Preparation method and application of vardenafil oral soluble film composition

Abstract

The invention discloses a preparation method and application of a vardenafil oral-soluble film composition, and the preparation method of the oral-soluble film composition comprises the following steps: weighing a corresponding weight of raw medicines according to a formula, and grinding the active ingredients; heating purified water in a mixing tank, adding a flavoring agent, and stirring until the flavoring agent is completely dispersed to prepare a flavoring agent solution for later use; adding a film-forming material into the flavoring agent solution, and fully homogenizing to prepare a water-soluble film-forming material solution for later use; adding the filler into the water-soluble film-forming material solution, fully stirring to obtain a mixed solution, and cooling the mixed solution, so that the vardenafil oral-soluble film composition provided by the invention has the advantages of no drug precipitation under the condition of higher drug loading rate, good mechanical property, complete dissolution in the oral cavity, no gravel feeling and no toxic or side effect. Compared with the prior art, the film agent provided by the invention has the advantages of good mouthfeel, low hygroscopicity and viscosity, good film release performance, greatly reduced disintegration time, and further improved use effect.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, in particular to a preparation method and application of a vardenafil orodispersible film composition. Background Art

[0002] Male sexual dysfunction refers to abnormalities in one, several or all of the five stages of sexual activity, including sexual desire, penile erection, sexual intercourse, orgasm and ejaculation, which affect the normal progress of sexual activity. The most common male sexual dysfunction is abnormal penile erection and ejaculation.

[0003] Vardenafil is a highly selective phosphodiesterase 5 inhibitor. It inhibits phosphodiesterase 5 type that degrades cGMP in the human corpus cavernosum, increases the release of local endogenous nitric oxide in the corpus cavernosum under sexual stimulation, relaxes smooth muscles, and increases blood flow in the human corpus cavernosum. Thus, vardenafil enhances the natural response to sexual stimulation and is clinically suitable for the treatment of erectile dysfunction in adult men.

[0004] After searching, the patent with announcement number CN104586820A discloses an oral fast-dissolving film composition with a high drug loading. The invention uses gelatin as a film-forming material, and the drug loading rate of the prepared film can reach 40%-80%. However, gelatin is a material that easily breeds bacteria, and the pharmacopoeia has an investigation on the microbial limits of film preparations. To ensure that they are within the limits, higher requirements are inevitably placed on the preparation process, which increases the difficulty of production. For this reason, the present application proposes a preparation method and application of a vardenafil orosoluble film composition. Summary of the invention

[0005] The object of the present invention is to provide a preparation method and application of a vardenafil orodispersible film composition to solve the problems raised in the above background technology.

[0006] To achieve the above object, the present invention provides the following technical solution: a method for preparing a vardenafil orodispersible film composition, wherein the orodispersible film composition is prepared from the following materials: an active ingredient, a filler, a disintegrant, a flavoring agent, a lubricant, a film-forming material, a humectant, a fragrance and purified water;

[0007] The preparation method of the orodispersible film composition comprises the following steps:

[0008] S1. Weigh the corresponding weight of the original drug according to the formula and grind the active ingredient;

[0009] S2, placing purified water in a mixing tank, heating it, adding a flavoring agent, and stirring until it is completely dispersed to prepare a flavoring agent solution for use;

[0010] S3, adding the film-forming material to the flavoring agent solution and fully homogenizing to obtain a water-soluble film-forming material solution for standby use;

[0011] S4. Add a filler to the water-soluble film-forming material solution, stir well to obtain a mixed solution, and cool down the mixed solution.

[0012] S5. After the cooling is completed, add the active ingredient and the disintegrant to the mixed solution, disperse and then perform degassing treatment to obtain a drug solution.

[0013] S6. Add a lubricant, a humectant and a flavoring agent to the drug solution to formulate the drug, and store it in a sealed tank.

[0014] S7. Use a film coating machine to evenly coat the above drug on a flat backing material, and then dry it. After drying, cut it according to the weight requirement to obtain the required orally disintegrating film.

[0015] Preferably, the temperature range for heating the purified water in step S2 is 50 - 65°C, preferably 60°C.

