Liposomal composition, pharmaceutical composition, and gel formulation.

Description

16 Liposomal composition, pharmaceutical composition, and gel formulation. FIELD OF THE INVENTION

[001] The present invention relates to a liposome composition comprising brilaroxazine, or a pharmaceutically acceptable salt thereof. The liposome composition comprises bilayer lipid vesicles encapsulating an aqueous solution, wherein the bilayer lipid vesicles comprise brilaroxazine, and the aqueous solution comprises maltodextrin. FUNDAMENTALS

[002] Liposomes are microparticulate or colloidal carrier systems, generally 0.025–5.0 μm in diameter. Liposomes are composed of biodegradable and biocompatible components and provide a unique opportunity to deliver drugs to cells or even within individual cellular compartments. Liposomes form spontaneously when lipids are hydrated in aqueous medium at the transition temperature. Lipids are composed of natural and / or synthetic lipids (phospholipids and sphingolipids) and may contain other bilayer constituents such as cholesterol and hydrophilic polymeric lipids. Figure 1 shows a representation of a general liposome structure.

[003] The compositions of liposomes determine their interaction with blood and tissues. The compositions determine the net physicochemical properties of liposomes, namely, membrane fluidity, charge density, and steric hindrance permeability. They prove to be useful carriers for both hydrophilic and hydrophobic drugs. These drug delivery systems are employed for the delivery of drugs with different lipophilicities, such that a water-soluble drug will be encapsulated in the aqueous compartment; the lipophilic drug is usually bound to the lipid bilayer or dissolved in the lipid phase. Petition 870250088294, dated 09 / 29 / 2025, page 11 / 40 / 16

[004] Brilaroxazine (RP5063) is a multimodal modulator of dopamine and 5-HT receptors. Brilaroxazine exhibits high binding affinity for D2-4 and 5-HT1A receptors as a partial agonist, 5-HT2A as a weak partial agonist or neutral antagonist, 5-HT2B / 7 as an antagonist, and moderate affinity for the serotonin transporter (SERT). Brilaroxazine has established efficacy, safety, and pharmacokinetic profile in phase 1 and 2 studies in healthy volunteers and patients with schizophrenia. In addition, preclinical work indicates that this agent inhibits the release of multiple pro-inflammatory cytokines. BRIEF DESCRIPTION OF THE DRAWINGS

[005] Figure 1 shows a diagram of a general structure of a liposome.

[006] Figure 2 shows the particle size (Z-mean) and particle distribution index in the liposomal dispersion by DLS measurement of brilaroxazine liposomes.

[007] Figure 3 shows the HPLC chromatogram of brilaroxazine liposomes.

[008] Figure 4 shows the HPLC chromatogram of a lipogel sample. The first peak is for brillaroxazine and the second peak is for the excipient.

[009] Figure 5 shows the in vitro diffusion study graph of lipogel through the membrane. DETAILED DESCRIPTION OF THE INVENTION Brilaroxazine Liposomes

[0010] The present invention is directed to a liposome composition comprising brillaroxazine incorporated into bilayer lipid vesicles. In one embodiment, the liposome composition comprises bilayer lipid vesicles encapsulating an aqueous solution, wherein the bilayer lipid vesicles comprise one or more phospholipids, Petition 870250088294, dated 09 / 29 / 2025, page 12 / 40 / 16 sterol and brilaroxazine, and the aqueous solution comprises maltodextrin.

[0011] Brilaroxazine (free base) is a basic, lipophilic molecule with a molecular weight of 450.36 g / mol. Its chemical structure is shown below.

[0012] Brilaroxazine is frequently found in the form of the HCl salt, with a molecular weight of 486.7 g / mol.

[0013] Maltodextrin consists of D-glucose units linked in chains of varying lengths. The glucose units are linked primarily by α(1^4) glycosidic bonds. Maltodextrin is typically composed of a mixture of chains ranging from three to 17 glucose units in length. Brilaroxazine liposomes encapsulating maltodextrin may provide a better drug release profile than brilaroxazine liposomes without maltodextrin.

