Drug-loaded filament comprising topiramate and pharmaceutical preparation for preventing or treating obesity prepared using same

Abstract

The present invention relates to a drug-loaded filament comprising topiramate and a pharmaceutical preparation for preventing or treating obesity prepared using same. Topiramate contained in the filament exhibits an amorphous nature, and thus can be used in the preparation of a pharmaceutical preparation that is easily dissolved, thereby facilitating application and absorption in the body. The drug-loaded filament comprising same can be applied to 3D printing such as fused deposition modeling (FDM) and effectively used in the preparation of a pharmaceutical preparation that can be administered via various mucosal administration routes, such as oral mucosa, e.g., sublingual and buccal mucosa, and nasal mucosa in the nasal cavity or the like.

Description

Drug-loaded filament containing topiramate and pharmaceutical preparation for preventing or treating obesity prepared using the same

[0001] The present invention relates to a drug-loaded filament comprising topiramate and a pharmaceutical preparation for preventing or treating obesity prepared using the same.

[0002] This invention was made possible with the support of the Small and Medium Business Administration's "Startup Growth Technology Development, Project No. 1425180230, Project No. 00271590" funded by the Ministry of SMEs and Startups.

[0003] Research is currently being conducted to manufacture various pharmaceutical formulations using 3D printing technology. This technology can enable the production of personalized medicines, leading to growing interest in 3D printing within the pharmaceutical industry. Furthermore, these advantages are expected to drive the development of new treatments and improve the safety and efficacy of pharmaceuticals. The FDA approved the first 3D-printed drug, SPRITAM, in August 2015. ® (Levetiracetam) has been approved, and research into 3D-printed drugs is accelerating further following FDA approval.

[0004] Among various 3D printing methods, fused deposition modeling (FDM) is a type of extrusion printing and the most widely used. FDM uses filament to create materials layer by layer. Therefore, manufacturing 3D printed pharmaceutical formulations requires drug-loaded filament.

[0005] Meanwhile, oral administration is the most commonly used route of administration for drugs, but the mucosa is being considered as a major alternative route of administration to increase the therapeutic effect by administering directly to the mucosal area or to increase the utilization of drugs that are effectively absorbed through the mucosa to increase bioavailability.

[0006] Mucosa exists in areas not exposed to the outside world, such as the gastrointestinal tract, as well as the oral cavity, nasal cavity, genitals, rectum, digestive tract, and skin ulcers. Pharmacologically active substances administered through mucosa can be absorbed into the bloodstream more immediately than substances administered orally, thus shortening the time required for the onset of drug effect. Furthermore, direct drug application to the oral, nasal, respiratory, ocular, genital, and skin ulcer mucosa has the advantage of enhancing drug efficacy compared to oral administration. However, there have been no reported studies on topiramate administered through the mucosal route to date.

[0007] Accordingly, the inventors of the present invention conducted research to improve the preventive or therapeutic effect of topiramate on obesity by administering topiramate via the mucosal route, thereby completing the present invention.

[0008] One object of the present invention is to provide a drug-loaded filament, wherein the filament comprises topiramate or a pharmaceutically acceptable salt thereof, a high molecular weight polymer, and an excipient, and the filament is hot melt extruded.

[0009] Another object of the present invention is to provide a pharmaceutical preparation for preventing or treating obesity comprising topiramate or a pharmaceutically acceptable salt thereof.

[0010] Another object of the present invention is to provide a method for preventing or treating obesity, comprising a step of administering the pharmaceutical preparation to the mucosa of a subject.

[0011] Another object of the present invention is to provide a kit comprising the above pharmaceutical preparation.

[0012] One aspect of the present invention provides a drug-loaded filament, wherein the filament comprises topiramate or a pharmaceutically acceptable salt thereof, a high molecular weight polymer, and an excipient, and the filament is hot melt extruded.

[0013] According to one specific example of the present invention, the filament may not have an endothermic peak by differential scanning calorimetry (DSC).

[0014] Another aspect of the present invention provides a pharmaceutical preparation for preventing or treating obesity comprising topiramate or a pharmaceutically acceptable salt thereof.

[0015] According to one specific example of the present invention, the pharmaceutical formulation may be a 3D printed pharmaceutical formulation.

[0016] According to one specific example of the present invention, the 3D printing may be fused deposition modeling 3D printing.

[0017] According to one specific example of the present invention, the filament used in the 3D printing may be the drug-loaded filament of claim 1.