[0016] Preferably, the stirring time for the filler in step S4 is 2 - 5 hours, and the stirring speed is 80 - 200 r / min.

[0017] Preferably, the temperature of the solution after cooling in step S5 is 20 - 30°C, preferably 25°C.

[0018] Preferably, the drying temperature for the drug in step S7 is 30 - 80°C, preferably 45 - 55°C.

[0019] Preferably, the active ingredient is a mixture of vardenafil and trace elements, where the weight ratio of vardenafil to trace elements is 7.3 - 9.2:1, and the trace element is preferably zinc.

[0020] Preferably, the film-forming material is a composition of hydroxypropyl cellulose and pullulan.

[0021] Preferably, the filler is one or a mixture of microcrystalline cellulose, lactose, calcium hydrogen phosphate, pregelatinized starch, etc.

[0022] Preferably, the humectant is one or a mixture of glycerol, polyethylene glycol, propylene glycol or butylene glycol.

[0023] Preferably, the vardenafil orally disintegrating film composition is used in the treatment of male sexual erectile function and improvement of ejaculation disorders.

[0024] Compared with the prior art, the beneficial effects of the present invention are as follows: the vardenafil orodispersible film composition provided by the present invention has a high drug loading rate, no drug precipitation, and still has good mechanical properties, and can be completely dissolved in the oral cavity without a sense of gravel and a good taste. At the same time, it has low hygroscopicity and viscosity, thereby having good demolding performance, and greatly reduces the disintegration time of the film, thereby improving the use effect. DETAILED DESCRIPTION

[0025] The present invention is described in detail below, and the technical solutions in the embodiments of the present invention are clearly and completely described. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0026] The present invention is described in detail below, and the technical solutions in the embodiments of the present invention are clearly and completely described. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention. The present invention provides a technical solution:

[0027] A method for preparing a vardenafil orodispersible film composition, wherein the orodispersible film composition is prepared from the following materials: an active ingredient, a filler, a disintegrant, a flavoring agent, a lubricant, a film-forming material, a humectant, a fragrance and purified water;

[0028] The preparation method of the orodispersible film composition comprises the following steps:

[0029] S1. Weigh the corresponding weight of the original drug according to the formula and grind the active ingredient;

[0030] S2, placing purified water in a mixing tank, heating it, adding a flavoring agent, and stirring until it is completely dispersed to prepare a flavoring agent solution for use;

[0031] S3, adding the film-forming material to the flavoring agent solution and fully homogenizing to obtain a water-soluble film-forming material solution for standby use;

[0032] S4, adding a filler to the water-soluble film-forming material solution, stirring thoroughly to obtain a mixed solution, and cooling the mixed solution;

[0033] S5, after the cooling is completed, the active ingredient and the disintegrant are added to the mixed solution, and after dispersion, degassing is performed to obtain a drug solution;

[0034] S6, adding lubricant, moisturizer and fragrance to the drug solution to prepare the drug, and storing the drug in a sealed can;

[0035] S7. Use a film coater to evenly coat the above-mentioned drug on a flat backing material, and then dry it. After drying, cut it according to the weight requirement to obtain the required orally dissolving film.

[0036] Among them, in step S2, the temperature range for heating the purified water is 50 - 65°C, preferably 60°C.

[0037] Among them, in step S4, the stirring time for the filler is 2 - 5 hours, and the stirring speed is 80 - 200 r / min.

[0038] Among them, in step S5, the temperature of the solution after cooling is 20 - 30°C, preferably 25°C.

[0039] Among them, in step S7, the drying temperature for the drug is 30 - 80°C, preferably 45 - 55°C.

[0040] Among them, the active ingredient is a mixture of vardenafil and trace elements, and the weight ratio of vardenafil to trace elements is 7.3 - 9.2:1. The trace element is preferably zinc.

[0041] Among them, the film-forming material is a composition of hydroxypropyl cellulose and pullulan polysaccharide.

[0042] Among them, the filler is a mixture of one or more of microcrystalline cellulose, lactose, calcium hydrogen phosphate, and pregelatinized starch.

[0043] Among them, the humectant is a mixture of one or more of glycerol, polyethylene glycol, propylene glycol, and butylene glycol.

