Polaprezinc gastric floating tablet and preparation method thereof

Abstract

The invention discloses a polaprezinc gastric floating tablet which sequentially comprises a tablet core layer, a shell layer and an outermost layer from inside to outside, and the tablet core layer comprises polaprezinc, a sustained-release material A, a coloring agent and a lubricating agent A; the shell layer composition comprises a sustained-release material B, a retardant and a lubricant B; the outermost layer comprises polaprezinc, a disintegrating agent, an adhesive, a filling agent and a lubricating agent C. The medicinal gastric floating tablet prepared by the formula and the method disclosed by the invention can effectively prolong the acting time of the medicine in the stomach, only needs to be taken once a day, and can be effectively used as a gastric mucosa protection medicine for assisting in treating gastric ulcer.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of medicine preparation, and particularly relates to a polaprezinc gastric floating tablet and a preparation method thereof. BACKGROUND

[0002] Gastric ulcer is a common digestive system disease, and most commonly refers to the appearance of ulcer on the inner wall of the stomach. The main causes of the disease are long-term helicobacter pylori infection and overuse of non-steroidal anti-inflammatory drugs, which cause damage to the gastric mucosa. The typical manifestations of the disease are stomach pain, decreased appetite, weight loss and other symptoms. In severe cases, gastric perforation or gastric bleeding may occur. The latest data from the National Digestive Disease Clinical Research Center shows that more than 1.3 million cases of gastric ulcer are diagnosed in China each year, of which 42% of patients have submucosal damage when they first seek medical treatment.

[0003] Polaprezinc is a gastric mucosa protective drug, which is used for the treatment of gastric ulcer. The main marketed dosage forms of polaprezinc are granules and oral disintegrating tablets, both of which have a specification of 75 mg. The bioavailability of polaprezinc in these two dosage forms is relatively low, and the drug needs to be taken twice a day, which is easy to be missed. Therefore, it is necessary to develop polaprezinc into a gastric floating tablet, which can not only prolong the action time of the drug in the stomach, but also is more convenient to take once a day. SUMMARY

[0004] The purpose of the present application is to provide a polaprezinc gastric floating tablet, and the second purpose of the present application is to provide a preparation method thereof. The polaprezinc gastric floating tablet prepared by the present application can effectively prolong the action time of the drug in the stomach, and only needs to be taken once a day, which can be effectively used as a gastric mucosa protective drug for the treatment of gastric ulcer.

[0005] To achieve the above-mentioned purposes, the present application adopts the following technical solutions:

[0006] A polaprezinc gastric floating tablet, which comprises, from inside to outside, a core layer, a shell layer and an outermost layer. The core layer comprises polaprezinc, a sustained-release material A, a coloring agent and a lubricant A. The shell layer composition comprises a sustained-release material B, a retarder and a lubricant B. The outermost layer comprises polaprezinc, a disintegrating agent, a binder, a filler and a lubricant C.

[0007] As a further preferred embodiment of the present invention, the core layer comprises, by weight: 75-85 parts of polymethyl methacrylate (PMMA), 18-20 parts of slow-release material A, 0.02-0.06 parts of colorant, and 0.4-0.6 parts of lubricant A, totaling 100 parts; the shell layer comprises, by weight: 250-260 parts of slow-release material B, 60-70 parts of inhibitor, and 1-2 parts of lubricant B, totaling 320 parts; the outermost layer comprises, by weight: 68-72 parts of PMMA, 10-14 parts of disintegrant, 10-14 parts of binder, 190-210 parts of filler, and 1-3 parts of lubricant C, totaling 300 parts.

[0008] As a further preferred embodiment of the present invention, the core layer comprises, by weight: 80 parts of polymethyl methacrylate (PMMA), 19.45 parts of slow-release material A, 0.05 parts of colorant, and 0.5 parts of lubricant A, totaling 100 parts; the shell layer comprises, by weight: 254.4 parts of slow-release material B, 64 parts of inhibitor, and 1.6 parts of lubricant B, totaling 320 parts; and the outermost layer comprises, by weight: 70 parts of PMMA, 12.5 parts of disintegrant, 12.5 parts of binder, 203.75 parts of filler, and 1.25 parts of lubricant C, totaling 300 parts.

[0009] As a further preferred embodiment of the present invention, the weight ratio of the core layer, the shell layer and the outermost layer is 100:320:300.

[0010] As a further preferred embodiment of the present invention, in the core layer, the sustained-release material A is one or a mixture of two of hydroxypropyl methylcellulose and hydroxypropyl cellulose.

[0011] As a further preferred embodiment of the present invention, in the core layer, the sustained-release material A is hydroxypropyl methylcellulose, which is one or both of the types K4M and K15M; the colorant is red iron oxide; and the lubricant A is magnesium stearate.

[0012] As a further preferred embodiment of the present invention, the sustained-release material B in the shell is hydroxypropyl cellulose, specifically HPC-LFP and HPC-MFP, and the ratio of the two is 6:1.

[0013] As a further preferred embodiment of the present invention, the retardant in the shell layer is Utec, the type of which is selected from one or two of L100-55 and RS PO; preferably, L100-55 and RS PO are mixed in a weight ratio of 1:1; the lubricant B is magnesium stearate.

[0014] As a further preferred embodiment of the present invention, in the outermost layer, the disintegrant is crospovidone; the binder is hydroxypropyl methylcellulose E5; the filler is microcrystalline cellulose pH101; and the lubricant C is magnesium stearate.