[0018] According to one specific example of the present invention, the formulation of the pharmaceutical preparation may be a mucosal administration formulation.

[0019] According to one specific example of the present invention, the mucosa may be any one mucosa selected from the group consisting of oral mucosa, pulmonary mucosa, ocular mucosa, nasal mucosa, vaginal mucosa, and digestive mucosa.

[0020] Another aspect of the present invention provides a method for preventing or treating obesity, comprising administering the pharmaceutical formulation to a mucosa of a subject.

[0021] Another aspect of the present invention provides a kit comprising the pharmaceutical formulation.

[0022] According to a drug-loaded filament containing topiramate and a pharmaceutical preparation for preventing or treating obesity manufactured using the same, topiramate contained in the filament exhibits an amorphous state, so it is easy to dissolve and can be used in the manufacture of a pharmaceutical preparation that is easy to apply and absorb in the body, and the drug-loaded filament containing the same can be effectively used in the manufacture of a pharmaceutical preparation that can be administered through various mucosal administration routes, such as oral mucosa such as sublingual and buccal mucosa, and nasal mucosa such as nasal cavity, by being applied to 3D printing such as FDM (fused deposition modeling).

[0023] FIG. 1 is a photograph showing an FDM-3D printed pharmaceutical formulation containing topiramate as an active drug ingredient according to one specific example of the present invention.

[0024] Figure 2 is a graph showing the results of differential scanning calorimetry analysis of topiramate crystal form.

[0025] FIG. 3 is a graph showing the results of differential scanning calorimetry analysis of a drug-loaded filament containing topiramate as an active drug ingredient according to one specific example of the present invention.

[0026] Figure 4 is a diagram showing the mouse experimental schedule for confirming the effects of weight loss and food intake reduction.

[0027] FIG. 5 is a graph showing an excellent weight loss effect when a 3D printed pharmaceutical formulation containing topiramate as an active drug ingredient according to one specific example of the present invention is administered via the buccal mucosa route.

[0028] FIG. 6 is a graph showing an excellent food intake reduction effect when a 3D printed pharmaceutical formulation containing topiramate as an active drug ingredient according to one specific example of the present invention is administered via the buccal mucosa route.

[0029] One aspect of the present invention provides a drug-loaded filament, wherein the filament comprises topiramate or a pharmaceutically acceptable salt thereof, a high molecular weight polymer, and an excipient, and the filament is hot melt extruded.

[0030] Topiramate is 2,3:4,5-Bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate, and its chemical structure is shown in Chemical Formula 1 below:

[0031] [Chemical Formula 1]

[0032] .

[0033]

[0034] Hot melt extrusion can be performed at a temperature higher than the melting temperature of the active pharmaceutical ingredient, topiramate, and one or more of the polymers and excipients. The screw speed during hot melt extrusion can be controlled, for example, at 10 to 500 rpm, more preferably at 20 to 300 rpm.

[0035] The drug-loaded filament of the present invention comprises a high molecular weight polymer and an excipient, wherein the high molecular weight polymer supports the filament to form a skeleton, and the high molecular weight polymer and the excipient provide strength and flexibility to the filament.

[0036] According to one specific example of the present invention, the high molecular weight polymer and excipient may be one or more high molecular weight polymers and excipients selected from the group consisting of PVA (Polyvinyl Alcohol), HPMC (Hydroxypropylmethyl cellulose), HPC (hydroxypropyl cellulose), povidone, co-povidone, MCC (Microcrystalline Cellulose), silica (SiO2), croscarmellose, mannitol, Eudragit, PEG (Polyethylene Glycol), and PEO (polyethylene oxide).

