Compositions for use in psoriasis and uses thereof

Abstract

The present invention provides compositions for treating nail disorders, the compositions comprising a film-forming solution comprising a combination of an active agent (such as an antibacterial agent, an antiviral agent, an antifungal agent, and an anti-inflammatory agent), a polymer, a volatile solvent, and a non-volatile solvent, and optionally a plasticizer. The present invention also provides methods of making the film-forming compositions and uses of the film-forming compositions.

Description

[0001] Cross-references

[0002] This application claims the benefit of PCT application No. PCT / CN2024 / 115875, filed on August 30, 2024, the entire contents of which are incorporated herein by reference. Background Technology

[0003] Nail diseases such as onychomycosis and psoriasis significantly impact an individual's quality of life, and in severe cases, can lead to discomfort and depression due to the physical changes they can cause. Many medications have been developed to treat these nail diseases. However, most of these medications can cause unintended systemic toxicity. To date, topical formulations have been the best therapeutic option. However, topical delivery via the nail presents challenges, including maintaining the active ingredient on the nail surface, penetrating the nail plate, and ensuring safety and patient compliance. Various dosage forms have been reported for nail diseases, such as solutions, creams, and gels, with film-forming nail polish appearing to be superior. Several commercial products are available, such as Loceryl® for onychomycosis. However, most of these products contain irritating solvents, such as ethyl acetate. Furthermore, the film formed does not remain on the nail surface for long periods and is easily removed by handwashing. Additionally, these commercial products have low penetration rates. Therefore, a drug delivery system for treating nail disorders is needed. Summary of the Invention

[0004] This document provides compositions comprising: an active pharmaceutical ingredient (API) in an amount not exceeding 20% ​​(w / v); a film-forming polymer present in an amount of 5%-15% (w / v); a plasticizer present in an amount not exceeding 5% (w / v); a volatile solvent, wherein the volatile solvent is ethanol; and a non-volatile solvent. This document further provides compositions wherein the film-forming polymer comprises a hydroxypropyl methylcellulose derivative, polymethyl methacrylate, polyurethane, or any combination thereof. This document further provides compositions wherein the film-forming polymer comprises a hydroxypropyl methylcellulose derivative, polymethyl methacrylate, or any combination thereof. This document further provides compositions wherein the hydroxypropyl methylcellulose derivative is hydroxypropyl methylcellulose acetate succinate (HPMC-AS). This document further provides compositions wherein HPMC-AS is present in an amount of about 0.5% (w / v) to about 1% (w / v). This document further provides compositions wherein the polymethyl methacrylate is Eudragit. This document further provides a composition wherein Eudragit is present in an amount of about 5%-15% (w / v). This document further provides a composition wherein Eudragit is present in an amount of about 10% (w / v). This document further provides a composition wherein the composition further comprises at least one solubilizer. This document further provides a composition wherein at least one solubilizer comprises propylene glycol, transcutol, polyethylene glycol, or any combination thereof. This document further provides a composition wherein at least one solubilizer comprises transcutol. This document further provides a composition wherein the composition further comprises a plasticizer. This document further provides a composition wherein the plasticizer is polyethylene glycol 6000. This document further provides a composition wherein the composition further comprises a penetration enhancer. This document further provides a composition wherein the penetration enhancer is selected from hydrating agents, keratolytic agents, acids, disulfide bond cleaving agents, chelating agents, or any combination thereof. This document further provides a composition wherein the penetration enhancer is an acid. This document further provides a composition wherein the acid is lactic acid. This document further provides a composition wherein lactic acid is present in an amount of about 3% (w / v) to about 30% (w / v). This document further provides a composition wherein lactic acid is present in an amount of about 10% (w / v). This document further provides a composition wherein the composition further comprises at least one thickener. This document further provides a composition wherein the at least one thickener comprises PEG400. This document further provides a composition wherein the composition further comprises a coloring substance. This document further provides a composition wherein the coloring substance comprises pigments, dyes, colorants, or any combination thereof.

[0005] This article provides a method for treating nail disorders, the method comprising topically applying the composition provided herein. This article further provides a method wherein the nail disorder is selected from eczema, atopic dermatitis, onycholysis, subungual hyperkeratosis, discoloration, onychotrophic nail, psoriatic nail, longitudinal nail splitting, onycholysis, lamellar splitting, onycholysis, brittle nail syndrome, transverse grooves, pitting, soft nail, nail dystrophy, brittle nail with intact or damaged nails, nail tumors, and any combination thereof. This article further provides a method wherein the nail disorder is onychomycosis. This article further provides a method wherein the nail disorder is psoriasis of the nail.

[0006] This document provides a method for improving the appearance of a subject's nails, the method comprising topically applying a composition provided herein to the nail. This document further provides a method wherein the method improves the color, surface smoothness, shape, and / or thickness of the nail. This document further provides a method wherein the topical application of the composition is performed at least once a week. This document further provides a method wherein the topical application of the composition is performed at least once a day.

[0007] This document provides a method for preparing a film-forming formulation, the method comprising: providing a solvent containing a volatile solvent, wherein the volatile solvent is present in the solvent in an amount of 60% to 100% by volume; adjusting the pH of the solvent to pH 8 to pH 11; after adjusting the pH, dissolving an active ingredient and at least one polymer in the solvent; and adding a plasticizer to form a film-forming formulation. This document further provides a method wherein the volatile solvent comprises ethanol, propanol, isopropanol, ethyl acetate, or mixtures thereof. This document further provides a method wherein the volatile solvent is ethanol. This document further provides a method wherein the polymer is selected from hydroxypropyl methylcellulose derivatives, polymethyl methacrylates, and combinations thereof. This document further provides a method wherein the active ingredient is selected from antibacterial, antiviral, antifungal, anti-inflammatory, and anti-tumor substances, and is present in an amount of 0.01% to 20% by weight. This document further provides a method wherein the antibacterial substance comprises at least one substance selected from: penicillin, sulfonamides, streptozotocins, polypeptides, tetracyclines, doxycyclines, amoxicillin, carbapenems, cephalosporins, fluoroquinolones, glycopeptides and lipoglycopeptides, macrolides, monocyclic β-lactams, and any combination thereof. This document further provides a method wherein the antifungal substance comprises ilfluconazole, tavaborone, ciclopirox, amorolfen, ruliconazole, terbinafine, miconazole, ketoconazole, itraconazole, fluconazole, econazole, oxiconazole, clotrimazole, naftifine, voriconazole, isaconazole, fenteconazole, tavaborone, amorolfen, anisofungin, caspofungin, micafungin, rezafungin, amphotericin B, terbinafine, or any combination thereof. This article further provides methods in which the anti-inflammatory substance comprises a JAK inhibitor, a PDE4 inhibitor, a corticosteroid, vitamin A, vitamin D3, an anti-IL-17 agent, an anti-IL-23 agent, an anti-TNFα agent, an anti-IL-4 agent, an S1PR inhibitor, a PI3Kδ inhibitor, or a TYK2 inhibitor. This article further provides methods in which the antitumor substance comprises a checkpoint inhibitor, an anti-IL-7 agent, 5-fluorouracil (F-FU), or any combination thereof. This article further provides methods in which the method further includes adding at least one solubilizer. This article further provides methods in which at least one solubilizer is propylene glycol, transcutol, or polyethylene glycol (PEG). This article further provides methods in which the method further includes adding a penetration enhancer. This article further provides methods in which the penetration enhancer comprises at least one substance selected from: cyclodextrin and its derivatives, urea and its derivatives, lactic acid and its derivatives, sodium sulfite and its derivatives, EDTA, cysteine ​​and its derivatives, and any combination thereof. This article further provides methods in which the penetration enhancer is an acid. This article further provides methods in which the acid is lactic acid. This document further provides a method, wherein the method further includes adding at least one thickener. This document further provides a method wherein the at least one thickener comprises PEG400.This document further provides a method, wherein the method further includes adding a coloring substance. This document further provides a method wherein the coloring substance comprises pigments, dyes, colorants, or any combination thereof.

[0008] This document provides a composition comprising: an active pharmaceutical ingredient (API) selected from antibacterial, antiviral, antifungal, anti-inflammatory, and antitumor substances, in an amount of 0.01% (w / v) to 20% (w / v); a film-forming polymer comprising HPMC-AS and Eudragit L100, wherein HPMC-AS is present in an amount of 0.5% (w / v) to 4% (w / v) and Eudragit L100 is present in an amount of 5% (w / v) to 15% (w / v); a plasticizer, wherein the plasticizer is PEG 6000 present in an amount of 0.5% (w / v) to 4% (w / v); a solubilizer, wherein the solubilizer is propylene glycol or transcutol; and a volatile solvent, wherein the volatile solvent is ethanol. This document further provides compositions wherein the antibacterial substance comprises at least one substance selected from: penicillin, sulfonamides, streptozotocins, polypeptides, tetracyclines, doxycyclines, amoxicillin, carbapenems, cephalosporins, fluoroquinolones, glycopeptides and lipoglycopeptides, macrolides, monocyclic β-lactams, and any combination thereof. This document further provides compositions wherein the antifungal substance comprises ilfluconazole, tavaborone, ciclopirox, amorolfen, ruliconazole, terbinafine, miconazole, ketoconazole, itraconazole, fluconazole, econazole, oxiconazole, clotrimazole, naftifine, voriconazole, isaconazole, fenteconazole, tavaborone, amorolfen, anisofungin, caspofungin, micafungin, rezafungin, amphotericin B, terbinafine, or any combination thereof. This article further provides compositions in which the anti-inflammatory substance comprises a JAK inhibitor, a PDE4 inhibitor, a corticosteroid, vitamin A, vitamin D3, an anti-IL-17 agent, an anti-IL-23 agent, an anti-TNFα agent, an anti-IL-4 agent, an S1PR inhibitor, a PI3Kδ inhibitor, or a TYK2 inhibitor. This article further provides compositions in which the antitumor substance comprises a checkpoint inhibitor, an anti-IL-7 agent, 5-fluorouracil (F-FU), or any combination thereof. This article further provides compositions in which the API is terbinafine HCl. This article further provides compositions in which HPMC-AS is present in an amount of 0.5% (w / v) to 4% (w / v). This article further provides compositions in which HPMC-AS is present in an amount of 0.5% (w / v). This article further provides compositions in which Eudragit L100 is present in an amount of 5%-15% (w / v). This article further provides compositions in which Eudragit L100 is present in an amount of 10% (w / v). This document further provides a composition wherein PEG 6000 is present in an amount of 2% (w / v) to 4% (w / v). This document further provides a composition wherein a solubilizer is present in an amount of 3% (w / v) to 5% (w / v).This document further provides compositions, wherein the compositions further comprise water. This document further provides compositions wherein the volume ratio of ethanol to water is from 9:1 to 6:4. This document further provides compositions wherein the volume ratio of ethanol to water is from 9:1 to 8:2. This document further provides compositions wherein the compositions further comprise a penetration enhancer, wherein the penetration enhancer is selected from hydrating agents, keratolytic agents, acids, disulfide bond cleaving agents, chelating agents, or any combination thereof. This document further provides compositions wherein the penetration enhancer is an acid. This document further provides compositions wherein the acid is lactic acid. This document further provides compositions wherein lactic acid is present in an amount from about 3% to about 30%. This document further provides compositions wherein lactic acid is present in an amount of 10%. This document further provides compositions wherein the compositions further comprise pigments. This document further provides compositions wherein the pigment is present in an amount of about 0.1%.

[0009] This document provides compositions comprising: terbinafine or terbinafine HCl in an amount of 0.5% to 20% by weight; a film-forming polymer present in an amount of 5% to 15% by weight; a plasticizer present in an amount of 0.5% to 5% by weight; a penetration enhancer present in an amount of lactic acid present in an amount of 2% to 30% by weight; a volatile solvent comprising ethanol; and a non-volatile solvent. This document further provides compositions in a topical form. This document further provides compositions wherein the film-forming polymer is selected from hydroxypropyl methylcellulose derivatives, polymethyl methacrylates, or any combination thereof. This document further provides compositions wherein the film-forming polymer comprises Eudragit L100 and HPMC-AS-LF. This document further provides compositions wherein HPMC-AS is present in an amount of 0.5% (w / v) to 4% (w / v), and Eudragit L100 is present in an amount of 5% (w / v) to 15% (w / v). This document further provides a composition wherein HPMC-AS is present in an amount of 0.5% (w / v) and Eudragit L100 is present in an amount of 10% (w / v). This document further provides a composition wherein the plasticizer is PEG 6000. This document further provides a composition wherein PEG 6000 is present in an amount equal to or less than 4%. This document further provides a composition wherein PEG 6000 is present in an amount of 4%. This document further provides a composition wherein the volatile solvent is ethanol and the non-volatile solvent is an aqueous solution. This document further provides a composition wherein the composition further comprises a solubilizer. This document further provides a composition wherein the solubilizer is Transcutol or PEG 400. This document further provides a composition wherein the solubilizer is Transcutol. This document further provides a composition wherein Transcutol is present in an amount equal to or less than 5%. This document further provides a composition wherein lactic acid is present in an amount of about 3% to about 10%. This document further provides a composition wherein lactic acid is present in an amount of about 10%. This document further provides compositions in which the volume ratio of ethanol to a non-volatile solvent is from 9:1 to 6:4. This document further provides compositions in which the non-volatile solvent is water. This document further provides compositions in which the volume ratio of ethanol to water is 4:1.

[0010] This document provides compositions comprising: terbinafine or terbinafine HCl; a film-forming polymer, wherein the film-forming polymer is present in an amount of 5% to 15% by weight; a plasticizer, wherein the amount of the plasticizer is 0.5% to 5% by weight; lactic acid, wherein the ratio of terbinafine to lactic acid is 1:10 (w:w) to 1:2 (w:w), and wherein the lactic acid is present in an amount sufficient to promote the penetration of terbinafine; a volatile solvent, wherein the volatile solvent comprises ethanol; and a non-volatile solvent. This document further provides compositions wherein terbinafine is present in an amount of 0.5% to 15% by weight. This document further provides compositions wherein the compositions are in a topical form. This document further provides compositions wherein the film-forming polymer is selected from hydroxypropyl methylcellulose derivatives, polymethyl methacrylates, or any combination thereof. This document further provides compositions wherein the film-forming polymer comprises Eudragit L100 and HPMC-AS-LF. This document further provides a composition wherein HPMC-AS is present in an amount of 0.5% (w / v) to 4% (w / v) and Eudragit L100 is present in an amount of 5% (w / v) to 15% (w / v). This document further provides a composition wherein HPMC-AS is present in an amount of 0.5% (w / v) and Eudragit L100 is present in an amount of 10% (w / v). This document further provides a composition wherein the plasticizer is PEG 6000. This document further provides a composition wherein PEG 6000 is present in an amount equal to or less than 4%. This document further provides a composition wherein PEG 6000 is present in an amount of 4%. This document further provides a composition wherein the volatile solvent is ethanol and the non-volatile solvent is an aqueous solution. This document further provides a composition wherein the composition further comprises a solubilizer. This document further provides a composition wherein the solubilizer is Transcutol or PEG 400. This document further provides a composition wherein the solubilizer is Transcutol. This document further provides a composition wherein Transcutol is present in an amount equal to or less than 5%. This document further provides a composition wherein lactic acid is present in an amount from about 3% to about 10%. This document further provides a composition wherein lactic acid is present in an amount of about 10%. This document further provides a composition wherein the volume ratio of ethanol to a non-volatile solvent is from 9:1 to 6:4. This document further provides a composition wherein the non-volatile solvent is water. This document further provides a composition wherein the volume ratio of ethanol to water is 4:1.

[0011] This document provides a method for treating nail disorders, the method comprising contacting the nail with an effective amount of the composition provided herein. This document further provides a method wherein, after contacting the nail, the composition forms a film on the nail surface in less than 2 minutes. This document further provides a method wherein the film is resistant to handwashing. Attached Figure Description

[0012] The features of this disclosure are particularly set forth in the appended claims. A better understanding of the features and advantages of this disclosure will be obtained by referring to the following detailed description of illustrative embodiments and their accompanying drawings, which utilize the principles of this disclosure: Figure 1 These are images showing membranes from different formulations.

[0013] Figure 2 This is a plot showing the X-ray diffraction (XRPD) pattern of a film prepared from a film-forming solution of the active pharmaceutical ingredient (API) terbinafine HCl at varying concentrations. The Y-axis represents the relative X-ray intensity (count) of the peaks. The X-axis represents the diffraction angle.

[0014] Figure 3 This is a plot showing the XRPD patterns of dried films prepared from film-forming solutions of varying concentrations of propylene glycol or transcutol. The Y-axis represents the relative X-ray intensity (count) of the peaks. The X-axis represents the diffraction angle.

[0015] Figure 4 This is a plot showing the XRPD patterns of films prepared from film-forming solutions of varying concentrations of propylene glycol or transcutol after contact with water. The Y-axis represents the relative X-ray intensity (count) of the peaks. The X-axis represents the diffraction angle.

[0016] Figures 5A-5E These are images showing the crystallization state of films prepared from different film-forming agents after contact with water, as observed under a polarizing microscope. The film-forming agents were prepared as follows: (a) without solubilizers ( Figure 5A (b) Contains 3% transcutol ( Figure 5B (c) Contains 5% transcutol ( Figure 5C (d) Contains 3% propylene glycol ( Figure 5D (e) Contains 5% propylene glycol ( Figure 5E ).

[0017] Figure 6 This is a plot showing the permeation analysis of the film-forming formulation at varying concentrations of transcutol. The Y-axis represents API concentration, and the X-axis represents time.

[0018] Figure 7 This is a graph showing the permeation analysis of film-forming formulations at varying concentrations of transcutol or propylene glycol. The Y-axis represents API concentration, and the X-axis represents time (hours).

[0019] Figure 8 The procedure for ex vivo infiltration of bovine or human carapace is shown.

[0020] Figures 9A-9B This shows the API penetration in bovine cartilage 48 hours after administration, with or without a penetration enhancer. Figure 9A API deposits in cattle decks ( Figure 9B The graph shows the amount of API on the Y-axis and the different formulations on the X-axis.

[0021] Figures 10A-10B This indicates the API permeation in bovine dermal cells 48 hours after administration of a formulation containing 10% cyclodextrin HP-β-CD, 10% urea, 10% acetylcysteine, saturated EDTA, or 10% lactic acid. Figure 10A API deposits in cattle decks ( Figure 10B The graph shows the amount of API on the Y-axis and the different formulations on the X-axis.

[0022] Figure 11A-11B This demonstrates the API permeation in bovine acetylene 48 hours after administration of formulations containing lactic acid and different solvents. Figure 11A API deposits in cattle decks ( Figure 11B The graph shows the amount of API on the Y-axis and the different formulations on the X-axis.

[0023] Figure 12A-12B This demonstrates the API permeation in bovine carapace 48 hours after administration of different formulations without an aqueous solvent. Figure 12A API deposits in cattle decks ( Figure 12B The graph shows the amount of API on the Y-axis and different formulations on the X-axis.

[0024] Figures 13A-13D This shows the API permeation in bovine cartilage 48 hours after administration, with or without solubilizers. Figures 13A-13B API deposits in cattle decks ( Figure 13C-13D The graph shows the amount of API on the Y-axis and the different formulations on the X-axis.

[0025] Figures 14A-14B This shows the API penetration in bovine cartilage 48 hours after administration of different formulations. Figure 14A API deposits in cattle decks ( Figure 14B (Drawings)

[0026] Figures 15A-15B This shows the API penetration curves of formulations containing 2.5% or 5% terbinafine HCl compared to conventional formulations containing 10% or 33% lactic acid. Figure 15A API deposits in cattle decks ( Figure 15B The graph shows the amount of API on the Y-axis and the different formulations on the X-axis.

[0027] Figures 16A-16BThis shows the API permeation curves of formulations containing different concentrations of terbinafine HCl compared to commercial formulations. Figure 16A ) and API deposits in human decks ( Figure 16B The graph shows the amount of API on the Y-axis and the different formulations on the X-axis.

[0028] Figures 17A-17B This shows the API permeation curve of an exemplary membrane solution compared to conventional formulations. Figure 17A ) and API deposits in human decks ( Figure 17B (Drawings)

[0029] Figures 18A-18F This illustrates the API penetration of bovine aspirate 48 hours after application of exemplary solutions or commercial products containing different APIs. Figures 18A-18C ) and the corresponding API deposits in the cow deck ( Figure 18D-18F (Drawings)

[0030] Figures 19A-19D This illustrates the API penetration of bovine ammonia 67 hours after the application of exemplary solutions containing different APIs. Figures 19A-19B ) and the corresponding API deposits in the cow deck ( Figure 19C-19D (Drawings)

[0031] Figures 20A-20B This shows the API penetration curves of formulations containing different concentrations of lactic acid compared to conventional formulations. Figure 20A ) and API deposits in human decks ( Figure 20B (Drawings) Detailed Implementation

[0032] This disclosure generally relates to compositions for treating nail disorders, the treatment using a film-forming composition comprising an active ingredient, a polymer, and volatile and non-volatile solvents. In particular, compositions and methods for treating nail disorders are provided herein, the treatment using a film-forming composition based on a volatile solvent such as ethanol, which has the advantages of being odorless and easy to apply. By appropriately adjusting the pH, the polymer can be dissolved in such a film-forming composition without adding additional solvents such as ethyl acetate or acetone. After applying the film-forming composition provided herein to a surface such as a nail plate, the composition rapidly forms a film (e.g., within 2 minutes) and cannot be removed by water or hand soap. In some embodiments, compositions are provided herein comprising an active pharmaceutical ingredient (API), a film-forming polymer, a plasticizer that promotes film formation, and volatile and non-volatile solvents comprising ethanol. In some embodiments, the API is present in an amount from 0.01% (w / v) to 15% (w / v). In some embodiments, the film-forming polymer is present in an amount from 5% (w / v) to 15% (w / v). In some embodiments, ethanol is present in an amount of 60% to 100% (v / v). In some embodiments, a plasticizer is present in an amount of 0.5% (w / v) to 5% (w / v). In some embodiments, the composition also contains additional excipients, such as plasticizers, solubilizers, and / or penetration enhancers. A method for preparing a film-forming composition is also provided herein, the method comprising providing an aqueous solution containing a volatile solvent, adjusting the pH of the solution to pH 8 to pH 11, dissolving a polymer and an active ingredient in the aqueous solution, and adding a plasticizer to form a film-forming solution.

[0033] The following description and examples illustrate implementations of this disclosure in detail. It should be understood that this disclosure is not limited to the specific embodiments described herein and therefore variations are possible. Those skilled in the art will recognize that numerous variations and modifications exist within the scope of this disclosure.

[0034] All terms are intended to be understood in accordance with the understanding of those skilled in the art. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure pertains.

[0035] The chapter titles used in this article are for organizational purposes only and should not be construed as limiting the topics described.

[0036] While many features of this disclosure may be described in the context of a single implementation, these features may also be provided individually or in any suitable combination. Conversely, while this disclosure may be described herein in the context of a single implementation for clarity purposes, this disclosure may also be implemented in a single implementation.

[0037] definition

[0038] The following definitions supplement those in the art, are specific to this application, and should not be attributed to any related or unrelated cases, such as any jointly owned patents or applications. While any methods and materials similar to or equivalent to those described herein may be used to practice the tests of this disclosure, preferred materials and methods are described herein. Therefore, the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting.

