Pharmaceutical composition containing ketoprofen and preparation method thereof

Abstract

According to the pharmaceutical composition containing ketoprofen and the preparation method of the pharmaceutical composition, the hydroxypropyl methylcellulose is used as a film-forming agent, the polyvinyl alcohol-polyethylene glycol copolymer is used as a plasticizer, and the dosage of each component is strictly controlled, so that the film dosage of the prepared pharmaceutical composition is accurate, the pharmaceutical composition can be taken without water, and the pharmaceutical composition can be quickly dissolved in the oral cavity; the oral liquid is good in compliance, small in size, light in weight, low in content of related substances, good in mechanical strength and convenient to carry, is particularly suitable for children, old people and dysphagia patients with vomiting symptoms to take, can be immediately dissolved when being put into the mouth, can prevent children from vomiting, and solves the problems that capsules, gel and patches are inaccurate in administration dosage, need to be taken with water, and are inconvenient to take. Children and elderly patients with dysphagia are poor in compliance, inconvenient to carry and the like.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a pharmaceutical composition containing ketoprofen and a preparation method thereof. Background Art

[0002] Ketoprofen is an aryl alkanoic acid compound. It has analgesic, anti-inflammatory and antipyretic effects. Its anti-inflammatory effect is stronger than that of ibuprofen, with fewer side effects and lower toxicity. It is mainly used for rheumatoid arthritis, rheumatic arthritis, osteoarthritis, ankylosing spondylitis and gout. Ketoprofen gel, ketoprofen sustained-release tablets, ketoprofen enteric-coated capsules, ketoprofen patches and ketoprofen sustained-release capsules are currently on the market in China, but no oral dissolving film is available on the market yet. Summary of the invention

[0003] The purpose of the present invention is to provide a pharmaceutical composition containing ketoprofen on the basis of the prior art, which has an accurate film dosage, does not need to be taken with water, dissolves quickly in the oral cavity, has good compliance, is small in size, light in weight, has a low content of related substances, has good mechanical strength, is convenient to carry, is particularly suitable for children, the elderly and patients with dysphagia who have vomiting symptoms, and dissolves immediately when put into the mouth, which can prevent children from vomiting the medicine, and solves the problems of inaccurate dosage of capsules, gels and patches, which need to be taken with water, poor compliance of children and elderly patients with dysphagia, and inconvenience in carrying.

[0004] Another object of the present invention is to provide a method for preparing the above-mentioned pharmaceutical composition containing ketoprofen.

[0005] The technical solution of the present invention is as follows:

[0006] A ketoprofen-containing pharmaceutical composition is prepared from the following components in parts by weight: 20-60 parts of ketoprofen, 20-45 parts of a film former, 10-35 parts of a plasticizer, 1-10 parts of a sweetener, 1-10 parts of a saliva stimulant, 1-10 parts of a taste masking agent, and 1-10 parts of a surfactant.

[0007] The pharmaceutical composition containing ketoprofen provided by the present invention comprises a raw material and an auxiliary material, wherein the raw material is ketoprofen, and the auxiliary material comprises a film former, a plasticizer, a sweetener, a salivary stimulant, a taste masking agent and a surfactant. Among them, the film former is hydroxypropyl methylcellulose; the plasticizer is a polyvinyl alcohol-polyethylene glycol copolymer; the sweetener is one or more of sucrose, sucralose or maltose, preferably sucralose; the salivary stimulant is one or more of vitamin C, citric acid or malic acid, preferably vitamin C; the taste masking agent is hydroxypropyl beta-cyclodextrin and / or maltodextrin, preferably maltodextrin. The surfactant is one or more of sodium lauryl sulfate, polysorbate or poloxamer, preferably sodium lauryl sulfate.

[0008] In a preferred embodiment, the pharmaceutical composition containing ketoprofen provided by the present invention comprises the following steps: firstly, ketoprofen and anhydrous ethanol are uniformly mixed to prepare a drug solution A; then, the drug solution A is uniformly mixed with a drug solution B prepared from a plasticizer, a sweetener, a salivary stimulant, a taste masking agent, a surfactant and water; and the obtained mixed solution is coated, dried and cut to obtain the pharmaceutical composition containing ketoprofen; wherein the sweetener is sucralose; the salivary stimulant is vitamin C; the taste masking agent is maltodextrin; and the surfactant is sodium lauryl sulfate.