[0037] High molecular weight polymers and excipients that can be included in the drug-loaded filament of the present invention include PEO (polyethylene oxide), EVA (ethylene vinyl acetate copolymer), PVA (polyvinyl alcohol), PVAc (polyvinyl acetate), PEG (polyethylene glycol), HPC (hydroxypropyl cellulose), PLA (polylactic acid), PCL (polycaprolactone), PLGA (polylactic acid-glycolic acid copolymer), PVP (polyvinylpyrrolidone), PVCap (polyvinyl caprolactam), MC (methylcellulose), CMC (carboxymethyl cellulose), MCC (microcrystalline cellulose), EC (ethyl cellulose), HEC (hydroxyethyl cellulose), HPMC (hydroxypropyl methylcellulose), HPMCP (hydroxypropyl methylcellulose phthalate), HPMCAS (hydroxypropyl methylcellulose acetate succinate), carbomer, PVP-PVAc copolymer, PVCap-PVAc copolymer, PVAc-PEG Graft copolymer (PVAc-PEG graft copolymer), PVCap-PVA-PEG copolymer, PVAc-methyl methacrylate chloride dimethylaminoethyl methacrylate copolymer (PVAc-methyl methacrylate chloride dimethylaminoethyl methacrylate polymer),Dimethylaminoethyl methacrylate-butyl acrylate-methyl methacrylate polymer, ethyl acetate-methyl methacrylate-butyl methacrylate polymer, poly(ethylene glycol) methyl methacrylate polymer, methacrylic acid-methyl methacrylate polymer, methacrylic acid-ethyl acrylate polymer, povidone, co-povidone, starch, chitosan, xanthan gum, carnauba wax, microcrystalline wax, It may be talc, tricalcium phosphate, lactose, silica (SiO2), croscarmellose, mannitol and / or Eudragit, and preferably PVA (Polyvinyl Alcohol), HPMC (Hydroxypropylmethyl cellulose), HPC (hydroxypropyl cellulose), povidone, co-povidone, MCC (Microcrystalline Cellulose), silica (SiO2), croscarmellose, mannitol, Eudragit,It may be one or more high molecular weight polymers and excipients selected from the group consisting of PEG (Polyethylene Glycol) and PEO (polyethylene oxide).

[0038] According to one specific example of the present invention, the high molecular weight polymer and excipient may be one or more high molecular weight polymers and excipients selected from the group consisting of PVA (Polyvinyl Alcohol), HPMC (Hydroxypropylmethyl cellulose), HPC (hydroxypropyl cellulose), povidone, co-povidone, MCC (Microcrystalline Cellulose), silica (SiO2), croscarmellose, mannitol, Eudragit, PEG (Polyethylene Glycol), and PEO (polyethylene oxide).

[0039] In addition, as a plasticizer that can be included in the drug-loaded filament of the present invention, methylparaben, acetone, methanol, ethanol, isopropanol, cetyl alcohol, stearyl alcohol, sucralose, mannitol, sorbitol, glycerin, bee wax, triethyl citric acid, PEG, PPG (propylene glycol), triacetin, dibutyl sebacic acid, glycerol stearate, monoglyceride acetic acid, tributyl citric acid, acetyltriethyl citric acid, acetyltributyl citric acid, butyl stearic acid, stearyl alcohol, diethyl phthalate, dibutyl phthalate, dioctyl phosphate, dimethyl phthalate, mineral oil, castor oil, benzyl benzoate, chlorobutanol, dextrin, lanolin alcohol, palmitic acid, petrolatum, propylene glycol, It may further include, but is not limited to, pyrrolidone, stearic acid, triethanolamine and / or vitamin E TPGS.

[0040] According to one specific example of the present invention, the hot melt extrusion temperature may be 40 to 300°C, preferably 50 to 200°C, and more preferably 65 to 160°C.

[0041] According to one specific example of the present invention, the hot melt extrusion speed may be 10 to 300 cm / min, preferably 20 to 280 cm / min, and more preferably 65 to 250 cm / min.

[0042] According to one specific example of the present invention, the filament may not have an endothermic peak by differential scanning calorimetry (DSC).

[0043] Since topiramate, an active drug ingredient included in the filament of the present invention, is amorphous, there is no problem of the stability and solubility of the drug changing depending on crystallization and crystallinity.

[0044]

[0045] Another aspect of the present invention provides a pharmaceutical preparation for preventing or treating obesity comprising topiramate or a pharmaceutically acceptable salt thereof.

[0046] The pharmaceutical preparation of the present invention may additionally include a pharmaceutically acceptable carrier. The pharmaceutically acceptable carrier included in the dosage form of the present invention is one commonly used in the manufacture of drugs, and includes, but is not limited to, lactose, dextrose, sucrose, sorbitol, sucralose, mannitol, starch, acacia gum, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil. In addition to the above components, the dosage form of the present invention may further include a lubricant, a wetting agent, a sweetening agent, a flavoring agent, an emulsifier, a suspending agent, a preservative, and the like. Suitable pharmaceutically acceptable carriers and formulations are detailed in Remington: the science and practice of pharmacy 22nd edition (2013).

