Preparation method of chemical medicine standard substance sample with preset moisture value

Abstract

The invention relates to the technical field of chemical medicine standard substance preparation, in particular to a preparation method of a chemical medicine standard substance sample with a preset moisture value. A sample preparation system with temperature control, humidity control and real-time quality detection functions is utilized, and according to the law of conservation of mass, a set of method capable of rapidly and accurately preparing the chemical medicine standard substance sample with the preset moisture value is designed. According to the method, the sample with the accurate moisture content can be prepared within half an hour, the cost is low, the consumed sample is less, the moisture content of the sample can be obtained after the sample is prepared, additional measurement and confirmation are not needed, the deviation between the moisture value of the actually obtained sample and the preset moisture value is within 0.2%, and the method has important significance in the field of medicine research.

Description

Technical Field

[0001] The present disclosure relates to the technical field of preparation of chemical standard substances, and in particular to a method for preparing a sample of a chemical standard substance with a preset moisture value. Background Art

[0002] In the field of pharmaceutical research, water directly affects the chemical degradation rate, crystal growth, dissolution rate, dispersibility and wettability, powder flowability, microbial contamination, etc. Therefore, how to prepare a series of samples with specific water content in relevant areas and strengthen targeted research has attracted increasing attention.

[0003] In traditional technology, the moisture content of the sample is roughly adjusted empirically by changing the process recipe ratio (water-related ratio) or through the drying and dehumidification stages. However, whether it is through the process recipe adjustment or drying, dehumidification and other means to change the moisture adsorption situation, it will inevitably go through a relatively long time period, at least half a day, and the above operation method relies heavily on the subjective experience of operators who are familiar with the specific varieties to estimate the change in the moisture value of the sample, which often deviates from the preset specific moisture content value by more than 2%. Therefore, after the sample is prepared using the above method, it is still necessary to consume part of the sample for testing to obtain the true value of the actual moisture content. In summary, how to prepare a series of samples with preset moisture contents in a more scientific and reasonable manner has become the focus and difficulty in similar research topics. Summary of the invention

[0004] In order to solve the above technical problems, the present disclosure provides a method for preparing a sample of a chemical standard substance with a preset moisture value. The preparation method is fast and accurate, and does not require additional consumption of samples for re-testing and confirmation, and has good application prospects.

[0005] In a first aspect, the present disclosure provides a method for preparing a chemical standard substance sample (CRS) with a preset moisture value, the preparation method comprising the following steps:

[0006] (1) determining an initial mass m0 and an initial moisture value w0 of an initial chemical; the initial chemical is in powder form;

[0007] (2) spreading the initial chemical on a sample preparation system, wherein the sample preparation system has the functions of temperature control, humidity control, and real-time quality detection;

[0008] (3) Under the condition that the temperature of the sample preparation system is stable, the ambient humidity of the sample preparation system is adjusted according to the preset moisture value w1, so that the chemical can achieve moisture adsorption or desorption. When the mass of the chemical reaches the mass m corresponding to the preset moisture value w1, x , that is, obtaining a sample of a chemical standard substance with a preset moisture value;

[0009] The mass m corresponding to the preset moisture value w1 x According to formula I, we get:

[0010]

[0011] In this disclosure, the moisture value refers to the water content of chemicals.

[0012] The following are preferred technical solutions of the present disclosure, but are not intended to be limitations of the technical solutions provided by the present disclosure. Through the following technical solutions, the technical objectives and beneficial effects of the present disclosure can be better achieved and realized.

[0013] As a preferred technical solution of the present disclosure, the thickness of the initial chemical drug spread in step (2) is 0.5-1 mm.

[0014] As a preferred technical solution of the present disclosure, in step (3), in step (3), the preset moisture value w1 is lower than the initial moisture value w0, and the ambient humidity of the sample preparation system is controlled to decompose and adsorb the water in the chemical, and as the mass of the chemical gradually approaches m x , increase the ambient humidity of the sample preparation system and slow down the rate of weight loss until the mass of the chemical reaches m x .

[0015] As a preferred technical solution of the present disclosure, in step (3), the preset moisture value w1 is higher than the initial moisture value w0, and the ambient humidity of the sample preparation system is controlled so that the chemical absorbs moisture, and as the mass of the chemical gradually approaches m x , reduce the ambient humidity of the sample preparation system and slow down the weight gain rate until the mass of the chemical reaches m x .