[0009] The present invention uses hypromellose as a film-forming agent. Experiments have found that only by strictly controlling the amount of hypromellose can the film-forming property, elasticity and mechanical strength of the pharmaceutical composition of the present invention be maintained at a good level, while too high or too low an amount of hypromellose is difficult to achieve the above effects. When the raw material drug ketoprofen is 20 to 60 parts, the amount of hypromellose is controlled to be 15 to 45 parts; preferably, the amount of hypromellose is 20 to 40 parts, and more preferably, the amount of hypromellose is 25-40 parts.

[0010] The present invention uses polyvinyl alcohol-polyethylene glycol copolymer as a plasticizer. Experiments have found that only by strictly controlling the amount of polyvinyl alcohol-polyethylene glycol copolymer can the elongation, tensile strength and plasticity of the pharmaceutical composition of the present invention be maintained at a good level, while too high or too low an amount of polyvinyl alcohol-polyethylene glycol copolymer is difficult to achieve the above effects. When the bulk drug ketoprofen is 20 to 60 parts, the amount of polyvinyl alcohol-polyethylene glycol is controlled to be 10 to 35 parts; preferably, the amount of polyvinyl alcohol-polyethylene glycol is 15 to 35 parts, and more preferably, the amount of polyvinyl alcohol-polyethylene glycol is 20-30 parts.

[0011] In the present invention, the polyvinyl alcohol-polyethylene glycol copolymer is made of 75% polyvinyl alcohol and 25% polyethylene glycol. Experiments have found that when the polyvinyl alcohol-polyethylene glycol copolymer is replaced with a mixture of polyvinyl alcohol and polyethylene glycol in the same proportion, the film has poor formability, and there is more residue after the film is removed, resulting in reduced content and solubility, high content of related substances, and poor stability.

[0012] In a preferred embodiment, the pharmaceutical composition containing ketoprofen provided by the present invention is prepared from the following components in parts by weight: 30 to 50 parts of ketoprofen, 20 to 40 parts of hydroxypropyl methylcellulose, 15 to 35 parts of polyvinyl alcohol-polyethylene glycol copolymer, 2 to 8 parts of sucralose, 2 to 8 parts of vitamin C, 2 to 8 parts of maltodextrin, and 2 to 8 parts of sodium lauryl sulfate.

[0013] In a more preferred embodiment, the pharmaceutical composition containing ketoprofen provided by the present invention is prepared from the following components in parts by weight: 40 parts of ketoprofen, 25-40 parts of hypromellose, 20-30 parts of polyvinyl alcohol-polyethylene glycol copolymer, 5 parts of sucralose, 5 parts of vitamin C, 5 parts of maltodextrin, and 5 parts of sodium lauryl sulfate.

[0014] For example, the pharmaceutical composition containing ketoprofen provided by the present invention is made of the following components in parts by weight: 40 parts of ketoprofen, 25 parts of hypromellose, 20 parts of polyvinyl alcohol-polyethylene glycol copolymer, 5 parts of sucralose, 5 parts of vitamin C, 5 parts of maltodextrin, and 5 parts of sodium lauryl sulfate.

[0015] For example, the pharmaceutical composition containing ketoprofen provided by the present invention is made of the following components in parts by weight: 40 parts of ketoprofen, 40 parts of hypromellose, 30 parts of polyvinyl alcohol-polyethylene glycol copolymer, 5 parts of sucralose, 5 parts of vitamin C, 5 parts of maltodextrin, and 5 parts of sodium lauryl sulfate.