[0047] The pharmaceutical preparation of the present invention may include various bases and / or additives necessary and appropriate for the formulation of the dosage form, and may be manufactured by further including known compounds such as nonionic surfactants, silicone polymers, pigments, fragrances, preservatives, bactericides, oxidation stabilizers, organic solvents, ionic or nonionic thickeners, softeners, antioxidants, free radical scavengers, opacifiers, stabilizers, emollients, silicones, α-hydroxy acids, antifoaming agents, moisturizers, vitamins, insect repellents, fragrances, preservatives, surfactants, anti-inflammatory agents, substance P antagonists, fillers, polymers, propellants, alkalizing or acidifying agents, or colorants, within a range that does not reduce the effectiveness thereof.

[0048] The appropriate dosage of the pharmaceutical formulation of the present invention may be prescribed in various ways depending on factors such as the formulation method, administration method, patient age, weight, sex, pathological condition, food, administration time, administration route, excretion rate, and response sensitivity. The dosage of the formulation of the present invention may be 0.001 to 1000 mg / kg for adults.

[0049] According to one specific example of the present invention, the pharmaceutical formulation may be a 3D printed pharmaceutical formulation.

[0050] According to one specific example of the present invention, the 3D printing may be fused deposition modeling 3D printing.

[0051] A drug-loaded filament according to one specific example of the present invention is applied to a 3D printer, and the applicable 3D printer is preferably a fused deposition modeling (FDM) 3D printer. The FDM method is one of the extrusion printing methods, and prints using filament in a layer-by-layer unit, and filaments that are too easily broken or too flexible may be difficult to apply to the FDM method.

[0052] According to one specific example of the present invention, the filament used in the 3D printing may be the drug-loaded filament.

[0053] A method for manufacturing a printed output tablet by applying a drug-loaded filament according to one embodiment of the present invention to an FDM-3D printer may include a step of introducing the filament into a chamber of the 3D printer and then molding it. The molding may be performed under temperature conditions higher than the melting temperature of the drug-loaded filament and at a diameter of a certain size, for example, at a speed of 65 to 250 cm / min and a diameter of 1.50 to 1.90 mm.

[0054] According to one specific example of the present invention, the formulation of the pharmaceutical preparation may be a mucosal administration formulation.

[0055] The pharmaceutical preparation of the present invention can be administered in various dosage forms when administered via the mucosal route, such as oral tablets, powders, spray formulations, ointment formulations, film formulations, or gel formulations, and may further include various excipients, such as wetting agents, sweeteners, fragrances, preservatives, etc. Specifically, when the formulation of the present invention is formulated as a mucosal administration formulation, it may further include appropriate carriers, excipients, and diluents commonly used in its manufacture. Examples of the carrier, excipient and diluent include, but are not limited to, lactose, dextrose, sucrose, sorbitol, sucralose, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate and / or mineral oil. In addition, the formulation may be prepared by including diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants and surfactants commonly used in formulation, and in addition to the excipients, a lubricant such as magnesium stearate or talc may be further included.

[0056] In addition, for oral administration for absorption through the digestive mucosa, it can be manufactured in the form of granules, microspheres, capsules, oral gels, etc. in addition to tablets. The pharmaceutical preparation of the present invention can be manufactured in various dosage forms such as liquid, spray, microsphere formulation, powder, aerosol, etc. for drug administration to the pulmonary mucosa. When designing a dosage form for drug administration to the nasal mucosa, ocular mucosa, etc., the pharmaceutical preparation of the present invention can be manufactured in various dosage forms such as liquid, spray, microsphere formulation, gel, ointment formulation, powder, etc. When designing a dosage form for drug administration to the vaginal mucosa, the pharmaceutical preparation of the present invention can be manufactured in various dosage forms such as mucoadhesive tablets, capsules, films, liquids, sprays, microsphere formulations, gels, ointment formulations, powder, etc.

[0057] The pharmaceutical preparation of the present invention can be manufactured as a tablet, film, liquid, ointment, gel, spray, gum, etc. to be applied to the mucosa, and specifically, it can be Troches, Sublingual Tablets, Buccal Tablets, Mucoadhesive Tablets, Medicated Chewing Gums, Liquids and Solutions for Oromucosal Application, Sprays for Oromucosal Application, Semisolid Preparations for Oro mucosal Application, Orodispersible films for Oromucosal Application, Ointments, Creams, Gels, or Nasal Dry Powder Inhalers, Nasal Solutions, or Vaginal Mucosa. It can be an absorbable vaginal tablet or a suppositories for vaginal use.