[0014] The lipids used in the formation of lipid vesicles typically include lipid mixtures composed predominantly of phospholipid(s) and sterol(s). A list of phospholipids commonly used in liposome preparations can be found on page 471 of Szoka et al. (Ann Rev Biophys Bioeng (1980) 9:467). The vesicles can be formulated to include negatively or positively charged lipids, such as phosphatidic acid (PA) and phosphatidylglycerol (PG), to provide a desired surface charge on the reactant vesicles. A small amount of antioxidant, such as α-tocopherol (0.1 to 1 mol%), can be added to the lipid mixture to increase stability. A typical lipid mixture used in the formation of the brilaroxazine liposome of the present invention includes phosphatidylcholine, Petition 870250088294, dated 09 / 29 / 2025, page 13 / 40 / 16 cholesterol and bronchoxazine.

[0015] Brilaroxazine liposomes are prepared by first dissolving vesicle-forming lipids (e.g., brilaroxazine, phosphatidylcholine, cholesterol) in an inert organic solvent or solvent system, for example, chloroform and / or ethanol, to form an organic-phase solution of the lipids. Generally, the inert organic solvent or solvent system is one in which the lipid components can be readily dissolved, at a concentration in the range of about 0.5–50 mg lipid / mL. Then the lipid solution is thoroughly dried to remove the organic solvent(s) and form a thin lipid film on the surface of a container. For example, the lipid solution can be dried at 45–50°C in a rotary evaporator, using vacuum to remove the solvent. Removing all the solvent leads to the formation of a thin film in the round-bottom flask, which is then kept under vacuum for 12-24 hours to completely remove any traces of the thin lipid film.After drying, the thin lipid film is then hydrated with an aqueous solution. In a preferred embodiment, the aqueous solution contains maltodextrin.

[0016] In one embodiment, the brilaroxazine liposomes comprise 10-40% or 20-30% by weight of brilaroxazine.

[0017] In one embodiment, the brylaroxazin liposomes comprise 20-60% or 30-45% by weight of maltodextrin.

[0018] In one embodiment, the average particle size of brilaroxazine liposomes is between 500-750 nm.

[0019] In one embodiment, the most intense peak of brilaroxazine liposomes has a peak size between 900-1000 nm. Pharmaceutical Compositions

[0020] The present invention provides pharmaceutical compositions comprising one or more pharmaceutically acceptable carriers and liposomes of brilaroxazine of the present invention. Brilaroxazine or its salt Petition 870250088294, dated 09 / 29 / 2025, page 14 / 40 / 16 pharmaceutically acceptable in pharmaceutical compositions in general is in an amount of about 0.01-20%, or 0.05-20%, or 0.1-20%, or 0.1-10%, or 0.1-5%, or 0.2-15%, or 0.2-10%, or 0.2-5%, or 0.2-2%, or 1-5% (w / w) for a topical formulation; about 0.1-5% for an injectable formulation, 0.1-5% for a transdermal patch formulation, about 190% for a tablet formulation, and 1-100% for a capsule formulation.

[0021] In one embodiment, the brilaroxazine liposome is incorporated into any acceptable carrier, including creams, gels, lotions, or other types of suspensions that can stabilize the active compound and release it to the affected area by topical application. In another embodiment, the pharmaceutical composition may be in a dosage form such as tablets, capsules, granules, fine granules, powders, syrups, suppositories, injectable solutions, transdermal patches, or the like. The above pharmaceutical composition may be prepared by conventional methods.