[0039] In this application, unless otherwise specifically stated, the use of the singular includes the plural. It must be noted that, as used in the specification, unless the context explicitly requires otherwise, the singular forms “a” and “an” include the plural indicator. In this application, unless otherwise stated, the use of “or” means “and / or”. Furthermore, the use of the term “comprising” and other forms such as “including” is not restrictive.

[0040] The references to "some embodiments", "implementation", "one embodiment" or "other embodiments" in the specification refer to specific features, structures or characteristics described in connection with the embodiments that are included in at least some embodiments of this disclosure, but not necessarily in all embodiments.

[0041] As used in this specification and claims, the terms “comprising” (and any form of comprising, such as “comprise” and “comprises”), “having” (and any form of having, such as “have” and “has”), “including” (and any form of including, such as “includes” and “include”), or “containing” (and any form of containing, such as “contains” and “contain”) are inclusive or open-ended and do not exclude additional unrepresented elements or method steps. Any embodiments discussed in this specification can be practiced with respect to any method or composition of this disclosure, and vice versa. Furthermore, the compositions of this disclosure can be used to implement the methods of this disclosure.

[0042] Unless specifically stated or obvious from the context, as used herein, the term “about” when referring to numbers or ranges of numbers should be understood to mean one or more numbers plus or minus 10% of them.

[0043] As used herein, the term "pharmaceutically acceptable salt" refers to any salt that is pharmaceutically acceptable and possesses the desired pharmacological properties. Such salts include those derived from inorganic or organic acids or inorganic or organic bases, including amino acids, and that are non-toxic or not undesirable in any respect. Suitable inorganic salts include those formed from alkali metals such as sodium and potassium, magnesium, calcium, and aluminum. Suitable organic salts include those formed from organic bases such as amine bases, such as ethanolamine, diethanolamine, triethanolamine, tromethamine, N-methylglucosamine, etc. Such salts also include acid addition salts formed from inorganic acids (e.g., hydrochloric acid and hydrobromic acid) and organic acids (e.g., acetic acid, citric acid, maleic acid, and alkyl sulfonic acids and aromatic sulfonic acids such as methanesulfonic acid, benzenesulfonic acid, sulfonic acid, and phosphoric acid). When two acidic groups are present, a pharmaceutically acceptable salt can be a monoacid monosalt or a disalt; similarly, when more than two acidic groups are present, some or all of such groups may be salted.

[0044] Composition

[0045] This document provides compositions comprising an active pharmaceutical ingredient, a film-forming polymer, a plasticizer, a volatile solvent, and a non-volatile solvent.

[0046] a. Active pharmaceutical ingredient (API)

[0047] This document provides compositions comprising an active pharmaceutical ingredient (API), wherein the API is selected from antibacterial, antifungal, antitumor, or anti-inflammatory substances, in an amount ranging from 0.01% to 20% by weight. Various embodiments described herein relate to compositions comprising an effective amount of the active pharmaceutical ingredient (API). The terms “active agent,” “API,” “drug,” “pharmaceutical active agent,” “bioactive agent,” “therapeutic agent,” and “active agent” are used interchangeably to refer to substances, such as compounds or complexes, that have a measurable beneficial physiological effect on the body, such as a therapeutic effect when administered in an effective amount in the treatment of a disease or disorder. Furthermore, when using these terms, or when a particular active ingredient is specifically identified by name or category, it should be understood that such a description is intended to include the active agent itself, its pharmaceutically acceptable pharmacologically active derivatives, or compounds significantly associated therewith, including but not limited to salts, pharmaceutically acceptable salts, N-oxides, prodrugs, active metabolites, isomers, fragments, analogs, solvates, hydrates, radioisotopes, etc.

[0048] In some embodiments, the APIs described herein are antibacterial substances. In some embodiments, the antibacterial substances described herein include penicillins, penicillin G, hetacillin potassium, benzathine cloxacillin, ampicillin, and amoxicillin trihydrate; aminocoumarins such as neomycin; and cephalosporins such as cephalexin, ceftiofur sodium, ceftiofur hydrochloride, and ceftiofur crystalline free acid. In some embodiments, the antibacterial substances described herein comprise macrolides. Macrolides described herein include, but are not limited to, tylosin, tylosin, tylosin, erythromycin, clarithromycin, and azithromycin. In some embodiments, the antibacterial substances described herein comprise quinolones or fluoroquinolones. Exemplary quinolones and fluoroquinolones include, but are not limited to, enrofloxacin, ciprofloxacin, levofloxacin, and ofloxacin. In some embodiments, the antibacterial substances described herein comprise sulfonamides. Exemplary sulfonamides include, but are not limited to, sulfamethoxypyrimidine, and trimethoprim-sulfamethoxazole. Azole and trimethoprim. In some embodiments, the antibacterial substances described herein comprise retinoids. Exemplary retinoids include, but are not limited to, retinol, retinoic acid (retinal), isotretinoin, retinoic acid, acitretin, adapalene, bexarotine, and tazarotene. In some embodiments, the antibacterial substances described herein comprise trefarotine. In some embodiments, the antibacterial substances described herein comprise tetracyclines. Exemplary tetracyclines include, but are not limited to, tetracycline, oxytetracycline, and doxycycline. In some embodiments, the antibacterial substances described herein comprise aminoglycosides. Exemplary aminoglycosides include, but are not limited to, dihydrostreptomycin sulfate, neomycin, gentamicin, and tobramycin. In some embodiments, the antibacterial substances described herein comprise lincosamides. Exemplary lincosamides include, but are not limited to, pyridamoleic acid hydrochloride, lincomycin, clindamycin, and pyridamoleic acid. In some embodiments, the antibacterial substances described herein comprise amide alcohols. Exemplary amide alcohols include, but are not limited to, florfenicol or any combination thereof. In some embodiments, the antibacterial substances described herein are selected from penicillins, sulfonamides, streptozotocins, polypeptides, tetracyclines, doxycyclines, amoxicillin, carbapenems, cephalosporins, fluoroquinolones, glycopeptides and lipoglycopeptides, macrolides, monocyclic β-lactams, and any combination thereof.

[0049] In some embodiments, the API described herein is an antifungal substance. In some embodiments, the antifungal substance described herein is an antifungal agent. In some embodiments, the antifungal substances described herein include polyenes such as amphotericin B, candidacloprid, phlebitisin, hamycin, natamycin, nystatin, and cytomegaloxin; azoles such as imidazole, triazole, thiazole, bifonazole, butonazole, clotrimazole, econazole, fenteconazole, isoconazole, ketoconazole, ruliconazole, miconazole, omeconazole, oxiconazole, sertaconazole, thioconazole, tiaconazole, abaconazole, ifluconazole, fluconazole, fluconazole, isaconazole, itraconazole, posaconazole, propiconazole, rivanazole, terconazole, voriconazole, and abafenoxam; allylamines such as amorolfine, butenafine, naftifine, and terbinafine; echinocandins such as anidulin, caspofungin, and micafungin; and aurones, benzoic acid, ciclopirox olamine, and flucytosine. Or 5-fluorocytosine, griseofulvin, chlorpropynyl iodine, tonaphthyl ester, undecenoic acid, triacetin, crystal violet, Castranil's ointment, orotomide (F901318), mitefonine, potassium iodide, coal tar, copper sulfate (ii), selenium disulfide, sodium thiosulfate, piroctone ethanolamine salt, diiodoquinoline, chloriodoquinoline, acridine soxine, zinc pyrithione and sulfur, antiprotozoal drugs such as melarisol, efornithine, metronidazole, tinidazole, mitefonine, antihelmintic drugs such as mebendazole, pyrantel thiamethoxam, thiabendazole, diethylcarbazine, ivermectin, antitachycephalosporin drugs such as niclosamide, praziquantel, albendazole, antitrematode drugs such as praziquantel, antiamoebic drugs such as rifampin and amphotericin B, and broad-spectrum drugs such as nizoxin, or any combination thereof. In some embodiments, the antifungal substances described herein are iriconazole, tavaborone, ciclopirox, amorolfen, ruliconazole, terbinafine, miconazole, ketoconazole, itraconazole, fluconazole, econazole, oxiconazole, clotrimazole, naftifine, voriconazole, isaconazole, fenteconazole, tavaborone, or amorolfen. In some embodiments, the antifungal substance described herein is terbinafine. In some embodiments, the antifungal substances described herein are imidazoles or triazoles. In some embodiments, the antifungal substances described herein are anidoxuridine, caspofungin, micafungin, or rezafungin. In some embodiments, the antifungal substance is flucytosine. In some embodiments, the antifungal substance described herein is amphotericin B. In some embodiments, the antifungal substance described herein is amorolfen hydrochloride. In some embodiments, the antifungal substance is terbinafine.

[0050] In some embodiments, the APIs described herein are antiviral substances. In some embodiments, the antiviral substances described herein include peramivir, zanamivir, oseltamivir phosphate, mabaloxavir, acyclovir, valacyclovir, valganciclovir, brivudine, cidofovir, famciclovir, fomivir, phosphonoformic acid, ganciclovir, penciclovir, amantadine, rimantadine, ribavirin, telbivudine, adefovir, entecavir, emtricitabine, lamivudine, tenofovir, boprevir, telaprevir, interferon, or any combination thereof.

[0051] In some embodiments, the API described herein is an anti-inflammatory substance. In some embodiments, the anti-inflammatory substance described herein is a substance targeting psoriasis and eczema. In some embodiments, the anti-inflammatory substance described herein includes, but is not limited to, glucocorticoids, JAK inhibitors, and phosphodiesterase-4 (PDE4) inhibitors. In some embodiments, the JAK inhibitor is baricitinib, tofacitinib, filogrinib, or utpatinib. In some embodiments, the PDE4 inhibitor is apremilast, criborone, or roflumilast. In some embodiments, the glucocorticoid is triamcinolone, prednisone, or dexamethasone.

[0052] In some embodiments, the API is present as a free base. In some embodiments, the API is present as a pharmaceutically acceptable salt. As used herein, pharmaceutically acceptable salts include, but are not limited to, metal salts such as sodium, potassium, and lithium salts; alkaline earth metal salts such as calcium and magnesium salts; organic amine salts such as triethylamine, pyridinium, methylpyridinium, ethanolamine, triethanolamine, dicyclohexylamine, and N,N'-dibenzylethylenediamine; inorganic acid salts such as hydrochloride, hydrobromide, sulfate, and phosphate; organic acid salts such as formate, acetate, trifluoroacetate, maleate, and tartrate; sulfonates such as methanesulfonate, benzenesulfonate, and p-toluenesulfonate; and amino acid salts such as arginine, aspartate, and glutamate. In some embodiments, the API is abiraterone acetate, alectinib, pazopanib, cabozantinib, veneclade, lurasidone, vilazorone, or a pharmaceutically acceptable salt or ester thereof. In some embodiments, the API is abiraterone acetate, alectinib, pazopanib, cabozantinib, veneclax, lurasidone, or vilazodone. In some embodiments, the API is a pharmaceutically acceptable salt of abiraterone acetate, alectinib, pazopanib, cabozantinib, veneclax, lurasidone, or vilazodone. In some embodiments, the API is lipophilic. In some embodiments, the lipophilic API is an API listed in Table 1 or a pharmaceutically acceptable salt thereof. In some embodiments, the API has a log P of 2.0 or higher. In some embodiments, the API has a log P of 3.0 or higher. In some embodiments, the API has a log P of 3.5 or higher. In some embodiments, the API has a log P of 4.0 or higher. In some embodiments, the API has a log P of 4.5 or higher. In some embodiments, the lipophilic API, hydrophilic polymer, and surfactant are formulated as an amorphous solid dispersion. In some embodiments, the amorphous solid dispersion comprises a lipophilic API, a hydrophilic polymer, and a surfactant. In some embodiments, the amorphous solid dispersion described herein additionally comprises one or more adsorbents. In some embodiments, the amorphous solid dispersion described herein additionally comprises one or more other additives. In some embodiments, the other additives include organic acids and inorganic acids. In some embodiments, the other additives include antioxidants.

[0053] Pharmaceutically acceptable salts include tartrate, tartrate hydrochloride, hydrochloride, p-toluenesulfonate, phosphate, sulfate, trifluoroacetate, tartrate hemipentahydrate, pentafluoropropionate, hydrobromide, mucilage, oleate, dihydrogen phosphate, dihydrogen phosphate, acetate trihydrate, bis(heptafluorobutyrate), bis(pentafluoropropionate), bis(pyridinecarboxylate), bis(trifluoroacetate), chlorhydrate, and sulfate pentahydrate. Other representative pharmaceutically acceptable salts include, for example, water-soluble and water-insoluble salts such as acetates, 4,4-diaminostilbene-2,2-disulfonate, benzenesulfonate, benzoate, bicarbonate, bisulfate, tartrate, borate, butyrate, calcium edetate, camphorsulfonate (camsylate), carbonate, citrate, clavulanate, dihydrochloride, edetate, ethanedisulfonate, etolate, ethanesulfonate, fiunarate, fumarate, gluconate, gluconate, glutamate, glycolylarsenoylbenzoate, hexafluorophosphate, hexylresorcinol, hyaluronic acid salt, hydrobromide, hydrochloride, hydroxynaphthylcarbamate, and iodine. Compounds, hydroxyapatite, lactates, lacturonates, laurates, malates, maleates, mandelates, methanesulfonates, methyl bromide, methyl nitrates, methyl sulfates, mucilages, naphthalenesulfonates, nitrates, N-methylglucosamine ammonium salts, 3-hydroxy-2-naphthylcarboxylate, oleates, oxalates, palmitates, bis(hydroxynaphthyl)ate (1,1-methylene-bis-2-hydroxy-3-naphthylcarboxylate, embezzate), pantothenates, phosphates / bisphosphonates, picrates, polygalacturonates, propionates, p-toluenesulfonates, salicylates, stearates, basic acetates, succinates, sulfates, sulfosalicylates, suraminates, tannates, tartrates, 8-chlorotheophylline salts, toluenesulfonates, triethyliodide, and valerates. Hydrates are another example of pharmaceutically acceptable salts. In some embodiments, the API is abiraterone acetate, alectinib, pazopanib, cabozantinib, veneclax, lurasidone, vilazodone, or a pharmaceutically acceptable salt thereof. In some embodiments, the API is abiraterone acetate, alectinib, pazopanib, cabozantinib, veneclax, lurasidone, or vilazodone. In some embodiments, the API is a pharmaceutically acceptable salt of abiraterone acetate, alectinib, pazopanib, cabozantinib, veneclax, lurasidone, or vilazodone.

[0054] Salts can also be formed from bases in the presence of negatively charged groups such as carboxyl or sulfonium groups. In some embodiments, the bases described herein comprise metal salts or ammonium salts. In some embodiments, the bases described herein comprise alkali metal salts or alkaline earth metal salts. Exemplary alkali metal salts and alkaline earth metal salts include, but are not limited to, examples of sodium, potassium, magnesium, or calcium salts. In some embodiments, the ammonium salts described herein comprise ammonia or suitable organic amines such as tertiary monoamines, such as triethylamine or tri(2-hydroxyethyl)amine, or heterocyclic bases, such as N-ethylpiperidine or N,N′-dimethylpiperazine.

[0055] The compounds disclosed herein may also form internal salts when basic and acidic groups are present in the same molecule. Pharmaceutically unacceptable salts, such as picrates or perchlorates, may also be used for separation or purification purposes. For therapeutic uses, only pharmaceutically acceptable salts or free compounds (in pharmaceutical formulation, where applicable) are used.

[0056] In some embodiments, the API or its salt described herein is present in amounts of about 0.1% (w / v) to about 20% (w / v). In some embodiments, the API or its salts described herein are present in amounts of about 0.1% (w / v) to about 1.0% (w / v), about 0.2% (w / v) to about 1.2% (w / v), about 0.3% (w / v) to about 1.3% (w / v), about 0.4% (w / v) to about 1.4% (w / v), about 0.5% (w / v) to about 1.5% (w / v), about 0.6% (w / v) to about 1.6% (w / v), about 0.7% (w / v) to about 1.7% (w / v), about 0.8% (w / v) to about 1.8% (w / v), about 0.9% (w / v) to about 2.9% (w / v), about 1.0% (w / v) to about 2.0% (w / v), about 1.5% (w / v) to about 2.5% (w / v), or about 2% (w / v) to about 3%. (w / v), approximately 2.5% (w / v) to approximately 3.5% (w / v), approximately 3% (w / v) to approximately 4% (w / v), approximately 3.5% (w / v) to approximately 4.5% (w / v), approximately 4% (w / v) to approximately 5% (w / v), approximately 4.5% (w / v) to approximately 5.5% (w / v), approximately 5% (w / v) to approximately 6% (w / v), approximately 5.5% (w / v) to approximately 6.5% (w / v), approximately 6% (w / v) to approximately 7% (w / v), approximately 6.5% (w / v) to approximately 7.5% (w / v), approximately 7% (w / v) to approximately 8% (w / v), approximately 7.5% (w / v) to approximately 8.5% (w / v), approximately 8% (w / v) to approximately 9% (w / v), approximately 8.5% (w / v) to approximately 9.5% (w / v), approximately 9% (w / v) to about 10% (w / v), about 9.5% (w / v) to about 10.5% (w / v), about 10% (w / v) to about 11% (w / v), about 10.5% (w / v) to about 11.5% (w / v), about 11% (w / v) to about 12% (w / v), about 11.5% (w / v) to about 12.5% ​​(w / v), about 12% (w / v) to about 13% (w / v), about 12.5% ​​(w / v) to about 13.5% (w / v), about 13% (w / v) to about 14% (w / v), about 13.5% (w / v) to about 14.5% (w / v), about 14% (w / v) to about 15% (w / v), about 14.5% (w / v) to about 15.5% (w / v), about 15% (w / v) to about 16% (w / v), about 15.5% (w / v) to about 16.5% (w / v), about 16% (w / v) to about 17% (w / v), about 16%.It is present in amounts of 5% (w / v) to about 17.5% (w / v), about 17% (w / v) to about 18% (w / v), about 17.5% (w / v) to about 18.5% (w / v), about 18% (w / v) to about 19% (w / v), about 18.5% (w / v) to about 19.5% (w / v), or about 19% (w / v) to about 20% (w / v). In some embodiments, the API or its salts described herein are used at concentrations of approximately 0.1% (w / v), approximately 0.2% (w / v), approximately 0.3% (w / v), approximately 0.4% (w / v), approximately 0.5% (w / v), approximately 0.6% (w / v), approximately 0.7% (w / v), approximately 0.8% (w / v), approximately 0.9% (w / v), approximately 1.0% (w / v), approximately 1.5% (w / v), approximately 2% (w / v), approximately 2.5% (w / v), approximately 3% (w / v), approximately 3.5% (w / v), approximately 4% (w / v), approximately 4.5% (w / v), approximately 5% (w / v), approximately 5.5% (w / v), approximately 6% (w / v), approximately 6.5% (w / v), approximately 7% (w / v), approximately 7.5% (w / v), and approximately 8%. It is present in amounts of approximately 8.5% (w / v), approximately 9% (w / v), approximately 9.5% (w / v), approximately 10% (w / v), approximately 11% (w / v), approximately 12% (w / v), approximately 13% (w / v), approximately 14% (w / v), approximately 15% (w / v), approximately 16% (w / v), approximately 17% (w / v), approximately 18% (w / v), approximately 19% (w / v), or approximately 20% (w / v).

[0057] b Film-forming polymers

[0058] In some embodiments, the compositions described herein comprise a film-forming polymer. In some embodiments, the film-forming polymer described herein is water-soluble. In some embodiments, the film-forming polymer described herein comprises a hydrophilic high molecular weight material. In some embodiments, the high molecular weight material comprises at least one of the following: polyvinylpyrrolidone (polyvinyl ketone) (e.g., PVP-K30), vinylpyrrolidone-vinyl acetate copolymer (copolyvinyl ketone or PVP-VA64, for example, sold under the trade name Kollidon® VA 64), polyvinyl alcohol (PVA), polysaccharide, hydroxypropyl methylcellulose (HPMC or hydroxypropyl methylcellulose; for example, HPMC-E5), hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), polyethylene oxide, hydroxypropyl-β-cyclodextrin (HP-β-CD), sulfobutyl ether-β-cyclodextrin, hydroxypropyl methylcellulose acetate succinate (HPMC-AS), hydroxypropyl methylcellulose phthalate (HPMCP), polyethylene glycol (PEG), polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (PVAc-PVCap-PEG, for example, sold under the trade name Soluplus), polysaccharide, polymethacrylate, or any combination thereof. In some embodiments, the hydrophilic polymeric material is polyvinylpyrrolidone (PVP), copovidone, crospovidone, HPMC, or any combination thereof. In some embodiments, the polymeric material comprises HPMC and crospovidone. In some embodiments, the polymeric material comprises HPMC and PVP. In some embodiments, the polymeric material comprises HPMC and copovidone. In some embodiments, the polymeric material comprises hydroxypropyl methylcellulose phthalate (HPMCP). In some embodiments, the film-forming polymer described herein is selected from hydroxypropyl methylcellulose derivatives, polymethacrylates, or any combination thereof. In some embodiments, the polymeric material comprises polymethacrylates (e.g., sold under the trade name Eudragit®). "Eudragit" as used herein refers to copolymers derived from methacrylic acid and methacrylates or acrylates. Depending on the specific grade, they may also contain other monomers such as methyl methacrylate, ethyl acrylate, butyl methacrylate, dimethylaminoethyl methacrylate, or trimethylammonium ethyl methacrylate chloride. Eudragit E-grade polymers contain poly(butyl methacrylate-co-(2-dimethylamino)ethyl methacrylate-co-methyl methacrylate). Eudragit S or L-grade polymers contain poly(methacrylate-co-methyl methacrylate). Eudragit RS or RL-grade polymers contain poly(ethyl acrylate-co-methyl methacrylate-trimethylammonium ethyl methacrylate chloride). Eudragit L100 is a methacrylate-methyl methacrylate copolymer in a 1:1 ratio.In some embodiments, the film-forming polymer described herein is Eudragit L100. In some embodiments, the high molecular weight material comprises HPMC-AS. In some embodiments, the high molecular weight material comprises polyurethane.

