Compound omeprazole quick-release capsule and preparation method thereof

Abstract

The invention provides a compound omeprazole capsule and a preparation method thereof. The compound omeprazole capsule is prepared from 20 mg of omeprazole, 1100 mg of sodium bicarbonate, 25-35 mg of croscarmellose sodium and 5-15 mg of stearic acid sodium fumarate according to a prescription per unit. The invention further provides a preparation method of the compound omeprazole capsule. The compound omeprazole capsule which takes effect quickly and can inhibit omeprazole from being degraded by gastric acid is obtained through premixing, total mixing and filling. According to the technical scheme, the omeprazole sodium bicarbonate capsule which is high in initial dissolution rate (10-15 min) and faster in effect taking is obtained by screening the prescription composition and dosage of the compound omeprazole capsule and simplifying the preparation process, and due to the fact that the preparation process is convenient and fast, the production cost and the technical difficulty are reduced, and industrial large-scale production is better facilitated.

Description

Technical Field

[0001] The invention relates to the technical field of pharmaceutical preparations, and in particular to a compound omeprazole capsule and a preparation method thereof. Background Art

[0002] Omeprazole is a selective, irreversible proton pump inhibitor that specifically inhibits the secretion of surface H + / K + -ATPase system to inhibit gastric acid secretion. It can be used as an oral drug for the treatment of gastroesophageal reflux, gastric and duodenal ulcers and gastrinoma, and is also used for the preventive treatment of people at high risk of upper gastrointestinal bleeding.

[0003] Because the stability of omeprazole is related to the pH value, it will degrade rapidly in acidic media, but has acceptable stability under alkaline conditions. In the prior art patents such as CN101036633A and CN101366703A, most products use enteric coating to make omeprazole into micropellets, or put omeprazole into enteric capsules to protect omeprazole from being degraded in gastric acid. However, enteric preparations require coating, which has high process requirements, increases the difficulty and cost of preparation preparation, and the preparation can only release and absorb the drug after reaching the intestine, which makes the drug take effect slowly and delays the initial inhibitory effect on gastric acid.

[0004] CN103006691A discloses a quick-release capsule composed of omeprazole, sodium bicarbonate, a solubilizer, a disintegrant, a binder and a lubricant. The preparation uses a variety of auxiliary materials, has a relatively complex process and a high production cost.

[0005] CN101843600A discloses a proton pump rapid-release capsule consisting of two gastric-soluble capsules, a large capsule and a small capsule. The large capsule contains carbonate or bicarbonate. The omeprazole capsule prepared in the patent has a maximum dissolution of 81.5% in 30 minutes, which is lower than the regulations for general rapid-release preparations.

[0006] Therefore, in view of the defects in the prior art, it is urgently needed to provide an omeprazole rapid-release capsule with simple process, fast dissolution rate and rapid onset of action. Summary of the invention

[0007] The main purpose of the present invention is to provide a compound omeprazole capsule and a preparation method thereof, aiming to solve the technical problems of the existing omeprazole rapid-release capsules having a relatively complex process and a slow dissolution rate.

[0008] To achieve the above object, the present invention provides a compound omeprazole capsule, wherein each unit of the preparation consists of 20 mg omeprazole, 1100 mg sodium bicarbonate, 25 mg to 35 mg disintegrant, and 5 to 15 mg lubricant.

[0009] Optionally, the disintegrant is any one or more of cross-linked polyvinylpyrrolidone, cross-linked sodium carboxymethyl cellulose, sodium carboxymethyl starch, and low-substituted hydroxypropyl cellulose, and the lubricant is any one or more of magnesium stearate, calcium stearate, sodium stearyl fumarate, and glyceryl behenate.

[0010] Optionally, the disintegrant is cross-linked sodium carboxymethyl cellulose and the lubricant is sodium stearate fumarate.

[0011] Optionally, the amount of the disintegrant is 30 mg to 35 mg, and the amount of the lubricant is 8 to 12 mg.

[0012] Optionally, each unit preparation prescription consists of 20 mg omeprazole, 1100 mg sodium bicarbonate, 30 mg sodium carboxymethyl cellulose, and 10 mg magnesium stearate fumarate.

[0013] Optionally, each unit of the preparation prescription consists of 20 mg omeprazole, 1100 mg sodium bicarbonate, 35 mg sodium carboxymethyl cellulose, and 10 mg magnesium stearate fumarate.