[0022] Pharmaceutically acceptable carriers, which are inactive ingredients, may be selected by a person skilled in the art using conventional criteria. Pharmaceutically acceptable carriers include, but are not limited to, non-aqueous solutions, suspensions, emulsions, microemulsions, micellar solutions, gels, and ointments.Pharmaceutically acceptable carriers may also contain ingredients that include, but are not limited to, saline solutions and aqueous electrolyte solutions; ionic and non-ionic osmotic agents such as sodium chloride, potassium chloride, glycerol and dextrose; pH adjusters and buffers such as hydroxide, phosphate, citrate, acetate, borate salts; and trolamine; antioxidants such as salts, acids and / or bases of bisulfite, sulfite, metabisulfite, thiosulfite, ascorbic acid, acetylcysteine, cysteine, glutathione, butylated hydroxyanisole, butylated hydroxytoluene, tocopherols and ascorbyl palmitate; surfactants such as lecithin, phospholipids, including, but not limited to. Petition 870250088294, dated 09 / 29 / 2025, page 15 / 40 / 16 limiting the following: phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol; poloxamers and poloxamines, polysorbates such as polysorbate 80, polysorbate 60 and polysorbate 20, polyethers such as polyethylene glycols and polypropylene glycols; polyvinyls such as polyvinyl alcohol and povidone; cellulose derivatives such as methylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, carboxymethylcellulose and hydroxypropylmethylcellulose and their salts; petroleum derivatives such as mineral oil and white petrolatum; fats such as lanolin, peanut oil, palm oil, soybean oil; mono-, di-, and triglycerides; Acrylic acid polymers such as carboxypolymethylene gel and hydrophobically modified cross-linked acrylate copolymer; polysaccharides such as dextrans and glycosaminoglycans such as sodium hyaluronate.Other pharmaceutically acceptable carriers include xanthan gum, carrageenan, Avicel RC-591 (a combination of microcrystalline cellulose and), and polyethylene glycol. Alternatively, the active compound may be dissolved or suspended in a pharmaceutically acceptable lipid formulation, such as those described by Kalepu et al. (Acta Pharmaceutica Sinica B, 3: 361-372, 2013), for example, vegetable oil, coconut oil, castor oil, etc.

[0023] Such pharmaceutically acceptable carriers may be preserved against bacterial contamination using well-known preservatives, which include, but are not limited to, benzalkonium chloride, ethylenediaminetetraacetic acid and its salts, benzethonium chloride, chlorhexidine, chlorobutanol, methylparaben, thimerosal, and phenylethyl alcohol, or may be formulated as a preservative-free formulation for single or multiple use.

[0024] For example, a tablet or capsule formulation of brilaroxazine liposome may contain other excipients that are not bioactive and do not react with the active compound. The excipients of a tablet or capsule may include diluents, binders, lubricants and glidants, disintegrants, wetting agents and Petition 870250088294, dated 09 / 29 / 2025, page 16 / 40 / 16 release rate modifiers. Binders promote the adhesion of the formulation particles and are important for a tablet formulation. Examples of excipients in a tablet or capsule include, but are not limited to, carboxymethylcellulose, cellulose, ethylcellulose, hydroxypropylmethylcellulose, methylcellulose, Karaya gum, starch, tragacanth gum, gelatin, magnesium stearate, titanium dioxide, poly(acrylic acid), and polyvinylpyrrolidone. For example, a tablet formulation may contain inactive ingredients such as colloidal silicon dioxide, crospovidone, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, sodium starch glycolate, and / or titanium dioxide. A capsule formulation may contain inactive ingredients such as gelatin, magnesium stearate, and / or titanium dioxide.

[0025] For example, a transdermal patch formulation of the active compound may comprise some inactive ingredients such as 1,3-butylene glycol, dihydroxyaluminum aminoacetate, disodium edetate, d-sorbitol, gelatin, kaolin, methylparaben, polysorbate 80, povidone, propylene glycol, propylparaben, sodium carboxymethylcellulose, sodium polyacrylate, tartaric acid, titanium dioxide, and purified water. A transdermal patch formulation may also contain a skin permeability enhancer, such as lactate esters or diethylene glycol monoethyl ether.