[0059] In some embodiments, the film-forming polymer described herein is present in an amount of about 0.1% (w / v) to about 15% (w / v). In some embodiments, the film-forming polymer described herein is present in amounts of about 0.1% (w / v) to about 1.0% (w / v), about 0.2% (w / v) to about 1.2% (w / v), about 0.3% (w / v) to about 1.3% (w / v), about 0.4% (w / v) to about 1.4% (w / v), about 0.5% (w / v) to about 1.5% (w / v), about 0.6% (w / v) to about 1.6% (w / v), about 0.7% (w / v) to about 1.7% (w / v), about 0.8% (w / v) to about 1.8% (w / v), about 0.9% (w / v) to about 2.9% (w / v), about 1.0% (w / v) to about 2.0% (w / v), about 1.5% (w / v) to about 2.5% (w / v), and about 2% (w / v) to about 3%. (w / v), approximately 2.5% (w / v) to approximately 3.5% (w / v), approximately 3% (w / v) to approximately 4% (w / v), approximately 3.5% (w / v) to approximately 4.5% (w / v), approximately 4% (w / v) to approximately 5% (w / v), approximately 4.5% (w / v) to approximately 5.5% (w / v), approximately 5% (w / v) to approximately 6% (w / v), approximately 5.5% (w / v) to approximately 6.5% (w / v), approximately 6% (w / v) to approximately 7% (w / v), approximately 6.5% (w / v) to approximately 7.5% (w / v), approximately 7% (w / v) to approximately 8% (w / v), approximately 7.5% (w / v) to approximately 8.5% (w / v), approximately 8% (w / v) to approximately 9% (w / v), approximately 8.5% (w / v) to approximately 9.5% (w / v), approximately 9% It is present in amounts of about 10% (w / v), about 9.5% (w / v) to about 10.5% (w / v), about 10% (w / v) to about 11% (w / v), about 10.5% (w / v) to about 11.5% (w / v), about 11% (w / v) to about 12% (w / v), about 11.5% (w / v) to about 12.5% ​​(w / v), about 12% (w / v) to about 13% (w / v), about 12.5% ​​(w / v) to about 13.5% (w / v), about 13% (w / v) to about 14% (w / v), about 13.5% (w / v) to about 14.5% (w / v), or about 14% (w / v) to about 15% (w / v).In some embodiments, the film-forming polymer described herein is present at concentrations of approximately 0.1% (w / v), approximately 0.2% (w / v), approximately 0.3% (w / v), approximately 0.4% (w / v), approximately 0.5% (w / v), approximately 0.6% (w / v), approximately 0.7% (w / v), approximately 0.8% (w / v), approximately 0.9% (w / v), approximately 1.0% (w / v), approximately 1.5% (w / v), approximately 2% (w / v), approximately 2.5% (w / v), approximately 3% (w / v), approximately 3.5% (w / v), approximately 4% (w / v), approximately 4.5% (w / v), approximately 5% (w / v), approximately 5.5% (w / v), approximately 6% (w / v), approximately 6.5% (w / v), approximately 7% (w / v), approximately 7.5% (w / v), approximately 8% (w / v), and approximately 8.5%. It is present in amounts of (w / v), about 9% (w / v), about 9.5% (w / v), about 10% (w / v), about 11% (w / v), about 12% (w / v), about 13% (w / v), about 14% (w / v), or about 15% (w / v).

[0060] In some embodiments, when used as the film-forming polymer described herein, Eudragit L100 is present in amounts of about 5% (w / v) to about 15% (w / v). In some embodiments, when used as the film-forming polymer described herein, Eudragit L100 is present in amounts of about 5% (w / v), about 5.5% (w / v), about 6% (w / v), about 6.5% (w / v), about 7% (w / v), about 7.5% (w / v), about 8% (w / v), about 8.5% (w / v), about 9% (w / v), about 9.5% (w / v), about 10% (w / v), about 11% (w / v), about 12% (w / v), about 13% (w / v), about 14% (w / v), or about 15% (w / v). In some embodiments, Eudragit L100 is present in an amount of about 10% (w / v) when used as the film-forming polymer described herein.

[0061] In some embodiments, when used as the film-forming polymer described herein, HPMC-AS LF is present in an amount of about 0.5% (w / v) to about 4% (w / v). In some embodiments, when used as the film-forming polymer described herein, HPMC-AS LF is present in an amount of about 0.5% (w / v) to about 1% (w / v). In some embodiments, when used as the film-forming polymer described herein, HPMC-AS is present in amounts of about 0.1% (w / v) to about 1.0% (w / v), about 0.2% (w / v) to about 1.2% (w / v), about 0.3% (w / v) to about 1.3% (w / v), about 0.4% (w / v) to about 1.4% (w / v), about 0.5% (w / v) to about 1.5% (w / v), about 0.6% (w / v) to about 1.6% (w / v), about 0.7% (w / v) to about 1.7% (w / v), about 0.8% (w / v) to about 1.8% (w / v), about 0.9% (w / v) to about 2.9% (w / v), about 1.0% (w / v) to about 2.0% (w / v), about 1.5% (w / v) to about 2.5% (w / v), and about 2%. It is present in amounts of about 3% (w / v), about 2.5% (w / v) to about 3.5% (w / v), or about 3% (w / v) to about 4% (w / v). In some embodiments, when used as the film-forming polymer described herein, HPMC-AS is present at concentrations of approximately 0.1% (w / v), approximately 0.2% (w / v), approximately 0.3% (w / v), approximately 0.4% (w / v), approximately 0.5% (w / v), approximately 0.6% (w / v), approximately 0.7% (w / v), approximately 0.8% (w / v), approximately 0.9% (w / v), approximately 1.0% (w / v), approximately 1.5% (w / v), approximately 1.6% (w / v), approximately 1.7% (w / v), approximately 1.8% (w / v), approximately 1.9% (w / v), approximately 2% (w / v), approximately 2.1% (w / v), approximately 2.2% (w / v), approximately 2.3% (w / v), approximately 2.4% (w / v), approximately 2.5% (w / v), approximately 2.6% (w / v), and approximately 2.7%. It is present in amounts of approximately 2.8% (w / v), approximately 2.9% (w / v), approximately 3% (w / v), approximately 3.1% (w / v), approximately 3.2% (w / v), approximately 3.3% (w / v), approximately 3.4% (w / v), approximately 3.5% (w / v), approximately 3.6% (w / v), approximately 3.7% (w / v), approximately 3.8% (w / v), approximately 3.9% (w / v), or approximately 4% (w / v).

[0062] In some embodiments, the compositions described herein comprise a hydroxypropyl methylcellulose derivative and a polymethacrylate. In some embodiments, the compositions described herein comprise both Eudragit L100 and HPMC-AS LF. In some embodiments, in the compositions described herein comprising both Eudragit L100 and HPMC-AS LF, Eudragit L100 is present in an amount of about 5% (w / v) to about 15% (w / v), and HPMC-AS LF is present in an amount of about 0.5% (w / v) to about 4% (w / v). In some embodiments, in the compositions comprising both Eudragit L100 and HPMC-AS LF described herein, Eudragit L100 is present in amounts of about 5% (w / v), about 6% (w / v), about 7% (w / v), about 8% (w / v), about 9% (w / v), about 10% (w / v), about 11% (w / v), about 12% (w / v), about 13% (w / v), about 14% (w / v), or about 15% (w / v), and HPMC-AS LF is present in amounts of about 0.5% (w / v), about 1% (w / v), about 1.5% (w / v), about 2% (w / v), about 2.5% (w / v), about 3% (w / v), about 3.5% (w / v), or about 4% (w / v). In some embodiments, in the composition comprising both Eudragit L100 and HPMC-AS LF described herein, Eudragit L100 is present in an amount of about 10% (w / v) and HPMC-AS LF is present in an amount of about 0.5% (w / v) to about 1% (w / v).

[0063] c. Plasticizers

[0064] In some embodiments, the compositions described herein comprise at least one plasticizer. The plasticizer imparts flexibility to the film formed from the compositions described herein. In some embodiments, the plasticizer described herein comprises polyethylene glycol, glyceryl trioctanoate, dibutyl sebacate, triethyl citrate, glyceryl triacetate, Myvacet® (acetylated monoglyceride), diethyl phthalate, butyl stearate, lauric acid, dioctyl glutarate, triglycerides, dioctyl oxalate, triethyl phosphate, acetylated tributyl citrate, or any combination thereof. In some embodiments, the plasticizer described herein is polyethylene glycol (PEG). In some embodiments, the plasticizer described herein is PEG 6000.

[0065] In some embodiments, the plasticizer described herein is present in an amount of about 0.1% (w / v) to about 5% (w / v). In some embodiments, the plasticizer described herein is present in amounts of about 0.1% (w / v) to about 1.0% (w / v), about 0.2% (w / v) to about 1.2% (w / v), about 0.3% (w / v) to about 1.3% (w / v), about 0.4% (w / v) to about 1.4% (w / v), about 0.5% (w / v) to about 1.5% (w / v), about 0.6% (w / v) to about 1.6% (w / v), about 0.7% (w / v) to about 1.7% (w / v), about 0.8% (w / v) to about 1.8% (w / v), about 0.9% (w / v) to about 2.9% (w / v), about 1.0% (w / v) to about 2.0% (w / v), about 1.5% (w / v) to about 2.5% (w / v), and about 2% (w / v) to about 3%. It is present in amounts of about 2.5% (w / v) to about 3.5% (w / v), about 3% (w / v) to about 4% (w / v), about 3.5% (w / v) to about 4.5% (w / v), or about 4% (w / v) to about 5% (w / v). In some embodiments, the plasticizer described herein is present in amounts of about 0.1% (w / v), about 0.2% (w / v), about 0.3% (w / v), about 0.4% (w / v), about 0.5% (w / v), about 0.6% (w / v), about 0.7% (w / v), about 0.8% (w / v), about 0.9% (w / v), about 1.0% (w / v), about 1.5% (w / v), about 2% (w / v), about 2.5% (w / v), about 3% (w / v), about 3.5% (w / v), about 4% (w / v), about 4.5% (w / v), or about 5% (w / v). In some embodiments, the plasticizer described herein is present in amounts of about 2% (w / v) to about 4% (w / v). In some embodiments, when PEG 6000 is present as a plasticizer in the compositions described herein, PEG 6000 is present in an amount of about 2% (w / v) to about 4% (w / v).

[0066] d. Solvent

[0067] In some embodiments, the compositions described herein comprise volatile and non-volatile solvents. The term "volatile solvent" refers to a portion of the composition that evaporates after application. That is, "volatile solvent" means one or more solvents, including co-solvents (if used), that leave the carrier, such as the delivery medium, in less than 24 hours at a specified selected temperature, typically at room temperature of about 23°C, such that the presence of the solvent in the composition is transient. Furthermore, "volatile solvent" is capable of dissolving APIs. Volatile solvents are generally cosmetically acceptable and are liquids at room temperature. Additionally, in some embodiments, the volatile solvent is miscible with water. "Miscible with water" means that the volatile solvent is completely soluble in water in all proportions. Suitable examples of water-miscible volatile solvents include ethanol, propanol, and isopropanol. If a volatile solvent is not miscible with water, in some embodiments, it is at least partially soluble in isopropanol. In some embodiments, the volatile solvents described herein include ethanol, propanol, isopropanol, ethyl acetate, or mixtures thereof. In some embodiments, the volatile solvent described herein is ethanol. The term "non-volatile solvent" refers to a solvent that is unlikely to evaporate easily. In some embodiments, the non-volatile solvent described herein is water.

[0068] In some embodiments, the ratio of volatile solvent to non-volatile solvent is about 9:1 (v / v) to about 5:5 (v / v). In some embodiments, the ratio of volatile solvent to non-volatile solvent is about 9:1 (v / v), about 8.5:1.5 (v / v), about 8:2 (v / v), about 7.5:3.5 (v / v), about 7:3 (v / v), about 6.5:5.5 (v / v), about 6:4 (v / v), about 5.5:4.5 (v / v), or about 5:5 (v / v).

[0069] In some embodiments, the volatile solvent is ethanol, and the non-volatile solvent is water. In some embodiments, the ethanol-to-water ratio is from 10:0 (v / v) to about 5:5 (v / v). In some embodiments, the ethanol-to-water ratio is 10:0 (v / v), about 9:1 (v / v), about 8.5:1.5 (v / v), about 8:2 (v / v), about 7.5:3.5 (v / v), about 7:3 (v / v), about 6.5:5.5 (v / v), about 6:4 (v / v), about 5.5:4.5 (v / v), or about 5:5 (v / v). In some embodiments, the ethanol-to-water ratio is about 9:1 (v / v). In some embodiments, the ethanol-to-water ratio is about 8:2 (v / v).

[0070] e. Solubilizer

[0071] In some embodiments, the compositions described herein contain a solubilizer. In some embodiments, the solubilizer described herein is transcutol, propylene glycol, labrasol, PEG400, isopropyl palmitate, or triethyl citrate. In some embodiments, the solubilizer described herein is transcutol or propylene glycol. In some embodiments, the solubilizer described herein is propylene glycol. In some embodiments, the solubilizer described herein is propylene glycol.

[0072] In some embodiments, the solubilizer described herein is present in an amount of about 0.1% (w / v) to about 5% (w / v). In some embodiments, the solubilizer described herein is present in amounts of about 0.1% (w / v) to about 1.0% (w / v), about 0.2% (w / v) to about 1.2% (w / v), about 0.3% (w / v) to about 1.3% (w / v), about 0.4% (w / v) to about 1.4% (w / v), about 0.5% (w / v) to about 1.5% (w / v), about 0.6% (w / v) to about 1.6% (w / v), about 0.7% (w / v) to about 1.7% (w / v), about 0.8% (w / v) to about 1.8% (w / v), about 0.9% (w / v) to about 2.9% (w / v), about 1.0% (w / v) to about 2.0% (w / v), about 1.5% (w / v) to about 2.5% (w / v), or about 2% (w / v) to about 3%. It is present in amounts of about 2.5% (w / v) to about 3.5% (w / v), about 3% (w / v) to about 4% (w / v), about 3.5% (w / v) to about 4.5% (w / v), or about 4% (w / v) to about 5% (w / v). In some embodiments, the solubilizer described herein is present in amounts of about 0.1% (w / v), about 0.2% (w / v), about 0.3% (w / v), about 0.4% (w / v), about 0.5% (w / v), about 0.6% (w / v), about 0.7% (w / v), about 0.8% (w / v), about 0.9% (w / v), about 1.0% (w / v), about 1.5% (w / v), about 2% (w / v), about 2.5% (w / v), about 3% (w / v), about 3.5% (w / v), about 4% (w / v), about 4.5% (w / v), or about 5% (w / v). In some embodiments, when used as a solubilizer as described herein, propylene glycol or transcutol is present in amounts of about 3% (w / v) to about 5% (w / v).

[0073] f. Other components

[0074] In some embodiments, the compositions described herein include additional excipients. In some embodiments, the additional excipients include, but are not limited to, penetration enhancers, thickeners, colorants, or any combination thereof.

[0075] In some embodiments, the compositions disclosed herein comprise a penetration enhancer. A "penetration enhancer" is a natural or synthetic compound that increases the flux of an API or combination of APIs across a barrier. In some embodiments, the compositions disclosed herein comprise an API, the polymer described herein, the plasticizer described herein, the volatile solvent described herein, the non-volatile solvent described herein, and a penetration enhancer. In some embodiments, the compositions disclosed herein comprise an API, the polymer described herein, the plasticizer described herein, the volatile solvent described herein, the non-volatile solvent described herein, the solubilizer described herein, and a penetration enhancer. In some embodiments, the penetration enhancer described herein is selected from hydrating agents, keratolytic agents, acids, disulfide bond cleaving agents, chelating agents, and any combination thereof. In some embodiments, the hydrating agent described herein is a cyclodextrin or a derivative thereof. In some embodiments, the acid described herein is phosphoric acid, lactic acid, or ethyl lactate. In some embodiments, the keratolytic agent described herein is urea or a derivative thereof. In some embodiments, the disulfide bond cleaving agent is acetylcysteine. In some embodiments, the chelating agent is EDTA or a derivative thereof. In some embodiments, the penetration enhancer described herein is selected from the following: cyclodextrin and its derivatives, urea and its derivatives, lactic acid and its derivatives, sodium sulfite and its derivatives, EDTA, and cysteine ​​and its derivatives, and any combination thereof. In some embodiments, the penetration enhancer described herein is hydroxypropyl-β-cyclodextrin. In some embodiments, the penetration enhancer described herein is lactic acid.

[0076] In some embodiments, the penetration enhancer described herein is present in an amount of about 0.1% (w / v) to about 15% (w / v). In some embodiments, the penetration enhancer described herein is present in amounts of about 0.1% (w / v) to about 1.0% (w / v), about 0.2% (w / v) to about 1.2% (w / v), about 0.3% (w / v) to about 1.3% (w / v), about 0.4% (w / v) to about 1.4% (w / v), about 0.5% (w / v) to about 1.5% (w / v), about 0.6% (w / v) to about 1.6% (w / v), about 0.7% (w / v) to about 1.7% (w / v), about 0.8% (w / v) to about 1.8% (w / v), about 0.9% (w / v) to about 2.9% (w / v), about 1.0% (w / v) to about 2.0% (w / v), about 1.5% (w / v) to about 2.5% (w / v), and about 2% (w / v) to about 3%. (w / v), approximately 2.5% (w / v) to approximately 3.5% (w / v), approximately 3% (w / v) to approximately 4% (w / v), approximately 3.5% (w / v) to approximately 4.5% (w / v), approximately 4% (w / v) to approximately 5% (w / v), approximately 4.5% (w / v) to approximately 5.5% (w / v), approximately 5% (w / v) to approximately 6% (w / v), approximately 5.5% (w / v) to approximately 6.5% (w / v), approximately 6% (w / v) to approximately 7% (w / v), approximately 6.5% (w / v) to approximately 7.5% (w / v), approximately 7% (w / v) to approximately 8% (w / v), approximately 7.5% (w / v) to approximately 8.5% (w / v), approximately 8% (w / v) to approximately 9% (w / v), approximately 8.5% (w / v) to approximately 9.5% (w / v), approximately 9% It is present in amounts of about 10% (w / v), about 9.5% (w / v) to about 10.5% (w / v), about 10% (w / v) to about 11% (w / v), about 10.5% (w / v) to about 11.5% (w / v), about 11% (w / v) to about 12% (w / v), about 11.5% (w / v) to about 12.5% ​​(w / v), about 12% (w / v) to about 13% (w / v), about 12.5% ​​(w / v) to about 13.5% (w / v), about 13% (w / v) to about 14% (w / v), about 13.5% (w / v) to about 14.5% (w / v), or about 14% (w / v) to about 15% (w / v).In some embodiments, the penetration enhancer described herein is used at concentrations of approximately 0.1% (w / v), approximately 0.2% (w / v), approximately 0.3% (w / v), approximately 0.4% (w / v), approximately 0.5% (w / v), approximately 0.6% (w / v), approximately 0.7% (w / v), approximately 0.8% (w / v), approximately 0.9% (w / v), approximately 1.0% (w / v), approximately 1.5% (w / v), approximately 2% (w / v), approximately 2.5% (w / v), approximately 3% (w / v), approximately 3.5% (w / v), approximately 4% (w / v), approximately 4.5% (w / v), approximately 5% (w / v), approximately 5.5% (w / v), approximately 6% (w / v), approximately 6.5% (w / v), approximately 7% (w / v), approximately 7.5% (w / v), approximately 8% (w / v), and approximately 8.5%. It is present in amounts of (w / v), about 9% (w / v), about 9.5% (w / v), about 10% (w / v), about 11% (w / v), about 12% (w / v), about 13% (w / v), about 14% (w / v), or about 15% (w / v).

[0077] In some embodiments, when used as a penetration enhancer in the compositions described herein, hydroxypropyl-β-cyclodextrin is present in an amount of about 0.1% (w / v) to about 10% (w / v). In some embodiments, when used as a penetration enhancer in the compositions described herein, hydroxypropyl-β-cyclodextrin is present at concentrations of about 0.1% (w / v), about 0.2% (w / v), about 0.3% (w / v), about 0.4% (w / v), about 0.5% (w / v), about 0.6% (w / v), about 0.7% (w / v), about 0.8% (w / v), about 0.9% (w / v), about 1.0% (w / v), about 1.5% (w / v), about 2% (w / v), about 2.5% (w / v), about 3% (w / v), about 3.5% (w / v), about 4% (w / v), about 4.5% (w / v), about 5% (w / v), about 5.5% (w / v), about 6% (w / v), about 6.5% (w / v), about 7% (w / v), and about 7.5%. It is present in amounts of (w / v), approximately 8% (w / v), approximately 8.5% (w / v), approximately 9% (w / v), approximately 9.5% (w / v), and approximately 10% (w / v).

[0078] In some embodiments, when used as a penetration enhancer in the compositions described herein, lactic acid is present in an amount of about 0.1% (w / v) to about 10% (w / v). In some embodiments, when used as a penetration enhancer in the compositions described herein, lactic acid is present at amounts of about 0.1% (w / v), about 0.2% (w / v), about 0.3% (w / v), about 0.4% (w / v), about 0.5% (w / v), about 0.6% (w / v), about 0.7% (w / v), about 0.8% (w / v), about 0.9% (w / v), about 1.0% (w / v), about 1.5% (w / v), about 2% (w / v), about 2.5% (w / v), about 3% (w / v), about 3.5% (w / v), about 4% (w / v), about 4.5% (w / v), about 5% (w / v), about 5.5% (w / v), about 6% (w / v), about 6.5% (w / v), about 7% (w / v), about 7.5% (w / v), or about 8%. It is present in amounts of approximately 8.5% (w / v), approximately 9% (w / v), approximately 9.5% (w / v), and approximately 10% (w / v).

[0079] In some embodiments, the compositions disclosed herein comprise a thickener or thickener. A thickener is added to the solution to provide the composition with varying degrees of viscosity and to stabilize films formed from the compositions described herein. In some embodiments, the thickeners described herein are selected from pharmaceutically acceptable hydrophilic polymers. Hydrophilic polymers include, but are not limited to, partially etherified cellulose derivatives, fully synthetic hydrophilic polymers, and natural gums. Partially etherified cellulose derivatives include, but are not limited to, carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, and methyl cellulose. Fully synthetic hydrophilic polymers include, but are not limited to, polyacrylates, polymethacrylates, polyhydroxyethyl methacrylates, polyhydroxypropyl methacrylates, polyhydroxypropyl methyl methacrylates, polyacrylonitrile, methylallyl methacrylate, polyethylene, polyoxyethylene, polyethylene glycol, polyethylene glycol-lactide, polyethylene glycol-diacrylate, polyvinylpyrrolidone, polyvinyl alcohol, poly(propyl methacrylamide), poly(propylene glycol fumarate-co-ethylene glycol), poloxamer, polyasparagine, (hydrazine-crosslinked) hyaluronic acid, and silicones. Natural gums include, but are not limited to, alginate, carrageenan, guar gum, gelatin, tragacanth gum, (amidated) pectin, xanthan gum, chitosan, collagen, agarose; mixtures thereof and further derivatives or copolymers, and / or other pharmaceutically or at least biologically acceptable polymers. In some embodiments, the thickener described herein comprises PEG 400. In some embodiments, the thickener described herein is propylene glycol. In some embodiments, the thickener described herein is selected from polyvinylpyrrolidone and its derivatives. In some embodiments, the thickener described herein is selected from polyurethane and its derivatives.

[0080] In some embodiments, the compositions described herein comprise a coloring substance. In some embodiments, the coloring substance described herein comprises a pigment, dye, colorant, or any combination thereof. In some embodiments, the coloring substance described herein is a pigment. Non-limiting examples of pigments in the compositions described herein include titanium dioxide, black iron oxide, D&C Black No. 2, FD&C Red No. 4, D&C Red No. 6, D&C Red No. 7, D&C Red No. 17, D&C Red No. 21, D&C Red No. 22, D&C Red No. 27, D&C Red No. 28, D&C Red No. 30, D&C Red No. 31, D&C Red No. 33, D&C Red No. 34, D&C Red No. 36, and D&C Red No. 36. C Red No. 40, FD&C Blue No. 1, D&C Orange No. 4, D&C Orange No. 5, D&C Orange No. 10, D&C Orange No. 11, D&C Blue No. 4, D&C Brown No. 1, FD&C Green No. 3, D&C Green No. 5, D&C Green No. 6, D&C Green No. 8, FD&C Yellow No. 5, FD&C Yellow No. 6, D&C Yellow No. 7, D&C Yellow No. 8, D&C Yellow No. 10, and D&C Yellow No. 11, and combinations thereof.

