A citrate sildenafil oral dissolving film and a preparation method thereof
By optimizing the composition and preparation process of sildenafil citrate oral disintegrating film, the problems of low drug loading and poor taste have been solved, providing better privacy and compliance, and ensuring rapid disintegration and efficacy.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- HANGZHOU FANHUIRONG PHARMACEUTICAL CO LTD
- Filing Date
- 2024-11-27
- Publication Date
- 2026-05-29
AI Technical Summary
Existing sildenafil citrate orally disintegrating film formulations have low drug loading and poor taste, making it difficult to meet patients' needs for privacy and compliance.
Sildenafil citrate oral dissolving films were prepared by using film-forming materials such as sildenafil citrate, hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyvinyl alcohol-polyethylene glycol copolymer, and povidone in specific proportions and particle sizes, combined with plasticizers, disintegrants, flavoring agents, and fragrances, through heating and stirring, vacuum homogenization, and coating and drying.
It improves the drug loading capacity and taste of orally disintegrating films, enhances patient compliance and medication privacy, ensures the properties and disintegration performance of the film, and achieves rapid dissolution and drug efficacy.
Smart Images
Figure CN122097312A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to an orally disintegrating film of sildenafil citrate and its preparation method. Background Technology
[0002] Sildenafil citrate is a specific inhibitor of phosphodiesterase type 5 (PDE5). Upon sexual stimulation, the nerves and endothelial cells of the corpora cavernosa release nitric oxide (NO). NO activates guanylate cyclase, which generates cyclic guanosine monophosphate (aGMP), causing relaxation of smooth muscle cells in arteries, arterioles, and the sinuses of the corpora cavernosa, leading to engorgement of erectile tissues and achieving an erection. Normally, aGMP is primarily degraded by phosphodiesterase, and PDE5 levels are relatively high in the genitals. Patients with erectile dysfunction often have difficulty producing sufficient amounts of aGMP. Sildenafil citrate specifically inhibits PDE5 activity, increasing aGMP levels, thereby triggering vasodilation and maintaining penile erection. Clinically, it is indicated for the treatment of erectile dysfunction in adult men.
[0003] Sildenafil citrate is currently available in tablet, oral disintegrating film, and suspension formulations both domestically and internationally.
[0004] Oral disintegrating films offer rapid drug release, convenient administration, and good patient compliance, while also effectively protecting patient privacy. They are widely used in the pharmaceutical and health supplement industries to improve compliance in specific populations (children, elderly patients, and patients with difficulty taking medication) and enhance the privacy of discreet medication use. While oral disintegrating films are convenient to take, easily accepted by patients, and effectively protect patient privacy, the drug loading capacity of commercially available oral disintegrating films is typically lower than that of tablets. Summary of the Invention
[0005] To overcome the shortcomings of existing technologies, this invention provides an oral dissolving film for sildenafil citrate and its preparation method, which can solve the technical problems of low drug loading and poor taste of current oral dissolving film formulations for sildenafil citrate.
[0006] The objective of this invention is achieved through the following technical solution:
[0007] A sildenafil citrate oral dissolving film, characterized in that it comprises the following raw materials: 40-55 wt% sildenafil citrate, wherein the particle size of the sildenafil citrate is 8-12 μm; 8-30 wt% hydroxypropyl methylcellulose; 5-15 wt% hydroxypropyl cellulose; 5-10 wt% polyvinyl alcohol-polyethylene glycol copolymer; 5-15 wt% povidone; 5-15 wt% plasticizer; 1-10 wt% disintegrant; 0.1-10 wt% colorant; 0.2-5 wt% flavoring agent; and 0.2-5 wt% fragrance.
[0008] In one embodiment, the plasticizer comprises polyethylene glycol.
[0009] In one embodiment, the disintegrant includes crospovidone.
[0010] In one embodiment, the colorant includes carmine.
[0011] In one embodiment, the flavoring agent comprises sodium saccharin.
[0012] In one embodiment, the flavoring includes menthol.
[0013] Secondly, the present invention also provides a method for preparing sildenafil citrate oral dissolving film, comprising the following steps: S1, heating and maintaining the temperature of deionized water at 50-80°C, adding the hydroxypropyl methylcellulose, hydroxypropyl cellulose, and povidone while stirring, and stopping heating after stirring evenly; S2, immediately adding plasticizer, flavoring agent, fragrance, and polyvinyl alcohol-polyethylene glycol copolymer under stirring conditions and stirring until transparent and free of lumps; S3, continuing to add disintegrant, colorant, and sildenafil citrate under stirring conditions until stirring evenly; S4, then performing vacuum homogenization and stirring to obtain a pharmaceutical solution; S5, placing the pharmaceutical solution in a buffer tank, coating it onto a backing material, and then drying it to obtain a film; S6, cutting the film and then packaging it to obtain the sildenafil citrate oral dissolving film.
