Laboratory quantitative determination method for residual quantity of paraffin on inner and outer surfaces of soft capsule

Abstract

The invention belongs to the technical field of pharmaceutical manufacturing quality control, and discloses a laboratory quantitative determination method for the residual quantity of paraffin on the inner and outer surfaces of a soft capsule, which comprises quantitative detection on the inner and outer surfaces of a capsule, and adopts the core scheme that a fat-soluble reagent is respectively adopted to dissolve a sample, and then evaporation treatment is carried out; and precisely weighing the weight difference value before and after evaporation, and calculating. The laboratory quantitative determination method has the advantages of simple operation, no need of complex pretreatment, simple and fast detection operation, fast detection result obtaining, suitableness for intermediate detection of batch samples, and facilitation of the guarantee of pharmaceutical production quality.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceutical manufacturing quality control, and particularly relates to a laboratory quantitative determination method for the amount of paraffin residue on the inner and outer surfaces of a soft capsule. Background Art

[0002] During the soft capsule production process, light liquid paraffin is typically used for lubrication and mold release during the transfer of the rubber sheet to the mold for compression molding. After compression molding, some paraffin residue may remain on both the inner and outer surfaces of the soft capsule. Currently, the soft capsule manufacturing industry lacks standardized operating procedures for paraffin residue detection, nor are there limits for residual paraffin oil. However, as an additive to drug formulations, controlling residual levels is beneficial to drug quality and human health. Therefore, to better control the quality of soft capsule production, it is necessary to develop a laboratory method for quantitatively detecting the amount of paraffin oil residue on the soft capsule surface. Summary of the Invention

[0003] In order to solve the above problems in the prior art, the present invention provides a laboratory quantitative determination method for the amount of paraffin residue on the inner and outer surfaces of soft capsules, so as to better control the production quality of soft capsules.

[0004] To achieve the above object, the present invention adopts the following technical solutions:

[0005] The present invention provides a laboratory quantitative determination method for the amount of paraffin residue on the inner and outer surfaces of soft capsules. The core scheme is to use a fat-soluble reagent to dissolve the sample and then evaporate it, and then calculate the weight difference before and after evaporation by precise weighing.

[0006] Preferably, the sample for detecting the amount of paraffin residue on the outer surface of the soft capsule is a finished soft capsule that has not been dried after pelleting.

[0007] Preferably, the sample for detecting the amount of paraffin residue on the inner surface of the soft capsule is a double-layer rubber sheet that has been screen-printed but not cut into pellets by a pill press.

[0008] Preferably, the fat-soluble reagent is one of ethyl acetate, petroleum ether and ethanol.

[0009] Preferably, the evaporation treatment process is: performing rotary evaporation on the sample after dissolving the fat-soluble reagent using a vacuum rotary dryer under vacuum conditions.

[0010] Preferably, the laboratory quantitative determination method of the amount of paraffin residue on the outer surface of the soft capsule comprises the following steps:

[0011] S11 Sampling: Take N pellets and place them into a clean beaker;

[0012] S12 Paraffin transfer: Add 60 ml of ethyl acetate to the beaker three times to thoroughly wash the pellet sample;

[0013] S13 weighing calculation: transfer the washing liquid to a precisely weighed rotary evaporation flask (weight W1), spin dry the washing liquid under vacuum at 50°C, and accurately weigh the total weight of the rotary evaporation flask (W2);

[0014] Calculate the amount of paraffin residue: the amount of paraffin residue on the outer surface of each capsule (mg) = (W2-W1) / N.

[0015] More preferably, in step S11, the number N of the capsule samples is 10-30 capsules, and the samples are taken at one time using a sampler.

[0016] Preferably, the laboratory quantitative determination method of the amount of paraffin residue on the inner surface of the soft capsule comprises the following steps:

[0017] S21 Sampling: At the pill pressing operation site, adjust the distance between the two roller dies of the pill pressing machine until the two rubber sheets are pressed together and only screen printed but not cut into pills. Cut a piece of rubber sheet with a size of 10cm*10cm, remove the double-layer rubber sheet, open it and place it in a clean beaker.

