorbitan esters, polysorbates, sorbitans, stearic acid, derivatives thereof, and combinations thereof. The film of claim 19, wherein the amount of surfactant is from 1% to 35% by weight, preferably from 8% to 25% by weight. The film of claims 19 and 20, wherein the surfactant is selected from Poloxamer 407 and Polysorbate. A film according to any one of the preceding claims, wherein the plasticizer is selected from polyethylene glycol, glycerol, triacetin, citric acid and triethyl citrate. The film of claim 22, wherein the amount of plasticizer is from 0.5% to 20% by weight, preferably from 2% to 15% by weight. A film according to any one of the preceding claims, wherein the film is prepared by a process comprising the following steps: a) preparation of a printable mixture; b) three-dimensional printing of the film; in c) drying the film. 25. Printable mixture comprising the following ingredients: a) Active substance, 10-47% by weight, b) At least one film-forming polymer, 10-35% by weight, c) At least one disintegrant, 5-25% by weight, d) Surfactant, 5-20% by weight, e) Plasticizer, 3-15% by weight, f) Ethanol, 200-400% by weight on non-volatile components, g) Water, 20 - 80% by weight on non-volatile components, h) Optional additional excipients, wherein the composition range for non-volatile components is defined for the solvent-free composition. The printable composition of claim 25, wherein the active ingredient is CBD oil and further comprising 2-20% by weight of mannitol. 27. A method of preparing a three-dimensionally printed film comprising the steps a) preparation of a printable mixture; b) three-dimensional film printing; in c) drying the film. The method of claim 27, wherein the film is printed with a dosing needle type with a pneumatic dosing valve. The method of claim 27, wherein the film is dried for 1 to 2 hours at 30 ° to 50 ° C. A film according to claim 1 for use as a medicament. A film according to claim 1 for use as a food supplement. The film of claims 1, 5 and 31 for use in adults with a daily intake of CBD of up to 130 mg. A film according to claim 1 for use in adults and children, containing at least CBD and THC as active substances. Use of a cannabinoid for the preparation of a three-dimensionally printed film according to claim