A method for detecting the content of dimethicone and silicon dioxide in simethicone orally dissolving film

Abstract

This invention belongs to the field of pharmaceutical analysis technology and relates to a method for detecting the content of dimethicone and silica in simethicone oral sol-coating membranes. The simethicone oral sol-coating membrane is dissolved in dimethyl sulfoxide, followed by a first extraction with n-hexane, and then a second extraction with sodium dodecyl sulfate. The material from the second extraction is centrifuged, and the supernatant is dehydrated to obtain a test solution. The absorbance of the test solution is detected using infrared spectrophotometry to obtain an infrared absorption spectrum. Data on the Si-CH3 and Si-O absorption peaks are obtained from the infrared absorption spectrum. The content of dimethicone is calculated based on the Si-CH3 absorption peak data, and the content of silica is calculated based on the Si-CH3 and Si-O absorption peak data. This invention can simultaneously detect the content of dimethicone and silica in simethicone oral sol-coating membranes with high accuracy and good repeatability.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical analysis technology and relates to a method for detecting the content of dimethicone and silica in simethicone oral sol-gel membranes. Background Technology

[0002] The information disclosed in this background section is intended only to enhance understanding of the overall background of the invention and is not necessarily to be construed as an admission or in any way implying that such information constitutes prior art known to those skilled in the art.

[0003] Simethicone is a complex of dimethicone and silica. Oral dissolving films are a novel type of oral film preparation, made by coating a solution of the active pharmaceutical ingredient and film-forming material onto a release film. This process requires high-temperature treatment, which alters the sample's morphology. According to the inventors' research, although pretreatment methods exist for determining dimethicone in various dosage forms such as emulsions, tablets, and suspensions, the unique preparation process of simethicone oral dissolving films prevents complete extraction of dimethicone from these forms. Therefore, these methods are not suitable for determining the dimethicone content in simethicone oral dissolving films. Furthermore, silica is a crucial component of simethicone, and its content is a key quality attribute; currently, there are no documented methods for detecting silica content in simethicone. Summary of the Invention

[0004] To address the shortcomings of existing technologies, the purpose of this invention is to provide a method for detecting the content of dimethicone and silica in simethicone oral films. This invention can simultaneously detect the content of dimethicone and silica in simethicone oral films, with high accuracy and good repeatability.

[0005] To achieve the above objectives, the technical solution of the present invention is as follows:

[0006] A method for detecting the content of dimethicone and silica in a simethicone oral film includes the following steps:

[0007] Simethicone is dissolved in dimethyl sulfoxide, then hexane is added for the first mixed extraction, followed by sodium dodecyl sulfate for the second mixed extraction. The material from the second mixed extraction is centrifuged, and the supernatant after centrifugation is dehydrated to obtain the test solution.

[0008] The absorbance of the test solution was detected by infrared spectrophotometry to obtain an infrared absorption spectrum. Data on the Si-CH3 absorption peak and the Si-O absorption peak were obtained from the infrared absorption spectrum. The content of dimethyl silicone oil was calculated based on the data of the Si-CH3 absorption peak, and the content of silicon dioxide was calculated based on the data of the Si-CH3 absorption peak and the Si-O absorption peak.

[0009] The beneficial technical effects of this invention are:

[0010] This invention uses dimethyl sulfoxide to dissolve the oral film of simethicone, separating simethicone and silica. Sodium dodecyl sulfate is added to form an insoluble precipitate with hydroxypropyl methylcellulose, disrupting the gel state of hydroxypropyl methylcellulose. This allows simethicone and silica to completely dissolve in n-hexane, completing the extraction. This method saves time and improves separation efficiency. The selected reagents are relatively environmentally friendly. Furthermore, method verification has proven that the method provided by this invention can simultaneously determine the content of simethicone and silica, and has the advantages of high accuracy and good reproducibility. Attached Figure Description

[0011] The accompanying drawings, which form part of this invention, are used to provide a further understanding of the invention. The illustrative embodiments of the invention and their descriptions are used to explain the invention and do not constitute an improper limitation of the invention.