[0016] The present invention also provides a method for preparing the above-mentioned pharmaceutical composition containing ketoprofen, comprising the following steps:

[0017] (1) Pretreatment: The raw material ketoprofen and the auxiliary materials are sieved and set aside;

[0018] (2) Preparation of drug solution A: The raw material drug ketoprofen and anhydrous ethanol are uniformly mixed to prepare drug solution A, i.e., ketoprofen solution;

[0019] (3) Preparation of liquid B: uniformly mix the plasticizer, sweetener, salivary stimulant, taste masking agent, surfactant and water to prepare liquid B;

[0020] (4) Mixing, drying and cutting: The drug solution A obtained in step (2) and the drug solution B obtained in step (3) are fully mixed and stirred evenly, and the obtained mixed solution is evenly coated, dried and cut to obtain a pharmaceutical composition containing ketoprofen.

[0021] In the present invention, in step (1), the API and excipients are sieved through a 40-80 mesh sieve, preferably a 60 mesh sieve.

[0022] In the present invention, in step (2), the mass fraction of ketoprofen in the medicinal solution A is 30-70%, which may be but is not limited to 30%, 35%, 40%, 45%, 50%, 55%, 60% or 70%; preferably, the mass fraction of ketoprofen is 50%.

[0023] In the drying process, the drying method can be reduced pressure drying, forced air drying or boiling drying, but the present invention finds that forced air drying can reduce the impurity content in the product to the greatest extent, so that the total impurity and the maximum single impurity content in the product are both minimized, which is more conducive to the storage and use of the pharmaceutical composition. Preferably, in forced air drying, the drying temperature is 60 to 70°C, preferably 65°C; the drying time is 1 to 5 hours, until the moisture content is no more than 3%.

[0024] In the present invention, in step (3), the dried product is cut into pieces with a length of 3 cm to 3.5 cm and a width of 2 cm to 2.5 cm; preferably, the length is 3 cm and the width is 2 cm.

[0025] Adopt the technical scheme of the present invention, the advantages are as follows:

[0026] The invention uses hydroxypropyl methylcellulose as a film-forming agent, polyvinyl alcohol-polyethylene glycol copolymer as a plasticizer, and adds auxiliary materials such as sweeteners, salivary stimulants, taste masking agents and surfactants, and strictly controls the amount of each component to prepare a drug composition containing ketoprofen that is quickly dissolved, quickly absorbed, has a simple preparation method, and has stable and reliable quality. The film has accurate dosage, small volume, light weight, low content of related substances, good mechanical strength, and is convenient to carry; it does not need to be taken with water, dissolves quickly in the oral cavity, and has good compliance; it is particularly suitable for children, the elderly, and patients with dysphagia who have vomiting symptoms, and dissolves immediately when put into the mouth, so as to prevent children from vomiting the medicine, and solves the problems of inaccurate dosage of capsules, gels, and patches, which need to be taken with water, poor compliance of children and elderly patients with dysphagia, and inconvenience in carrying. DETAILED DESCRIPTION

[0027] The present invention can be better understood according to the following examples. However, it is easy for those skilled in the art to understand that the contents described in the examples are only used to illustrate the present invention, and should not and will not limit the present invention described in detail in the claims.

[0028] Example 1

[0029] A pharmaceutical composition containing ketoprofen, wherein each 1000 dosage units are made of the following components by weight:

[0030]

[0031] The preparation method of the above-mentioned pharmaceutical composition containing ketoprofen comprises the following steps:

[0032] (1) Pretreatment: Weigh the raw material ketoprofen and excipients, wherein the excipients are hydroxypropyl methylcellulose, polyvinyl alcohol-polyethylene glycol copolymer, sodium lauryl sulfate, sucralose, vitamin C and maltodextrin, and pass them through a 60-mesh sieve respectively for later use.

[0033] (2) Preparation of drug solution A: Add the raw material ketoprofen to 40 g of anhydrous ethanol, stir and dissolve, and prepare drug solution A, i.e., ketoprofen solution, for later use; wherein the mass fraction of ketoprofen in the ketoprofen solution is 50%.

[0034] (3) Preparation of Solution B: Add hydroxypropyl methylcellulose, polyvinyl alcohol-polyethylene glycol copolymer, sodium lauryl sulfate, sucralose, vitamin C and maltodextrin to 250 g of purified water, stir thoroughly to dissolve, and prepare Solution B for later use.