[0081] In some embodiments, the coloring substance described herein is present in an amount from about 0.05% (w / v) to about 0.2% (w / v). In some embodiments, the coloring substance described herein is present in an amount from about 0.05% (w / v), about 0.06% (w / v), about 0.07% (w / v), about 0.08% (w / v), about 0.09% (w / v), about 0.1% (w / v), about 0.15% (w / v) to about 0.2%. In some embodiments, the coloring substance described herein is present in an amount of about 0.1%.

[0082] This document provides a methyl film-forming composition comprising 0.01%-15% (w / v) of the active pharmaceutical ingredient (API) described herein, 5%-15% (w / v) of the film-forming polymer described herein, 0.5%-5% (w / v) of the plasticizer described herein, ethanol, and the non-volatile solvent described herein. This document also provides a methyl film-forming composition comprising 0.01%-15% (w / v) of the active pharmaceutical ingredient (API), 5%-15% (w / v) of the film-forming polymer described herein, 3%-15% (w / v) of the penetration enhancer described herein, 0.5%-5% (w / v) of the plasticizer described herein, ethanol, and the non-volatile solvent described herein. In some embodiments, the API is selected from antibacterial, antiviral, antifungal, anti-inflammatory, and antitumor substances. In some embodiments, the API comprises an antibacterial substance selected from penicillins, sulfonamides, streptozotocins, polypeptides, tetracyclines, doxycyclines, amoxicillin, carbapenems, cephalosporins, fluoroquinolones, glycopeptides and lipoglycopeptides, macrolides, monocyclic β-lactams, and any combination thereof. In some embodiments, the API comprises an antiviral substance described herein. In some embodiments, the API comprises an antifungal substance selected from ivermectin, tavaborone, ciclopirox, amorolfen, ruliconazole, terbinafine, miconazole, ketoconazole, itraconazole, fluconazole, econazole, oxiconazole, clotrimazole, naftifine, voriconazole, isaconazole, fenteconazole, tavaborone, amorolfen, anisofungin, caspofungin, micafungin, rezafungin, amphotericin B, terbinafine, and any combination thereof. In some embodiments, the API comprises an anti-inflammatory substance described herein, including JAK inhibitors, PDE4 inhibitors, corticosteroids, vitamin A, vitamin D3, anti-IL-17 agents, anti-IL-23 agents, anti-TNFα agents, anti-IL-4 agents, S1PR inhibitors, PI3Kδ inhibitors, or TYK2 inhibitors. In some embodiments, the API comprises an antitumor substance described herein, selected from JAK inhibitors, PDE4 inhibitors, corticosteroids, checkpoint inhibitors, anti-TNFα agents, anti-IL-7 agents, 5-fluorouracil (F-FU), and any combination thereof. In some embodiments, the film-forming polymer is polymethyl methacrylate or a cellulose derivative. In some embodiments, the film-forming polymer comprises Eudragit L100 and HPMC-AS-LF. In some embodiments, the penetration enhancer is an acid. In some embodiments, the penetration enhancer is lactic acid. In some embodiments, the plasticizer is PEG. In some embodiments, the PEG is PEG 6000. In some embodiments, the non-volatile solvent is water.In some embodiments, the composition further comprises a solubilizer. In some embodiments, the solubilizer is Transcutol, PEG400, or benzyl alcohol.

[0083] In some embodiments, the pharmaceutical compositions provided herein comprise an API in an amount from about 1.0 mg to about 1000 mg, including but not limited to about 1.0 mg, 1.5 mg, 2.5 mg, 3.0 mg, 4.0 mg, 5.0 mg, 6.0 mg, 6.5 mg, 7.0 mg, 7.5 mg, 8.0 mg, 8.5 mg, 9.0 mg, 9.5 mg, 10.0 mg, 10.5 mg, 11.0 mg, 12.0 mg, 12.5 mg, 13.0 mg, 13.5 mg, 14.0 mg, 14.5 mg, 15.0 mg, 15.5 mg, 16 mg, 16.5 mg, 17 mg, 17.5 mg, 18 mg, 18.5 mg, 19 mg, 19.5 mg, 20 mg, 20.5 mg, 21 mg, 21.5 mg, 22 mg, 22.5 mg, 23 mg, 23.5 mg, etc. mg, 24 mg, 24.5 mg, 25 mg, 25.5 mg, 26 mg, 26.5 mg, 27 mg, 27.5 mg, 28mg, 28.5 mg, 29 mg, 29.5 mg, 30 mg, 30.5 mg, 31 mg, 31.5 mg, 32 mg, 32.5 mg, 33 mg, 33.5mg, 36 mg, 36.5 mg, 37 mg 37.5 mg mg, 49 mg, 49.5 mg、50 mg、55 mg、60 mg、65 mg、70 mg、75mg、80 mg、85 mg、90 mg、95 mg、100 mg、105 mg、110 mg、115 mg、120 mg、125 mg、130 mg、135 mg、140 mg、145 mg、150 mg、155 mg、160 mg、165 mg、170 mg、175 mg、180 mg、185 mg、190 mg、200 mg、205 mg、210 mg、215 mg、220 mg、225 mg、230 mg、235 mg、240 mg、245 mg、250 mg、255 mg、260 mg、265 mg、270 mg、275 mg、280 mg、285 mg、290 mg、295 mg、300 mg、305 mg、310 mg、315 mg、320 mg、325 mg、326 mg、326.5 mg、327 mg、327.5 mg、328 mg、328.5 mg、329 mg、329.5 mg、330 mg、330.5 mg、331 mg、331.5 mg、332 mg、332.5 mg、333mg、333.5 mg、334 mg、334.5 mg、335 mg、335.5 mg、336 mg、336.5 mg、337 mg、337.5 mg、338 mg、338.5 mg、339 mg、339.5 mg、340 mg、340.5 mg、341 mg、341.5 mg、342 mg、342.5mg、343 mg、343.5 mg、344 mg、344.5 mg、345 mg、345.5 mg、346 mg、346.5 mg、347 mg、347.5 mg、348 mg、348.5 mg、349 mg、349.5 mg、350 mg、350.5 mg、351 mg、351.5 mg、352mg、352.5 mg、353 mg、353.5 mg、354 mg、354.5 mg、355 mg、355.5 mg、356 mg、356.5 mg、357 mg、357.5 mg、358 mg、358.5 mg、359 mg、359.5 mg、360 mg、360.5 mg、361 mg、361.5mg、362 mg、362.5 mg、363 mg、363.5 mg、364 mg、364.5 mg、365 mg、365.5 mg、366 mg、366.5 mg、367 mg、367.5 mg、368 mg、369.5 mg、370 mg、370.5 mg、371 mg、371.5 mg、372mg、372.5 mg、373 mg、373.5 mg、374 mg、374.5 mg、375 mg、375.5 mg、376 mg、376.5 mg、377 mg、377.5 mg、378 mg、378.5 mg、379 mg、379.5 mg、380 mg、380.5 mg、381 mg、381.5mg、382 mg、382.5 mg、383 mg、383.5 mg、384 mg、384.5 mg、385 mg、385.5 mg、386 mg、386.5 mg、387 mg、387.5 mg、388 mg、388.5 mg、389 mg、389.5 mg、390 mg、390.5 mg、391mg、391.5 mg、392 mg、392.5 mg、393 mg、393.5 mg、394 mg、394.5 mg、395 mg、395.5 mg、396 mg、396.5 mg、397 mg、397.5 mg、398 mg、398.5 mg、399 mg、399.5 mg, 400 mg, 405 mg, 410 mg, 415 mg, 420 mg, 425 mg, 430 mg, 435 mg, 440 mg, 445 mg, 450 mg, 455 mg, 460 mg, 465 mg, 470 mg, 475 mg, 480 mg, 485 mg, 490 mg, 495 mg, 500 mg, 505 mg, 510 mg, 515 mg, 520 mg, 525 mg, 530 mg, 535 mg, 540 mg, 545 mg, 550 mg, 555 mg, 560 mg, 565 mg, 570 mg, 575 mg, 580 mg, 585 mg, 590 mg, 595 mg, 600 mg, 605 mg, 610 mg, 615 mg, 620 mg, 625 mg, 630 mg, 635 mg, 640 mg, 645 mg, 650 mg, 655 mg, 660 mg, 665 mg, 675 mg, 680 mg, 685 mg, 690 mg, 695 mg, 700 mg, 705 mg, 710 mg, 715 mg, 720 mg, 725 mg, 730 mg, 735 mg, 740 mg, 745 mg, 750 mg, 755 mg, 760 mg, 765 mg, 770 mg, 775 mg, 780 mg, 785 mg, 790 mg, 795 mg, 800 mg, 805 mg, 810 mg, 815 mg, 820 mg, 825 mg, 830 mg, 835 mg, 840 mg, 845 mg, 850 mg, 855 mg, 860 mg, 865 mg, 870 mg, 875 mg, 880 mg, 885 mg, 890 mg, 895 mg, 900 mg, 905 mg, 910 mg, 915 mg, 920 mg, 925 mg, 930 mg, 935 mg, 940 mg, 945 mg, 950 mg, 955 mg, 960 mg, 965 mg, 970 mg, 975 mg, 980 mg, 985 mg, 990 mg, 995 mg or 1000 mg.

[0084] In some embodiments, the compositions provided herein comprise an API in an amount of about 0.01% (w / v) to about 20% (w / v). In some embodiments, the pharmaceutical compositions provided herein comprise an API in amounts of about 0.01% (w / v), about 0.02% (w / v), about 0.03% (w / v), about 0.04% (w / v), about 0.05% (w / v), about 0.06% (w / v), about 0.07% (w / v), about 0.08% (w / v), about 0.09% (w / v), about 0.1% (w / v), about 0.2% (w / v), about 0.3% (w / v), about 0.4% (w / v), about 0.5% (w / v), about 0.6% (w / v), about 0.7% (w / v), about 0.8% (w / v), about 0.9% (w / v), about 1.0% (w / v), about 1.5% (w / v), about 2% (w / v), about 2.5% (w / v), or about 3%. (w / v), approximately 3.5% (w / v), approximately 4% (w / v), approximately 4.5% (w / v), approximately 5% (w / v), approximately 5.5% (w / v), approximately 6% (w / v), approximately 6.5% (w / v), approximately 7% (w / v), approximately 7.5% (w / v), approximately 8% (w / v), approximately 8.5% (w / v), approximately 9% (w / v), approximately 9.5% (w / v), approximately 10% (w / v), approximately 11% (w / v), approximately 12% (w / v), approximately 13% (w / v), approximately 14% (w / v), approximately 15% (w / v), approximately 16% (w / v), approximately 17% (w / v), approximately 18% (w / v), approximately 19% (w / v), or approximately 20% (w / v).In some embodiments, the compositions provided herein comprise an API comprising the following amounts of terbinafine: 0.01% (w / v), about 0.02% (w / v), about 0.03% (w / v), about 0.04% (w / v), about 0.05% (w / v), about 0.06% (w / v), about 0.07% (w / v), about 0.08% (w / v), about 0.09% (w / v), about 0.1% (w / v), about 0.2% (w / v), about 0.3% (w / v), about 0.4% (w / v), about 0.5% (w / v), about 0.6% (w / v), about 0.7% (w / v), about 0.8% (w / v), about 0.9% (w / v), about 1.0% (w / v), about 1.5% (w / v), about 2% (w / v), about 2.5%. (w / v), about 3% (w / v), about 3.5% (w / v), about 4% (w / v), about 4.5% (w / v), about 5% (w / v), about 5.5% (w / v), about 6% (w / v), about 6.5% (w / v), about 7% (w / v), about 7.5% (w / v), about 8% (w / v), about 8.5% (w / v), about 9% (w / v), about 9.5% (w / v), about 10% (w / v), about 11% (w / v), about 12% (w / v), about 13% (w / v), about 14% (w / v), or about 15% (w / v).In some embodiments, the compositions provided herein comprise an API comprising the following amounts of iefluconazole: 0.01% (w / v), about 0.02% (w / v), about 0.03% (w / v), about 0.04% (w / v), about 0.05% (w / v), about 0.06% (w / v), about 0.07% (w / v), about 0.08% (w / v), about 0.09% (w / v), about 0.1% (w / v), about 0.2% (w / v), about 0.3% (w / v), about 0.4% (w / v), about 0.5% (w / v), about 0.6% (w / v), about 0.7% (w / v), about 0.8% (w / v), about 0.9% (w / v), about 1.0% (w / v), about 1.5% (w / v), about 2% (w / v), about 2.5%. (w / v), about 3% (w / v), about 3.5% (w / v), about 4% (w / v), about 4.5% (w / v), about 5% (w / v), about 5.5% (w / v), about 6% (w / v), about 6.5% (w / v), about 7% (w / v), about 7.5% (w / v), about 8% (w / v), about 8.5% (w / v), about 9% (w / v), about 9.5% (w / v), about 10% (w / v), about 11% (w / v), about 12% (w / v), about 13% (w / v), about 14% (w / v), or about 15% (w / v).

[0085] In some embodiments, the film-forming polymer described herein comprises Eudragit L100 and HPMC-AS. In some embodiments, the composition described herein comprises about 1.0 mg to about 1000 mg of Eudragit L100 and about 1.0 mg to about 1000 mg of HPMC-AS. In some embodiments, the pharmaceutical compositions described herein comprise Eudragit L100 in amounts from about 1.0 mg to about 1000 mg, including but not limited to about 1.0 mg, 1.5 mg, 2.5 mg, 3.0 mg, 4.0 mg, 5.0 mg, 6.0 mg, 6.5 mg, 7.0 mg, 7.5 mg, 8.0 mg, 8.5 mg, 9.0 mg, 9.5 mg, 10.0 mg, 10.5 mg, 11.0 mg, 12.0 mg, 12.5 mg, 13.0 mg, 13.5 mg, 14.0 mg, 14.5 mg, 15.0 mg, 15.5 mg, 16 mg, 16.5 mg, 17 mg, 17.5 mg, 18 mg, 18.5 mg, 19 mg, 19.5 mg, 20 mg, 20.5 mg, 21 mg, 21.5 mg, 22 mg, 22.5 mg, 23 ... mg, 23.5 mg, 24 mg, 24.5 mg, 25 mg, 25.5mg, 26 mg, 26.5 mg, 27 mg, 27.5 mg, 28 mg, 28.5 mg, 29 mg, 29.5 mg, 30 mg, 30.5 mg, 31mg, 31.5 mg, 32 mg, 32.5 mg, 33 mg, 33.5 mg, 36 mg, 36.5 mg, 37 mg, 37.5 mg, 38 mg, 38.5 mg, 39 mg, 39.5 mg, 40 mg, 40.5 mg, 41 mg, 41.5 mg, 42 mg, 42.5 mg, 43 mg, 43.5 mg, 44mg, 44.5 mg, 45 mg, 45.5 mg, 46 mg, 46.5 mg, 47 mg, 47.5 mg, 48 mg, 48.5 mg, 49 mg, 49.5mg、50 mg、55 mg、60 mg、65 mg、70 mg、75 mg、80 mg、85 mg、90 mg、95 mg、100 mg、105 mg、110 mg、115 mg、120 mg、125 mg、130 mg、135 mg、140 mg、145 mg、150 mg、155 mg、160 mg、165 mg、170 mg、175 mg、180 mg、185 mg、190 mg、200 mg、205 mg、210 mg、215 mg、220 mg、225 mg、230 mg、235 mg、240 mg、245 mg、250 mg、255 mg、260 mg、265 mg、270 mg、275 mg、280 mg、285 mg、290 mg、295 mg、300 mg、305 mg、310 mg、315 mg、320 mg、325 mg、326 mg、326.5 mg、327 mg、327.5 mg、328 mg、328.5 mg、329 mg、329.5 mg、330 mg、330.5 mg、331mg、331.5 mg、332 mg、332.5 mg、333 mg、333.5 mg、334 mg、334.5 mg、335 mg、335.5 mg、336 mg、336.5 mg、337 mg、337.5 mg、338 mg、338.5 mg、339 mg、339.5 mg、340 mg、340.5mg、341 mg、341.5 mg、342 mg、342.5 mg、343 mg、343.5 mg、344 mg、344.5 mg、345 mg、345.5 mg、346 mg、346.5 mg、347 mg、347.5 mg、348 mg、348.5 mg、349 mg、349.5 mg、350mg、350.5 mg、351 mg、351.5 mg、352 mg、352.5 mg、353 mg、353.5 mg、354 mg、354.5 mg、355 mg、355.5 mg、356 mg、356.5 mg、357 mg、357.5 mg、358 mg、358.5 mg、359 mg、359.5mg、360 mg、360.5 mg、361 mg、361.5 mg、362 mg、362.5 mg、363 mg、363.5 mg、364 mg、364.5 mg、365 mg、365.5 mg、366 mg、366.5 mg、367 mg、367.5 mg、368 mg、369.5 mg、370mg、370.5 mg、371 mg、371.5 mg、372 mg、372.5 mg、373 mg、373.5 mg、374 mg、374.5 mg、375 mg、375.5 mg、376 mg、376.5 mg、377 mg、377.5 mg、378 mg、378.5 mg、379 mg、379.5mg、380 mg、380.5 mg、381 mg、381.5 mg、382 mg、382.5 mg、383 mg、383.5 mg、384 mg、384.5 mg、385 mg、385.5 mg、386 mg、386.5 mg、387 mg、387.5 mg、388 mg、388.5 mg、389mg、389.5 mg、390 mg、390.5 mg、391 mg、391.5 mg、392 mg、392.5 mg、393 mg、393.5 mg、394 mg、394.5 mg、395 mg、395.5 mg、396 mg、396.5 mg、397 mg、397.5 mg、398 mg、398.5mg、399 mg、399.5 mg, 400 mg, 405 mg, 410 mg, 415 mg, 420 mg, 425 mg, 430 mg, 435 mg, 440 mg, 445 mg, 450 mg, 455 mg, 460 mg, 465 mg, 470 mg, 475 mg, 480 mg, 485 mg, 490 mg, 495 mg, 500 mg, 505 mg, 510 mg, 515 mg, 520 mg, 525 mg, 530 mg, 535 mg, 540 mg, 545 mg, 550 mg, 555 mg, 560 mg, 565 mg, 570 mg, 575 mg, 580 mg, 585 mg, 590 mg, 595 mg, 600 mg, 605 mg, 610 mg, 615 mg, 620 mg, 625 mg, 630 mg, 635 mg, 640 mg, 645 mg, 650 mg, 655 mg, 660 mg, 665 mg, 675 mg, 680 mg, 685 mg, 690 mg, 695 mg, 700 mg, 705 mg, 710 mg, 715 mg, 720 mg, 725 mg, 730 mg, 735 mg, 740 mg, 745 mg, 750 mg, 755 mg, 760 mg, 765 mg, 770 mg, 775 mg, 780 mg, 785 mg, 790 mg, 795 mg, 800 mg, 805 mg, 810 mg, 815 mg, 820 mg, 825 mg, 830 mg, 835 mg, 840 mg, 845 mg, 850 mg, 855 mg, 860 mg, 865 mg, 870 mg, 875 mg, 880 mg, 885 mg, 890 mg, 895 mg, 900 mg, 905 mg, 910 mg, 915 mg, 920 mg, 925 mg, 930 mg, 935 mg, 940 mg, 945 mg, 950 mg, 955 mg, 960 mg, 965 mg, 970 mg, 975 mg, 980 mg, 985 mg, 990 mg, 995 mg or 1000 mg.