[0012] Figure 1 The infrared spectrum of the blank solution in this embodiment of the invention;

[0013] Figure 2 The infrared spectrum of the blank excipient in this embodiment of the invention;

[0014] Figure 3 The infrared spectrum of the dimethicone reference solution in the embodiments of the present invention;

[0015] Figure 4 The infrared spectrum of the simethicone reference solution in this embodiment of the invention;

[0016] Figure 5 The infrared spectrum of the test solution in this embodiment of the invention is shown. Detailed Implementation

[0017] It should be noted that the following detailed descriptions are exemplary and intended to provide further illustration of the invention. Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0018] It should be noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the scope of exemplary embodiments according to the invention. As used herein, the singular form is intended to include the plural form as well, unless the context clearly indicates otherwise. Furthermore, it should be understood that when the terms "comprising" and / or "including" are used in this specification, they indicate the presence of features, steps, operations, devices, components, and / or combinations thereof.

[0019] Given that existing methods are insufficient for accurately quantifying dimethicone and silica in simethicone oral films, this invention proposes a method for detecting the content of dimethicone and silica in simethicone oral films.

[0020] A typical embodiment of the present invention provides a method for detecting the content of dimethicone and silica in a simethicone oral film, comprising the following steps:

[0021] Simethicone is dissolved in dimethyl sulfoxide, then hexane is added for the first mixed extraction, followed by sodium dodecyl sulfate for the second mixed extraction. The material from the second mixed extraction is centrifuged, and the supernatant after centrifugation is dehydrated to obtain the test solution.

[0022] The absorbance of the test solution was detected by infrared spectrophotometry to obtain an infrared absorption spectrum. Data on the Si-CH3 absorption peak and the Si-O absorption peak were obtained from the infrared absorption spectrum. The content of dimethyl silicone oil was calculated based on the data of the Si-CH3 absorption peak, and the content of silicon dioxide was calculated based on the data of the Si-CH3 absorption peak and the Si-O absorption peak.

[0023] Specifically, the amount of dimethyl sulfoxide added is based on the mass of simethicone in the simethicone oral film, with 0.5 to 2 ml of dimethyl sulfoxide added per gram of simethicone.

[0024] Specifically, the volume ratio of dimethyl sulfoxide to n-hexane is 1:0.1 to 10, for example, 1:0.1 to 5, 1:5 to 10, 1:0.5 to 2, 1:0.5 to 1.5, etc. In some embodiments, the volume ratio of dimethyl sulfoxide to n-hexane is 1:1.8 to 2.2.

[0025] Specifically, methods for dissolving simethicone oral films using dimethyl sulfoxide include stirring, shaking, and sonication. In some embodiments, the simethicone oral film is added to dimethyl sulfoxide and sonicated until dissolved. Sonication allows dimethyl sulfoxide to better disrupt the structure of the simethicone oral film, thereby better combining with sodium dodecyl sulfate to disrupt the gel state of hydroxypropyl methylcellulose. Preferably, the sonication is performed while simultaneously shaking.

[0026] Specifically, the first mixing and extraction was performed by vigorous hand shaking for 3–8 seconds.

[0027] In some embodiments, the ratio of sodium dodecyl sulfate to dimethyl sulfoxide is 0.5–1.5:30–50 g / ml.

[0028] In some embodiments, the second mixing extraction is a reciprocating shaking.

[0029] In one or more embodiments, the reciprocating oscillation speed is 100-300 rpm, and the reciprocating oscillation time is 10-20 min.

[0030] In some embodiments, the supernatant is dehydrated by adding a dehydrating agent to absorb water, followed by centrifugation to remove the dehydrating agent after water absorption. The dehydrating agent may be, for example, anhydrous sodium sulfate.

[0031] In some embodiments, the infrared absorption spectrum range is 1400 cm⁻¹. -1 ~850cm -1 .

[0032] In some embodiments, the absorption peak of Si-CH3 is in the range of 1280 cm⁻¹. -1 ~1230cm -1 .

[0033] In some embodiments, the Si-O absorption peak range is 1160 cm⁻¹. -1 ~950cm -1 .

[0034] In some embodiments, the content of dimethicone and silica is calculated by peak area using the external standard method.

[0035] In some embodiments, when infrared spectrophotometry is used for detection, infrared spectrophotometry is also used to detect the dimethicone reference solution.

[0036] In one or more embodiments, the preparation process of the dimethicone reference solution is as follows: The dimethicone reference standard is dissolved in hexane, dimethyl sulfoxide is added for a first mixed extraction, followed by sodium dodecyl sulfate for a second mixed extraction. The material from the second mixed extraction is centrifuged, and the supernatant after centrifugation is dehydrated to obtain the dimethicone solution. The viscosity of the dimethicone reference standard is 450–550 mmHg. 2 / s.