[0058] According to one specific example of the present invention, the mucosa may be any one mucosa selected from the group consisting of oral mucosa, pulmonary mucosa, ocular mucosa, nasal mucosa, vaginal mucosa, and digestive mucosa.

[0059] The mucosal administration formulation of the present invention can be directly applied to the mucosal area to be treated, so that a therapeutically effective amount of the drug is released to the area to which the formulation is applied. For example, oral mucosal areas may include the gums, palate, tongue, sublingual mucosa, or the mucosal area inside the cheek. In some cases, the formulation can be applied to various biological mucosal areas such as the pulmonary mucosa, ocular mucosa, nasal mucosa, vaginal mucosa, and digestive mucosa.

[0060]

[0061] Another aspect of the present invention provides a method for preventing or treating obesity, comprising administering the pharmaceutical formulation to a mucosa of a subject.

[0062] Topiramate or a pharmaceutically acceptable salt thereof included in the pharmaceutical composition of the present invention may be administered by a mucosal administration method in an amount effective for the treatment or prevention of an individual or patient, depending on the purpose. It should be understood that the dosage to be administered to a specific individual or patient at the time of administration should be determined based on various related factors such as the patient's weight, age, race, sex, health condition, diet, administration time, administration method, and severity of the disease, and may be appropriately increased or decreased by a specialist. For example, a physician may start the dosage of the pharmaceutical preparation of the present invention at a level lower than that required to achieve the desired therapeutic effect, and gradually increase the dosage until the desired effect is achieved, and may easily determine and prescribe the dosage as needed.

[0063] Another aspect of the present invention provides a kit comprising the pharmaceutical formulation.

[0064] The kit of the present invention may include a pharmaceutical preparation comprising topiramate or a pharmaceutically acceptable salt thereof and capable of being administered via the mucosal route. The kit may be administered via the mucosal route.

[0065] The present invention will be described in more detail below through one or more examples. However, these examples are intended to exemplify the present invention and the scope of the present invention is not limited to these examples.

[0066]

[0067] Manufacturing Example 1. Manufacturing of a 3D-printed pharmaceutical formulation containing topiramate as an active pharmaceutical ingredient.

[0068] A slurry composition for manufacturing a drug-loaded filament was prepared by mixing PVA (polyvinyl alcohol) and / or HPC (hydroxypropyl cellulose) as high molecular weight polymers, PVP (polyvinylpyrrolidone), HPMC (hydroxypropylmethyl cellulose), co-povidone and / or PEO (polyethylene oxide) as excipients, and topiramate as an active drug ingredient. The prepared slurry composition was hot melt extruded (HME) under the conditions of a nozzle size of 1.75 mm, an extrusion speed of 180 cm / min, and an extrusion temperature of 130°C, and then dried at room temperature to manufacture a drug-loaded filament containing topiramate as an active drug ingredient. Thereafter, the prepared drug-loaded filament was supplied and output to a commercial Fused Deposition Modeling (FDM)-3D printer (Prusa kit) to manufacture a film-type pharmaceutical formulation (Fig. 1) that can be administered via the mucosal route.

[0069]

[0070] Experimental Example 1. Confirmation of the amorphous nature of topiramate in drug-loaded filaments by differential scanning calorimetry analysis.

[0071] For the drug-loaded filament manufactured in Manufacturing Example 1, it was analyzed whether the active drug ingredient, topiramate, maintained an amorphous state within the filament using differential scanning calorimetry (DSC).

[0072] Specifically, 5 mg of drug-loaded filament samples were analyzed using differential scanning calorimetry at a heating rate of 10 °C / min over a temperature range of 25 to 250 °C. Calibration for cell constant and enthalpy was performed using indium (Tm = 156.6 °C, DHf = 28.71 J / g) according to the manufacturer's instructions, and nitrogen was used as a purge gas at a flow rate of 50 mL / min in all experiments. Data were collected using STARe software for the DSC 3 series and analyzed using a STARe Thermal Analysis system.

[0073] As a result, unlike the topiramate crystal form (Fig. 2), no specific peak was identified in the drug-loaded filament manufactured in Manufacturing Example 1 (Fig. 3), confirming the amorphous nature of topiramate, the active drug ingredient.