[0014] The present invention also proposes a method for preparing the above-mentioned compound omeprazole capsule, which comprises the following steps: Weigh the prescribed amount of omeprazole, sodium bicarbonate, disintegrant and lubricant and sieve; Premixing the omeprazole, sodium bicarbonate and disintegrant obtained after screening to obtain a premix; Adding a lubricant to the premix and mixing the mixture to obtain a mixture; Filling the total mixture into capsule shells to obtain compound omeprazole capsules; Wherein, the disintegrant is cross-linked sodium carboxymethyl cellulose, and the lubricant is sodium stearate fumarate.

[0015] Optionally, in the step of weighing the prescribed amounts of omeprazole, sodium bicarbonate, disintegrant and lubricant, omeprazole, sodium bicarbonate and croscarmellose sodium are sieved together through a 40-mesh sieve, and sodium stearyl fumarate is sieved alone through a 20-mesh sieve.

[0016] Optionally, in the step of premixing the sieved omeprazole, sodium bicarbonate and disintegrant to obtain a premix, the premixing time is 20 to 40 minutes and the premixing speed is 12 rpm.

[0017] Optionally, in the step of premixing the sieved omeprazole, sodium bicarbonate and disintegrant to obtain a premix, the premixing time is 30 minutes.

[0018] Optionally, in the step of adding the sieved lubricant to the premix and mixing to obtain the total mixture, the total mixing time is 5 to 20 minutes and the total mixing speed is 12 rpm.

[0019] Optionally, in the step of adding the sieved lubricant to the premix and mixing to obtain the total mixture, the total mixing time is 10 minutes.

[0020] In the technical scheme of the present invention, the prescription composition and dosage of the compound omeprazole capsule are screened and the preparation process is simplified to obtain omeprazole sodium bicarbonate capsules with fast initial dissolution rate (10-15min) and faster effect. Due to the convenience of the preparation process, the production cost and technical difficulty are reduced, which is more conducive to large-scale industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on the structures shown in these drawings without paying creative work.

[0022] Figure 1 It is a schematic flow chart of an embodiment of a method for preparing omeprazole rapid-release capsules provided by the present invention; Figure 2 The figure is a dissolution curve diagram of an embodiment of the omeprazole rapid-release capsule provided by the present invention.

[0023] The realization of the purpose, functional features and advantages of the present invention will be further explained in conjunction with embodiments and with reference to the accompanying drawings. DETAILED DESCRIPTION

[0024] To make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the technical solution in the embodiments of the present invention will be described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them.

[0025] It should be noted that, in the embodiments, those without specifying specific conditions are carried out according to normal conditions or conditions recommended by the manufacturer. Those without specifying the manufacturer of reagents or instruments used are conventional products that can be purchased commercially. In addition, the meaning of "and / or" appearing in the full text includes three parallel schemes, and "A and / or B" is taken as an example, including schemes A, B, or A and B that meet the same time. In addition, the technical schemes between the various embodiments can be combined with each other, but must be based on the ability of ordinary technicians in the field to achieve. When the combination of the technical schemes is contradictory or cannot be achieved, it should be considered that the combination of such technical schemes does not exist, and is not within the scope of protection required by the present invention. Based on the embodiments in the present invention, all other embodiments obtained by ordinary technicians in the field without making creative work, all belong to the scope of protection of the present invention.

[0026] The omeprazole capsules in the prior art use a variety of excipients and have a relatively complex process, resulting in a high production cost. In addition, the maximum dissolution rate of the omeprazole capsules prepared by some processes is 81.5% in 30 minutes, which is lower than the regulations for general quick-release preparations.

[0027] In view of this, the present invention proposes a capsule of compound omeprazole, wherein each unit of the preparation consists of 20 mg omeprazole, 1100 mg sodium bicarbonate, 25 mg to 35 mg disintegrant, and 5 to 15 mg lubricant. Among them, the disintegrant is cross-linked sodium carboxymethyl cellulose, preferably in an amount of 30 mg to 35 mg; the lubricant is sodium stearate fumarate, preferably in an amount of 8 to 12 mg. In other embodiments, the disintegrant can also be selected from any one or more of cross-linked polyvinylpyrrolidone, sodium carboxymethyl starch, and low-substituted hydroxypropyl cellulose, and the lubricant can also be selected from any one or more of magnesium stearate, calcium stearate, and glyceryl behenate, which will not be described in detail here.

[0028] The present invention also proposes a method for preparing the above-mentioned compound omeprazole capsules, Figure 1 A schematic flow chart of an embodiment of a method for preparing an omeprazole rapid-release capsule is provided, which comprises the following steps: Step S10, weighing the prescribed amount of omeprazole, sodium bicarbonate, disintegrant and lubricant, and sieving.