[0014] The vacuum degree of the vacuum homogenization is -0.085±0.010Mpa, the stirring rate in S1, S2 and S3 is 1000±100rpm, and the stirring rate in S4 is 2500±100rpm.
[0015] In one embodiment, in S5, the backing material comprises a dimethyl silicone oil polyester film, and the drying temperature is 60–90°C.
[0016] In one embodiment, in S6, the material of the packaging comprises a polyester aluminum polyethylene pharmaceutical composite film.
[0017] In one embodiment, in step S6, the size of the cut membrane is (24±2)mm×(32±2)mm, and the weight difference is ±8%.
[0018] The beneficial effects of this invention are as follows:
[0019] 1. The above prescription and preparation process can produce qualified sildenafil citrate oral disintegrating film, which can effectively protect patients' medication privacy and provide more medication options.
[0020] 2. Adding sweeteners and flavorings during the preparation process can effectively improve the compliance of sildenafil citrate oral disintegrating film.
[0021] 3. The type and amount of film-forming materials and disintegrants can effectively ensure the properties and disintegration performance of the film.
[0022] 4. Controlling the particle size of the active pharmaceutical ingredient to 8–12 μm can ensure excellent product properties and improve patient compliance. Attached Figure Description
[0023] The invention will now be described in more detail with reference to embodiments and the accompanying drawings.
[0024] Figure 1 This is a process flow diagram of an embodiment of the present invention;
[0025] Figure 2 The images show a comparison of the appearance of the oral dissolving films prepared in Comparative Example 1 and Example 3 in Test Example 1 of the present invention, where (a) is the sample prepared in Comparative Example 1 and (b) is the sample prepared in Example 3.
[0026] Figure 3 The graphs show the dissolution rate curves of the oral dissolution film prepared in Example 3 of Experimental Example 3 of the present invention and the oral dissolution film prepared in Comparative Example 2 under different pH conditions, where A is at pH 1.0, B is at pH 4.5, C is in water, and D is at pH 6.8. Detailed Implementation
[0027] The invention will now be further described with reference to the accompanying drawings.
[0028] Example 1
[0029] This embodiment provides an oral dissolving film of sildenafil citrate and its preparation method. The raw materials include: 40 kg of sildenafil citrate with a particle size of 8 μm, 30 kg of hydroxypropyl methylcellulose, 5 kg of hydroxypropyl cellulose, 5 kg of polyvinyl alcohol-polyethylene glycol copolymer, 5 kg of povidone, 5 kg of polyethylene glycol 400, 1 kg of crosslinked povidone, 5 kg of carmine, 2 kg of sodium saccharin, and 2 kg of menthol.
[0030] The specific method is as follows (refer to...) Figure 1 ):
[0031] S1. Heat and maintain the deionized water temperature at 50°C, while stirring, add the hydroxypropyl methylcellulose, hydroxypropyl cellulose and povidone, stir evenly and then stop heating;
[0032] S2. Immediately add polyethylene glycol 400, sodium saccharin, menthol, and polyvinyl alcohol-polyethylene glycol copolymer under stirring and stir until transparent and free of lumps;
[0033] S3. Continue to add crospovidone, carmine and sildenafil citrate under stirring until well mixed;
[0034] S4. Vacuum homogenization and stirring are then performed to obtain the medicinal solution;
[0035] S5. Place the drug solution in a buffer tank, coat it onto a dimethyl silicone oil polyester film, and then dry it at 60°C to obtain a film.
[0036] S6. Cut the membrane into small pieces with a size of (24±2)mm×(32±2)mm, and control the weight difference of the pieces to ±8%, and then package them with a polyester aluminum polyethylene pharmaceutical composite film to obtain sildenafil citrate oral dissolving film. The storage temperature shall not exceed 30℃.
[0037] Example 2
[0038] This embodiment provides an oral dissolving membrane of sildenafil citrate and its preparation method. The raw materials include: 55 kg of sildenafil citrate with a particle size of 12 μm, 8.5 kg of hydroxypropyl methylcellulose, 15 kg of hydroxypropyl cellulose, 5 kg of polyvinyl alcohol-polyethylene glycol copolymer, 5 kg of povidone, 5 kg of polyethylene glycol 400, 1 kg of crosslinked povidone, 0.1 kg of carmine, 0.4 kg of sodium saccharin, and 5 kg of menthol.