[0037] In some embodiments, when infrared spectrophotometry is used for detection, infrared spectrophotometry is also used to detect the simethicone reference solution.

[0038] In one or more embodiments, the preparation process of the dimethicone reference solution is as follows: the dimethicone reference solution is dissolved in n-hexane, and after adding methyl sulfoxide, a first mixed extraction is performed. Then, sodium dodecyl sulfate is added for a second mixed extraction. The material from the second mixed extraction is centrifuged, and the supernatant after centrifugation is dehydrated to obtain the dimethicone solution.

[0039] To enable those skilled in the art to better understand the technical solution of the present invention, the technical solution of the present invention will be described in detail below with reference to specific embodiments.

[0040] Example

[0041] Preparation of the test solution:

[0042] Take one simethicone soluble film and place it in a stoppered conical flask. Add 40 ml of dimethyl sulfoxide and sonicate to dissolve. Add 40 ml of n-hexane and shake vigorously by hand for 5 seconds. Add 1 g of sodium dodecyl sulfate and place the flask in a constant temperature shaker. Shake at 200 rpm for 15 minutes. Remove the flask and centrifuge. Take the upper n-hexane layer, add 1 g of anhydrous sodium sulfate, centrifuge, and take the supernatant to obtain the test solution.

[0043] Preparation of dimethicone reference solution:

[0044] Accurately weigh 50 mg of dimethicone reference standard, add 50 ml of n-hexane and mix well to prepare a reference standard stock solution. Take 40 ml of the reference standard stock solution and place it in a 250 ml stoppered glass conical flask. Add 40 ml of dimethyl sulfoxide, shake vigorously by hand for 5 seconds, add 1 g of sodium dodecyl sulfate, place in a constant temperature shaker, shake repeatedly at 200 rpm for 15 minutes, remove, centrifuge, take the upper n-hexane layer, add 1 g of anhydrous sodium sulfate, centrifuge, and take the supernatant to obtain the dimethicone reference standard solution.

[0045] Preparation of simethicone reference solution:

[0046] Accurately weigh 50 mg of simethicone reference standard, add 50 ml of n-hexane and mix well to prepare a reference standard stock solution. Take 40 ml of the reference standard stock solution and place it in a 250 ml stoppered glass conical flask. Add 40 ml of dimethyl sulfoxide, shake vigorously by hand for 5 seconds, add 1 g of sodium dodecyl sulfate, place in a constant temperature shaker, shake repeatedly at 200 rpm for 15 minutes, remove, centrifuge, take the upper n-hexane layer, add 1 g of anhydrous sodium sulfate, centrifuge, and take the supernatant to obtain the simethicone reference standard solution.

[0047] Preparation of blank solution:

[0048] Add 40 ml of dimethyl sulfoxide to a stoppered glass conical flask, sonicate, then add 40 ml of n-hexane, shake vigorously by hand for 5 seconds, add 1 g of sodium dodecyl sulfate, place in a constant temperature shaker, shake repeatedly at 200 rpm for 15 minutes, remove, centrifuge, take the upper n-hexane layer, add 1 g of anhydrous sodium sulfate, centrifuge, take the supernatant to obtain the blank solution.

[0049] Preparation of blank excipient solution:

[0050] Accurately weigh 32 mg of blank excipient and place it in a stoppered conical flask. Add 40 ml of dimethyl sulfoxide and sonicate to dissolve. Add 40 ml of n-hexane and shake vigorously by hand for 5 seconds. Add 1 g of sodium dodecyl sulfate and place in a constant temperature shaker. Shake at 200 rpm for 15 minutes. Remove the flask, centrifuge, and take the upper n-hexane layer. Add 1 g of anhydrous sodium sulfate, centrifuge, and take the supernatant to obtain the blank excipient solution.

[0051] Infrared spectrophotometry detection:

[0052] The detection conditions were as follows: a 0.5mm absorption cell (model HF-8) was selected, and the scanning range was from 1400 cm⁻¹. -1 up to 850cm -1 The scan was performed twice, with a resolution of 4cm. -1 The signal range corresponding to dimethicone in the test sample is 1280 cm⁻¹. -1 ~1230cm -1 (Range 1) The signal range corresponding to the sum of dimethicone and silica in the test sample is within 1160 cm⁻¹. -1 ~950cm -1 (Range 2), record the spectrum, see spectrum. Figures 1-5 .