[0035] (4) Mixing, drying and cutting: The drug solution A obtained in step (2) and the drug solution B obtained in step (3) are fully mixed and stirred evenly. The obtained mixed solution is evenly coated and placed in a forced air drying oven. Drying is carried out at 65° C. for 1 to 5 hours until the moisture content is no more than 3%. After drying, the mixture is cut into a size of 3 cm in length and 2 cm in width to obtain a pharmaceutical composition containing ketoprofen.

[0036] Example 2

[0037] A pharmaceutical composition containing ketoprofen, wherein each 1000 dosage units are made of the following components by weight:

[0038]

[0039]

[0040] The preparation method of the above-mentioned pharmaceutical composition containing ketoprofen is the same as that of Example 1.

[0041] Comparative Example 1

[0042] A pharmaceutical composition containing ketoprofen, wherein each 1000 dosage units are made of the following components by weight:

[0043]

[0044] The preparation method of the above-mentioned pharmaceutical composition containing ketoprofen comprises the following steps:

[0045] (1) Pretreatment: Weigh the raw material ketoprofen and excipients, wherein the excipients are hydroxypropyl methylcellulose, polyvinyl alcohol-polyethylene glycol copolymer, sodium lauryl sulfate, sucralose, vitamin C and maltodextrin, and pass them through a 60-mesh sieve respectively for later use.

[0046] (2) Preparation of drug solution A: Add the raw material ketoprofen to 40 g of anhydrous ethanol, stir and dissolve, and prepare drug solution A, i.e., ketoprofen solution, for later use; wherein the mass fraction of ketoprofen in the ketoprofen solution is 50%.

[0047] (3) Preparation of Solution B: Add polyvinyl alcohol-polyethylene glycol copolymer, sodium lauryl sulfate, sucralose, vitamin C and maltodextrin to 250 g of purified water, stir thoroughly to dissolve, and prepare Solution B for later use.

[0048] (4) Mixing, drying and cutting: The drug solution A obtained in step (2) and the drug solution B obtained in step (3) are fully mixed and stirred evenly. The obtained mixed solution is evenly coated and placed in a forced air drying oven. Drying is carried out at 65° C. for 1 to 5 hours until the moisture content is no more than 3%. After drying, the mixture is cut into a size of 3 cm in length and 2 cm in width to obtain a pharmaceutical composition containing ketoprofen.

[0049] Comparative Example 2

[0050] A pharmaceutical composition containing ketoprofen, wherein each 1000 dosage units are made of the following components by weight:

[0051]

[0052]

[0053] The preparation method of the above-mentioned pharmaceutical composition containing ketoprofen comprises the following steps:

[0054] (1) Pretreatment: Weigh the raw material ketoprofen and excipients, wherein the excipients are hydroxypropyl methylcellulose, polyvinyl alcohol-polyethylene glycol copolymer, sodium lauryl sulfate, sucralose, vitamin C and maltodextrin, and pass them through a 60-mesh sieve respectively for later use.

[0055] (2) Preparation of drug solution A: Add the raw material ketoprofen to 40 g of anhydrous ethanol, stir and dissolve, and prepare drug solution A, i.e., ketoprofen solution, for later use; wherein the mass fraction of ketoprofen in the ketoprofen solution is 50%.

[0056] (3) Preparation of Solution B: Add hydroxypropyl methylcellulose, polyvinyl alcohol, polyethylene glycol, sodium lauryl sulfate, sucralose, vitamin C and maltodextrin to 250 g of purified water, stir thoroughly to dissolve, and prepare Solution B for later use.

[0057] (4) Mixing, drying and cutting: The drug solution A obtained in step (2) and the drug solution B obtained in step (3) are fully mixed and stirred evenly. The obtained mixed solution is evenly coated and placed in a forced air drying oven. Drying is carried out at 65° C. for 1 to 5 hours until the moisture content is no more than 3%. After drying, the mixture is cut into a size of 3 cm in length and 2 cm in width to obtain a pharmaceutical composition containing ketoprofen.

[0058] Comparative Example 3

[0059] A pharmaceutical composition containing ketoprofen, wherein each 1000 dosage units are made of the following components by weight:

[0060]

[0061] The preparation method of the above-mentioned pharmaceutical composition containing ketoprofen is as described in Example 1.