[0026] Topical formulations including the active compound may be in the form of gel, cream, lotion, liquid, emulsion, ointment, spray, solution, and suspension. Inactive ingredients in topical formulations include, for example, but are not limited to, (emollient / permeation enhancer), diethylene glycol monoethyl ether (emollient / permeation enhancer), DMSO (solubility enhancer), silicone elastomer (rheology / texture modifier), caprylic / capric triglyceride (emollient), octisalate (emollient / UV filter), silicone fluid (emollient / diluent), squalene Petition 870250088294, dated 09 / 29 / 2025, page 17 / 40 / 16 (emollient), sunflower oil (emollient) and silicon dioxide (thickening agent).

[0027] The present application further provides a gel formulation comprising a liposome composition of brilaroxazine, a gelling and humectant agent. In one embodiment, the gel formulation comprises brilaroxazine in an amount of 0.005-10%, 0.01-5% or 0.12% by weight. In one embodiment, the formulation has a gel-like appearance, and the bilayer lipid vesicles are intact and stable in the gel. In one embodiment, the gelling agent is carbomer 940, and the humectant is glycerin. Method of Use

[0028] This application provides a method for treating psoriasis. The method comprises administering an effective amount of brilaroxazine liposomes to an individual in need. “An effective amount,” as used herein, is the amount effective for treating psoriasis by improving the pathological condition or by reducing the symptoms of psoriasis. The method reduces one or more selected signs and symptoms from the group consisting of: red patches of skin covered with thick, silvery scales; small scaly patches; dry, cracked skin; itching, burning, or sensitivity of the skin; thickened nails with pits or ridges; and swollen, stiff joints.

[0029] The pharmaceutical composition of the present invention can be applied by local administration and by systemic administration. Local administration includes topical administration. Conventional semi-solid dosage forms commonly used have certain limitations in drug release due to the barrier properties of the skin. The skin is continuously involved in building an efficient homeostatic barrier.

[0030] The liposome gel formulation of brilaroxazine offers the following advantages. Liposomes are microscopic vesicles that Petition 870250088294, dated 09 / 29 / 2025, page 18 / 40 / 16, contains amphipathic phospholipids organized in one or more concentric bilayers that enclose aqueous compartments. Like a spherical capsule, liposomes resemble biological membranes. Liposomes are composed of biodegradable and biocompatible components and provide a drug delivery system to deliver drugs to cells or even within individual cellular compartments. Therefore, the liposome gel formulation of brilaroxazine may release brilaroxazine into the deeper layer of the skin in severe psoriatic conditions.

[0031] Systemic administration includes oral, parenteral (such as intravenous, intramuscular, subcutaneous, or rectal), and other systemic routes of administration. In systemic administration, the active compound first reaches the plasma and then distributes to the target tissues. Topical administration and oral administration are the preferred routes of administration for the present invention.

[0032] In one embodiment, the composition is applied topically to the affected area and rubbed into the skin. The composition is applied topically at least once or twice daily, or three to four times daily, depending on the medical condition and the pathology of the disease, whether chronic or acute. In general, the topical composition comprises about 0.01-10% (w / w) of the active compound. For example, the topical composition comprises about 0.1 to 2% (w / w) of the active compound. Depending on the size of the affected area, 0.2-85 mL, typically 0.2-10 mL, of the topical composition is applied to the individual per dose. The active compound penetrates the skin and is released at the site of discomfort.

[0033] A person skilled in the art will recognize that a wide variety of release mechanisms are also suitable for the present invention.

[0034] The present composition of brilaroxazine liposomes is useful Petition 870250088294, dated 09 / 29 / 2025, page 19 / 40 / 16 in the treatment of a mammalian individual, such as humans, horses and dogs. The present invention is particularly useful in the treatment of humans.