[0086] In some embodiments, the compositions described herein comprise HPMC-AS in an amount from about 1.0 mg to about 1000 mg, including but not limited to about 1.0 mg, 1.5 mg, 2.5 mg, 3.0 mg, 4.0 mg, 5.0 mg, 6.0 mg, 6.5 mg, 7.0 mg, 7.5 mg, 8.0 mg, 8.5 mg, 9.0 mg, 9.5 mg, 10.0, 10.5 mg, 11.0 mg, 12.0 mg, 12.5 mg, 13.0 mg, 13.5 mg, 14.0 mg, 14.5 mg, 15.0 mg, 15.5 mg, 16 mg, 16.5 mg, 17 mg, 17.5 mg, 18 mg, 18.5 mg, 19 mg, 19.5 mg, 20 mg, 20.5 mg, 21 mg, 21.5 mg, 22 mg, 22.5 mg, 23 mg, 23.5 mg. mg,24 mg,24.5 mg,25 mg,25.5 mg,26 mg,26.5 mg,27 mg,27.5 mg,28 mg,28.5 mg,29 mg,29.5 mg,30 mg,30.5 mg,31 mg,31.5 mg,32 mg,32.5 mg,33 mg,33.5 mg,36 mg,36.5 mg mg, 37.5 mg, 38 mg, 38.5 mg, 39 mg, 39.5 mg, 40 mg, 40.5 mg, 41 mg, 41.5 mg, 42 mg, 42.5 mg, 43 mg, 43.5 mg, 44 mg, 44.5 mg, 45 mg, 45.5 mg, 46 mg, 46.5 mg, 47mg, 47.5 mg, 48 mg, 48.5 mg, 49 mg, 49.5 mg、50 mg、55 mg、60 mg、65 mg、70 mg、75 mg、80mg、85 mg、90 mg、95 mg、100 mg、105 mg、110 mg、115 mg、120 mg、125 mg、130 mg、135 mg、140 mg、145 mg、150 mg、155 mg、160 mg、165 mg、170 mg、175 mg、180 mg、185 mg、190 mg、200 mg、205 mg、210 mg、215 mg、220 mg、225 mg、230 mg、235 mg、240 mg、245 mg、250 mg、255 mg、260 mg、265 mg、270 mg、275 mg、280 mg、285 mg、290 mg、295 mg、300 mg、305 mg、310 mg、315 mg、320 mg、325 mg、326 mg、326.5 mg、327 mg、327.5 mg、328 mg、328.5 mg、329 mg、329.5 mg、330 mg、330.5 mg、331 mg、331.5 mg、332 mg、332.5 mg、333 mg、333.5mg、334 mg、334.5 mg、335 mg、335.5 mg、336 mg、336.5 mg、337 mg、337.5 mg、338 mg、338.5 mg、339 mg、339.5 mg、340 mg、340.5 mg、341 mg、341.5 mg、342 mg、342.5 mg、343mg、343.5 mg、344 mg、344.5 mg、345 mg、345.5 mg、346 mg、346.5 mg、347 mg、347.5 mg、348 mg、348.5 mg、349 mg、349.5 mg、350 mg、350.5 mg、351 mg、351.5 mg、352 mg、352.5mg、353 mg、353.5 mg、354 mg、354.5 mg、355 mg、355.5 mg、356 mg、356.5 mg、357 mg、357.5 mg、358 mg、358.5 mg、359 mg、359.5 mg、360 mg、360.5 mg、361 mg、361.5 mg、362mg、362.5 mg、363 mg、363.5 mg、364 mg、364.5 mg、365 mg、365.5 mg、366 mg、366.5 mg、367 mg、367.5 mg、368 mg、369.5 mg、370 mg、370.5 mg、371 mg、371.5 mg、372 mg、372.5mg、373 mg、373.5 mg、374 mg、374.5 mg、375 mg、375.5 mg、376 mg、376.5 mg、377 mg、377.5 mg、378 mg、378.5 mg、379 mg、379.5 mg、380 mg、380.5 mg、381 mg、381.5 mg、382mg、382.5 mg、383 mg、383.5 mg、384 mg、384.5 mg、385 mg、385.5 mg、386 mg、386.5 mg、387 mg、387.5 mg、388 mg、388.5 mg、389 mg、389.5 mg、390 mg、390.5 mg、391 mg、391.5mg、392 mg、392.5 mg、393 mg、393.5 mg、394 mg、394.5 mg、395 mg、395.5 mg、396 mg、396.5 mg、397 mg、397.5 mg、398 mg、398.5 mg、399 mg、399.5 mg, 400 mg, 405 mg, 410 mg, 415 mg, 420 mg, 425 mg, 430 mg, 435 mg, 440 mg, 445 mg, 450 mg, 455 mg, 460 mg, 465 mg, 470 mg, 475 mg, 480 mg, 485 mg, 490 mg, 495 mg, 500 mg, 505 mg, 510 mg, 515 mg, 520 mg, 525 mg, 530 mg, 535 mg, 540 mg, 545 mg, 550 mg, 555 mg, 560 mg, 565 mg, 570 mg, 575 mg, 580 mg, 585 mg, 590 mg, 595 mg, 600 mg, 605 mg, 610 mg, 615 mg, 620 mg, 625 mg, 630mg, 635 640 mg mg, 760 mg, 765 mg, 770 mg, 775 mg, 780 mg, 785 mg, 790 mg, 795 mg, 800mg, 805 mg, 810 mg, 815 mg, 820 mg, 825 mg, 830 mg, 835 mg, 840 mg, 845 mg, 850 mg, 855mg, 860 mg, 865 mg, 870 mg, 875 mg, 880 mg, 885 mg, 890 mg, 895 mg, 900 mg, 905 mg, 910 mg, 915 mg, 920 mg, 925 mg, 930 mg, 935 mg, 940 mg, 945 mg, 950 mg, 955 mg, 960 mg, 965 mg, 970 mg, 975 mg, 980 mg, 985 mg, 990 mg, 995 mg, or 1000 mg. In some embodiments, the compositions described herein comprise about 5% (w / v) to about 15% (w / v) of Eudragit L100 and about 0.5% (w / v) to about 4% (w / v) of HPMC-AS. In some embodiments, the compositions described herein comprise Eudragit L100 in amounts of about 5% (w / v), about 5.1% (w / v), about 5.2% (w / v), or about 5.3% (w / v), approximately 5.4% (w / v), approximately 5.5% (w / v), approximately 5.6% (w / v), approximately 5.7% (w / v), approximately 5.8% (w / v), approximately 5.9% (w / v), approximately 6% (w / v), approximately 6.1% (w / v), approximately 6.2% (w / v), approximately 6.3% (w / v), approximately 6.4% (w / v), approximately 6.5% (w / v), approximately 6.6% (w / v), approximately 6.7% (w / v), approximately 6.8% (w / v), approximately 6.9% (w / v), approximately 7% (w / v), approximately 7.1% (w / v), approximately 7.2% (w / v), approximately 7.3% (w / v), approximately 7.4% (w / v), approximately 7.5% (w / v), approximately 7.6% (w / v), approximately 7.7% (w / v), approximately 7.8% (w / v), approximately 7.9% (w / v), approximately 8% (w / v), approximately 8.1% (w / v), approximately 8.2% (w / v), approximately 8.3% (w / v), approximately 8.4% (w / v), approximately 8.5% (w / v), approximately 8.6% (w / v), approximately 8.7% (w / v), approximately 8.8% (w / v), approximately 8.9% (w / v), approximately 9% (w / v), approximately 9.1% (w / v), approximately 9.2% (w / v), approximately 9.3% (w / v), approximately 9.4% (w / v), approximately 9.5% (w / v), approximately 9.6% (w / v), approximately 9.7% (w / v), approximately 9.8% (w / v), approximately 9.9% (w / v), approximately 10% (w / v), approximately 10.1% (w / v), approximately 10.2% (w / v), approximately 10.3% (w / v), approximately 10.4% (w / v), approximately 10.5% (w / v), approximately 10.6% (w / v), approximately 10.7% (w / v), approximately 10.8% (w / v), approximately 10.9% (w / v), approximately 11% (w / v), approximately 11.1% (w / v), approximately 11.2% (w / v), approximately 11.3% (w / v), approximately 11.4% (w / v), approximately 11.5% (w / v), approximately 11.6% (w / v), approximately 11.7% (w / v), approximately 11.8% (w / v), approximately 11.9% (w / v), approximately 12% (w / v), approximately 12.1% (w / v), approximately 12.2% (w / v), approximately 12.3% (w / v), approximately 12.4% (w / v), approximately 12.5% ​​(w / v), approximately 12.6% (w / v), approximately 12.7% (w / v), approximately 12.8% (w / v), approximately 12.9% (w / v), approximately 13% (w / v), 13.1% (w / v), 13.2% (w / v), 13.3% (w / v), 13.4% (w / v), 13.5% (w / v), 13.6% (w / v), 13.7% (w / v), 13.8% (w / v), 13.9% (w / v), about 14% (w / v), 14.1% (w / v), 14.2% (w / v), 14.3% (w / v), 14.4% (w / v), 14.5% (w / v), 14.6% (w / v), 14.7% (w / v), 14.8% (w / v), 14.9% (w / v) or about 15% (w / v). In some embodiments, the compositions described herein comprise HPMC-AS in amounts of about 0.1% (w / v), about 0.2% (w / v), about 0.3% (w / v), about 0.4% (w / v), about 0.5% (w / v), about 0.6% (w / v), about 0.7% (w / v), about 0.8% (w / v), about 0.9% (w / v), about 1.0% (w / v), about 1.5% (w / v), about 1.6% (w / v), about 1.7% (w / v), about 1.8% (w / v), about 1.9% (w / v), about 2% (w / v), about 2.1% (w / v), about 2.2% (w / v), about 2.3% (w / v), about 2.4% (w / v), about 2.5% (w / v), about 2.6% (w / v), and about 2.7%. (w / v), approximately 2.8% (w / v), approximately 2.9% (w / v), approximately 3% (w / v), approximately 3.1% (w / v), approximately 3.2% (w / v), approximately 3.3% (w / v), approximately 3.4% (w / v), approximately 3.5% (w / v), approximately 3.6% (w / v), approximately 3.7% (w / v), approximately 3.8% (w / v), approximately 3.9% (w / v), or approximately 4% (w / v).

[0087] In some embodiments, the compositions described herein comprise about 10% (w / v) of Eudragit L100 and the following amounts of HPMC-AS: about 0.1% (w / v) to about 1.0% (w / v), about 0.2% (w / v) to about 1.2% (w / v), about 0.3% (w / v) to about 1.3% (w / v), about 0.4% (w / v) to about 1.4% (w / v), about 0.5% (w / v) to about 1.5% (w / v), about 0.6% (w / v) to about 1.6% (w / v), about 0.7% (w / v) to about 1.7% (w / v), about 0.8% (w / v) to about 1.8% (w / v), about 0.9% (w / v) to about 2.9% (w / v), about 1.0% (w / v) to about 2.0% (w / v), about 1.5% (w / v). (w / v) to about 2.5% (w / v), about 2% (w / v) to about 3% (w / v), about 2.5% (w / v) to about 3.5% (w / v) or about 3% (w / v) to about 4% (w / v).

[0088] In some embodiments, the compositions described herein comprise about 5% (w / v) of Eudragit L100 and the following amounts of HPMC-AS: about 0.1% (w / v), about 0.2% (w / v), about 0.3% (w / v), about 0.4% (w / v), about 0.5% (w / v), about 0.6% (w / v), about 0.7% (w / v), about 0.8% (w / v), about 0.9% (w / v), about 1.0% (w / v), about 1.5% (w / v), about 1.6% (w / v), about 1.7% (w / v), about 1.8% (w / v), about 1.9% (w / v), about 2% (w / v), about 2.1% (w / v), about 2.2% (w / v), about 2.3% (w / v), about 2.4% (w / v), about 2.5%. (w / v), about 2.6% (w / v), about 2.7% (w / v), about 2.8% (w / v), about 2.9% (w / v), about 3% (w / v), about 3.1% (w / v), about 3.2% (w / v), about 3.3% (w / v), about 3.4% (w / v), about 3.5% (w / v), about 3.6% (w / v), about 3.7% (w / v), about 3.8% (w / v), about 3.9% (w / v), or about 4% (w / v). In some embodiments, the compositions described herein comprise about 10% (w / v) of Eudragit L100 and about 0.5% (w / v) to about 1.0% (w / v) of HPMC-AS.

[0089] In some embodiments, the compositions provided herein comprise a plasticizer in an amount from about 1.0 mg to about 1000 mg, including but not limited to about 1.0 mg, 1.5 mg, 2.5 mg, 3.0 mg, 4.0 mg, 5.0 mg, 6.0 mg, 6.5 mg, 7.0 mg, 7.5 mg, 8.0 mg, 8.5 mg, 9.0 mg, 9.5 mg, 10.0 mg, 10.5 mg, 11.0 mg, 12.0 mg, 12.5 mg, 13.0 mg, 13.5 mg, 14.0 mg, 14.5 mg, 15.0 mg, 15.5 mg, 16 mg, 16.5 mg, 17 mg, 17.5 mg, 18 mg, 18.5 mg, 19 mg, 19.5 mg, 20 mg, 20.5 mg, 21 mg, 21.5 mg, 22 mg, 22.5 mg, 23 mg, 23.5 mg. mg, 24 mg, 24.5 mg, 25 mg, 25.5 mg, 26 mg, 26.5 mg, 27 mg, 27.5 mg, 28mg, 28.5 mg, 29 mg, 29.5 mg, 30 mg, 30.5 mg, 31 mg, 31.5 mg, 32 mg, 32.5 mg, 33 mg, 33.5mg, 36 mg, 36.5 mg, 37 mg 37.5 mg mg, 49 mg, 49.5 mg、50 mg、55 mg、60 mg、65 mg、70 mg、75mg、80 mg、85 mg、90 mg、95 mg、100 mg、105 mg、110 mg、115 mg、120 mg、125 mg、130 mg、135 mg、140 mg、145 mg、150 mg、155 mg、160 mg、165 mg、170 mg、175 mg、180 mg、185 mg、190 mg、200 mg、205 mg、210 mg、215 mg、220 mg、225 mg、230 mg、235 mg、240 mg、245 mg、250 mg、255 mg、260 mg、265 mg、270 mg、275 mg、280 mg、285 mg、290 mg、295 mg、300 mg、305 mg、310 mg、315 mg、320 mg、325 mg、326 mg、326.5 mg、327 mg、327.5 mg、328 mg、328.5 mg、329 mg、329.5 mg、330 mg、330.5 mg、331 mg、331.5 mg、332 mg、332.5 mg、333mg、333.5 mg、334 mg、334.5 mg、335 mg、335.5 mg、336 mg、336.5 mg、337 mg、337.5 mg、338 mg、338.5 mg、339 mg、339.5 mg、340 mg、340.5 mg、341 mg、341.5 mg、342 mg、342.5mg、343 mg、343.5 mg、344 mg、344.5 mg、345 mg、345.5 mg、346 mg、346.5 mg、347 mg、347.5 mg、348 mg、348.5 mg、349 mg、349.5 mg、350 mg、350.5 mg、351 mg、351.5 mg、352mg、352.5 mg、353 mg、353.5 mg、354 mg、354.5 mg、355 mg、355.5 mg、356 mg、356.5 mg、357 mg、357.5 mg、358 mg、358.5 mg、359 mg、359.5 mg、360 mg、360.5 mg、361 mg、361.5mg、362 mg、362.5 mg、363 mg、363.5 mg、364 mg、364.5 mg、365 mg、365.5 mg、366 mg、366.5 mg、367 mg、367.5 mg、368 mg、369.5 mg、370 mg、370.5 mg、371 mg、371.5 mg、372mg、372.5 mg、373 mg、373.5 mg、374 mg、374.5 mg、375 mg、375.5 mg、376 mg、376.5 mg、377 mg、377.5 mg、378 mg、378.5 mg、379 mg、379.5 mg、380 mg、380.5 mg、381 mg、381.5mg、382 mg、382.5 mg、383 mg、383.5 mg、384 mg、384.5 mg、385 mg、385.5 mg、386 mg、386.5 mg、387 mg、387.5 mg、388 mg、388.5 mg、389 mg、389.5 mg、390 mg、390.5 mg、391mg、391.5 mg、392 mg、392.5 mg、393 mg、393.5 mg、394 mg、394.5 mg、395 mg、395.5 mg、396 mg、396.5 mg、397 mg、397.5 mg、398 mg、398.5 mg、399 mg、399.5 mg, 400 mg, 405 mg, 410 mg, 415 mg, 420 mg, 425 mg, 430 mg, 435 mg, 440 mg, 445 mg, 450 mg, 455 mg, 460 mg, 465 mg, 470 mg, 475 mg, 480 mg, 485 mg, 490 mg, 495 mg, 500 mg, 505 mg, 510 mg, 515 mg, 520 mg, 525 mg, 530 mg, 535 mg, 540 mg, 545 mg, 550 mg, 555 mg, 560 mg, 565 mg, 570 mg, 575 mg, 580 mg, 585 mg, 590 mg, 595 mg, 600 mg, 605 mg, 610 mg, 615 mg, 620 mg, 625 mg, 630 mg, 635 mg, 640 mg, 645 mg, 650 mg, 655 mg, 660 mg, 665 mg, 675 mg, 680 mg, 685 mg, 690 mg, 695 mg, 700 mg, 705 mg, 710 mg, 715 mg, 720 mg, 725 mg, 730 mg, 735 mg, 740 mg, 745 mg, 750 mg, 755 mg, 760 mg, 765 mg, 770 mg, 775 mg, 780 mg, 785 mg, 790 mg, 795 mg, 800 mg, 805 mg, 810 mg, 815 mg, 820 mg, 825 mg, 830 mg, 835 mg, 840 mg, 845 mg, 850 mg, 855 mg, 860 mg, 865 mg, 870 mg, 875 mg, 880 mg, 885 mg, 890 mg, 895 mg, 900 mg, 905 mg, 910 mg, 915 mg, 920 mg, 925 mg, 930 mg, 935 mg, 940 mg, 945 mg, 950 mg, 955 mg, 960 mg, 965 mg, 970 mg, 975 mg, 980 mg, 985 mg, 990 mg, 995 mg or 1000 mg.

[0090] In some embodiments, the compositions provided herein contain a plasticizer in an amount of about 0.1% (w / v) to about 5% (w / v). In some embodiments, the compositions provided herein comprise a plasticizer in amounts of about 0.1% (w / v) to about 1.0% (w / v), about 0.2% (w / v) to about 1.2% (w / v), about 0.3% (w / v) to about 1.3% (w / v), about 0.4% (w / v) to about 1.4% (w / v), about 0.5% (w / v) to about 1.5% (w / v), about 0.6% (w / v) to about 1.6% (w / v), about 0.7% (w / v) to about 1.7% (w / v), about 0.8% (w / v) to about 1.8% (w / v), about 0.9% (w / v) to about 2.9% (w / v), about 1.0% (w / v) to about 2.0% (w / v), about 1.5% (w / v) to about 2.5% (w / v), or about 2% (w / v) to about 3%. (w / v), about 2.5% (w / v) to about 3.5% (w / v), about 3% (w / v) to about 4% (w / v), about 3.5% (w / v) to about 4.5% (w / v), about 4% (w / v) to about 5% (w / v). In some embodiments, the compositions provided herein contain a plasticizer in an amount of about 2% (w / v) to about 4% (w / v). In some embodiments, the plasticizer is PEG 6000. In some embodiments, the compositions provided herein contain PEG 6000 in an amount of about 2% (w / v) to about 4% (w / v).

[0091] In some embodiments, the compositions provided herein further comprise the solubilizers described herein. In some embodiments, the solubilizers described herein are transcutol or propylene glycol. In some embodiments, the solubilizers described herein are propylene glycol. In some embodiments, the solubilizers described herein are transcutol.

[0092] In some embodiments, the compositions described herein contain a solubilizer in an amount from about 1.0 mg to about 1000 mg, including but not limited to about 1.0 mg, 1.5 mg, 2.5 mg, 3.0 mg, 4.0 mg, 5.0 mg, 6.0 mg, 6.5 mg, 7.0 mg, 7.5 mg, 8.0 mg, 8.5 mg, 9.0 mg, 9.5 mg, 10.0 mg, 10.5 mg, 11.0 mg, 12.0 mg, 12.5 mg, 13.0 mg, 13.5 mg, 14.0 mg, 14.5 mg, 15.0 mg, 15.5 mg, 16 mg, 16.5 mg, 17 mg, 17.5 mg, 18 mg, 18.5 mg, 19 mg, 19.5 mg, 20 mg, 20.5 mg, 21 mg, 21.5 mg, 22 mg, 22.5 mg, 23 mg, 23.5 mg. mg, 24 mg, 24.5 mg, 25 mg, 25.5 mg, 26 mg, 26.5 mg, 27 mg, 27.5 mg, 28mg, 28.5 mg, 29 mg, 29.5 mg, 30 mg, 30.5 mg, 31 mg, 31.5 mg, 32 mg, 32.5 mg, 33 mg, 33.5mg, 36 mg, 36.5 mg, 37 mg 37.5 mg mg, 49 mg, 49.5 mg、50 mg、55 mg、60 mg、65 mg、70 mg、75mg、80 mg、85 mg、90 mg、95 mg、100 mg、105 mg、110 mg、115 mg、120 mg、125 mg、130 mg、135 mg、140 mg、145 mg、150 mg、155 mg、160 mg、165 mg、170 mg、175 mg、180 mg、185 mg、190 mg、200 mg、205 mg、210 mg、215 mg、220 mg、225 mg、230 mg、235 mg、240 mg、245 mg、250 mg、255 mg、260 mg、265 mg、270 mg、275 mg、280 mg、285 mg、290 mg、295 mg、300 mg、305 mg、310 mg、315 mg、320 mg、325 mg、326 mg、326.5 mg、327 mg、327.5 mg、328 mg、328.5 mg、329 mg、329.5 mg、330 mg、330.5 mg、331 mg、331.5 mg、332 mg、332.5 mg、333mg、333.5 mg、334 mg、334.5 mg、335 mg、335.5 mg、336 mg、336.5 mg、337 mg、337.5 mg、338 mg、338.5 mg、339 mg、339.5 mg、340 mg、340.5 mg、341 mg、341.5 mg、342 mg、342.5mg、343 mg、343.5 mg、344 mg、344.5 mg、345 mg、345.5 mg、346 mg、346.5 mg、347 mg、347.5 mg、348 mg、348.5 mg、349 mg、349.5 mg、350 mg、350.5 mg、351 mg、351.5 mg、352mg、352.5 mg、353 mg、353.5 mg、354 mg、354.5 mg、355 mg、355.5 mg、356 mg、356.5 mg、357 mg、357.5 mg、358 mg、358.5 mg、359 mg、359.5 mg、360 mg、360.5 mg、361 mg、361.5mg、362 mg、362.5 mg、363 mg、363.5 mg、364 mg、364.5 mg、365 mg、365.5 mg、366 mg、366.5 mg、367 mg、367.5 mg、368 mg、369.5 mg、370 mg、370.5 mg、371 mg、371.5 mg、372mg、372.5 mg、373 mg、373.5 mg、374 mg、374.5 mg、375 mg、375.5 mg、376 mg、376.5 mg、377 mg、377.5 mg、378 mg、378.5 mg、379 mg、379.5 mg、380 mg、380.5 mg、381 mg、381.5mg、382 mg、382.5 mg、383 mg、383.5 mg、384 mg、384.5 mg、385 mg、385.5 mg、386 mg、386.5 mg、387 mg、387.5 mg、388 mg、388.5 mg、389 mg、389.5 mg、390 mg、390.5 mg、391mg、391.5 mg、392 mg、392.5 mg、393 mg、393.5 mg、394 mg、394.5 mg、395 mg、395.5 mg、396 mg、396.5 mg、397 mg、397.5 mg、398 mg、398.5 mg、399 mg、399.5 mg, 400 mg, 405 mg, 410 mg, 415 mg, 420 mg, 425 mg, 430 mg, 435 mg, 440 mg, 445 mg, 450 mg, 455 mg, 460 mg, 465 mg, 470 mg, 475 mg, 480 mg, 485 mg, 490 mg, 495 mg, 500 mg, 505 mg, 510 mg, 515 mg, 520 mg, 525 mg, 530 mg, 535 mg, 540 mg, 545 mg, 550 mg, 555 mg, 560 mg, 565 mg, 570 mg, 575 mg, 580 mg, 585 mg, 590 mg, 595 mg, 600 mg, 605 mg, 610 mg, 615 mg, 620 mg, 625 mg, 630 mg, 635 mg, 640 mg, 645 mg, 650 mg, 655 mg, 660 mg, 665 mg, 675 mg, 680 mg, 685 mg, 690 mg, 695 mg, 700 mg, 705 mg, 710 mg, 715 mg, 720 mg, 725 mg, 730 mg, 735 mg, 740 mg, 745 mg, 750 mg, 755 mg, 760 mg, 765 mg, 770 mg, 775 mg, 780 mg, 785 mg, 790 mg, 795 mg, 800 mg, 805 mg, 810 mg, 815 mg, 820 mg, 825 mg, 830 mg, 835 mg, 840 mg, 845 mg, 850 mg, 855 mg, 860 mg, 865 mg, 870 mg, 875 mg, 880 mg, 885 mg, 890 mg, 895 mg, 900 mg, 905 mg, 910 mg, 915 mg, 920 mg, 925 mg, 930 mg, 935 mg, 940 mg, 945 mg, 950 mg, 955 mg, 960 mg, 965 mg, 970 mg, 975 mg, 980 mg, 985 mg, 990 mg, 995 mg or 1000 mg.

[0093] In some embodiments, the compositions described herein contain a solubilizer present in an amount of about 0.1% (w / v) to about 5% (w / v). In some embodiments, the compositions described herein comprise a solubilizer in the amounts of about 0.1% (w / v) to about 1.0% (w / v), about 0.2% (w / v) to about 1.2% (w / v), about 0.3% (w / v) to about 1.3% (w / v), about 0.4% (w / v) to about 1.4% (w / v), about 0.5% (w / v) to about 1.5% (w / v), about 0.6% (w / v) to about 1.6% (w / v), about 0.7% (w / v) to about 1.7% (w / v), about 0.8% (w / v) to about 1.8% (w / v), about 0.9% (w / v) to about 2.9% (w / v), about 1.0% (w / v) to about 2.0% (w / v), about 1.5% (w / v) to about 2.5% (w / v), or about 2% (w / v) to about 3%. It is present in amounts of about 2.5% (w / v) to about 3.5% (w / v), about 3% (w / v) to about 4% (w / v), about 3.5% (w / v) to about 4.5% (w / v), or about 4% (w / v) to about 5% (w / v). In some embodiments, the compositions described herein contain a solubilizer present in amounts of about 0.1% (w / v), about 0.2% (w / v), about 0.3% (w / v), about 0.4% (w / v), about 0.5% (w / v), about 0.6% (w / v), about 0.7% (w / v), about 0.8% (w / v), about 0.9% (w / v), about 1.0% (w / v), about 1.5% (w / v), about 2% (w / v), about 2.5% (w / v), about 3% (w / v), about 3.5% (w / v), about 4% (w / v), about 4.5% (w / v), or about 5% (w / v). In some embodiments, the compositions described herein contain propylene glycol or transcutol, which, when used as a solubilizer as described herein, is present in amounts of about 3% (w / v) to about 5% (w / v). In some embodiments, the compositions described herein comprise propylene glycol in an amount of about 3% (w / v) to about 5% (w / v). In some embodiments, the compositions described herein comprise transcutol in an amount of about 3% (w / v) to about 5% (w / v).