[0016] As a preferred technical solution of the present disclosure, in step (3), as the mass of the chemical gradually approaches m x The timing for adjusting the ambient humidity of the sample preparation system includes: when the difference between the moisture value corresponding to the real-time mass of the chemical and the preset moisture value w1 reaches 0.5%±0.1%, start adjusting the ambient humidity of the sample preparation system to slow down the weight loss rate or weight gain rate of the chemical until the mass of the chemical reaches m x .

[0017] As a preferred technical solution of the present disclosure, in step (3), the ambient humidity of the sample preparation system is increased or decreased by a difference of 2-8% in ambient humidity.

[0018] Compared with the prior art, the technical solution provided by the embodiments of the present disclosure has the following advantages:

[0019] The present invention uses a sample preparation system with temperature control, humidity control, and real-time quality detection functions, and designs a method for quickly and accurately preparing chemical drug standard substance samples with preset moisture values ​​according to the law of conservation of mass. The method can prepare samples with accurate moisture content within half an hour, is low-cost, consumes little sample, and the moisture content of the sample can be known as soon as it is prepared, without the need for additional measurement and confirmation. The deviation between the moisture value of the actual sample and the preset moisture value is within 0.2%, which is of great significance to the field of drug research. DETAILED DESCRIPTION

[0020] In order to more clearly understand the above-mentioned objectives, features and advantages of the present disclosure, the scheme of the present disclosure will be further described below. It should be noted that the embodiments of the present disclosure and the features in the embodiments can be combined with each other without conflict.

[0021] In the following description, many specific details are set forth to facilitate a full understanding of the present disclosure, but the present disclosure may also be implemented in other ways different from those described herein; it is obvious that the embodiments in the specification are only part of the embodiments of the present disclosure, rather than all of the embodiments.

[0022] In a first aspect, the present disclosure provides a method for preparing a chemical standard substance sample with a preset moisture value, the preparation method comprising the following steps:

[0023] (1) determining an initial mass m0 and an initial moisture value w0 of an initial chemical; the initial chemical is in powder form;

[0024] (2) spreading the initial chemical on a sample preparation system, wherein the sample preparation system has the functions of temperature control, humidity control, and real-time quality detection;

[0025] (3) Under the condition that the temperature of the sample preparation system is stable, the ambient humidity of the sample preparation system is adjusted according to the preset moisture value w1, so that the chemical can achieve moisture adsorption or desorption. When the mass of the chemical reaches the mass m corresponding to the preset moisture value w1, x , that is, obtaining a sample of a chemical standard substance with a preset moisture value;

[0026] The mass m corresponding to the preset moisture value w1 x According to formula I, we get:

[0027]

[0028] The present disclosure utilizes a sample preparation system with the functions of temperature control, humidity control, and real-time quality detection, and designs a method for quickly and accurately preparing samples of chemical standard substances with preset moisture values ​​according to the law of conservation of mass. The method overcomes the problems of relatively complex experiments, long experimental cycles, high experimental costs, large sample consumption, and large result deviations in the prior art. It can intuitively prepare samples with accurate water content within hours, has low costs, consumes less samples, and the moisture content of the samples can be known as soon as they are prepared, without the need for additional measurement and confirmation. The deviation between the moisture value of the actual sample and the preset moisture value is within 0.2%, and can be used for drug development and quality control research related to moisture, such as the hygroscopicity of raw materials, powder fluidity, and microorganisms of finished drugs.

[0029] In the present disclosure, a sample preparation system with temperature control, humidity control, and real-time quality detection functions can be built by the experimenter himself, or a dynamic moisture adsorption tester (DVS) can be used, as long as it has the above functions.

[0030] The following are preferred technical solutions of the present disclosure, but are not intended to be limitations of the technical solutions provided by the present disclosure. Through the following technical solutions, the technical objectives and beneficial effects of the present disclosure can be better achieved and realized.

[0031] As a preferred technical solution of the present disclosure, the thickness of the initial chemical drug in step (2) is 0.5-1 mm, for example, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm or 1 mm, but is not limited to the listed values, and other unlisted values ​​within the range are also applicable.

[0032] The appropriate paving thickness helps the sample to adsorb or desorb moisture evenly and quickly, avoiding uneven moisture distribution in the final sample and substandard products due to the sample being spread too thickly.

[0033] As a preferred technical solution of the present disclosure, in step (3), the preset moisture value w1 is lower than the initial moisture value w0, and the ambient humidity of the sample preparation system is controlled to decompose and adsorb the water in the chemical, and as the mass of the chemical gradually approaches m x , increase the ambient humidity of the sample preparation system and slow down the rate of weight loss until the mass of the chemical reaches m x .