[0018] S22 Paraffin transfer: Add 60 ml of ethyl acetate to a beaker and wash the rubber sample thoroughly three times;

[0019] S23 weighing calculation: transfer the washing liquid to a precisely weighed rotary evaporation bottle (weight W1), spin dry the washing liquid under vacuum at 50°C, and accurately weigh the total weight of the rotary evaporation bottle (W2);

[0020] Calculate the paraffin residue: paraffin content on the inner surface of each capsule (mg) = (W2-W1) / sampling rubber area × inner surface area of ​​each capsule.

[0021] More preferably, in step S21, before the removed double-layer rubber is opened and placed in a clean beaker, the light liquid paraffin on the outer surface of the rubber sample is removed in advance using an oil-absorbing cotton cloth dipped in 95% ethanol.

[0022] Preferably, in step S23, the inner surface area of ​​each capsule is calculated based on the geometric shape and size of each capsule in the texture on the rubber.

[0023] More preferably, in step S23, for irregular-shaped soft capsule products, the surface area of ​​a single capsule can also be calculated by the average capsule weight ÷ the total weight of the sampled capsules × the sampled capsule area.

[0024] The present invention adopts the above technical solution, which has the following technical effects compared with the prior art:

[0025] The laboratory quantitative determination method for the residual amount of paraffin in soft capsules of the present invention comprises quantitative detection of the inner and outer surfaces of the capsules, and mainly calculates the weight difference of the evaporated weight after the dissolution of a fat-soluble reagent to obtain the result. The determination method is simple to operate, does not require complex pre-treatment, and has a simple and quick detection operation and rapid detection results. The method is suitable for intermediate detection of batch samples and is beneficial to the quality assurance of drug production. Common reagents such as ethyl acetate and simple instruments are used, and the detection cost is low. Through multiple washing and quantitative evaporation, the detection limit can reach 0.1 mg / capsule, and the detection accuracy is high. The determination method can also be extended to the detection of residual amounts of other fat-soluble substances, and has wide applicability. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 Schematic diagram of the structure of a double-layer rubber sample in the laboratory quantitative determination method of the paraffin residue on the inner and outer surfaces of the soft capsule of the present invention;

[0027] Figure 2 This is a schematic diagram of a double-layer rubber sample cut out in the laboratory quantitative determination method of the paraffin residue on the inner and outer surfaces of the soft capsule of the present invention. DETAILED DESCRIPTION

[0028] To better control the production quality of soft capsules (such as medicines and health products), the present invention provides a laboratory quantitative determination method for the amount of paraffin residue on the inner and outer surfaces of soft capsules. The method includes two parts: quantitative detection of the inner surface of the capsule and quantitative detection of the outer surface of the capsule. The core scheme is to calculate the result by the weight difference of the evaporated fat-soluble reagent after dissolution.

[0029] The present invention will be described in detail and specifically below through specific examples to provide a better understanding of the present invention, but the following examples do not limit the scope of the present invention.

[0030] Example 1

[0031] A laboratory quantitative determination method for the amount of paraffin residue on the outer surface of a soft capsule comprises the following steps:

[0032] S11 Sampling: Use a clean and dry sampler to take 20 capsules at a time and place them into a clean beaker;

[0033] S12 Paraffin transfer: Add 60 ml of ethyl acetate to the beaker three times to thoroughly wash the pellet sample;

[0034] S13 weighing calculation: transfer the washing liquid to a precisely weighed rotary evaporation flask (weight W1), spin dry the washing liquid under vacuum at 50°C, and accurately weigh the total weight of the rotary evaporation flask (W2);

[0035] Calculate the amount of paraffin residue: the amount of paraffin residue on the outer surface of each capsule (mg) = (W2-W1) / 20.