[0094] In some embodiments, the compositions provided herein also include the penetration enhancers described herein. In some embodiments, the compositions described herein comprise a penetration enhancer in an amount from about 1.0 mg to about 1000 mg, including but not limited to about 1.0 mg, 1.5 mg, 2.5 mg, 3.0 mg, 4.0 mg, 5.0 mg, 6.0 mg, 6.5 mg, 7.0 mg, 7.5 mg, 8.0 mg, 8.5 mg, 9.0 mg, 9.5 mg, 10.0 mg, 10.5 mg, 11.0 mg, 12.0 mg, 12.5 mg, 13.0 mg, 13.5 mg, 14.0 mg, 14.5 mg, 15.0 mg, 15.5 mg, 16 mg, 16.5 mg, 17 mg, 17.5 mg, 18 mg, 18.5 mg, 19 mg, 19.5 mg, 20 mg, 20.5 mg, 21 mg, 21.5 mg, 22 mg, 22.5 mg, 23 ... mg, 23.5mg, 24 mg, 24.5 mg, 25 mg, 25.5 mg, 26 mg, 26.5 mg, 27 mg, 27.5 mg, 28 mg, 28.5 mg, 29mg, 29.5 mg, 30 mg, 30.5 mg, 31 mg, 31.5 mg, 32 mg, 32.5 mg, 33 mg, 33.5 mg, 36 mg, 36.5mg, 37 mg, 37.5 mg, 38 mg, 38.5 mg, 39 mg, 39.5 mg, 40 mg, 40.5 mg, 41 mg, 41.5 mg, 42mg, 42.5 mg, 43 mg, 43.5 mg, 44 mg, 44.5 mg, 45 mg, 45.5 mg, 46 mg, 46.5 mg, 47 mg, 47.5 mg, 48 mg, 48.5 mg, 49 mg, 49.5 mg、50 mg、55 mg、60 mg、65 mg、70 mg、75 mg、80 mg、85mg、90 mg、95 mg、100 mg、105 mg、110 mg、115 mg、120 mg、125 mg、130 mg、135 mg、140mg、145 mg、150 mg、155 mg、160 mg、165 mg、170 mg、175 mg、180 mg、185 mg、190 mg、200mg、205 mg、210 mg、215 mg、220 mg、225 mg、230 mg、235 mg、240 mg、245 mg、250 mg、255mg、260 mg、265 mg、270 mg、275 mg、280 mg、285 mg、290 mg、295 mg、300 mg、305 mg、310mg、315 mg、320 mg、325 mg、326 mg、326.5 mg、327 mg、327.5 mg、328 mg、328.5 mg、329mg、329.5 mg、330 mg、330.5 mg、331 mg、331.5 mg、332 mg、332.5 mg、333 mg、333.5 mg、334 mg、334.5 mg、335 mg、335.5 mg、336 mg、336.5 mg、337 mg、337.5 mg、338 mg、338.5mg、339 mg、339.5 mg、340 mg、340.5 mg、341 mg、341.5 mg、342 mg、342.5 mg、343 mg、343.5 mg、344 mg、344.5 mg、345 mg、345.5 mg、346 mg、346.5 mg、347 mg、347.5 mg、348mg、348.5 mg、349 mg、349.5 mg、350 mg、350.5 mg、351 mg、351.5 mg、352 mg、352.5 mg、353 mg、353.5 mg、354 mg、354.5 mg、355 mg、355.5 mg、356 mg、356.5 mg、357 mg、357.5mg、358 mg、358.5 mg、359 mg、359.5 mg、360 mg、360.5 mg、361 mg、361.5 mg、362 mg、362.5 mg、363 mg、363.5 mg、364 mg、364.5 mg、365 mg、365.5 mg、366 mg、366.5 mg、367mg、367.5 mg、368 mg、369.5 mg、370 mg、370.5 mg、371 mg、371.5 mg、372 mg、372.5 mg、373 mg、373.5 mg、374 mg、374.5 mg、375 mg、375.5 mg、376 mg、376.5 mg、377 mg、377.5mg、378 mg、378.5 mg、379 mg、379.5 mg、380 mg、380.5 mg、381 mg、381.5 mg、382 mg、382.5 mg、383 mg、383.5 mg、384 mg、384.5 mg、385 mg、385.5 mg、386 mg、386.5 mg、387mg、387.5 mg、388 mg、388.5 mg、389 mg、389.5 mg、390 mg、390.5 mg、391 mg、391.5 mg、392 mg、392.5 mg、393 mg、393.5 mg、394 mg、394.5 mg、395 mg、395.5 mg、396 mg、396.5mg、397 mg、397.5 mg、398 mg、398.5 mg、399 mg、399.5 mg, 400 mg, 405 mg, 410 mg, 415 mg, 420 mg, 425 mg, 430 mg, 435 mg, 440 mg, 445 mg, 450 mg, 455 mg, 460 mg, 465 mg, 470 mg, 475 mg, 480 mg, 485 mg, 490 mg, 495 mg, 500 mg, 505 mg, 510 515 mg mg, 630 635 mg 750 mg mg, 860mg, 865 mg, 870 mg, 875 mg, 880 mg, 885 mg, 890 mg, 895 mg, 900 mg, 905 mg, 910 mg, 915 mg, 920 mg, 925 mg, 930 mg, 935 mg, 940 mg, 945 mg, 950 mg, 955 mg, 960 mg, 965 mg, 970 mg, 975 mg, 980 mg, 985 mg, 990 mg, 995 mg, or 1000 mg. In some embodiments, the penetration enhancer described herein is hydroxypropyl-β-cyclodextrin. In some embodiments, when used as a penetration enhancer in the compositions described herein, hydroxypropyl-β-cyclodextrin is present in an amount of about 0.1% (w / v) to about 10% (w / v). In some embodiments, when used as a penetration enhancer in the compositions described herein, hydroxypropyl-β-cyclodextrin is present in an amount of about 0.1% (w / v), about 0.2% (w / v), or about 0.The following amounts are present: 3% (w / v), about 0.4% (w / v), about 0.5% (w / v), about 0.6% (w / v), about 0.7% (w / v), about 0.8% (w / v), about 0.9% (w / v), about 1.0% (w / v), about 1.5% (w / v), about 2% (w / v), about 2.5% (w / v), about 3% (w / v), about 3.5% (w / v), about 4% (w / v), about 4.5% (w / v), about 5% (w / v), about 5.5% (w / v), about 6% (w / v), about 6.5% (w / v), about 7% (w / v), about 7.5% (w / v), about 8% (w / v), about 8.5% (w / v), about 9% (w / v), about 9.5% (w / v), and about 10% (w / v). In some embodiments, hydroxypropyl-β-cyclodextrin is present in an amount of about 10% (w / v) when used as a penetration enhancer in the compositions described herein. In some embodiments, the compositions provided herein also contain a coloring substance. In some embodiments, the compositions described herein contain a solubilizer in an amount from about 1.0 mg to about 100 mg, including but not limited to about 1.0 mg, 1.5 mg, 2.5 mg, 3.0 mg, 4.0 mg, 5.0 mg, 6.0 mg, 6.5 mg, 7.0 mg, 7.5 mg, 8.0 mg, 8.5 mg, 9.0 mg, 9.5 mg, 10.0 mg, 10.5 mg, 11.0 mg, 12.0 mg, 12.5 mg, 13.0 mg, 13.5 mg, 14.0 mg, 14.5 mg, 15.0 mg, 15.5 mg, 16 mg, 16.5 mg, 17 mg, 17.5 mg, 18 mg, 18.5 mg, 19 mg, 19.5 mg, 20 mg, 20.5 mg, 21 mg, 21.5 mg, 22 mg, 22.5 mg, 23 mg, 23.5 mg. mg, 24 mg, 24.5 mg, 25 mg, 25.5 mg, 26 mg, 26.5 mg, 27 mg, 27.5 mg, 28mg, 28.5 mg, 29 mg, 29.5 mg, 30 mg, 30.5 mg, 31 mg, 31.5 mg, 32 mg, 32.5 mg, 33 mg, 33.5mg, 36 mg, 36.5 mg, 37 mg, 37.5 mg, 38 mg, 38.5 mg, 39 mg, 39.5 mg, 40 mg, 40.5 mg, 41mg, 41.5 mg, 42 mg, 42.5 mg, 43 mg, 43.5 mg, 44 mg, 44.5 mg, 45 mg, 45.5 mg, 46 mg, 46.5 mg, 47 mg, 47.5 mg, 48 mg, 48.5 mg, 49 mg, 49.5 mg, 50 mg, 55 mg, 60 mg, 65 mg, 70 mg, 75 mg, 80 mg, 85 mg, 90 mg, 95 mg or 100 mg. .

[0095] In some embodiments, the compositions described herein contain the coloring substance described herein in an amount of about 0.1%. The coloring substance described herein is a pigment. In some embodiments, the pigment is present in an amount of about 0.1% of D&C Red 27, D&C Red 17, or Yellow 7.

[0096] In some embodiments, the film-forming composition described herein comprises: terbinafine or terbinafine HCl in an amount of 0.5% to 20% by weight; a film-forming polymer, wherein the film-forming polymer is present in an amount of 5% to 15% by weight; a plasticizer, wherein the plasticizer is present in an amount of 0.5% to 5% by weight; a penetration enhancer, wherein the penetration enhancer is present in an amount of lactic acid in an amount of 2% to 30% by weight; a volatile solvent, wherein the volatile solvent comprises ethanol; and a non-volatile solvent.

[0097] In some embodiments, the film-forming composition described herein comprises: terbinafine or terbinafine HCl; a film-forming polymer, wherein the film-forming polymer is present in an amount of 5% to 15% by weight; a plasticizer, wherein the amount of the plasticizer is 0.5% to 5% by weight; lactic acid, wherein the ratio of terbinafine to lactic acid is 1:10 (w:w) to 1:2 (w:w), and wherein the lactic acid is present in an amount sufficient to promote the penetration of terbinafine; a volatile solvent, wherein the volatile solvent comprises ethanol; and a non-volatile solvent. In some embodiments, the ratio of terbinafine to lactic acid is 1:10 (w:w), 1:9 (w:w), 1:8 (w:w), 1:7 (w:w), 1:6 (w:w), 1:5 (w:w), 1:4 (w:w), 1:3 (w:w), or 1:2 (w:w).

[0098] In some embodiments, the film-forming composition described herein comprises: 0.5% to 20% by weight of ioconazole; a film-forming polymer, wherein the film-forming polymer is present in an amount of 5% to 15% by weight; a plasticizer, wherein the plasticizer is present in an amount of 0.5% to 5% by weight; a penetration enhancer, wherein the penetration enhancer is present in an amount of 2% to 30% by weight of lactic acid; a volatile solvent, wherein the volatile solvent comprises ethanol; and a non-volatile solvent.

[0099] In some embodiments, the film-forming composition described herein comprises: iefluconazole; a film-forming polymer, wherein the film-forming polymer is present in an amount of 5% to 15% by weight; a plasticizer, wherein the amount of the plasticizer is 0.5% to 5% by weight; lactic acid, wherein the ratio of iefluconazole to lactic acid is 1:10 (w:w) to 1:2 (w:w), and wherein the lactic acid is present in an amount sufficient to promote the penetration of terbinafine; a volatile solvent, wherein the volatile solvent comprises ethanol; and a non-volatile solvent. In some embodiments, the ratio of terbinafine to lactic acid is 1:10 (w:w), 1:9 (w:w), 1:8 (w:w), 1:7 (w:w), 1:6 (w:w), 1:5 (w:w), 1:4 (w:w), 1:3 (w:w), or 1:2 (w:w).

[0100] Preparation method

[0101] This document provides a method for preparing a film-forming solution, the method comprising: providing a solution comprising a volatile solvent and a non-volatile solvent as described herein, wherein the volatile solvent is present in the solvent in an amount of 60% to 100% by volume; adjusting the pH of the solvent to pH 7 to pH 11; adding the active pharmaceutical ingredient (API) and the polymer as described herein to an aqueous solvent; and adding the plasticizer or other excipient as described herein to form a film-forming composition.

[0102] In some embodiments, the step of adjusting the pH includes raising the pH of the solvent. In some embodiments, the step of adjusting the pH includes adding a strong base to the solution. Strong bases used to adjust the pH include, but are not limited to, sodium hydroxide (NaOH), potassium hydroxide (KOH), and sodium bicarbonate.

[0103] In some embodiments, the step of adjusting the pH includes adjusting the pH to pH 7 to pH 9. In some embodiments, the step of adjusting the pH includes adjusting the pH to pH 8 to pH 10. In some embodiments, the step of adjusting the pH includes adjusting the pH to pH 9 to pH 11.

[0104] In some embodiments, adjusting the pH includes adjusting the pH to pH 9.0. In some embodiments, adjusting the pH includes adjusting the pH to pH 9.1. In some embodiments, adjusting the pH includes adjusting the pH to pH 9.2. In some embodiments, adjusting the pH includes adjusting the pH to pH 9.3. In some embodiments, adjusting the pH includes adjusting the pH to pH 9.4. In some embodiments, adjusting the pH includes adjusting the pH to pH 9.5. In some embodiments, adjusting the pH includes adjusting the pH to pH 9.6. In some embodiments, adjusting the pH includes adjusting the pH to pH 9.7. In some embodiments, adjusting the pH includes adjusting the pH to pH 9.8. In some embodiments, adjusting the pH includes adjusting the pH to pH 9.9. In some embodiments, adjusting the pH includes adjusting the pH to pH 10.

[0105] In some embodiments, the API is added to the solution before the polymer is added. In some embodiments, the polymer is added before the API is added to the solution. In some embodiments, the API and the polymer are added to the solution simultaneously. In some embodiments, the API, one or more polymers, and a plasticizer are added to the solution simultaneously.

[0106] Treatment

[0107] This article provides a method for treating nail disorders, the method comprising contacting the nail with a composition described herein. Exemplary nail disorders that can be treated and / or prevented using the systems and / or methods described herein include, but are not limited to, onychopsy, psoriatic nail dystrophy, onychogryposis, onychobitis, onychogryposis, nail atrophy, ingrown toenails, onychodystrophy, onychomycosis, onychogryposis, onycholysis, nail detachment, onychohypoplasia, onychomas, onychospasticity, onychomas, onychomas, onychomas, onychomas, onychomas, onychomas, onychomas, tinea unguium, nail bed keratosis, onychomas, paronychia, Pseudomonas infection, pterygium and retrograde pterygium, koilonychia, subungual hematoma or other nail trauma, folic acid deficiency, subungual hyperkeratosis, leukonychia, patellar nail syndrome, melanonychia, protein deficiency, brittle and flaky nails, methyl methacrylate-induced nail damage, vitamin C deficiency, vitamin deficiency, and tinea unguium. Nail disorders include onychomycosis, lichen planus-related thinning of the nail, Raynaud's disease, rheumatoid arthritis-related nail dystrophy, Beau's lines, Mie's lines associated with certain types of poisoning, discoloration, lamellar splitting, longitudinal grooves and / or longitudinal ridges, transverse grooves, pitting, soft nails, brittle nail syndrome, eczema, atopic dermatitis, and any combination thereof. In some embodiments, the nail disorder is not onychomycosis, and / or the nail disorder is not induced and / or caused by onychomycosis. In some embodiments, the nail disorder is eczema, atopic dermatitis, onycholysis, subungual hyperkeratosis, discoloration, onychotrophic nail, psoriatic nails, longitudinal splitting of the nail, nail splitting, lamellar splitting, onycholysis, brittle nail syndrome, transverse grooves, pitting, soft nails, nail dystrophy, brittle nails with intact or damaged nails, or any combination thereof.

[0108] In some embodiments, the compositions and / or methods disclosed herein are used to treat and / or prevent nail dystrophy (i.e., onychodystrophy) in a subject. As used herein, nail dystrophy (and onychodystrophy) refers to poorly formed, deformed, damaged, and / or discolored nails. Nail dystrophy may be caused by endogenous and / or exogenous factors, and / or may be a secondary manifestation of complete or partial destruction of the nail matrix, proximal nail fold, nail bed, nail bed cuticle, and / or underlying phalanges / phalanges. In some embodiments, nail dystrophy is induced and / or caused by onychomycosis. In some embodiments, nail dystrophy is not induced and / or caused by onychomycosis. In some embodiments, one or more signs and / or symptoms of nail dystrophy are treated and / or prevented by the compositions and / or methods described herein. In some embodiments, nail splitting and / or nail brittleness are treated and / or prevented by the systems and / or methods described herein.

[0109] In some embodiments, the nail disorders described herein are selected from onycholysis (e.g., distal separation of the nail plate), psoriatic nail splitting (e.g., longitudinal grooves and / or ridges of the nail plate), subungual hyperkeratosis (e.g., excessive growth of skin cells under the nail plate), discoloration, nail splitting (e.g., peeling of the nail plate surface), lamellar splitting, nail alopecia (e.g., proximal separation of the nail plate), brittle nail syndrome, transverse grooves, onychotrophic nails (e.g., thickening of the nail plate), pitting nails, soft nails, nail dystrophy, brittle nails of intact or damaged nails, nail tumors, and any combination thereof. In some embodiments, the compositions and / or methods described herein are used to treat and / or prevent nail splitting and / or nail brittleness. In some embodiments, the compositions and / or methods described herein are used to treat and / or prevent direct abrasion and / or friction on the nail surface, and / or to provide protection against moisture and / or the effects of dampness. The compositions and / or methods described herein are used to protect the nails from subsequent infection (i.e., reinfection) of fungal diseases.

[0110] In some embodiments, nail disorders, such as but not limited to nail dystrophy, may or may not be induced and / or caused by infectious pathogens such as bacteria, fungi, viruses, parasites, and / or protozoa. In some embodiments, nail disorders, such as but not limited to nail dystrophy, may or may not be induced and / or caused by fungi. According to some embodiments, the compositions and / or methods provided herein are used to prevent nail disorders induced and / or caused by infectious pathogens.

[0111] In some embodiments, the treatment methods described herein include cleaning the nail before and / or after applying the composition described herein to the nail. The nail may be cleaned by washing, soaking, wiping, and / or similar treatment with water, soap and water, and / or nail polish remover, such as, but not limited to, solutions containing organic solvents such as acetone. In some embodiments, the nail is cleaned once, twice, three times, or more daily, or once, twice, three times, four times, five times, six times, seven times, or more weekly. In some embodiments, the nail is cleaned once a week or as needed. In some embodiments, the nail is optionally dried after cleaning. In some embodiments, the nail may be cleaned and optionally dried before applying the composition described herein.

[0112] In some embodiments, the treatment methods described herein further include cleaning the nail prior to applying the composition of the invention, optionally drying the nail, topically applying the composition of the invention, and drying the composition to form a coating and / or film. After the coating or film has formed and dried, the coating and / or film may be cleaned as needed to remove debris accumulated on the nail. However, cleaning does not remove the coating and / or film, which may allow the nail to be protected for a longer period of time.

[0113] In some embodiments, the compositions and / or methods of the present invention further include as part of a multiple treatment regimen. In some embodiments, a medicament is used in parallel with the compositions and / or methods provided herein to treat an underlying disease, and the compositions of the present invention are used to improve the appearance and / or protect the nails.

[0114] In some embodiments, the treatment methods described herein further include topical application of the composition of the invention to the nail and / or the skin around the nail in an amount of about 1 μL to about 15 μL, or any range and / or individual values ​​thereof. In some embodiments, about 1 μL, 2 μL, 3 μL, 4 μL, 5 μL, 6 μL, 7 μL, 8 μL, 9 μL, 10 μL, 11 μL, 12 μL, 13 μL, 14 μL, or 15 μL of the composition may be topical applied to the nail and / or the skin around the nail. The composition may be topical applied to the nail and / or the skin around the nail at least once daily. The composition may be applied topically in the form of a thin layer and / or may cover at least a portion of the nail and / or the skin around the nail. In some embodiments, the composition covers the entire nail. The composition may be applied in the form of a thin layer that substantially uniformly covers the nail. The composition may be allowed to dry, for example, the composition may be allowed to dry for about 2 minutes to about 3 minutes.

[0115] In some embodiments, the composition may be topically applied to the nail and / or the skin around the nail in an amount having a weight of about 1 mg to about 10 mg or any range and / or individual value therein. In some embodiments, the composition may be topically applied to the nail and / or the skin around the nail in amounts of about 1 mg, 2 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, or 10 mg. Once dry, this may provide a coating and / or film on the nail and / or the skin around the nail having a weight of about 0.1 mg to about 2 mg or any range and / or individual value therein, such as, but not limited to, about 0.1 mg, 0.2 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg, 0.9 mg, 1.0 mg, 1.1 mg, 1.2 mg, 1.3 mg, 1.4 mg, 1.5 mg, 1.6 mg, 1.7 mg, 1.8 mg, 1.9 mg, or 2.0 mg.

[0116] In some embodiments, the composition is applied topically to the nail and / or the skin around the nail at least once a day for at least five consecutive days. In some embodiments, the treatment regimen includes applying the composition described herein topically once a day for five consecutive days; on the sixth day, cleaning the nail and / or the skin around the nail, for example, but not limited to, with a nail polish remover (e.g., acetone solution); and on the sixth and seventh days, no composition is applied. In some embodiments, the treatment regimen includes applying the composition topically to the nail and / or the skin around the nail once a day, and cleaning the nail and / or the skin around the nail at least once a week. Any exemplary treatment regimen may be repeated for a defined period of time (e.g., 2 weeks, 1 month, etc.), or until at least one sign and / or symptom improvement and / or relief is observed.

[0117] In some embodiments, loose debris and / or nail material is removed from the nail and / or the skin around the nail before the composition is applied topically. In some embodiments, nail pliers and / or a nail file are used to remove loose debris and / or nail material.

[0118] This document also discloses methods for improving nail appearance. Infected nails exhibit symptoms such as thickening, discoloration, brittleness or fragility, deformity, separation from the nail bed, foul odor, white spots or streaks, pain, or discomfort. Improvement in nail appearance can be determined by visual assessment of the nail, such as visual evaluation of color, surface smoothness, shape, and / or thickness. In some embodiments, the methods provided herein reduce nail discoloration. In some embodiments, the methods provided herein reduce nail thickness. In some embodiments, the methods provided herein remove fungal debris. In some embodiments, the systems and / or methods of this invention improve nail strength compared to nail strength in the absence of the systems and / or methods of this invention.