[0034] Exemplarily, the preset moisture value w1 is lower than the initial moisture value w0, and the ambient humidity of the sample preparation system is controlled to be 20%-30%, such as 20%, 25%, 27% or 30%, etc., but is not limited to the listed values, and other unlisted values ​​within the range are also applicable.

[0035] As a preferred technical solution of the present disclosure, in step (3), the preset moisture value w1 is higher than the initial moisture value w0, and the ambient humidity of the sample preparation system is controlled so that the chemical absorbs moisture, and as the mass of the chemical gradually approaches m x , reduce the ambient humidity of the sample preparation system and slow down the weight gain rate until the mass of the chemical reaches m x .

[0036] Exemplarily, the preset moisture value w1 is higher than the initial moisture value w0, and the ambient humidity of the sample preparation system is controlled to be 40%-80%, such as 40%, 50%, 60%, 65%, 70% or 80%, etc., but is not limited to the listed values, and other unlisted values ​​within the range are also applicable.

[0037] The present invention sets a more reasonable initial environmental humidity according to different preset moisture values, and can obtain the required sample more accurately and quickly. Generally, the required sample can be obtained within 20 minutes, and there is no need to waste the obtained sample for re-testing.

[0038] As a preferred technical solution of the present disclosure, in step (3), as the mass of the chemical gradually approaches m x The timing for adjusting the ambient humidity of the sample preparation system includes: when the difference between the moisture value corresponding to the real-time mass of the chemical and the preset moisture value w1 reaches 0.5%±0.1%, start adjusting the ambient humidity of the sample preparation system to slow down the weight loss rate or weight gain rate of the chemical until the mass of the chemical reaches m x .

[0039] In the actual preparation process, generally, the mass corresponding to the value near the preset moisture value can be calculated, so that the operator can more clearly and conveniently judge the timing of adjusting the ambient humidity of the sample control system.

[0040] As a preferred technical solution of the present invention, in step (3), the ambient humidity of the sample preparation system is increased or decreased by an ambient humidity difference of 2-8%, for example, increased or decreased by 2%, increased or decreased by 3%, increased or decreased by 4%, increased or decreased by 5%, increased or decreased by 6%, increased or decreased by 7%, or increased or decreased by 8%, etc., but is not limited to the listed values, and other values ​​not listed within the range are equally applicable.

[0041] Example 1

[0042] Preparation of samples with a preset moisture value of 3% in the development of methylcobalamin CRS

[0043] (1) Weigh 48.17 mg of powdered methylcobalamin and determine the moisture content to be 5.1%;

[0044] (2) Spread the powdered methylcobalamin on the sample preparation system with a thickness of 0.5 mm;

[0045] (3) According to formula I, the chemical quality corresponding to the preset moisture value and its nearby values ​​is calculated, as shown in Table 1:

[0046] Table 1

[0047] <![CDATA[Preset moisture value w1 (%)]]> 4.0 3.5 3.0 2.8 <![CDATA[The corresponding mass m x (mg)]]> 47.62 47.37 47.13 47.03

[0048] (4) Under the premise of ensuring the stability of methylcobalamin (no chemical change), the environmental humidity (RH%) is adjusted to enable methylcobalamin to desorb water:

[0049] First, the ambient humidity was set to 20%, and methylcobalamin was observed to be in a weightless state. After about 5 minutes, the mass was monitored to decrease by 0.8 mg in real time. At this time, the mass of methylcobalamin was 47.4 mg, and the corresponding moisture value was around 3.5%;

[0050] Next, the ambient humidity was adjusted to 25% to slow down the decreasing trend of the mass of methylcobalamin so as to control its moisture value. After 4 minutes, the mass of methylcobalamin monitored in real time reached 47.1 mg, and a chemical drug standard substance sample with a preset moisture value of 3% was obtained.

[0051] It was calculated that when the mass of methylcobalamin reached 47.1 mg, its moisture content was 2.94% (with two decimal places), and the difference from the preset moisture content of 3% was only -0.06%.

[0052] Example 2

[0053] Preparation of samples with a preset moisture value of 4% in the development of acarbose CRS

[0054] (1) Weigh 38.92 mg of powdered acarbose and determine the moisture content to be 2.6%;

[0055] (2) spreading the powdered acarbose on a sample preparation system with a thickness of 1 mm;

[0056] (3) According to formula I, the sample mass corresponding to the preset moisture value and its nearby values ​​is calculated, as shown in Table 2:

[0057] Table 2

[0058] <![CDATA[Preset moisture value w1(%)]]> 3.0 3.5 4.0 4.2 <![CDATA[The corresponding mass m x (mg)]]> 39.08 39.28 39.49 39.57

[0059] (4) Under the premise of ensuring the stability of acarbose (no chemical change), the environmental humidity (RH%) is adjusted to enable acarbose to absorb water:

[0060] First, the ambient humidity was set to 50%, and acarbose was observed to be in a state of weight gain. After about 7 minutes, the mass was monitored to increase by 0.4 mg in real time. At this time, the mass of acarbose was 39.3 mg, and the corresponding moisture value was around 3.5%.

