Lipophilic active oral film formulation and method of making the same
Inventors
Madwar, Carolin • Paiement, Nadine • Obeid, Rodolphe • Conway, Justin • Gonzalez-Labrada, Erick
Assignees
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Publication Number
US-11602504-B2
Publication Date
2023-03-14
Expiration Date
Abstract
Disclosed is a description and methods for formulating oral films containing lipophilic active ingredient(s), more particularly lipophilic active having a positive log P. The method involves dispersing the lipophilic active(s) in a carrier oil and uniformly distributing them as emulsified oil droplets into a polymer matrix. The methods reported here produce oral films containing a stable emulsion with up to 40% oil phase. The oil phase consists of the carrier oil and lipophilic active(s). This offers the possibility to enhance the amount of lipophilic actives to be included in the film formulation while preserving the film characteristics. The resulting oral films offer a standardized dosage form for lipophilic actives as well as easier and more convenient administration, transportation, handling, and storage.
Core Innovation
The invention relates to an oral film dosage form for human or animal administration that uses a film layer formed with an oil-in-water emulsion. The thin layer includes a safe and effective amount of a lipophilic active chosen from cannabinoids, together with a carrier oil selected from specified edible or pharmaceutically acceptable oils. The film layer further includes a water-soluble film forming polymer and a combination of surfactants including a small-molecule surfactant selected from polysorbate and sorbitan, and a phospholipid.
The oral film dosage form is structured so that the combined quantity of carrier oil and lipophilic pharmaceutical active is from about 25% to about 40% (wt/wt) of the dosage form, and the film contact angle is from about 39 degrees to about 90 degrees. In related aspects, the carrier oil content is greater than the lipophilic active agent content, and the film layer is characterized by a surface pH from about 4 to less than 5.5. The film is further defined by a disintegration time upon administration from about 1 minute to about 20 minutes.
The described approach addresses problems with pH-sensitive solubility and precipitation as well as large-scale foaming by using emulsion-based buffering and containment strategies within an oil-in-water emulsion film layer. Optional multilayer oral films are discussed, including protective and base buffering layers, and colon-targeting using pectin. The disclosed design is supported by measurements of film stability and handling, including non-sticky and handleable films with uniform content, and by oil retention and active stability observations.
Claims Coverage
The document includes two independent claims. Each independent claim requires an oil-in-water emulsion-based oral film layer with cannabinoid lipophilic actives, specified carrier oils and water-soluble film forming polymers, and performance or characterization constraints including oil/active fraction or carrier-oil dominance, film contact angle or surface pH, and disintegration time in the second independent claim.
Oil-in-water emulsion oral film for cannabinoids
An oral film dosage form for human or animal administration having a film layer formed with an oil-in-water emulsion, the thin layer comprising a safe and effective amount of a lipophilic active chosen from cannabinoids; a carrier oil selected from medium-chain triglyceride oil, polyethoxylated fatty acid glycerides, CBD oil, sesame oil, cannabis oil, castor oil, soybean oil, cocoa butter and mixtures thereof; and at least about 50% (wt/wt) of a water-soluble film forming polymer selected from cellulose derivatives, polyvinyl alcohol, polyvinyl pyrrolidone, polyethylene oxide, starches, polyacrylates, gums and mixtures thereof.
Surfactant/phospholipid emulsion stabilization and constrained oil-phase loading
The film layer includes from about 2% to about 10% (wt/wt) of a combination of surfactants including a small-molecule surfactant selected from polysorbate and sorbitan, and a phospholipid, wherein the combined quantity of carrier oil and lipophilic pharmaceutical active is from about 25% to about 40% (wt/wt) of the oral film dosage form.
Film hydrophobicity via contact angle window
The film layer has a contact angle from about 39 degrees to about 90 degrees.
Surface pH controlled emulsion film with rapid disintegration
An oral film dosage form comprising a film layer formed with an oil-in-water emulsion including a safe and effective amount of a lipophilic active agent chosen from cannabinoids; a carrier oil selected from medium-chain triglyceride oil, cannabis oil, castor oil, and mixtures thereof; and at least about 50% (wt/wt) of a water-soluble film forming polymer selected from cellulose derivatives, polyvinyl alcohol, polyvinyl pyrrolidone, polyethylene oxide, starches, polyacrylates, gums and mixtures thereof, wherein the carrier oil content is greater than the lipophilic active agent content and the film layer has a surface pH from about 4 to less than 5.5.
Disintegration time constraint
The oral film dosage form has a disintegration time upon administration from about 1 minute to about 20 minutes.
Across the two independent claims, the claim coverage centers on an oil-in-water emulsion thin film layer for cannabinoid lipophilic actives, using specified carrier oils and water-soluble film forming polymers, optionally including a defined surfactant/phospholipid combination, and enforcing characterization or performance constraints via film contact angle, surface pH, and disintegration time, while also requiring specified oil/active content relationships.
Stated Advantages
Stable high oil-phase loadings in an oral film dosage form while preserving film properties such as non-sticky, handleable, uniform content.
Improved stability of lipophilic cannabinoid (THC) in oil-in-water emulsion film formulations versus carrier oil.
Reduced issues associated with pH-sensitive solubility and precipitation and large-scale foaming through emulsion-based buffering and containment strategies.
Optional multilayer designs provide protective and base buffering and colon-targeting using pectin.
Documented Applications
Oral thin film dosage form for human or animal administration of lipophilic cannabinoids.
Colon or large intestine targeted enteric delivery using pectin in protective or film layers associated with the oral film.
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