[0035] The following examples further illustrate the present invention. These examples are merely illustrative of the present invention and should not be interpreted as limiting. EXAMPLES Example 1. Preparation of Brilaroxazine Liposomes

[0036] Table 1 shows the composition of the brilaroxazine liposome formulation. Table 1. No. List of Ingredients Percentage CAS No. 1. Briloxazin 24.53 1239729-06-6 2. Lecithin 34.76 8002-43-5 3. Cholesterol 2.97 57-88-5 4. Maltodextrin 37.74 9050-36-6 5. Purified water (for hydration of the lipid film) Qs NA Solvents used for the preparation of the dry lipid film 6. Chloroform (which was dried in the process) NA 67-66-3 7. Ethanol (which was dried in the process) NA 64-17-5

[0037] Brilaroxazine liposomes were prepared by the lipid hydration method. Briefly, phosphatidylcholine and cholesterol were dissolved in a suitable solvent (chloroform and / or ethanol) and brilaroxazine was dissolved in the same solvent. The drug-lipid solution was then dried at 45-50°C in a rotary evaporator, using vacuum to completely remove the solvent. After all solvent removal, a thin film formed in the round-bottom flask. The round-bottom flask containing the lipid film was kept under vacuum for 12-24 h to completely remove any traces of solvents present in the thin lipid film. After 12-24 h of drying, the thin film was hydrated with 66 mL of maltodextrin solution at 60°C (concentration of 39.57 mg / mL). Example 2. Particle Size Analysis and Zeta Potential of Brilaroxazine Liposomes

[0038] The liposomes prepared from Example 1 were Petition 870250088294, dated 09 / 29 / 2025, page 20 / 40 / 16 observed at different magnifications under an optical microscope for confirmation during the hydration process. Observation under an optical microscope at different magnifications (10x, 20x and 40x) to confirm the prepared spherical liposomal vesicles occurred throughout the hydration process.

[0039] Liposomes were analyzed for particle size using the DLS (dynamic light scattering) method for particle size and drug content analysis. The Z-mean (particle size) was measured for the prepared liposomes. Figure 2 shows the particle size (Z-mean) and particle distribution index in the liposomal dispersion by DLS measurement of brilaroxazine liposomes.

[0040] Zeta potentials were estimated from the experimentally determined electrophoretic mobility of the particles. The value of the zeta potential indicates the stability of the colloidal dispersion.

[0041] Zeta potential value (mV): • 0 to 5 - Rapid coagulation or flocculation • 10 to 30 - Incipient instability • 30 to 40 - Moderate stability • 40 to 60 - Good stability • > 61 - Excellent stability

[0042] In general, colloidal dispersions with zeta potential values ​​greater than +30 mV or less than -30 mV exhibit a high degree of stability. The higher the zeta potential value (both positive and negative), the better the stability.

[0043] Table 2 shows the particle size and zeta potential analysis of liposomes by the DLS method. Table 2. Liposomes No. Particle Size (Z-Average) nm Zeta Potential (mV) Liposomes RP5063 630.9 38.8 Example 3. Measurement of Drug Content by HPLC Petition 870250088294, dated 09 / 29 / 2025, page 21 / 40 / 16

[0044] The drug content in liposomes was analyzed by the HPLC method. HPLC System

[0045] Shimadzu HPLC system (LC-2030C Plus, Serial No.: L21445711704 AE, Made in Japan), autosampler, UV detector, data acquisition system. An equivalent system may be used as a substitute. HPLC column

[0046] Shimadzu Shim-Pack GIST C18, 5 pm, 250 x 4.6 mm or equivalent column. Reagent preparation Mobile phase A

[0047] · Dissolve 2.72 g of KH2PO4 in 1000 mL of ultrapure water (0.02M solution).

[0048] · Adjust the pH to 3.0 with phosphoric acid.

[0049] · Mix 90 parts of the above buffer with 10 parts of acetonitrile.

[0050] · Filter through membrane before use. Mobile phase B

[0051] •Mix 90 parts acetonitrile with 10 parts ultrapure water. Adjust the pH to 3.0 with phosphoric acid.

[0052] · Filter through membrane before use. Diluent

[0053] · Prepare a mixture of acetonitrile and phosphate buffer (section 6.2.1.1) (85:15) for drug content / encapsulation efficiency. Sample preparation for drug content and incorporation efficiency. Drug content.