[0044] Among them, the vardenafil orally dissolving film composition is used in the treatment of male sexual erectile function and improvement of ejaculation disorders.

[0045] Example 1:

[0046] The orally dissolving film composition is prepared from the following materials: active ingredient, filler, disintegrant, flavoring agent, lubricant, film-forming material, humectant, fragrance, and purified water;

[0047] Among them, the active ingredient is a vardenafil-zinc mixture blended at 7.3:1, the filler is a mixture of microcrystalline cellulose and lactose, and the flavoring agent is 0.3% orange essence;

[0048] The preparation method comprises the following steps: weighing the original medicine of corresponding weight, grinding the active ingredient to make the particle size smaller than 200 meshes; placing purified water in a mixing tank, heating it to 55 DEG C, adding 0.3% orange essence, stirring it until it is completely dispersed, and preparing a flavoring agent solution for standby use; adding a film-forming material to the flavoring agent solution, and fully homogenizing it, and preparing a water-soluble film-forming material solution for standby use; adding a filler to the water-soluble film-forming material solution, and fully stirring it to obtain a mixed solution, and cooling the mixed solution to 22 DEG C, adding the active ingredient and the disintegrant to the mixed solution, and performing a degassing treatment after dispersion, and preparing a drug solution; adding a lubricant, a moisturizing agent and a fragrance to the drug solution to prepare the drug, and storing it in a sealed tank; using a coating machine to evenly coat the drug on a flat backing material, and drying it at a temperature of 45 DEG C, and cutting it according to weight requirements after drying to obtain the required orally dissolving film.

[0049] Embodiment 2:

[0050] The orodispersible film composition is prepared from the following materials: active ingredient, filler, disintegrant, flavoring agent, lubricant, film-forming material, humectant, fragrance and purified water;

[0051] The active ingredient is a mixture of vardenafil and zinc blended in a ratio of 8.2:1, the filler is microcrystalline cellulose, and the flavoring agent is 0.5% apple flavor;

[0052] The preparation method comprises the following steps: weighing the original medicine of corresponding weight, grinding the active ingredient to make the particle size smaller than 200 meshes; placing purified water in a mixing tank, heating it to 60 DEG C, adding 0.5% apple essence, stirring it until it is completely dispersed, and preparing a flavoring agent solution for standby use; adding a film-forming material to the flavoring agent solution, and fully homogenizing it, and preparing a water-soluble film-forming material solution for standby use; adding a filler to the water-soluble film-forming material solution, and fully stirring it to obtain a mixed solution, and cooling the mixed solution to 25 DEG C, adding the active ingredient and the disintegrant to the mixed solution, and performing a degassing treatment after dispersion, and preparing a drug solution; adding a lubricant, a moisturizing agent and a fragrance to the drug solution to prepare the drug, and storing it in a sealed tank; using a coating machine to evenly coat the drug on a flat backing material, and drying it at a temperature of 50 DEG C, and cutting it according to weight requirements after drying to obtain the required orally dissolving film.

[0053] Embodiment 3:

[0054] The orodispersible film composition is prepared from the following materials: active ingredient, filler, disintegrant, flavoring agent, lubricant, film-forming material, humectant, fragrance and purified water;

[0055] The active ingredient is a 7.3:1 blend of vardenafil and zinc, the filler is calcium hydrogen phosphate, and the flavoring agent is 0.5% cantaloupe flavor;

[0056] The preparation method comprises the following steps: weighing the original medicine of corresponding weight, grinding the active ingredient to make the particle size smaller than 200 meshes; placing purified water in a mixing tank, heating it to 60 DEG C, adding 0.5% Hami melon essence, stirring until completely dispersed, and preparing a flavoring agent solution for standby use; adding a film-forming material to the flavoring agent solution, and fully homogenizing it to prepare a water-soluble film-forming material solution for standby use; adding a filler to the water-soluble film-forming material solution, and fully stirring it to obtain a mixed solution, and cooling the mixed solution to 30 DEG C, adding the active ingredient and the disintegrant to the mixed solution, and performing a degassing treatment after dispersion to obtain a drug solution; adding a lubricant, a moisturizing agent and a fragrance to the drug solution to prepare the drug, and storing it in a sealed tank; using a coating machine to evenly coat the drug on a flat backing material, and drying it at a temperature of 55 DEG C, and cutting it according to weight requirements after drying to obtain the required orally dissolving film.