[0119] Example

[0120] Example 1. Ethanol as a solvent for polymers

[0121] To optimize the polymers and concentrations used in the nail film formulation, film-forming solutions of various polymers (HPMC-AS-LF, HPMC E5, HPMC K100, HPC EF, PVP K30) prepared according to Table 1 at multiple concentrations were evaluated based on their ease of film formation, film quality (film smoothness, durability on nails, etc.), and ease of removal by water. The solutions were vortexed until clear. The solutions were applied to nails, and the film appearance, water resistance, drying time, formulation viscosity, and polymer solubility were evaluated.

[0122] Table 1. Formulations

[0123] As shown in Table 2, the polymers in most formulations are poorly soluble in ethanol or ethanol-water mixtures, which can be observed from the formation of white patches during film drying. In particular, film-forming formulations with higher Eudragit content (≥5%) are difficult to dissolve and form white patches in the film after drying and contact with water.

[0124] Table 2.

[0125] Formulation A1 exhibits a good film after drying and remains on the nail even after non-vigorous hand washing. However, drying is time-consuming and remains sticky during the drying process. Reducing the PEG400 content to 5% (as in A2) decreases the film viscosity, shortens the drying time, and eliminates the stickiness. Reducing the Eudragit L100 content to 2% (A3) allows the dried film to be easily removed by hand washing.

[0126] Formulation B1 produces a thin film after drying, but it can be easily removed from the nail by hand washing. When the HPMC E5 content is increased to 4%, as in B2, the film takes longer to dry and remains prone to cracking. When 5% Eudragit L100 is added (B3), the dried film again achieves good water resistance.

[0127] Formulations C1 and C2 resulted in the formation of a stronger film after drying, indicating that the inclusion of HPC EF in the formulation promoted film formation.

[0128] Formulations D1-D5 show Carfil 9235NP, also known as polyurethane, which helps enhance the adhesion of the film to the substrate and improves the smoothness of the film. However, when its content exceeds 5%, the drying rate decreases. Furthermore, the inclusion of 10% Eudragit L100 results in a thicker film than when containing 5%, and exhibits better water-resistant properties.

[0129] Formulation E3 showed a better dry film, which could remain on the surface of the nail for more than 2 days when HPMC-AS-LF was added, but PVP K30 and HPMC K100 were not soluble in ethanol-water solution (Formulations E1-2).

[0130] Although the addition of Carfil 9235NP and HPMC-AS-LF caused the solution to become turbid, they also promoted membrane formation.

[0131] When the polymer content is less than 5%, the solution has low viscosity, making it difficult to hold on the substrate. However, with the addition of PEG400 and Carfil 9235NP, and a high polymer content (10%), the solution viscosity increases, and the solution stops flowing out.

[0132] Example 2. Solubility of the polymer in ethanol / water solvent

[0133] To confirm the advantage of ethanol / water solvents with a pH above 7 in dissolving polymers, formulations according to Table 3 were prepared as follows: ethanol and water were mixed in different ratios, and then the pH of the solvent was adjusted to pH 8 to pH 11 using 10 M sodium hydroxide or triethanolamine. The pH of the solvent was determined using pH test strips. Formulations prepared with unadjusted solvents were included as a control group. Then, appropriate amounts of HPMC-AS-LF and Eudragit L100 were weighed and added to the solvent. After stirring the components in the solution until they transitioned from a coated state to a dispersed state, the solution was vortexed using a vortex mixer (VORTEX-GENIE 2). The solution conditions and dissolution time were recorded.

[0134] Table 3. Formulation Table

[0135] Table 4. Solubility characteristics of polymers in solvents (unadjusted pH)

[0136] Table 5. Solubility characteristics of polymers in solvents (pH=8)

[0137] Table 6. Solubility characteristics of polymers in solvents (pH=9)

[0138] Table 7. Solubility characteristics of polymers in solvents (pH=10)

[0139] Table 8. Solubility characteristics of polymers in solvents (pH=11)

[0140] Table 9. Record of polymer dissolution time in ethanol / aqueous solution (unadjusted pH)

[0141] Table 10. Record of polymer dissolution time in ethanol / aqueous solution (pH=8)

[0142] Table 11. Record of polymer dissolution time in ethanol / aqueous solution (pH=9)

[0143] Table 12. Record of polymer dissolution time in ethanol / aqueous solution (pH=10)

[0144] Table 13. Record of polymer dissolution time in ethanol / aqueous solution (pH=11)

[0145] It was confirmed that, at certain ratios, enteric polymers are not completely soluble in ethanol or ethanol-water mixtures. They are insoluble or require a very long time to dissolve. Enteric polymers are more soluble in alkaline ethanol-water mixtures. However, they exhibit extremely low solubility in solvents when pH > 11 (Table 7). The solubility of polymers in ethanol-water mixtures increases when the pH of the ethanol solution is adjusted to above pH 8. Based on the results in Tables 4-13, adjusting the pH to pH 8 to pH 11, preferably pH 9 to pH 10, improves the solubility of enteric polymers in ethanol / water solvents.

[0146] Once an enteric polymer is dissolved in a high-pH ethanol / water solvent, the pH of the solution decreases. For example, if the pH of the ethanol / water solvent is adjusted to 9-10, the final pH will be 7-8 after the polymer is completely dissolved.

[0147] The amount of Eudragit L100 also affects the solubility of the enteric polymer. The content of Eudragit L100 is about 5%-15%, with a preferred concentration of 5%-10% (w / v). When the content of Eudragit L100 exceeds 15%, dissolution becomes difficult.

[0148] The ethanol percentage (v / v) used in the assay is between 60% and 100%, with a preferred concentration of 80%-90%. When the concentration is below 80%, not only does the solubility decrease, but the viscosity of the formulation also increases significantly, resulting in a significant extension of the drying time.

[0149] Compared to solutions containing only Eudragit L100, the addition of HPMC-AS LF resulted in better film formation and water resistance, and increased polymer solubility. Dissolution time was shortened when HPMC-AS LF concentration was less than 2%.

[0150] The polymer's solubility reaches its maximum when the ratio of Eudragit L100 to HPMC-AS LF is between 10 and 20. Outside this range, solubility decreases. When HPMC-AS LF is less than 2%, increasing its concentration is beneficial for dissolution.

[0151] Example 3. Effect of plasticizers on film formulations

[0152] To confirm the advantages of plasticizers for film formation, formulations of Eudragit L100, HPMC-AS-LF, and PEG 6000 (plasticizer) with varying percentages (w / v) according to Table 14 were prepared using the following steps: Ethanol and water were mixed in different ratios, and the pH of the ethanol / water solvent was adjusted to approximately pH 10 using 10 M sodium hydroxide. After pH adjustment, the final volume of each solvent was 5 mL. Then, the corresponding amounts of HPMC-AS-LF, Eudragit L100, and PEG6000 were weighed and added to the solvents. The components were stirred in the solution until they transitioned from an encapsulated state to a dispersed state. The solution was vortexed using a vortex mixer (VORTEX-GENIE 2), and the dissolution time was recorded. For each formulation, the same volume was removed, wiped onto a glass slide at room temperature, and the drying time was recorded. After drying, the glass slide was immersed in water for 20 minutes. After 20 minutes, the glass slide was removed and wiped with a paper towel. After the slide surface dries, use tweezers to remove the film formed on each slide. Take an image of the film, such as... Figure 1 As shown. The characteristics of each formulation are recorded in Table 15.

[0153] Table 14. Formulation Table

[0154] Table 15. Characteristics of formulations containing PEG6000

[0155] like Figure 1 As shown, adding 2% or 4% PEG6000 makes the dried film more flexible and intact. Without PEG6000, or when the PEG6000 content is less than 2%, opaque white patches or film cracking occur during the drying process after immersion in water for 20 minutes, regardless of the Eudragit L100 / HPMC-AS LF ratio. Furthermore, PEG6000 also enhances the film's water resistance.

[0156] The ethanol-water ratio also affects membrane formation. Formulations with an ethanol-water ratio of 6:4 or 7:3 and PEG6000 content of less than 2% result in poorly dried membranes.

[0157] Example 4. Effect of solubilizers on film formulations

[0158] Before determining the effect of the solubilizer on the film formulation, the film-forming solution was optimized by varying the terbinafine HCl content in an ethanol / water (8 / 2) solution containing Eudragit L100, HPMC-AS LF, and PEG 600, according to Table 16. The solution was prepared using the same method as in Example 3. 1 mL of the above solution was wiped onto a glass slide to form a dry film. XRPD measurements were performed with the dry film in contact with or without water, and the results are shown in... Figure 2 Terbinafine HCl was used as the model active pharmaceutical ingredient (API) and presented at three different concentrations of 5% (w / v), 10% (w / v) and 15% (w / v).

[0159] Table 16. Formulation Table

[0160] like Figure 2 As shown, solutions with a low API content (5%) did not undergo crystallization during film formation (no peaks were detected). When the API percentage increased to 10% or 15%, API crystallization occurred during film formation, especially when the membrane was in contact with water. API crystallization during film formation is undesirable and should be avoided. Therefore, a low API content is preferred for membrane formulations.

[0161] Next, to confirm the advantages of solubilizers such as propylene glycol and transcutol, film-forming solutions were prepared according to Table 17. Specifically, to prepare the film-forming solutions, ethanol and water were mixed to make 5 mL of ethanol / water solution, and the pH was adjusted to approximately 10. Then, the solubilizer and API were added to the solution. After the API was completely dissolved, HPMC-AS-LF, Eudragit L100, and PEG6000 were added to the solution for dissolution. 1 mL of each solution was wiped onto a glass slide until a film formed and dried. For the group tested in contact with water, 1 mL of water was dropped onto a glass slide. The film was then removed from the glass slide for XRPD measurements and observed under a polarizing microscope.

[0162] Table 17. Formulation Table

[0163] XRPD analysis of the dried film from the above formulation showed that... Figure 3In the middle, polymers in ethanol / water solutions containing propylene glycol or transcutol do not show any peaks (BE), indicating that their solubility is higher than that of polymers in ethanol / water solutions without solubilizers (A).

[0164] XRPD analysis of the membrane from the above formulation after contact with water showed that... Figure 4 In the case of water-contacted dry films, API precipitates are formed at high API concentrations. However, API crystallization is significantly reduced when a solubilizer is added to the formulation, and the crystallization inhibition effect is more pronounced with increasing solubilizer concentration. Higher solubilizer concentrations (5%) show better crystallization inhibition. From the perspective of reducing crystal peak intensity, 5% Transcutol shows better results than 5% propylene glycol.

[0165] Polarizing microscopes distinguish between crystalline and amorphous substances. Crystalline substances show highlights, while amorphous substances appear darker. For example... Figures 5A-5E As shown in the image from a polarizing microscope, the dried film formulation without solubilizer exhibits a large number of crystals under the microscope. Figure 5A Fewer crystals were observed in 3% Transcutol or propylene glycol. Figure 5B and Figure 5D ), almost no crystals were observed with 5% solubilizer. Figure 5C and Figure 5E ).

[0166] To further confirm the advantages of including a solubilizer in the film-forming formulation described herein, the solubilizer was selected from Transcutol, propylene glycol, Labrasol, PEG400, isopropyl palmitate, and triethyl citrate. 1.0% HPMC-AS-LF and 10% Eudragit L100 were added to a tube, followed by 2 mL of solubilizer. The tube was then vortexed using a vortex mixer to dissolve the polymer. The dissolution was recorded for each solubilizer addition.

[0167] Based on observations of the solution state, the polymer exhibits higher solubility in propylene glycol and transcutol, lower solubility in Labrasol and PEG400, and is insoluble in isopropyl palmitate and triethyl citrate. According to Table 18, transcutol and propylene glycol were selected to prepare the film-forming solution using the same method as described above.

[0168] Table 18. Formulation Table

[0169] Since the film-forming solution also exhibits good properties when propylene glycol and transcutol are used as solubilizers, propylene glycol and transcutol can be chosen as solubilizers when using terbinafine HCl as the API.

[0170] To confirm the advantages of the solubilizer in solutions with varying concentrations of polymer and ethanol, film-forming solutions were prepared using the same method as described above, according to Table 19. The solutions were vortexed, and the dissolution time was recorded. An equal volume of liquid was taken from each solution, wiped onto a glass slide at room temperature, and the drying time was recorded. The glass slide was then immersed in water for 20 minutes. After 20 minutes, the glass slide was removed, and the film on the slide was scraped off with tweezers for observation. The dissolution status and quality of the film are recorded in Table 20.

[0171] Table 19. Formulation Table

[0172] Table 20. Characteristics of film formulations containing solubilizers

[0173] The results in Table 20 indicate that solubilizers such as transcutol and propylene glycol enhanced the adhesion of the film to the glass slide, prevented water ingress, and optimized the physical properties of the formulation. Furthermore, the solubilizers shortened the drying time of the formulation containing 10% Eudragit L100 compared to the formulation containing 5% Eudragit L100.

[0174] To confirm the advantages of transcutol as a solubilizer in dissolving APIs from dried membranes, formulations were prepared according to Table 21 using the same method described above. For each formulation solution, 500 μL was dropped onto a dialysis membrane (cutoff molecular weight: 7000) to form a dried membrane. The membranes for each group were then immobilized on Franz cells, and the receiving cells were filled with PBS buffer. The Franz cells were then placed in a water bath at 32°C. Samples were taken at 1, 2, 3, 4, 5, and 6 hours for API assay to measure API concentration. The results are shown in... Figure 6 middle.

[0175] Table 21. Formulation Table

[0176] Figure 6The results showed that formulations with more solubilizers dissolved well from the dry membrane, which may facilitate API penetration. As mentioned above, the 15% API membrane formulation did not show a much higher content compared to the 10% API formulation, while the 15% API formulation showed significant API precipitation, suggesting that the inclusion of solubilizers to reduce the API concentration should be considered to achieve the same penetration.

[0177] To confirm the advantage of solubilizers in accelerating API dissolution from the dried membrane, formulations were prepared using the same method described above, according to Table 22. The dialysis membrane (cutoff molecular weight: 7000) was immersed in water for 1 hour before being immobilized on the Franz cell. 500 μL of each formulation was injected into the supply cell for drying. Then, PBS solution was injected into the receiving cell, and the Franz cell was placed in a water bath at 32°C. The solution from the receiving cell was collected at 1, 2, 3, 4, 5, and 6 hours, and the API concentration was determined.

[0178] Table 22. Formulations.

[0179] like Figure 7 The dissolution of API at different times indicates that API dissolves from the dry film when solutions are prepared with a solubilizer. Specifically, Transcutol is better than propylene glycol as a solubilizer in accelerating dissolution.

[0180] Example 5. Effect of penetration enhancers on membrane formulations

[0181] To determine the penetration of the membrane formulation into human nail, nail penetration experiments were conducted using different formulations and bovine nail, and the effect of penetration enhancers on API penetration was investigated. Formulations were prepared according to Table 23 below. Briefly, PEG 400 and API were added to ethanol and allowed to dissolve completely. Then, Eudragit L100 and hydroxypropyl-β-cyclodextrin were added to the ethanol solution to bring the final volume to 5 ml.

[0182] Table 23. Formulation Table

[0183] Bovine pegs were soaked in physiological saline and hydrated for 3 hours. Each peg was then placed with its surface facing the supply tank and its back facing the receiving tank, and fixed in a specific peg Franz tank. 20% ethanol-saline solution was injected into the receiving tank, and 50 μL of the formulation was injected into the supply tank to allow film formation. The Franz tank was then incubated in a 32°C water bath for 48 hours. When the penetration test was complete, the solution was collected from the receiving tank. Any remaining formulation on each bovine peg was cleaned with ethanol, the peg was ground, and the API was extracted from the peg with ethanol. Finally, ethanol was used to extract the API adsorbed on the rotor. The API content of each peg, the receiving solution, and the rotor were determined separately, and the results are summarized in Table 24.

[0184] Table 24. Membrane formulations containing penetration enhancers

[0185] Compared to formulations without a penetration enhancer, formulations containing a penetration enhancer (hydroxypropyl-β-cyclodextrin) resulted in a relatively higher amount of API entering and penetrating. The results indicate that the addition of a penetration enhancer such as hydroxypropyl-β-cyclodextrin is beneficial for API penetration.

[0186] Example 6. Effect of Penetration Enhancer

[0187] Based on the results from Examples 2 to 5 regarding the types of polymer coating agents, plasticizers, and solubilizers, solvent pH, their content ranges, and ratios, exemplary suitable formulations are listed in Table 25. To prepare the formulations listed in Table 25, appropriate amounts of ethanol and purified water were taken and mixed in different ratios of ethanol-water solvents. 10 M sodium hydroxide was added to adjust the pH. The API was added to the ethanol / water solution.

[0188] Table 25. Exemplary Formulations

[0189] Example 7. Nail film formulations containing different APIs

[0190] To confirm the advantages of membrane formulations for use with multiple APIs, different antifungal formulations were prepared according to Table 25. Furthermore, different Jak, PED4, and glucocorticoid molecular formulations were prepared according to Table 26. All formulations were soluble, forming clear solutions, and were readily soluble.

[0191] Table 25. Formulation Table

[0192] Table 26. Formulation Table

[0193] Example 7. Effect of Penetration Enhancer

[0194] The effects of etchants, solid reagents, and liquid reagents on API permeability were determined. Liquid and solid acids were used as penetrants, and API permeability was compared. Solid reagents were selected from tartaric acid, citric acid, malic acid, fumaric acid, and succinic acid. Liquid reagents were selected from lactic acid and phosphoric acid. Fumaric acid and succinic acid dissolve slowly or not at all in the solvent. Therefore, tartaric acid and citric acid were chosen as solid acids.

[0195] Table 27. Formulations

[0196] like Figure 8 The following is a brief demonstration of how the armor penetration test is conducted: 1. Bovine or human nails were used as membranes. Bovine nail membranes were prepared from healthy bovine hooves through precise cutting and processing. The bovine nails had a thickness ranging from 0.3 mm to 0.4 mm and a diameter of 25 mm. Batch-to-batch variability of bovine nail membranes (source of the bovine nails or processing of the membranes) may affect the results. To standardize the formulation evaluation, the same batch of bovine nail membranes was used in each example. Human nails were obtained from healthy volunteers.

[0197] 2. Before the experiment, specimen A was hydrated by soaking in physiological saline for 24 hours.

[0198] 3. Fix the nasal membrane onto a custom-designed nasal diffusion chamber, in which the receiving chamber is filled with physiological saline and 5% Transcutol to ensure that the receiving liquid has sufficient solubility for the permeated API and to ensure complete removal of air bubbles.

[0199] 4. Uniformly load 100 μL of test solution onto the surface of membrane A. Then place the diffusion cell in a temperature-controlled water bath (32℃±0.5℃). Prepare five to six replicate samples for each test solution.

[0200] 5. The determination of methyl permeability is performed by collecting samples from the receiving chamber at specified time intervals and then performing HPLC analysis.

[0201] 6. The determination of the drug content in A was carried out as follows: After the experiment, A was cleaned and crushed, and then extracted by ultrasonic treatment with ethanol for 30 minutes. The content was then measured by HPLC analysis.

[0202] After 48 hours, the permeation and deposition of the drug in the receiving pool and in container A showed that both liquid and solid acids had an effect of promoting drug permeation. Figures 9A-9BOf these, liquid acids showed a greater promoting effect than solid acids. This may be because liquid acids retain free hydrogen ions after the nail polish dries and may volatilize. Phosphoric acid was most effective in promoting drug penetration; however, when the phosphoric acid concentration exceeded 5%, polymer precipitation occurred, making the formulation unstable. Therefore, lactic acid was the most suitable penetration enhancer.

[0203] Example 8. Effect of different penetrating agents on the permeability of formaldehyde

[0204] The effect of different penetration enhancers on nail penetration was determined. Penetration enhancers could be selected from: hydrating agents (cyclodextrin HP-β-CD), keratolytic agents (urea or its derivatives), disulfide bond cleaving agents (acetylcysteine), chelating agents (EDTA or its derivatives), and acids (lactic acid). Formulations containing different penetration enhancers are shown in Table 28. Nail penetration tests were performed according to the procedure described in Example 7.

[0205] Table 28. Formulations

[0206] The permeation and deposition of drugs in the receiving pool and in the thallium showed that both urea and acetylcysteine ​​had a moderate effect on promoting permeation. Figures 10A-10B Furthermore, urea and EDTA promoted drug deposition on the nail compared to formulations without penetration enhancers. Lactic acid still showed the best effect compared to cyclodextrin HP-β-CD, urea, acetylcysteine, and EDTA.

[0207] Example 9. The effect of solvent on permeation

[0208] Determinations were performed to confirm whether acid esterification could also promote drug penetration, and whether the solvent in the formulation would affect drug penetration. The formulation was prepared according to Table 29. Acid penetration testing was performed according to the procedure described in Example 7.

[0209] Table 29. Formulations

[0210] like Figure 11A and 11B As shown, the solvent in the formulation significantly affects permeation. When ethanol is used as the solvent, the solution exhibits the best permeation effect (301.84 μg) (first column). The permeation effect decreases because the esterified acid can provide free protons.

[0211] Example 10. The Effect of Water

[0212] The formulation was prepared according to Table 30 to test the effect of water on penetration. A substance penetration test was performed according to the procedure described in Example 7.

[0213] Table 30. Formulations

[0214] like Figure 12A and 12B As shown, after removing water from the solvent, drug penetration was relatively reduced compared to the results of Example 10, indicating that water in the formulation helps improve penetration.

[0215] Example 11. Effect of Solubilizer

[0216] Phosphoric acid, lactate, acetylcysteine, and EDTA were also determined under the same settings to compare their effects. Formulations containing Transcutol or PEG 400 were prepared according to Tables 31 and 32. A methylbenzene penetration test was performed according to the procedure described in Example 7.

[0217] Table 31. Formulations

[0218] Table 32. Formulations

[0219] After 48 hours, the results showed no difference between formulations containing or without the solubilizer transcutol and PEG400. Figures 13A-13B However, in the case of transcutol, drug deposition in A was higher, suggesting that transcutol-containing formulations may tend to enter and remain in A. Figure 13C-13D Since nail penetration is a key factor in antifungal efficacy, assays showed that Transcutol and PEG400 offered minimal therapeutic advantage in lower drug concentration formulations (5%).

[0220] All results from Examples 7-11 are summarized and plotted. Figures 14A-14B In summary, membrane formulations with ethanol and water as solvents and lactic acid as a penetration enhancer exhibit the best penetration effect and are therefore used as nail polish.

[0221] Example 12. Comparison of Exemplary Formulations with Conventional Formulations

[0222] To compare the efficacy of the terbinafine formulation of this disclosure with that of a conventional terbinafine formulation, an exemplary terbinafine HCl formulation was prepared according to Table 33. The conventional terbinafine formulation used in the assay contained the ingredients listed in Table 34. A methylphenidate penetration test was performed according to the procedure described in Example 7.

[0223] Table 33. Terbinafine HCl Formulation

[0224] Table 34. Conventional Formulations

[0225] like Figure 15A and 15B As shown, at the same lactic acid concentration and a lower terbinafine HCl concentration (5%, compared to 10%), the exemplary ethanol-based nail polish containing 5% terbinafine HCl exhibits greater penetration over time compared to known non-ethanol-based formulations containing 10% terbinafine HCl. Therefore, the ethanol-based nail polish with a lower terbinafine HCl concentration (5%) is superior to known formulations with a higher terbinafine HCl concentration (10%).