[0054] Place the required amount of liposome sample (complete dispersion) into a volumetric flask, add the volume Petition 870250088294, dated 09 / 29 / 2025, page 22 / 40 / 16 necessary diluent (6.2.3) and mix well. Keep this mixture in an ultrasonic bath for 30-45 minutes at 60°C. Remove the required volume of the prepared sample and dilute to the required concentration. The assay concentration / drug content is 20 mg / mL. Incorporation efficiency

[0055] Place the required amount of liposome sample in a centrifuge tube and centrifuge the liposome dispersion at 10000 rpm for 30 minutes at 20°C. Remove the supernatant solution and collect the pellet. Add the required volume of diluent to the liposomal pellet and mix well. Keep this mixture in an ultrasonic bath for 30-45 minutes at 60°C. Withdraw the required volume of the prepared sample and dilute to a drug concentration of 20 mg / mL. Standard solution

[0056] Prepare a standard solution of 20 mg / mL with the diluent above. Analysis

[0057] Configure HPLC using the following parameters: Column: Shimadzu Shim-Pack GIST C18, 5 gm, 250 x 4.6 mm or equivalent Flow rate: 1 mL / min Injection volume: 20 g / L Detection: UV @215 nm Column temperature: 30°C Execution time: 5-7 minutes HPLC conditions: mobile phase A, 25%; mobile phase B, 75% Identification

[0058] Compare the peak retention time of the standard / pure drug and the peak of the sample drug. Result

[0059] The HPLC chromatogram is shown in Figure 3. The Petition 870250088294, dated 09 / 29 / 2025, page 23 / 40 / 16 HPLC results show that the drug content is 96% and the drug incorporation efficiency in the liposome is 73%.

[0060] The final composition of the formulation was consistent with bryoxazin (24.53%), lecithin (34.75%), cholesterol (2.97%), maltodextrin (37.74%) and purified water for hydration of the lipid film. Example 4. Preparation of Liposomal Gel Formulations

[0061] The liposomal gel was prepared by incorporating a liposome dispersion into a gel formulation. First, the base gel was prepared, and then the liposome dispersion was added and thoroughly mixed to result in the liposomal gel or lipogel. Various percentages of lipogel formulation (0.25% to 1.5% brilaroxazin) were prepared as needed. Table 3 shows the composition of the lipogel formulation. Table 3. Function of ingredients Lipogel Formulation - RPLG Percentage (%) Gelling agent Carbomer 940 0.65 - 0.85 Humectant Glycerin 5.00 pH modifier Triethanolamine 0.10-0.25 Preservative Phenoxyethanol 1.00 Vehicle Purified water Qs Brilaroxazine Liposomal dispersion RP5063 Equivalent to 0.25% or 1.5% brilaroxazine

[0062] The prepared liposomal gel formulation was evaluated for physical appearance and pH. All gel formulations were observed under an optical microscope to verify intact liposomes in the gel formulation. The liposomal gel formulation presented a white cream gel appearance, with a pH of 5-6, and microscopic examination showed the presence of liposomes. Furthermore, the liposomal particles were intact and stable in all gel formulations. Example 5. Lipogel Analysis by HPLC

[0063] The lipogel sample was placed in a volumetric flask, diluent was added, and the mixture was thoroughly mixed. The brilaroxazine content was analyzed by HPLC according to the same protocols as in Example 3. Petition 870250088294, dated 09 / 29 / 2025, page 24 / 40 / 16

[0064] Comparing the retention time of the pure drug peak and the sample peak, the drug content was calculated to be 95.12%.