[0029] In the specific implementation, the prescription amount of omeprazole, sodium bicarbonate, disintegrant and lubricant are weighed. In the sieving step, omeprazole, sodium bicarbonate and cross-linked sodium carboxymethyl cellulose are sieved through a 40-mesh sieve together, and sodium stearyl fumarate is sieved through a 20-mesh sieve alone. Among them, the disintegrant is cross-linked sodium carboxymethyl cellulose, and the lubricant is sodium stearate fumarate. Each unit of the preparation prescription consists of 20 mg of omeprazole, 1100 mg of sodium bicarbonate, 25 mg to 35 mg of cross-linked sodium carboxymethyl cellulose, and 5 to 15 mg of sodium stearate fumarate. The preferred amount of cross-linked sodium carboxymethyl cellulose is 30 mg to 35 mg; the preferred amount of sodium stearate fumarate is 8 to 12 mg.

[0030] Step S20: premix the sieved omeprazole, sodium bicarbonate and disintegrant to obtain a premix.

[0031] In specific implementation, premixing is performed by a stirrer, the premixing time is 20 to 40 minutes, and the premixing speed is 12 rpm. Preferably, the premixing time is 30 minutes.

[0032] Step S30: adding the sieved lubricant to the premix and mixing them to obtain a final mixture.

[0033] In specific implementation, the total mixing is performed by a stirrer, the total mixing time is 5 to 20 minutes, and the total mixing speed is 12 rpm. Preferably, the total mixing time is 10 minutes.

[0034] Step S40, filling the total mixture into capsule shells to obtain compound omeprazole capsules.

[0035] In the technical scheme of the present invention, the prescription composition and dosage of the compound omeprazole capsule are screened and the preparation process is simplified to obtain omeprazole sodium bicarbonate capsules with fast initial dissolution rate (10-15min) and faster effect, and the screening, mixing and other processes are simple and convenient, which reduces the production cost and technical difficulty and is more conducive to large-scale industrial production.

[0036] The technical solution of the present invention is further described in detail below in conjunction with specific embodiments and drawings. It should be understood that the following embodiments are only used to explain the present invention, and are not used to limit the present invention. Example 1 Prescription 1 and its preparation

[0037] Table 1 Prescription 1

[0038] Preparation process: Weigh the omeprazole, sodium bicarbonate, croscarmellose sodium and sodium stearyl fumarate in the prescription amount in Table 1, sieve omeprazole, sodium bicarbonate and croscarmellose sodium together with a 40-mesh sieve (first add part of the sodium bicarbonate and sieve, then add omeprazole, croscarmellose sodium and sodium bicarbonate alternately, and finally add the remaining sodium bicarbonate), and sieve sodium stearyl fumarate alone with a 20-mesh sieve; add the sieved omeprazole-sodium bicarbonate-croscarmellose sodium mixture to a hopper mixer for premixing, set the mixing speed to 12 rpm, and the mixing time to 30 min to obtain a premix; add the sieved sodium stearyl fumarate to the premix, mix it, set the speed to 12 rpm, and the mixing time to 20 min to obtain a total mixture; fill the total mixture into capsule shells to obtain omeprazole sodium bicarbonate capsules. Experimental Example 2 Investigation of the Dosage of Cross-linked Sodium Carboxymethyl Cellulose

[0039] Based on the prescription of Example 1, only the amount of cross-linked carboxymethyl cellulose sodium was changed (set to 25 mg, 30 mg, and 35 mg, respectively), and the types and amounts of other components in the prescription remained unchanged. The dissolution (%) differences of different prescriptions in a phosphate buffer solution medium of pH=7.4 were investigated. The results are shown in Table 2 below.

[0040] Table 2 Effect of different disintegrant dosages on dissolution behavior

[0041] As can be seen from the above table, when the dosage of cross-linked sodium carboxymethyl cellulose is between 25 mg and 35 mg, it has little effect on the dissolution of the preparation, and the cumulative dissolution amount in 15 minutes is greater than 85%, which is similar to the dissolution of the reference preparation (Zegerid®). Experimental Example 3 Investigation of the dosage of sodium stearate fumarate

[0042] Based on the prescription of Example 1, only the amount of sodium fumarate stearate was changed (set to 5 mg, 10 mg, and 15 mg respectively), and the types and amounts of other components in the prescription remained unchanged. The dissolution (%) differences of different prescriptions in a phosphate buffer solution medium of pH=7.4 were investigated. The results are shown in Table 3 below.

[0043] Table 3 Effect of different lubricant dosage on dissolution behavior

[0044] It can be seen from the above table that when the amount of lubricant is between 5mg and 15mg, it has little effect on the dissolution of the preparation, and the cumulative dissolution amount in 15 minutes is greater than 85%, which is similar to the dissolution of the reference preparation. Example 4 Investigation of factors affecting total mixing time

[0045] Based on the preparation process of Example 1, only the total mixing time was changed (set to 5 min, 10 min, and 15 min respectively), the prescription composition type and dosage, and the preparation steps were the same, and the solubility (%) of the prescriptions obtained at different total mixing times in a phosphate buffer solution medium of pH=7.4 was investigated. The results are shown in Table 4 below.