[0036] Example 2

[0037] A laboratory quantitative determination method for the amount of paraffin residue on the inner surface of a soft capsule comprises the following steps:

[0038] S21 Sampling: At the pill pressing operation site, adjust the distance between the two rollers of the pill pressing machine until the two rubber sheets are pressed together and only screen printed without being cut into pills. Cut a piece of rubber sheet with a size of 10cm*10cm. Figure 1 and Figure 2 As shown, wipe the outer surface with oil-absorbing cotton cloth dipped in 95% ethanol to remove the light liquid paraffin, remove the double-layer rubber, open it and place it in a clean beaker;

[0039] S22 Paraffin transfer: Add 60 ml of ethyl acetate to the beaker three times to thoroughly wash the pellet sample;

[0040] S23 weighing calculation: the washing liquid is transferred to a precisely weighed rotary evaporation bottle (weight W1), the washing liquid is vacuum-dried at 50°C, and the total weight of the rotary evaporation bottle is precisely weighed (W2);

[0041] Calculate the paraffin residue: Paraffin content on the inner surface of each capsule (mg) = (W2-W1) / sampling rubber area × inner surface area of ​​each capsule;

[0042] The internal surface area of ​​each capsule needs to be calculated based on the geometric shape and size of each capsule in the reticular pattern on the rubber.

[0043] Application Examples

[0044] 1. Materials and Instruments

[0045] Electronic balance: Mettler ME203TE, precision 1mg, calibration validity period within the validity period, weight calibration completed on the same day

[0046] Sampler: Clean and dry stainless steel tweezers

[0047] Beaker: Clean and dry 50ml glass beaker

[0048] Oil-absorbing cotton cloth: microfiber oil-absorbing cotton (lipophilic, chemical-free)

[0049] Reagent: Analytical grade ethyl acetate (GB / T 3728-2007)

[0050] Instrument: Rotary evaporator (equipped with constant temperature water bath)

[0051] 2. Operation steps

[0052] 1. A method for detecting the amount of paraffin residue on the outer surface of a soft capsule, comprising the following steps:

[0053] S11 Sampling: Use clean and dry stainless steel tweezers to randomly pick out 20 freshly compressed vitamin E soft capsules (specification 0.1g) and place them in a clean and dry 50ml beaker;

[0054] S12 Paraffin transfer: Add 60 ml of ethyl acetate to the beaker three times to thoroughly wash the pellet sample. Use a glass rod to stir in one direction to ensure that the paraffin is dissolved in the reagent.

[0055] S13 Weighing calculation: Transfer the washing liquid to a precisely weighed 100 ml rotary evaporation flask (weight 62.505 g). Place the rotary evaporation flask in a 50°C water bath. Turn on the vacuum pump and evaporate until no solvent remains (approximately 30 minutes). Accurately weigh the total weight of the rotary evaporation flask (62.554 g).

[0056] Calculate the amount of paraffin residue: the amount of paraffin residue on the outer surface of each capsule = (62.554-62.505) / 20 = 0.00245g = 2.45mg.

[0057] 2. A method for detecting the amount of paraffin residue on the inner surface of a soft capsule, comprising the following steps:

[0058] S21 Sampling: Vitamin E soft capsules (specification 0.1g) were prepared by adjusting the distance between the two rollers of the pellet press until the two rubber sheets were pressed together and only screen-printed without being cut into pellets. A 10cm×10cm piece of double-layer rubber sheet was cut with scissors. The outer surface of the double-layer rubber sheet was immediately wiped in one direction with an oil-absorbing cotton cloth dipped in 95% ethanol to remove the light liquid paraffin. The removed double-layer rubber sheet was opened and placed in a clean, dry 50ml beaker.

[0059] S22 Paraffin wax transfer: Add 60 ml of ethyl acetate to the beaker three times to thoroughly wash the rubber sample. Use a glass rod to stir in one direction to ensure that the paraffin wax is dissolved in the reagent.

[0060] S23 Weighing calculation: Transfer the washing liquid to a precisely weighed 100 ml rotary evaporation flask (weight 62.488 g). Place the rotary evaporation flask in a 50°C water bath, turn on the vacuum pump, and evaporate until no solvent remains (approximately 30 minutes). Accurately weigh the total weight of the rotary evaporation flask (62.520 g).

[0061] Vitamin E soft capsules (specification 0.1g) are ellipsoidal in shape. When the capsule is cut in half, it is a uniform ellipse with a major axis length of 1.5cm and a minor axis length of 1.0cm.