[0065] The HPLC chromatogram of a lipogel sample is shown in Figure 4. The first peak is for brilaroxazine and the second peak is for the excipient. The brilaroxazine peak is sharp and separate from the excipient peak. Example 6. In vitro diffusion / permeation studies of Lipogel

[0066] The prepared lipogels were analyzed for drug diffusion / permeation using a Franz diffusion cell. The Franz diffusion cell was filled with PBS buffer pH 7.4. A regenerated cellulose dialysis membrane, surface-treated and neutralized with PBS pH 7.4 (molar mass cutoff point: 12000 to 14000), was placed in the receiving compartment, and a weighed amount of lipogel was placed in the donor compartment. The receiving solution was stirred with a magnetic stirrer, and skin temperature was maintained in the diffusion cell by circulating thermostated water in the outer jacket. At different time intervals, samples were withdrawn through a sampling port and replaced with the same volume of plain PBS. The withdrawn sample was mixed with an equal volume of diluent for HPLC and analyzed for drug content at different time intervals.The percentage of drug diffusion, flow rate, and permeation coefficient were calculated for each lipogel formulation. Time versus percentage of drug diffusion / release was plotted using GraphPad Prism software Version 6.01. HPLC analysis of drug diffusion samples

[0067] The HPLC analysis method, system and columns were the same as described in Example 3, except that a mixture of acetonitrile and phosphate buffer (60:40) was used for the drug diffusion / permeation studies. Petition 870250088294, dated 09 / 29 / 2025, page 25 / 40 / 16 Sample preparation for diffusion / permeation analysis

[0068] Mix an equal volume of diluent with the diffusion / permeation sample fluid taken from the Franz diffusion apparatus. Mix well in a vortex mixer and filter the solution through a syringe filter. Results

[0069] The HPLC chromatogram results of the lipogel diffusion sample show a sharp and separate brilaroxazine peak.

[0070] Figure 5 shows the in vitro diffusion study graph of the lipogel through the membrane. The release profile showed constant and sustained release of brilaroxazine from the formulation throughout the 8-hour study period.

[0071] Table 4 shows the results of the in vitro diffusion study of the lipogel formulations. Table 4. Formulation Flow (pg / cm2 / h) Permeation coefficient (cm / h) R2 value Lipogel formulation with maltodextrin 12.02 3.28 0.9984 Lipogel formulation without maltodextrin 5.48 1.92 0.9633

[0072] The lipogel formulation containing liposomes with maltodextrin showed a better drug release profile and higher flux and permeation values ​​in the in vitro diffusion study than liposomes without maltodextrin. This may be due to the increased solubility of RP5063 in the liposomal gel and the optimal particle size distribution in the formulation.

[0073] It should be understood that the foregoing describes preferred embodiments of the present invention and that modifications may be made without departing from the scope of the present invention as set forth in the claims. Petition 870250088294, dated 09 / 29 / 2025, page 26 / 40

Claims

CLAIMS 1. Liposome composition, characterized in that it comprises bilayer lipid vesicles encapsulating an aqueous solution, wherein the bilayer lipid vesicles comprise one or more phospholipids, sterol and brilloxazin or a pharmaceutically acceptable salt thereof, and the aqueous solution comprises maltodextrin.

2. Liposome composition according to claim 1, characterized in that the phospholipid comprises phosphatidylcholine, and the sterol comprises cholesterol.

2. Liposome composition according to claim 1, characterized in that it comprises 20-30% by weight of briloxazin.

3. Liposome composition according to claim 1, characterized in that it comprises 30-45% by weight of maltodextrin.

4. Liposome composition according to claim 1, characterized in that the average particle size of the lipid vesicles is between 500-750 nm.

5. Pharmaceutical composition, characterized in that it comprises the liposome composition as defined in claim 1, and a pharmaceutically acceptable carrier.

6. Gel formulation, characterized in that it comprises the liposome composition as defined in any one of claims 1 to 4, a gelling agent and a humectant, wherein the gel formulation comprises briloxazin in an amount of 0.1-2% by weight, the formulation has a gel-like appearance, and the bilayer lipid vesicles are intact and stable in the gel.

7. Gel formulation according to claim 5, characterized in that the gelling agent is carbomer 940, and the humectant is glycerin. Petition 870250088294, dated 09 / 29 / 2025, page 27 / 40

Images