[0062] Comparative Example 4

[0063] A pharmaceutical composition containing ketoprofen, wherein each 1000 dosage units are made of the following components by weight:

[0064]

[0065] The preparation method of the above-mentioned pharmaceutical composition containing ketoprofen is as described in Example 1.

[0066] Comparative Example 5

[0067] A pharmaceutical composition containing ketoprofen, wherein each 1000 dosage units are made of the following components by weight:

[0068]

[0069] The preparation method of the above-mentioned pharmaceutical composition containing ketoprofen is as described in Example 1.

[0070] Effect verification

[0071] 1. The comparative data of the effects of the pharmaceutical compositions in the examples and comparative examples in terms of formability, disintegration time, solubility, stability, etc. are shown in Table 1.

[0072] Table 1 Experimental results

[0073]

[0074]

[0075] It can be seen from the dissolution data in Table 1 that the pharmaceutical compositions prepared in Examples 1 to 2 of the present invention use hydroxypropyl methylcellulose as a film-forming material and polyvinyl alcohol-polyethylene glycol copolymer as a plasticizer, and control the amount of the film-forming material and the plasticizer, so that the prepared pharmaceutical compositions have good formability, are easy to peel off the film, have good mechanical strength, and the disintegration time and solubility meet the requirements.

[0076] In Comparative Example 1, no film-forming agent, hydroxypropyl methylcellulose, was added, and the prepared sample could not be formed;

[0077] In Comparative Example 2, the plasticizer polyvinyl alcohol-polyethylene glycol copolymer was replaced with a mixture of polyvinyl alcohol and polyethylene glycol in the same proportion. The resulting drug film had poor formability and had more residue after peeling off the film, resulting in reduced content and solubility, high content of related substances, and poor stability.

[0078] In Comparative Example 3, the amount of film-forming agent hydroxypropyl methylcellulose was increased. Although film formation was possible, the ductility was poor, the mechanical strength was increased, resulting in an increase in the disintegration time, a decrease in the solubility, a high content of related substances, and poor stability.

[0079] In Comparative Example 4, the amount of the plasticizer polyvinyl alcohol-polyethylene glycol copolymer was increased, the mechanical strength was increased, resulting in an increase in the disintegration time, while the solubility was reduced, the content of related substances was high, and the stability was poor.

[0080] In Comparative Example 5, the film-forming agent was replaced by povidone K30 from hydroxypropyl methylcellulose. Although the film could be formed, the properties and film removability were poor, and there was a lot of residue after the film was removed, resulting in reduced content and solubility, high content of related substances, and poor stability.

[0081] 2. The stability of the pharmaceutical composition in Example 1 is investigated. The specific experimental results are shown in Table 2.

[0082] Table 2 Stability test results

[0083]

[0084]

[0085] As shown in Table 2, the pharmaceutical composition containing ketoprofen prepared in Example 1 was subjected to a 24-month stability test. The results showed that the properties, content, mechanical strength, disintegration time, solubility and other related properties of the sample did not change significantly, and the sample quality was stable.

[0086] The pharmaceutical composition containing ketoprofen prepared in Example 2 was tested for stability for 24 months, and the stability result was not much different from that in Example 1, and the pharmaceutical composition also had good stability.

[0087] The above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, a person skilled in the art should understand that it is still possible to modify the technical solutions described in the aforementioned embodiments, or to perform equivalent replacements on some of the technical features therein. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A pharmaceutical composition containing ketoprofen, characterized in that, The invention is prepared from the following components in parts by weight: 20-60 parts of ketoprofen, 15-45 parts of film formers, 10-35 parts of plasticizers, 1-10 parts of sweeteners, 1-10 parts of salivary stimulants, 1-10 parts of taste-masking agents, and 1-10 parts of surfactants; wherein the film former is hydroxypropyl methylcellulose; the plasticizer is polyvinyl alcohol-polyethylene glycol copolymer; the sweetener is one or more of sucrose, sucralose or maltose; the salivary stimulant is one or more of vitamin C, citric acid or malic acid; the taste-masking agent is hydroxypropyl beta-cyclodextrin and / or maltodextrin; and the surfactant is one or more of sodium lauryl sulfate, polysorbate or poloxamer.