[0057] Fifty patients with primary premature ejaculation and erectile dysfunction were selected, with an age range of 25-40 years, and an average age of 28.7 years;

[0058] A total of 50 patients with premature ejaculation and erectile dysfunction were recruited, 6 of whom were lost to follow-up or dropped out, and 44 patients finally completed the trial. After 4 weeks of treatment, the IELT of patients with premature ejaculation and erectile dysfunction was significantly improved compared with that before treatment, the ejaculation time increased from an average of 3.3 minutes to 5.8 minutes, and the erection speed decreased from an average of 11.3 minutes to 6.7 minutes;

[0059] Safety observation: No abnormality was found in the liver and kidney functions and blood and urine routine tests of the patients treated with the orodispersible film composition before and after treatment.

[0060] The above description enables those skilled in the art to implement or use the present invention. Various modifications to these embodiments will be apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to the embodiments shown herein, but will conform to the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A method for preparing a vardenafil orodispersible film composition, characterized in that: The orally dissolving film composition is prepared from the following materials: active ingredients, fillers, disintegrants, flavoring agents, lubricants, film-forming materials, moisturizers, fragrances and purified water; The preparation method of the orodispersible film composition comprises the following steps: S1. Weigh the corresponding weight of the original drug according to the formula and grind the active ingredient; S2, placing purified water in a mixing tank, heating it, adding a flavoring agent, and stirring until it is completely dispersed to prepare a flavoring agent solution for use; S3, adding the film-forming material to the flavoring agent solution and fully homogenizing to obtain a water-soluble film-forming material solution for standby use; S4, adding a filler to the water-soluble film-forming material solution, stirring thoroughly to obtain a mixed solution, and cooling the mixed solution; S5, after the cooling is completed, the active ingredient and the disintegrant are added to the mixed solution, and after dispersion, degassing is performed to obtain a drug solution; S6, adding lubricant, moisturizer and fragrance to the drug solution to prepare the drug, and storing the drug in a sealed can; S7. Use a coating machine to evenly coat the above-mentioned medicine on a flat backing material, and dry it. After drying, cut it according to weight requirements to obtain the required orodispersible film.

2. The method for preparing a vardenafil orodispersible film composition according to claim 1, characterized in that: The temperature range for heating the purified water in step S2 is 50-65°C, preferably 60°C.

3. The method for preparing a vardenafil orodispersible film composition according to claim 1, characterized in that: In step S4, the filler is stirred for 2-5 hours, and the stirring speed is 80-200 r / min.

4. The method for preparing a vardenafil orodispersible film composition according to claim 1, characterized in that: The temperature of the solution after cooling in step S5 is 20-30°C, preferably 25°C.

5. The method for preparing a vardenafil orodispersible film composition according to claim 1, characterized in that: The temperature for drying the medicine in step S7 is 30-80°C, preferably 45-55°C.

6. The method for preparing a vardenafil orodispersible film composition according to claim 1, characterized in that: The active ingredient is a mixture of vardenafil and trace elements, wherein the weight ratio of vardenafil to trace elements is 7.3-9.2:1, and the trace elements are preferably zinc.

7. The method for preparing a vardenafil orodispersible film composition according to claim 1, characterized in that: The film-forming material is a composition of hydroxypropyl cellulose and pullulan.

8. The method for preparing a vardenafil orodispersible film composition according to claim 1, characterized in that: The filler is a mixture of one or more of microcrystalline cellulose, lactose, calcium hydrogen phosphate, and pregelatinized starch.

9. The method for preparing a vardenafil orodispersible film composition according to claim 1, characterized in that: The moisturizing agent is a mixture of one or more of glycerol, polyethylene glycol, propylene glycol or butylene glycol.

10. Use of a vardenafil orodispersible film composition according to claims 1-9, characterized in that: The vardenafil orodispersible film composition is used in treating male sexual erection and improving abnormal ejaculation.