[0061] Next, the ambient humidity was adjusted to 45% to slow down the mass growth trend of acarbose to control its moisture value. After 4.5 minutes, the mass of acarbose monitored in real time reached 39.5 mg, and a chemical drug standard substance sample with a preset moisture value of 4% was obtained.

[0062] According to calculation, when the mass of acarbose reaches 39.5 mg, its moisture content is 4.03% (retain two decimal places), and the deviation from the preset moisture content of 4% is +0.03%.

[0063] Example 3

[0064] Preparation of a series of samples with preset moisture values ​​of 1%, 2%, 3%, 5%, and 6% in the development of phenylephrine hydrochloride CRS

[0065] (1) Weigh 40.00 mg of powdered phenylephrine hydrochloride and dry to constant weight, at which point the moisture content is 0;

[0066] (2) Spread the powdered phenylephrine hydrochloride on the sample preparation system with a thickness of 0.7 mm;

[0067] (3) According to formula I, the chemical quality corresponding to the preset moisture value and its nearby values ​​is calculated, as shown in Table 3:

[0068] Table 3

[0069] <![CDATA[Preset moisture value w1 (%)]]> 1.0 1.5 2.0 2.5 3.0 4.5 <![CDATA[The corresponding mass m x (mg)]]> 40.40 40.61 40.82 41.03 41.24 41.88 Preset moisture value w1(%) 5.0 5.5 6.0 6.2 Corresponding mass mx (mg) 42.11 42.33 42.55 42.64

[0070] (4) Under the premise of ensuring the stability of phenylephrine hydrochloride (no chemical change), the environmental humidity (RH%) is adjusted to enable phenylephrine hydrochloride to achieve water adsorption:

[0071] First, the ambient humidity was set to 75%, and it was observed that phenylephrine hydrochloride was in a weight gain state. After about 8 minutes, the mass was monitored to increase by 0.4 mg in real time. At this time, the mass of phenylephrine hydrochloride was 40.4 mg, and the corresponding moisture value was 1%, that is, a chemical drug standard substance sample with a preset moisture value of 1% was obtained;

[0072] After calculation, when the mass of phenylephrine hydrochloride reaches 40.4 mg, its moisture value is 1.00% (retain two decimal places), which has no deviation from the preset moisture value of 1%;

[0073] (5) Repeating steps (1) to (2), adjusting the ambient humidity to 80%, observing that phenylephrine hydrochloride is in a weight gain state, and after about 2 minutes, real-time monitoring shows that the mass increases by 0.8 mg. At this time, the mass of phenylephrine hydrochloride is 40.8 mg, and the corresponding moisture value is 2%, that is, a chemical drug standard substance sample with a preset moisture value of 2% is obtained;

[0074] After calculation, when the mass of phenylephrine hydrochloride reaches 40.8 mg, its moisture value is 1.96% (retain two decimal places), and the deviation from the preset moisture value of 2% is -0.04%;

[0075] (6) Repeating steps (1) to (2), the ambient humidity was controlled to 80%, and the phenylephrine hydrochloride was observed to be in a weight gain state. After about 4 minutes, the mass was monitored to increase by 1.0 mg in real time. At this time, the mass of the phenylephrine hydrochloride was 41.0 mg, and the corresponding moisture value was around 2.5%;

[0076] Then the environmental humidity was adjusted to 75% to slow down the mass growth trend of phenylephrine hydrochloride to control its moisture value. After 3 minutes, the mass of phenylephrine hydrochloride monitored in real time reached 41.2 mg, that is, a chemical drug standard substance sample with a preset moisture value of 3% was obtained.

[0077] After calculation, when the mass of phenylephrine hydrochloride reaches 41.2 mg, its moisture value is 2.91% (retain two decimal places), and the deviation from the preset moisture value of 3% is -0.09%;

[0078] (7) Repeating steps (1) to (2), the ambient humidity was controlled to 80%, and the phenylephrine hydrochloride was observed to be in a weight gain state. After about 7 minutes, the mass was monitored to increase by 1.9 mg in real time. At this time, the mass of the phenylephrine hydrochloride was 41.9 mg, and the corresponding moisture value was around 4.5%;

[0079] Then the ambient humidity was adjusted to 75% to slow down the mass growth trend of phenylephrine hydrochloride to control its moisture value. After 5 minutes, the mass of phenylephrine hydrochloride monitored in real time reached 42.1 mg, that is, a chemical drug standard substance sample with a preset moisture value of 5% was obtained.