[0039] The specific method is as follows (refer to...) Figure 1 ):
[0040] S1. Heat and maintain the deionized water temperature at 80℃, while stirring, add the hydroxypropyl methylcellulose, hydroxypropyl cellulose and povidone, stir evenly and then stop heating;
[0041] S2. Immediately add polyethylene glycol 400, sodium saccharin, menthol, and polyvinyl alcohol-polyethylene glycol copolymer under stirring and stir until transparent and free of lumps;
[0042] S3. Continue to add crospovidone, carmine and sildenafil citrate under stirring until well mixed;
[0043] S4. Vacuum homogenization and stirring are then performed to obtain the medicinal solution;
[0044] S5. The drug solution is placed in a buffer tank, coated onto a dimethyl silicone oil polyester film, and then dried at 90°C to obtain a film sheet.
[0045] S6. Cut the membrane into small pieces with a size of (24±2)mm×(32±2)mm, and control the weight difference of the pieces to ±8%, and then package them with a polyester aluminum polyethylene pharmaceutical composite film to obtain sildenafil citrate oral dissolving film. The storage temperature shall not exceed 30℃.
[0046] Example 3
[0047] This embodiment provides an oral dissolving film of sildenafil citrate and its preparation method. The raw materials include: 47 kg of sildenafil citrate with a particle size of 10 μm, 10 kg of hydroxypropyl methylcellulose, 12 kg of hydroxypropyl cellulose, 10 kg of polyvinyl alcohol-polyethylene glycol copolymer, 8 kg of povidone, 8 kg of polyethylene glycol 400, 2 kg of crosslinked povidone, 0.23 kg of carmine, 0.5 kg of sodium saccharin, and 2.27 kg of menthol.
[0048] The specific method is as follows (refer to...) Figure 1 ):
[0049] S1. Heat and maintain the deionized water temperature at 65°C, while stirring, add the hydroxypropyl methylcellulose, hydroxypropyl cellulose, and povidone, and stop heating after stirring evenly.
[0050] S2. Immediately add polyethylene glycol 400, sodium saccharin, menthol, and polyvinyl alcohol-polyethylene glycol copolymer under stirring and stir until transparent and free of lumps;
[0051] S3. Continue to add crospovidone, carmine and sildenafil citrate under stirring until well mixed;
[0052] S4. Vacuum homogenization and stirring are then performed to obtain the medicinal solution;
[0053] S5. The drug solution is placed in a buffer tank, coated onto a dimethyl silicone oil polyester film, and then dried at 75°C to obtain a film sheet.
[0054] S6. Cut the membrane into small pieces with a size of (24±2)mm×(32±2)mm, and control the weight difference of the pieces to ±8%, and then package them with a polyester aluminum polyethylene pharmaceutical composite film to obtain sildenafil citrate oral dissolving film. The storage temperature shall not exceed 30℃.
[0055] Comparative Example 1
[0056] The particle size of sildenafil citrate was adjusted to 50 μm, and the remaining steps were the same as in Example 3.
[0057] Comparative Example 2
[0058] Commercially available product (produced by Sildenafil Citrate Oral Soluble Film, manufactured by Sildenafil Citrate Oral Soluble Film Co., Ltd.).
[0059] Experimental Example 1
[0060] Comparing the appearance of the oral films prepared in Comparative Example 1 and Example 3, the results are as follows: Figure 2 As shown, according to Figure 2The results showed that when the raw material particle size was controlled at about 50 μm, obvious uneven particles appeared on the surface of the prepared sample. However, when the raw material particle size was reduced to about 10 μm, the prepared sample had a complete and smooth appearance, no obvious uneven particles, and uniform color.
[0061] Experimental Example 2
[0062] Compliance assessment test
[0063] The oral dissolving film prepared in Example 3 was compared with the taste of a commercially available product (Sildenafil Citrate Oral Soluble Film, Viatris Pharmaceutical Co., Ltd.), i.e., Compliance, to examine its compliance. The scoring criteria are shown in Table 1.
[0064] Table 1 Compliance Scoring Criteria
[0065]
[0066] The test results are shown in Table 2:
[0067] Table 2 Compliance Scores
[0068]
[0069] As can be seen from the experimental data in Table 2, both the self-made sample and the commercially available product received high scores in the taste evaluation, and the scores were similar, indicating that patients had good compliance when taking the product.