[0074]

[0075] Experimental Example 2. Confirmation of Morphological Characteristics Suitable for Mucosal Administration of 3D-Printed Pharmaceutical Formulations

[0076] For the film-shaped 3D printed pharmaceutical formulation manufactured in Manufacturing Example 1, a thin platinum layer was pre-coated for 10 minutes, and the surface morphology was analyzed using a field emission scanning electron microscope (FE-SEM, JEOL, JSM-7900F, Tokyo, Japan) at 5 kV.

[0077] As a result, the roughness and uniformity of the film surface were found to be suitable, and it was confirmed to be suitable as a mucosal administration formulation.

[0078]

[0079] Experimental Example 3. Confirmation of excellent weight loss and food intake reduction effects following mucosal administration of a 3D-printed pharmaceutical formulation containing topiramate.

[0080] It was analyzed whether topiramate, which was not previously used as a mucosal administration route, could exhibit superior weight loss and food intake reduction effects compared to oral administration when included in the film-type 3D printed pharmaceutical preparation manufactured in Manufacturing Example 1 and applied as a mucosal administration route.

[0081] Specifically, 40 5-week-old C57BL6-J mice were prepared, and 8 mice were divided into each group. Group T01 was prepared with a normal-fat diet for 4 weeks, and groups T02 to T05 were prepared with a high-fat diet (Fig. 4). Thereafter, groups T01 and T02 were repeatedly administered the vehicle once a day for 5 weeks. Group T03 was administered the film-type 3D printed pharmaceutical formulation manufactured in Manufacturing Example 1 dissolved in water and orally swallowed. Group T04 was administered the topiramate active ingredient dissolved in water and orally swallowed. Group T05 was administered the film-type 3D printed pharmaceutical formulation manufactured in Manufacturing Example 1 by attaching it to the buccal mucosa and administering it via the mucosal route. Topiramate was administered to groups T03 to T05 at a dose of 2 mg / kg daily.

[0082] As a result, the weight loss effect was confirmed in the T03 to T05 groups administered topiramate compared to the T02 group administered a high-fat diet, and in particular, the weight loss effect of T05 administered topiramate through the buccal mucosa was significantly superior to that of the T03 and T04 groups administered topiramate orally (Fig. 5). In addition, in terms of food intake, the T03 and T04 groups showed a recovery in food intake to a level similar to that of the T02 group administered a high-fat diet from the 4th week after topiramate administration, whereas the reduced food intake in the T05 group was confirmed to be maintained until the end of the experiment (Fig. 6).

[0083] Through these results, it was confirmed that the effects of topiramate on weight loss and food intake reduction were improved when administered via the mucosal route compared to the oral route.

[0084]

[0085] The present invention has been described above, focusing on specific embodiments thereof. Those skilled in the art will appreciate that the present invention can be implemented in modified forms without departing from its essential characteristics. Therefore, the disclosed embodiments should be considered illustrative rather than limiting. The scope of the present invention is set forth in the claims, not the foregoing description, and all differences within the scope equivalent thereto should be construed as being encompassed by the present invention.

Claims

1. In drug-loaded filaments, The above filament comprises topiramate or a pharmaceutically acceptable salt thereof, a high molecular weight polymer and an excipient, The above filament is hot melt extruded. Drug-loaded filament.

2. In paragraph 1, A drug-loaded filament having no endothermic peak as measured by differential scanning calorimetry (DSC).

3. A pharmaceutical preparation for preventing or treating obesity containing topiramate or a pharmaceutically acceptable salt thereof.

4. A pharmaceutical preparation for preventing or treating obesity, wherein the pharmaceutical preparation in paragraph 3 is a 3D printed pharmaceutical preparation.

5. A pharmaceutical preparation for preventing or treating obesity, wherein the 3D printing in the fourth paragraph is fused deposition modeling 3D printing.

6. A pharmaceutical preparation for preventing or treating obesity, wherein the filament used in the 3D printing according to claim 4 is a drug-loaded filament according to claim 1.

7. A pharmaceutical preparation for preventing or treating obesity, wherein the pharmaceutical preparation is in the form of a mucosal administration preparation in accordance with paragraph 3.

8. A pharmaceutical preparation for preventing or treating obesity, wherein the mucosa in paragraph 7 is any one mucosa selected from the group consisting of oral mucosa, pulmonary mucosa, ocular mucosa, nasal mucosa, vaginal mucosa, and digestive mucosa.

9. A method for preventing or treating obesity, comprising administering the pharmaceutical preparation of claim 3 to the mucosa of a subject.

10. A kit containing the pharmaceutical preparation of Article 3.

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