[0080] After calculation, when the mass of phenylephrine hydrochloride reaches 42.1 mg, its moisture value is 4.99% (retain two decimal places), and the deviation from the preset moisture value of 3% is -0.01%;

[0081] (8) Repeating steps (1) to (2), controlling the ambient humidity to 80%, observing that the phenylephrine hydrochloride was in a weight gain state, and after about 10 minutes, real-time monitoring showed that the mass increased by 2.3 mg. At this time, the mass of the phenylephrine hydrochloride was 42.3 mg, and the corresponding moisture value was around 5.5%;

[0082] Then the environmental humidity was adjusted to 75% to slow down the mass growth trend of phenylephrine hydrochloride to control its moisture value. After 6 minutes, the mass of phenylephrine hydrochloride monitored in real time reached 42.5 mg, that is, a chemical drug standard substance sample with a preset moisture value of 6% was obtained.

[0083] After calculation, when the mass of phenylephrine hydrochloride reaches 42.5 mg, its moisture content is 5.88% (retain two decimal places), and the deviation from the preset moisture content of 3% is -0.12%.

[0084] It can be seen from Examples 1-3 that by adopting the preparation method disclosed in the present invention, a sample of a chemical standard substance with a preset moisture value can be prepared within half an hour, with a deviation not exceeding 0.2%, or even not exceeding 0.1%, and there is no need to waste additional samples for re-measurement to confirm the true value, which has good application prospects.

[0085] It should be noted that, in this article, relational terms such as "first" and "second" are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Moreover, the terms "include", "comprise" or any other variants thereof are intended to cover non-exclusive inclusion, so that a process, method, article or device including a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements inherent to such process, method, article or device. In the absence of further restrictions, the elements defined by the sentence "comprise a ..." do not exclude the existence of other identical elements in the process, method, article or device including the elements.

[0086] The above description is only a specific embodiment of the present disclosure, so that those skilled in the art can understand or implement the present disclosure. 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 disclosure. Therefore, the present disclosure will not be limited to the embodiments described herein, but will conform to the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A method for preparing a chemical standard substance sample with a preset moisture value, characterized in that: The preparation method comprises the following steps: (1) determining an initial mass m0 and an initial moisture value w0 of an initial chemical; the initial chemical is in powder form; (2) spreading the initial chemical on a sample preparation system, wherein the sample preparation system has the functions of temperature control, humidity control, and real-time quality detection; (3) Under the condition that the temperature of the sample preparation system is stable, the ambient humidity of the sample preparation system is adjusted according to the preset moisture value w1, so that the chemical can achieve moisture adsorption or desorption. When the mass of the chemical reaches the mass m corresponding to the preset moisture value w1, x , that is, obtaining a sample of a chemical standard substance with a preset moisture value; The mass m corresponding to the preset moisture value w1 x According to formula I, we get:

2. The preparation method according to claim 1, characterized in that: The thickness of the initial chemical applied in step (2) is 0.5-1 mm.

3. The preparation method according to claim 1 or 2, characterized in that: In step (3), the preset moisture value w1 is lower than the initial moisture value w0, and the ambient humidity of the sample preparation system is controlled to decompose and adsorb the water in the chemical, and as the mass of the chemical gradually approaches m x , increase the ambient humidity of the sample preparation system and slow down the rate of weight loss until the mass of the chemical reaches m x .

4. The preparation method according to claim 1 or 2, characterized in that: In step (3), the preset moisture value w1 is higher than the initial moisture value w0, and the ambient humidity of the sample preparation system is controlled so that the chemical absorbs moisture, and as the mass of the chemical gradually approaches m x , reduce the ambient humidity of the sample preparation system and slow down the weight gain rate until the mass of the chemical reaches m x .

5. The preparation method according to claim 3 or 4, characterized in that: In step (3), as the mass of the chemical approaches m x The timing for adjusting the ambient humidity of the sample preparation system includes: when the difference between the moisture value corresponding to the real-time mass of the chemical and the preset moisture value w1 reaches 0.5%±0.1%, start adjusting the ambient humidity of the sample preparation system to slow down the weight loss rate or weight gain rate of the chemical until the mass of the chemical reaches m x .

6. The preparation method according to claim 5, characterized in that: In step (3), the ambient humidity of the sample preparation system is increased or decreased by a difference of 2-8% in ambient humidity.

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