[0046] Table 4 Effect of different total mixing time on dissolution behavior

[0047] It can be seen from the above table that when the total mixing time is 5~15min, it has little effect on the overall dissolution of the preparation, and the cumulative dissolution amount in 15min is greater than 85%, which is similar to the dissolution of the reference preparation. Test Example 1 Comparison of dissolution behavior between homemade products and commercially available samples

[0048] The difference in dissolution rate (%) between the homemade product of Example 1 and the commercially available Zegerid® sample in the phosphate buffer solution medium with a pH of 7.4 is shown in Table 5 and Figure 2 shown.

[0049] Table 5 Comparison of dissolution behavior of Example 1 and commercially available Zegerid®

[0050] From the above table and Figure 1 It can be seen that the omeprazole sodium bicarbonate capsule prepared in Example 1 has a faster dissolution rate than the commercially available Zegerid® at 10-15 min, indicating that in the early stage of drug dissolution, the drug release rate of the present invention is better than that of the reference preparation.

[0051] The technical features of the above embodiments may be combined arbitrarily. To make the description concise, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0052] The above embodiments only express several implementation methods of the present application, and the descriptions thereof are relatively specific and detailed, but they cannot be understood as limiting the scope of the invention patent. It should be pointed out that, for a person of ordinary skill in the art, several variations and improvements can be made without departing from the concept of the present application, and these all belong to the protection scope of the present application. Therefore, the protection scope of the patent of the present application shall be subject to the attached claims.

Claims

1. A compound omeprazole capsule, characterized in that: Each unit of preparation consists of 20 mg omeprazole, 1100 mg sodium bicarbonate, 25 mg~35 mg cross-linked sodium carboxymethyl cellulose, and 5~15 mg sodium stearate fumarate.

2. The compound omeprazole capsule according to claim 1, characterized in that: The amount of the cross-linked sodium carboxymethyl cellulose is 30 mg to 35 mg, and the amount of the sodium stearate fumarate is 8 mg to 12 mg.

3. The compound omeprazole capsule according to claim 2, characterized in that: Each unit of preparation consists of 20 mg of omeprazole, 1100 mg of sodium bicarbonate, 30 mg of sodium carboxymethyl cellulose, and 10 mg of magnesium stearate fumarate.

4. The compound omeprazole capsule according to claim 2, characterized in that: Each unit of preparation consists of 20 mg of omeprazole, 1100 mg of sodium bicarbonate, 35 mg of sodium carboxymethyl cellulose, and 10 mg of magnesium stearate fumarate.

5. A method for preparing the compound omeprazole capsule according to any one of claims 1 to 4, characterized in that: The following steps are involved: Weigh the prescribed amount of omeprazole, sodium bicarbonate, disintegrant and lubricant and sieve; Premixing the sieved omeprazole, sodium bicarbonate and disintegrant to obtain a premix; adding the sieved lubricant to the premix and mixing them to obtain a total mixture; Filling the total mixture into capsule shells to obtain compound omeprazole capsules; Wherein, the disintegrant is cross-linked sodium carboxymethyl cellulose, and the lubricant is sodium stearate fumarate.

6. The method for preparing the compound omeprazole capsule according to claim 5, characterized in that: In the step of weighing the prescribed amount of omeprazole, sodium bicarbonate, disintegrant and lubricant, omeprazole, sodium bicarbonate and croscarmellose sodium are sieved through a 40-mesh sieve together, and sodium stearyl fumarate is sieved through a 20-mesh sieve alone.

7. The method for preparing the compound omeprazole capsule according to claim 5, characterized in that: In the step of premixing the sieved omeprazole, sodium bicarbonate and disintegrant to obtain a premix, the premixing time is 20 to 40 minutes and the premixing speed is 12 rpm.

8. The method for preparing the compound omeprazole capsule according to claim 7, characterized in that: In the step of premixing the sieved omeprazole, sodium bicarbonate and disintegrant to obtain a premix, the premixing time is 30 minutes.

9. The method for preparing the compound omeprazole capsule according to claim 5, characterized in that: In the step of adding the sieved lubricant to the premix and mixing to obtain the total mixture, the total mixing time is 5 to 20 minutes and the total mixing speed is 12 rpm.

10. The method for preparing the compound omeprazole capsule according to claim 9, characterized in that: In the step of adding the sieved lubricant to the premix and mixing to obtain the total mixture, the total mixing time is 10 minutes.

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