[0053] Depend on Figures 1-5 The results showed that neither the blank solution nor the blank excipient solution interfered with the determination of the content of dimethicone and silica, indicating that the specificity of the detection method in this embodiment meets the requirements.

[0054] Precision:

[0055] Prepare six parallel test solutions and perform detection according to the infrared spectrophotometry method described above. Record the spectra and calculate the contents of dimethicone and silica using the following formulas according to the external standard method.

[0056]

[0057] W R Weight of dimethicone reference standard (mg)

[0058] W T Sample weight (mg)

[0059] A T1 : Absorbance of the test solution 1

[0060] A R1 : Absorbance of dimethicone reference solution 1

[0061] C R Content (%) of dimethicone reference standard

[0062] 38.38: Theoretical content of dimethicone in oral dissolving film (mg / tablet)

[0063] Calculate the dimethicone content (mg / tablet) using the following formula:

[0064]

[0065] W R Weight of dimethicone reference standard (mg)

[0066] W T Sample weight (mg)

[0067] A T1 : Absorbance of the test solution 1

[0068] A R1 : Absorbance of dimethicone reference solution 1

[0069] C R Content (%) of dimethicone reference standard

[0070] Calculate the silica content (mg / tablet) using the following formula:

[0071]

[0072] W R Simethicone reference standard sample weight (mg)

[0073] W T Sample weight (mg)

[0074] A T1 : Absorbance of the test solution 1

[0075] A T2 : Absorbance of the test solution 2

[0076] A R1 : Simethicone reference solution absorbance 1

[0077] A R2 : Simethicone reference solution absorbance 2

[0078] C R,SiO2 Silica content (%) in simethicone reference standard

[0079] C 聚二甲基硅氧烷 Content of dimethicone in the test sample (%)

[0080] C R,聚二甲基硅氧烷 Content (%) of dimethicone in simethicone reference standard

[0081] D: The dimethicone content indicated on the simethicone oral coating (fixed value: 38.38 mg / tablet).

[0082] U f Conversion factor for silica content (fixed value: 100)

[0083] The results are shown in Table 1.

[0084] Table 1 Precision test results

[0085] 1 2 3 4 5 6 average value RSD% Dimethicone content (%) 102.2 102.0 100.6 101.5 102.6 103.9 102.1 1.1 Silica content (%) 2.37 2.38 2.37 2.36 2.36 2.35 2.37 0.4

[0086] The results in Table 1 show that the RSD of dimethicone content was 1.1% and the RSD of silica content was 0.4% in the six tests, proving that the injection precision of the method in this embodiment is good.

[0087] Linear relationship and range:

[0088] A series of linear solutions equivalent to 80%, 90%, 100%, 110%, and 120% of the dimethicone concentration in the test sample were prepared, and then detected under infrared spectrophotometric conditions. The linear regression equation for dimethicone was obtained by plotting the concentration (mg / ml) of dimethicone on the x-axis and the peak area on the y-axis: Y = 2.4896X + 0.1407, r = 0.9998. The results indicate that dimethicone exhibits good linearity in the range of 0.8 mg / ml to 1.2 mg / ml.

[0089] A series of linear solutions equivalent to 80%, 90%, 100%, 110%, and 120% of the simethicone concentration in the test sample were prepared, and then detected under infrared spectrophotometric conditions. The linear regression equation for range 1 of simethicone was obtained by plotting the simethicone concentration (mg / ml) on the x-axis and the peak area on the y-axis: Y = 2.9014X - 0.0787, r = 0.9996; the linear regression equation for range 2 was: Y =

[0090] 21.702X - 1.528, r = 0.9986. The results indicate that simethicone exhibits good linearity in the range of 0.8 mg / ml to 1.2 mg / ml.

[0091] Accuracy

[0092] Test solution solutions equivalent to 80%, 100%, and 120% of the test sample concentration were prepared, with three replicates for each concentration. The absorbance was then measured using infrared spectrophotometry, and the ratio between the measured result and the theoretical value (recovery rate) was calculated. Results: The average recoveries of dimethicone in the 80%, 100%, and 120% test solution were 102.94%, 101.73%, and 101.92%, respectively, with an RSD% of 1.0%; the average recoveries of silica were 100.18%, 101.01%, and 101.87%, respectively, with an RSD% of 0.76%.