[0062] Internal surface area of ​​each capsule = π × 1.5 × 1.0 × 2 = 3π cm 2 ;

[0063] The paraffin content on the inner surface of each capsule = (62.520-62.488)÷(10×10×2)×3π=0.00151=1.51 mg.

[0064] While the specific embodiments of the present invention have been described in detail above, these are merely exemplary and the present invention is not limited thereto. For those skilled in the art, any equivalent modifications and substitutions to the present invention are also within the scope of the present invention. Therefore, any equivalent changes and modifications made without departing from the spirit and scope of the present invention are intended to be encompassed within the scope of the present invention.

Claims

1. A laboratory quantitative determination method for the amount of paraffin residue on the inner and outer surfaces of soft capsules, characterized in that: The samples are dissolved in fat-soluble reagents and then evaporated. The weight difference before and after evaporation is then accurately weighed and calculated.

2. The laboratory quantitative determination method according to claim 1, characterized in that The sample for detecting the amount of paraffin residue on the outer surface of the soft capsule is a finished soft capsule that has not been dried after pelleting.

3. The laboratory quantitative determination method according to claim 1, characterized in that The sample for detecting the amount of paraffin residue on the inner surface of the soft capsule is a double-layer rubber sheet that has been screen-printed but not cut into pellets by a pill press.

4. The laboratory quantitative determination method according to claim 1, characterized in that The fat-soluble reagent is one of ethyl acetate, petroleum ether and ethanol.

5. The laboratory quantitative determination method according to claim 1, characterized in that The evaporation treatment process comprises the following steps: performing rotary evaporation on the sample after dissolving the fat-soluble reagent using a vacuum rotary dryer under vacuum conditions.

6. The laboratory quantitative determination method according to claim 1, characterized in that The laboratory quantitative determination method of the amount of paraffin residue on the outer surface of the soft capsule comprises the following steps: S11 Sampling: Take N pellets and place them into a clean beaker; S12 Paraffin transfer: Add 60 ml of ethyl acetate to the beaker three times to thoroughly wash the pellet sample; S13 weighing calculation: transfer the washing liquid to a precisely weighed rotary evaporation flask (weight W1), spin dry the washing liquid under vacuum at 50°C, and accurately weigh the total weight of the rotary evaporation flask (W2); Calculate the amount of paraffin residue: the amount of paraffin residue on the outer surface of each capsule (mg) = (W2-W1) / N.

7. The laboratory quantitative determination method according to claim 6, characterized in that In step S11, the number N of the capsule samples is 10-30 capsules, and the sample is taken at one time using a sampler.

8. The laboratory quantitative determination method according to claim 1, characterized in that The laboratory quantitative determination method of the amount of paraffin residue on the inner surface of the soft capsule comprises the following steps: S21 Sampling: At the pill pressing operation site, adjust the distance between the two roller dies of the pill pressing machine until the two rubber sheets are pressed together and only screen printed but not cut into pills. Cut a piece of rubber sheet with a size of 10cm*10cm, remove the double-layer rubber sheet, open it and place it in a clean beaker. S22 Paraffin transfer: Add 60 ml of ethyl acetate to a beaker and wash the rubber sample thoroughly three times; S23 weighing calculation: transfer the washing liquid to a precisely weighed rotary evaporation bottle (weight W1), spin dry the washing liquid under vacuum at 50°C, and accurately weigh the total weight of the rotary evaporation bottle (W2); Calculate the paraffin residue: paraffin content on the inner surface of each capsule (mg) = (W2-W1) / sampling rubber area × inner surface area of ​​each capsule.

9. The laboratory quantitative determination method according to claim 8, characterized in that In step S21, before the removed double-layer rubber is opened and placed in a clean beaker, the light liquid paraffin on the outer surface of the rubber sample is removed in advance using an oil-absorbing cotton cloth dipped in 95% ethanol.

10. The laboratory quantitative determination method according to claim 8, characterized in that: In step S23, the inner surface area of ​​each capsule is calculated based on the geometric shape and size of each capsule in the texture on the rubber.

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