[0226] To compare the penetration of exemplary ethanol-based nail polishes with different API concentrations with that of commercial terbinafine products, samples were prepared according to Table 35. Four different treatments were performed after loading the samples, according to the methods in Table 36. In short, after treatment, the exemplary ethanol-based nail polishes dried and formed a film that could not be removed by touch or washing. In contrast, the commercial product did not dry after application to the nail surface and could be easily removed by touch or washing. Nail penetration tests were performed according to the procedure described in Example 7.

[0227] Table 35. Formulations

[0228] Table 36. Treatment Methods

[0229] like Figures 16A-16B As shown, after removal and washing of conventional formulations, the API did not continue to penetrate, while Pharmacin nail polish continued to penetrate. When the API concentration of the exemplary ethanol-based nail polish exceeded 10%, the difference in penetration was not significant. Overall, at the same API concentration, the exemplary ethanol-based nail polish outperformed commercial nail formulations in terms of penetration.

[0230] For further comparison on human nails, exemplary ethanol-based nail polish was prepared according to Table 37 and loaded onto human nails according to the procedure in Table 38.

[0231] Table 37. Acetone Formulations

[0232] Table 38. Treatment

[0233] like Figures 17A-17B As shown, the exemplary ethanol-based nail polish is superior to commercial formulations in both penetration and deposition in human nails.

[0234] Example 13. Another exemplary ethanol-based methyl ester paint

[0235] To confirm that the ethanol-based nail polish developed using other APIs in this disclosure is also superior to the corresponding commercial nail polishes, film-forming formulations containing multiple APIs (amorolfen hydrochloride, eloxonazole, ciclopirox ketone, triamcinolone acetonide, tofacitinib, ruxolitinib, and roflumilast) were prepared according to Tables 39 and 40. Nail penetration tests were performed according to the procedure described in Example 7.

[0236] Table 39. Formulations

[0237] Table 40. Formulations

[0238] like Figures 18A-18F and Figures 19A-19B As shown, in each assay comparing the test membrane formulation containing the same API to the commercial product, the test membrane formulation outperformed the commercial product in both bovine cartilage permeation at 67 hours and bovine cartilage API deposition.

[0239] For formulations containing tofacitinib (a JAK inhibitor), ruxolitinib (a JAK inhibitor), or roflumilast (PDE4) as an API, there are currently no commercially available topical acetylcholine formulations for comparison. Figure 19C-19D As shown, both tofacitinib and ruxolitinib formulations exhibit effective penetration and API deposition in bovine cartilage.

[0240] Example 14. Therapeutic efficacy of nail film preparations

[0241] To confirm the therapeutic efficacy of the exemplary formulation in patients with onychomycosis, a nail film-forming solution was prepared according to Table 41. A nail penetration test was performed according to the procedure described in Example 7. The formulation was applied to patients as follows: (1) hands were dried before application; (2) it was applied once evening, spread on the nail with a brush, and allowed to dry for 2 minutes to form a film; (3) no contact with other objects was allowed during drying, no contact with water was allowed for 1 hour after application, and the film was not intentionally scratched after application. Prior to treatment, all patients had symptoms associated with onychomycosis, including thickened nails, nail discoloration (yellow or brown), and / or brittleness. After 3 months of treatment, the patients' nail symptoms significantly improved. Reduced nail discoloration was observed, and the nails began to retain their natural color, with yellow, brown, or white patches almost completely disappearing. All patients' thickened nails began to return to normal, indicating the removal of fungal debris.

[0242] Table 41. Terbinafine HCl Formulation

[0243] Example 15. Methyl permeability test

[0244] The formulations disclosed herein are also compared with conventional formulations containing lactic acid, benzyl alcohol, and ethanol. Exemplary and conventional formulations are prepared according to Table 42.

[0245] Table 42. Formulations

[0246] like Figures 20A-20B As shown, for the exemplary formulation, when the lactic acid content is reduced from 10% to 4%, the formaldehyde permeability decreases significantly, consistent with other results. In conventional formulations, lactic acid concentration appears to be unrelated to formaldehyde permeability. When PVP is added to these formulations, formaldehyde permeability increases while API content decreases. However, when PVP is increased from 0.5% to 10%, the solution cannot readily form a dry film but exists only as a thick gel, and permeability decreases significantly. Therefore, the exemplary formulations of this disclosure are superior to conventional formulations.

[0247] Example 16. Lactic acid concentration

[0248] To determine the optimal lactic acid concentration for the film-forming formulation, different formulations with varying lactic acid concentrations were prepared according to Tables 43 (without API) and 44 (with API). It was noted that for the API-free formulation, the maximum lactic acid content could be as high as 40%. If the content was increased further, the solution could not dry to form a film after application to the surface. In the presence of API, when the maximum lactic acid content exceeded 20%, the drying time was significantly prolonged, and the solution failed to form a dry film after application to the surface.

[0249] Table 43 Formulations

[0250] Table 44 Formulations

[0251] Example 17. Film-forming formulation.

[0252] This article describes different combinations of components used to generate formulations, including film-forming formulations for the treatment of infections, inflammation, and tumors. The combinations are listed in Table 45. The top row of the table lists F1-F12, representing the components of the formulation indicated by "X" in the columns below. For each formulation, the pH of the solution was adjusted to pH 9 to pH 10.

[0253] Table 45

[0254] Additional formulations containing antifungal APIs are provided in F1, F2, and F3, wherein the antifungal APIs are: ivorconazole, tavaborone, ciclopirox, amorolfen, ruliconazole, miconazole, ketoconazole, itraconazole, fluconazole, econazole, oxiconazole, clotrimazole, naftifine, voriconazole, isaconazole, fenteconazole, tavaborone, amorolfen, anisofungin, caspofungin, micafungin, rezafungin, amphotericin B, and terbinafine. These formulations are numbered F1.1-F1.24, F2.1-F2.24, and F3.1-F3.24. For these additional formulations, the last number corresponds to the specific API number in this paragraph.

[0255] Additional formulations containing antibacterial APIs are provided in F4, F5, and F6, wherein the antibacterial APIs are: penicillins, sulfonamides, streptozotocins, polypeptides, tetracyclines, doxycyclines, amoxicillin, carbapenems, cephalosporins, fluoroquinolones, glycopeptides and lipoglycopeptides, macrolides, and monocyclic β-lactams. These formulations are numbered F4.1-F4.13, F5.1-F5.13, and F6.1-F6.13. For these additional formulations, the last number corresponds to the specific API number in this paragraph.

[0256] Additional formulations containing anti-inflammatory APIs are provided in F7, F8, and F9, wherein the anti-inflammatory APIs are: JAK inhibitors, PDE4 inhibitors, corticosteroids, vitamin A, vitamin D3, anti-IL-17 agents, anti-IL-23 agents, anti-TNFα agents, anti-IL-4 agents, S1PR inhibitors, PI3Kδ inhibitors, and TYK2 inhibitors. These formulations are numbered F7.1-F7.12, F8.1-F8.12, and F9.1-F9.12. For these additional formulations, the last number corresponds to the specific API number in this paragraph.

[0257] Additional formulations containing antitumor APIs are provided in F10, F11, and F12, wherein the antitumor APIs are checkpoint inhibitors, anti-IL-7 agents, and 5-fluorouracil (F-FU). These formulations are numbered as formulations F10.1-F10.3, F11.1-F11.3, and F12.1-F12.3. For these additional formulations, the last number corresponds to the specific API number in this paragraph.

[0258] The foregoing description and figures illustrate many currently representative embodiments. Of course, various modifications, additions, and optional designs will become apparent to those skilled in the art based on the foregoing teachings without departing from the scope of the invention, the scope of which is indicated by the following claims rather than the foregoing description. All changes and variations falling within the meaning and scope of the claims should be included within the scope of the claims.

Claims

1. A composition comprising: An active pharmaceutical ingredient (API), wherein the amount of said API does not exceed 20% (w / v); Film-forming polymer, wherein the film-forming polymer is present in an amount of 5%-15% (w / v); Plasticizer, wherein the amount of said plasticizer does not exceed 5% (w / v); A volatile solvent, wherein the volatile solvent is ethanol; and Non-volatile solvents.

2. The composition of claim 1, wherein the film-forming polymer comprises hydroxypropyl methylcellulose derivatives, polymethacrylates, polyurethane, or any combination thereof.

3. The composition of claim 1, wherein the film-forming polymer comprises hydroxypropyl methylcellulose derivatives, polymethacrylates, or any combination thereof.

4. The composition according to claim 3, wherein the hydroxypropyl methylcellulose derivative is hydroxypropyl methylcellulose acetate succinate (HPMC-AS).

5. The composition of claim 4, wherein the HPMC-AS is present in an amount of about 0.5% (w / v) to about 1% (w / v).

6. The composition according to claim 3, wherein the polymethacrylate is Eudragit.

7. The composition of claim 6, wherein the Eudragit is present in an amount of about 5%-15% (w / v).

8. The composition of claim 6, wherein the Eudragit is present in an amount of about 10% (w / v).

9. The composition according to claim 1, wherein the composition further comprises at least one solubilizer.

10. The composition of claim 9, wherein the at least one solubilizer comprises propylene glycol, transcutol, polyethylene glycol, or any combination thereof.

11. The composition according to claim 9, wherein the at least one solubilizer comprises transcutol.

12. The composition according to claim 1, wherein the composition further comprises a plasticizer.

13. The composition of claim 12, wherein the plasticizer is polyethylene glycol 6000.

14. The composition according to claim 1, wherein the composition further comprises a penetration enhancer.

15. The composition of claim 14, wherein the penetration enhancer is selected from hydrating agents, keratolytic agents, acids, disulfide bond cleaving agents, chelating agents, and any combination thereof.

16. The composition of claim 14, wherein the penetration enhancer is an acid.

17. The composition according to claim 16, wherein the acid is lactic acid.

18. The composition of claim 17, wherein the lactic acid is present in an amount of about 3% (w / v) to about 30% (w / v).

19. The composition of claim 17, wherein the lactic acid is present in an amount of about 10% (w / v).

20. The composition according to claim 1, wherein the composition further comprises at least one thickener.

21. The composition of claim 20, wherein the at least one thickener comprises PEG400.

22. The composition according to claim 1, wherein the composition further comprises a coloring substance.

23. The composition of claim 22, wherein the coloring substance comprises pigment, dye, colorant, or any combination thereof.

24. A method for treating nail disorders, the method comprising applying topically to the nail a composition according to any one of claims 1 to 23.

25. The method of claim 24, wherein the nail disorder is selected from eczema, atopic dermatitis, onycholysis, subungual hyperkeratosis, discoloration, onychotrophic nail, psoriatic nail, longitudinal nail splitting, onycholysis, lamellar splitting, nail alopecia, brittle nail syndrome, transverse grooves, pitting nails, soft nails, nail dystrophy, brittle nails of intact or damaged nails, nail tumors, and any combination thereof.

26. The method of claim 24, wherein the nail barrier is onychomycosis.

27. The method of claim 24, wherein the nail disorder is nail psoriasis.

28. A method for improving the appearance of a subject's nails, the method comprising applying to a specific area of ​​the nail a composition according to any one of claims 1 to 23.

29. The method of claim 28, wherein the method improves the color, surface smoothness, shape and / or thickness of the a.

30. The method of claim 28, wherein the composition is applied topically at least once a week.

31. The method of claim 28, wherein the composition is applied topically at least once a day.

32. A method for preparing a film-forming formulation, the method comprising: A solvent comprising a volatile solvent is provided, wherein the volatile solvent is present in the solvent in an amount of 60% to 100% by volume; Adjust the pH of the solvent to between pH 8 and pH 11; After adjusting the pH, the active ingredient and at least one polymer are dissolved in the solvent; as well as A plasticizer is added to form the film-forming formulation.

33. The method of claim 32, wherein the volatile solvent comprises ethanol, propanol, isopropanol, ethyl acetate, or any mixture thereof.

34. The method of claim 32, wherein the volatile solvent is ethanol.

35. The method of claim 32, wherein the polymer is selected from hydroxypropyl methylcellulose derivatives, polymethacrylates, and any combination thereof.

36. The method according to claim 32, wherein the active ingredient is selected from antibacterial substances, antiviral substances, antifungal substances, anti-inflammatory substances and antitumor substances, and the amount is 0.01%-20% by weight.

37. The method of claim 36, wherein the antibacterial substance comprises at least one substance selected from: penicillin, sulfonamides, streptozotocins, polypeptides, tetracyclines, doxycyclines, amoxicillin, carbapenems, cephalosporins, fluoroquinolones, glycopeptides and lipoglycopeptides, macrolides, monocyclic β-lactams, and any combination thereof.

38. The method of claim 36, wherein the antifungal substance comprises iriconazole, tavaborone, ciclopirox, amorolfen, ruliconazole, terbinafine, miconazole, ketoconazole, itraconazole, fluconazole, econazole, oxiconazole, clotrimazole, naftifine, voriconazole, isaconazole, fenteconazole, tavaborone, amorolfen, anisofungin, caspofungin, micafungin, rezafungin, amphotericin B, terbinafine, or any combination thereof.

39. The method of claim 36, wherein the anti-inflammatory substance comprises a JAK inhibitor, a PDE4 inhibitor, a corticosteroid, vitamin A, vitamin D3, an anti-IL-17 agent, an anti-IL-23 agent, an anti-TNFα agent, an anti-IL-4 agent, an S1PR inhibitor, a PI3Kδ inhibitor, or a TYK2 inhibitor.

40. The method of claim 36, wherein the antitumor substance comprises a checkpoint inhibitor, an anti-IL-7 agent, 5-fluorouracil (F-FU), or any combination thereof.

41. The method of claim 32, further comprising adding at least one solubilizer.

42. The method of claim 41, wherein the at least one solubilizer is propylene glycol, transcutol, or polyethylene glycol (PEG).

43. The method of claim 32, further comprising adding a penetration enhancer.

44. The method of claim 43, wherein the penetration enhancer comprises at least one substance selected from: cyclodextrin and its derivatives, urea and its derivatives, lactic acid and its derivatives, sodium sulfite and its derivatives, EDTA, cysteine ​​and its derivatives, and any combination thereof.

45. The method of claim 43, wherein the penetration enhancer is an acid.

46. ​​The method of claim 45, wherein the acid is lactic acid.

47. The method of claim 32, further comprising adding at least one thickener.

48. The method of claim 47, wherein the at least one thickener comprises PEG400.

49. The method of claim 32, further comprising adding a coloring substance.

50. The method of claim 49, wherein the coloring substance comprises pigment, dye, colorant, or any combination thereof.

51. A composition comprising: An active pharmaceutical ingredient (API), wherein the active pharmaceutical ingredient is selected from antibacterial substances, antiviral substances, antifungal substances, anti-inflammatory substances and antitumor substances, and is present in an amount of 0.01% (w / v) to 20% (w / v); A film-forming polymer comprising HPMC-AS and Eudragit L100, wherein the HPMC-AS is present in an amount of 0.5% (w / v) to 4% (w / v) and the Eudragit L100 is present in an amount of 5% (w / v) to 15% (w / v); Plasticizer, wherein the plasticizer is present in an amount of 0.5% (w / v) to 4% (w / v) of PEG 6000; Solubilizer, wherein the solubilizer is propylene glycol or transcutol; and A volatile solvent, wherein the volatile solvent is ethanol.

52. The composition according to claim 51, wherein the antibacterial substance comprises at least one substance selected from: penicillin, sulfonamides, streptozotocins, polypeptides, tetracyclines, doxycyclines, amoxicillin, carbapenems, cephalosporins, fluoroquinolones, glycopeptides and lipoglycopeptides, macrolides, monocyclic β-lactams, and any combination thereof.

53. The composition of claim 51, wherein the antifungal substance comprises iriconazole, tavaborone, ciclopirox, amorolfen, ruliconazole, terbinafine, miconazole, ketoconazole, itraconazole, fluconazole, econazole, oxiconazole, clotrimazole, naftifine, voriconazole, isaconazole, fenteconazole, tavaborone, amorolfen, anisofungin, caspofungin, micafungin, rezafungin, amphotericin B, terbinafine, or any combination thereof.

54. The composition of claim 51, wherein the anti-inflammatory substance comprises a JAK inhibitor, a PDE4 inhibitor, a corticosteroid, vitamin A, vitamin D3, an anti-IL-17 agent, an anti-IL-23 agent, an anti-TNFα agent, an anti-IL-4 agent, an S1PR inhibitor, a PI3Kδ inhibitor, or a TYK2 inhibitor.

55. The composition of claim 51, wherein the antitumor substance comprises a checkpoint inhibitor, an anti-IL-7 agent, 5-fluorouracil (F-FU), or any combination thereof.

56. The composition of claim 51, wherein the API is terbinafine HCl.

57. The composition of claim 51, wherein the HPMC-AS is present in an amount of 0.5% (w / v) to 4% (w / v).

58. The composition of claim 51, wherein the HPMC-AS is present in an amount of 0.5% (w / v).

59. The composition of claim 51, wherein the Eudragit L100 is present in an amount of 5%-15% (w / v).

60. The composition of claim 51, wherein the Eudragit L100 is present in an amount of 10% (w / v).

61. The composition of claim 51, wherein the PEG 6000 is present in an amount of 2% (w / v) to 4% (w / v).

62. The composition according to claim 51, wherein the solubilizer is present in an amount of 3% (w / v) to 5% (w / v).

63. The composition according to any one of claims 51 to 62, wherein the composition further comprises water.

64. The composition according to claim 63, wherein the volume ratio of ethanol to water is from 9:1 to 6:

4.

65. The composition according to claim 63, wherein the volume ratio of ethanol to water is from 9:1 to 8:

2.

66. The composition of claim 51, further comprising a penetration enhancer, wherein the penetration enhancer is selected from hydrating agents, keratolytic agents, acids, disulfide bond cleaving agents, chelating agents, and any combination thereof.

67. The composition of claim 66, wherein the penetration enhancer is an acid.

68. The composition according to claim 67, wherein the acid is lactic acid.

69. The composition of claim 68, wherein the lactic acid is present in an amount of about 3% to about 30%.

70. The composition of claim 68, wherein the lactic acid is present in an amount of 10%.

71. The composition according to claim 66, wherein the composition further comprises a pigment.

72. The composition of claim 71, wherein the pigment is present in an amount of about 0.1%.

73. A composition comprising: Terbinafine or terbinafine HCl, in an amount of 0.5% to 20% by weight; Film-forming polymer, wherein the film-forming polymer is present in an amount of 5% to 15% by weight; Plasticizer, wherein the plasticizer is present in an amount of 0.5% to 5% by weight; A penetration enhancer, wherein the penetration enhancer is lactic acid present in an amount of 2% to 30% by weight; A volatile solvent, wherein the volatile solvent comprises ethanol; and Non-volatile solvents.

74. The composition of claim 73, wherein the composition is in a local form.

75. The composition of claim 73, wherein the film-forming polymer is selected from hydroxypropyl methylcellulose derivatives, polymethacrylates, or any combination thereof.

76. The composition of claim 75, wherein the film-forming polymer comprises Eudragit L100 and HPMC-AS-LF.

77. The composition of claim 76, wherein the HPMC-AS-LF is present in an amount of 0.5% (w / v) to 4% (w / v) and the Eudragit L100 is present in an amount of 5% (w / v) to 15% (w / v).

78. The composition of claim 76, wherein the HPMC-AS-LF is present in an amount of 0.5% (w / v) and the Eudragit L100 is present in an amount of 10% (w / v).

79. The composition of claim 73, wherein the plasticizer is PEG 6000.

80. The composition of claim 79, wherein PEG 6000 is present in an amount equal to or less than 4%.

81. The composition according to claim 79, wherein PEG 6000 is present in an amount of 4%.

82. The composition according to claim 73, wherein the volatile solvent is ethanol and the non-volatile solvent is an aqueous solution.

83. The composition according to claim 73, wherein the composition further comprises a solubilizer.

84. The composition according to claim 83, wherein the solubilizer is Transcutol or PEG 400.

85. The composition according to claim 84, wherein the solubilizer is Transcutol.

86. The composition of claim 85, wherein the Transcutol is present in an amount equal to or less than 5%.

87. The composition of claim 73, wherein the lactic acid is present in an amount of about 3% to about 10%.

88. The composition according to claim 87, wherein the lactic acid is present in an amount of about 10%.

89. The composition of claim 73, wherein the volume ratio of ethanol to the non-volatile solvent is from 9:1 to 6:

4.

90. The composition of claim 73, wherein the non-volatile solvent is water.

91. The composition according to claim 90, wherein the volume ratio of ethanol to water is 4:

1.

92. A composition comprising: Terbinafine or terbinafine HCl; Film-forming polymer, wherein the film-forming polymer is present in an amount of 5% to 15% by weight; Plasticizer, wherein the amount of said plasticizer is 0.5% to 5% by weight; Lactic acid, wherein the ratio of terbinafine or terbinafine HCl to said lactic acid is 1:10 (w:w) to 1:2 (w:w), and wherein said lactic acid is present in an amount sufficient to promote the penetration of terbinafine or terbinafine HCl; A volatile solvent, wherein the volatile solvent comprises ethanol; and Non-volatile solvents.

93. The composition according to claim 92, wherein the terbinafine or terbinafine HCl is present in an amount of 0.5% to 15% by weight.

94. The composition of claim 92, wherein the composition is in a local form.

95. The composition of claim 92, wherein the film-forming polymer is selected from hydroxypropyl methylcellulose derivatives, polymethyl methacrylates, or any combination thereof.

96. The composition of claim 95, wherein the film-forming polymer comprises Eudragit L100 and HPMC-AS-LF.

97. The composition of claim 96, wherein the HPMC-AS-LF is present in an amount of 0.5% (w / v) to 4% (w / v) and the Eudragit L100 is present in an amount of 5% (w / v) to 15% (w / v).

98. The composition of claim 97, wherein the HPMC-AS-LF is present in an amount of 0.5% (w / v) and the Eudragit L100 is present in an amount of 10% (w / v).

99. The composition of claim 92, wherein the plasticizer is PEG 6000.

100. The composition of claim 99, wherein PEG 6000 is present in an amount equal to or less than 4%.

101. The composition of claim 100, wherein PEG 6000 is present in an amount of 4%.

102. The composition according to claim 92, wherein the volatile solvent is ethanol and the non-volatile solvent is an aqueous solution.

103. The composition according to claim 92, wherein the composition further comprises a solubilizer.

104. The composition according to claim 103, wherein the solubilizer is Transcutol or PEG 400.

105. The composition according to claim 103, wherein the solubilizer is Transcutol.

106. The composition of claim 105, wherein the Transcutol is present in an amount equal to or less than 5%.

107. The composition of claim 92, wherein the lactic acid is present in an amount of about 3% to about 10%.

108. The composition according to claim 107, wherein the lactic acid is present in an amount of about 10%.

109. The composition of claim 92, wherein the volume ratio of ethanol to the non-volatile solvent is from 9:1 to 6:

4.

110. The composition according to claim 92, wherein the non-volatile solvent is water.

111. The composition according to claim 110, wherein the volume ratio of ethanol to water is 4:

1.

112. A method for treating nail disorders, the method comprising contacting the nail with an effective amount of the composition according to any one of claims 1 to 23 or 51 to 111.

113. The method of claim 112, wherein after contact with the a, the composition forms a film on the surface of the a within less than 2 minutes.

114. The method of claim 112, wherein the membrane is resistant to handwashing.

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