[0093] The results show that the detection method provided in this embodiment has high accuracy for dimethicone and silica.

[0094] Solution stability:

[0095] The test solution, dimethicone reference solution, and simethicone reference solution were placed at room temperature for 0, 1, 2, 3, and 4 hours. The peak areas of dimethicone and silica at different placement times were measured under infrared spectrophotometric detection conditions. The results showed that the RSD of the peak height of the dimethicone reference solution was 2.28%, the RSD of the peak area in range 1 of the simethicone reference solution was 2.55%, and the RSD of the peak area in range 2 was 2.52%. In the test solution, the RSD of the peak area in range 1 was 1.49%, and the RSD of the peak area in range 2 was 1.56%. The results indicate that the test solution, dimethicone reference solution, and simethicone reference solution are stable within 4 hours.

[0096] Durability:

[0097] The effects of slight changes in the sample preparation method (dosage of dimethyl sulfoxide, sodium dodecyl sulfate, and anhydrous sodium sulfate) and instrument detection conditions (resolution, number of scans, and different liquid cells) on the determination of dimethyl methacrylate and silica content were investigated. The specific test results are shown in Table 2.

[0098] Table 2 Durability test results

[0099]

[0100]

[0101] Table 2 shows that the RSDs of dimethicone and silica content under different conditions are all between 0.2% and 2.7%, proving that the detection method in this embodiment has good robustness.

[0102] The methodological validation results show that the determination of dimethicone and silica content in simethicone oral films in this embodiment is highly specific, accurate, precise, and robust, and is suitable for the accurate control of dimethicone and silica content in simethicone oral films.

[0103] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A method for detecting the content of dimethicone and silica in a simethicone oral film, characterized in that, Includes the following steps: Simethicone is dissolved in dimethyl sulfoxide, then hexane is added for the first mixed extraction, followed by sodium dodecyl sulfate for the second mixed extraction. The material from the second mixed extraction is centrifuged, and the supernatant after centrifugation is dehydrated to obtain the test solution. The volume ratio of dimethyl sulfoxide to n-hexane is 1:1.8~2.2; the ratio of sodium dodecyl sulfate to dimethyl sulfoxide is 0.5~1.5:30~50 g / ml; the second mixing extraction is performed by reciprocating shaking; the reciprocating shaking speed is 200~300 rpm, and the reciprocating shaking time is 10~20 min; The absorbance of the test solution was detected by infrared spectrophotometry to obtain an infrared absorption spectrum. Data on the Si-CH3 absorption peak and the Si-O absorption peak were obtained from the infrared absorption spectrum. The content of dimethyl silicone oil was calculated based on the data of the Si-CH3 absorption peak, and the content of silicon dioxide was calculated based on the data of the Si-CH3 absorption peak and the Si-O absorption peak. The absorption peak of Si-CH3 is located at 1280 cm⁻¹. -1 ~1230 cm -1 The absorption peak of Si-O is located at 1160 cm⁻¹. -1 ~950 cm -1 .

2. The method for detecting the content of dimethicone and silica in a simethicone oral film as described in claim 1, characterized in that, Simethicone ether film was added to dimethyl sulfoxide and sonicated until dissolved.

3. The method for detecting the content of dimethicone and silica in a simethicone oral film as described in claim 1, characterized in that, The supernatant is dehydrated by adding a dehydrating agent to absorb water, followed by centrifugation to remove the dehydrating agent after water absorption.

4. The method for detecting the content of dimethicone and silica in a simethicone oral film as described in claim 1, characterized in that, The infrared absorption spectrum ranges from 1400 cm⁻¹ -1 ~850 cm -1 .

5. The method for detecting the content of dimethicone and silica in a simethicone oral film as described in claim 1, characterized in that, The content of dimethicone and silica was calculated based on peak area using the external standard method.

6. The method for detecting the content of dimethicone and silica in a simethicone oral film as described in claim 1, characterized in that, When using infrared spectrophotometry for detection, infrared spectrophotometry is also used to detect the dimethicone reference solution. Alternatively, when using infrared spectrophotometry for detection, infrared spectrophotometry can also be used to detect the simethicone reference solution simultaneously.

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