2. The pharmaceutical composition containing ketoprofen according to claim 1, characterized in that In the preparation process, ketoprofen and anhydrous ethanol are first mixed evenly to prepare a drug solution A; then mixed evenly with a drug solution B prepared from a plasticizer, a sweetener, a salivary stimulant, a taste masking agent, a surfactant and water; the obtained mixed solution is coated, dried and cut to obtain a drug composition containing ketoprofen; wherein the sweetener is sucralose; the salivary stimulant is vitamin C; The taste masking agent is maltodextrin; the surfactant is sodium lauryl sulfate.

3. The pharmaceutical composition containing ketoprofen according to claim 2, characterized in that The invention is prepared from the following components in parts by weight: 30-50 parts of ketoprofen, 20-40 parts of hydroxypropyl methylcellulose, 15-35 parts of polyvinyl alcohol-polyethylene glycol copolymer, 2-8 parts of sucralose, 2-8 parts of vitamin C, 2-8 parts of maltodextrin and 2-8 parts of sodium lauryl sulfate.

4. The pharmaceutical composition containing ketoprofen according to claim 3, characterized in that The polyvinyl alcohol-polyethylene glycol copolymer is made of 75% polyvinyl alcohol and 25% polyethylene glycol.

5. The pharmaceutical composition containing ketoprofen according to claim 4, characterized in that The invention is prepared from the following components in parts by weight: 40 parts of ketoprofen, 25-40 parts of hypromellose, 20-30 parts of polyvinyl alcohol-polyethylene glycol copolymer, 5 parts of sucralose, 5 parts of vitamin C, 5 parts of maltodextrin and 5 parts of sodium lauryl sulfate.

6. The pharmaceutical composition containing ketoprofen according to claim 5, characterized in that The invention is prepared from the following components in parts by weight: 40 parts of ketoprofen, 25 parts of hypromellose, 20 parts of polyvinyl alcohol-polyethylene glycol copolymer, 5 parts of sucralose, 5 parts of vitamin C, 5 parts of maltodextrin and 5 parts of sodium lauryl sulfate.

7. The pharmaceutical composition containing ketoprofen according to claim 5, characterized in that The invention is prepared from the following components in parts by weight: 40 parts of ketoprofen, 40 parts of hypromellose, 30 parts of polyvinyl alcohol-polyethylene glycol copolymer, 5 parts of sucralose, 5 parts of vitamin C, 5 parts of maltodextrin and 5 parts of sodium lauryl sulfate.

8. The method for preparing the pharmaceutical composition containing ketoprofen according to claim 1, characterized in that: The steps include: (1) Pretreatment: The raw material ketoprofen and the auxiliary materials are sieved and set aside; (2) Preparation of drug solution A: The raw material drug ketoprofen and anhydrous ethanol are uniformly mixed to prepare drug solution A, i.e., ketoprofen solution; (3) Preparation of liquid B: uniformly mix the plasticizer, sweetener, salivary stimulant, taste masking agent, surfactant and water to prepare liquid B; (4) Mixing, drying and cutting: The drug solution A obtained in step (2) and the drug solution B obtained in step (3) are fully mixed and stirred evenly, and the obtained mixed solution is evenly coated, dried and cut to obtain a pharmaceutical composition containing ketoprofen.

9. The method for preparing a pharmaceutical composition containing ketoprofen according to claim 7, characterized in that: In step (1), the raw materials and auxiliary materials are sieved through a 40-80 mesh sieve, preferably a 60 mesh sieve; in step (2), the mass fraction of ketoprofen in the drug solution A is 30-70%, preferably 50%.

10. The method for preparing the pharmaceutical composition containing ketoprofen according to claim 7, characterized in that: In step (3), the drying method is forced air drying, the drying temperature is 60-70°C, preferably 65°C; the drying time is 1-5 hours, until the moisture content is no more than 3%; after drying, the cutting is carried out, and the cutting size is 3cm-3.5cm in length and 2cm-2.5cm in width; preferably, the length is 3cm and the width is 2cm.

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