[0070] Experimental Example 3
[0071] The orally dissolving films from Example 3 and Comparative Example 2 were placed in solvents with pH values of 1.0, 4.5, and 6.8, respectively, and their dissolution rates were measured from 0 to 60 hours. Water volume was used as a control group. The results are as follows: Figure 3 As shown, according to Figure 3 The results show that the orally disintegrating film prepared by this invention has good properties, can disintegrate rapidly in the oral cavity, has the characteristic of rapid dissolution, and its dissolution behavior in vitro is similar to that of commercially available products. At the same time, it is small in size, lightweight, convenient to carry and take, can exert drug efficacy quickly, has high compliance, and effectively protects the privacy of patients' medication use.
[0072] In summary, the sildenafil citrate orally dissolving membrane and its preparation method provided by this invention have the following advantages:
[0073] Beneficial effects:
[0074] 1. The above prescription and preparation process can produce qualified sildenafil citrate oral disintegrating film, which can effectively protect patients' medication privacy and provide more medication options.
[0075] 2. Adding sweeteners and flavorings during the preparation process can effectively improve the compliance of sildenafil citrate oral disintegrating film.
[0076] 3. The type and amount of film-forming materials and disintegrants can effectively ensure the properties and disintegration performance of the film.
[0077] 4. Controlling the particle size of the active pharmaceutical ingredient to 8–12 μm can ensure excellent product properties and improve patient compliance.
[0078] In the description of this invention, it should be understood that the terms "upper", "lower", "bottom", "top", "front", "rear", "inner", "outer", "left", "right", etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are only for the convenience of describing this invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on this invention.
[0079] While the invention has been described herein with reference to specific embodiments, it should be understood that these embodiments are merely examples of the principles and applications of the invention. Therefore, it should be understood that many modifications can be made to the exemplary embodiments, and other arrangements can be designed without departing from the spirit and scope of the invention as defined by the appended claims. It should be understood that different dependent claims and features described herein can be combined in ways different from those described in the original claims. It is also understood that features described in conjunction with individual embodiments can be used in other described embodiments.
Claims
1. A sildenafil citrate orally disintegrating film, characterized in that, Including the following raw materials: Sildenafil citrate 40-55 wt%, wherein the particle size of sildenafil citrate is 8-12 μm; Hydroxypropyl methylcellulose 8–30 wt%; Hydroxypropyl cellulose 5–15 wt%; 5-10 wt% polyvinyl alcohol-polyethylene glycol copolymer; Povidone 5-15 wt%; Plasticizer 5-15 wt%; Disintegrant 1-10 wt%; Colorant 0.1–10 wt%; Flavoring agent 0.2–5 wt%; Fragrance 0.2–5 wt%.
2. The sildenafil citrate orally disintegrating film according to claim 1, characterized in that, The plasticizer includes polyethylene glycol.
3. The sildenafil citrate orally dissolving film according to claim 1, characterized in that, The disintegrant includes crospovidone.
4. The sildenafil citrate oral dissolving film according to claim 1, characterized in that, The colorant includes carmine.
5. The sildenafil citrate orally dissolving film according to claim 1, characterized in that, The flavoring agent includes sodium saccharin.
6. The sildenafil citrate orally disintegrating film according to claim 1, characterized in that, The flavoring includes menthol.
7. A method for preparing a sildenafil citrate orally dissolving film as described in any one of claims 1 to 6, characterized in that, Includes the following steps: S1. Heat and maintain the temperature of deionized water at 50-80℃, while stirring, add the hydroxypropyl methylcellulose, hydroxypropyl cellulose and povidone, and stop heating after stirring evenly; S2. Immediately add the plasticizer, flavoring agent, fragrance and polyvinyl alcohol-polyethylene glycol copolymer under stirring and stir until transparent and free of lumps; S3. Continue to add disintegrant, colorant and sildenafil citrate under stirring until the mixture is homogeneous; S4. Vacuum homogenization and stirring are then performed to obtain the medicinal solution; S5. The drug solution is placed in a buffer tank, coated onto the backing material, and then dried to obtain a film; S6. Cut the film and then package it to obtain the sildenafil citrate oral dissolving film.
8. The method for preparing the sildenafil citrate orally dissolving film according to claim 7, characterized in that, In step S5, the backing material comprises a dimethyl silicone oil polyester film, and the drying temperature is 60–90°C.
9. The method for preparing the sildenafil citrate orally dissolving film according to claim 7, characterized in that, In S6, the packaging material includes a polyester aluminum polyethylene pharmaceutical composite film.
10. The method for preparing the sildenafil citrate orally dissolving film according to claim 7, characterized in that, In step S6, the size of the cut membrane is (24±2)mm×(32±2)mm, and the weight difference is ±8%.