[0015] The present invention further discloses a method for preparing the aforementioned polyprene zinc gastric floating tablet, comprising the following steps:

[0016] S1. Preparation of tablet core: Mix polymethyl methacrylate zinc, red iron oxide, HPMC-K4M and magnesium stearate evenly; compress to obtain tablet core, and use a 7mm circular flat angled punch for tableting.

[0017] S2, Shell: All excipients are mixed and compressed into tablets. An 11mm circular shallow concave die is used to wrap the tablet core layer with the shell excipients and compress the tablets to prepare the shell structure that wraps the tablet core layer.

[0018] S3, Outermost layer: First, sieve and mix all raw and auxiliary materials together; use water as a binder, wet granulate, wet granulate through a 24-mesh sieve; dry at 60℃, dry granulate through a 20-mesh sieve; add auxiliary materials and mix evenly; wrap the shell layer from step S2 inside and press to obtain polyprepared zinc gastric floating tablets.

[0019] Compared with the prior art, the present invention has the following technical effects:

[0020] The polyprene zinc gastric floating tablets prepared by this invention can effectively prolong the time the drug acts in the stomach, and only need to be taken once a day. It can be effectively used as a gastric mucosa protectant and as an adjunct to the treatment of gastric ulcers. Attached Figure Description

[0021] Figure 1 This is the dissolution result of Example 1;

[0022] Figure 2 This is the dissolution result of Example 2;

[0023] Figure 3 This is the dissolution result of Example 3. Specific Implementation

[0024] The present invention will be further described below with reference to specific embodiments.

[0025] Example 1: Effect of different sustained-release materials on the core composition of the present invention

[0026] To investigate the effect of sustained-release materials on the present invention, tablet core compositions containing different sustained-release materials were prepared, namely Formula 1, Formula 2 and Formula 3, the raw material composition of which is shown in Table 1.

[0027] Table 1 Composition of each raw material in Example 1

[0028]

[0029] The preparation process in this embodiment is as follows:

[0030] 1. Mix the materials together by sieving them through a 40-mesh sieve;

[0031] 2. Tableting: The die used is a 7mm round flat-slant punch.

[0032] Dissolution experiments were conducted on the prepared core layer, and the dissolution results are shown in Table 2 and 3. Figure 2 As shown:

[0033] Table 2 Dissolution results of Example 1

[0034]

[0035]

[0036] From Table 2 and Figure 2 The results show that the choice of buffer material plays a crucial role in the dissolution effect of the core layer. When the sustained-release material is HPMC-K15M, the dissolution is slow (Formula 1); when HPC-MFP is selected as the sustained-release material, the dissolution is too fast (Formula 3); when HPMC-K4M is selected as the sustained-release material (Formula 3), the dissolution result meets expectations. Therefore, HPMC-K4M is the preferred sustained-release material for the core layer of this invention.

[0037] Example 2: Effect of different proportions of sustained-release materials on the shell composition of the present invention

[0038] To investigate the effect of the amount of sustained-release material on the shell composition of the present invention, tablet core compositions containing different sustained-release materials were prepared, namely Formula 1, Formula 2 and Formula 3, the raw material composition of which is shown in Table 3.

[0039] Table 3 Composition of each raw material in Example 2

[0040]

[0041] The preparation process in this embodiment is as follows:

[0042] 1. Weigh out all excipients in the shell formulation;

[0043] 2. Mix all the auxiliary materials together by passing them through a 40-mesh sieve;

[0044] 3. Pressing the chip: The die is made of 11mm round shallow concave punch, and the chip core layer is wrapped with shell auxiliary material for pressing.

[0045] Dissolution experiments were conducted on the chip cores of this embodiment, and the dissolution results are shown in Table 4 and... Figure 2 As shown:

[0046] Table 4 Dissolution results of Example 2

[0047]

[0048] Conclusion: From Table 4 and Figure 2The results show that when the ratio of HPC-LFP to HPC-MFP in the shell of formulation 5 is 6:1, it is almost completely dissolved in 5 hours, while the ratio of HPC-LFP to HPC-MFP in the shell of formulation 4 is 10:1, and it dissolves slightly faster. Therefore, the shell should be selected with a ratio of HPC-LFP to HPC-MFP of 6:1.

[0049] Example 3

[0050] Based on Examples 1 and 2, polyprene zinc gastric floating tablets were prepared, and the raw material composition of the outermost layer is shown in Table 5.

[0051] Table 5 Raw material composition of Example 3

[0052]

[0053] The preparation process in this embodiment is as follows:

[0054] S1. Preparation of tablet core (Formula 1): Mix polypyridine zinc, red iron oxide, HPMC-K4M and magnesium stearate evenly; compress to obtain tablet core, and use a 7mm round flat angled punch for tableting;

[0055] S2, Shell (Formula 5): Mix all excipients and compress them into tablets. Use an 11mm round shallow concave die to wrap the tablet core layer with the shell excipients and compress the tablets to prepare the shell structure that wraps the tablet core layer.

[0056] S3, Outermost layer: First, mix all the raw and auxiliary materials together by sieving; use water as a binder, wet granulate, and wet granulate through a 24-mesh sieve; dry at 60℃, and dry granulate through a 20-mesh sieve; mix the external auxiliary materials evenly; wrap the shell layer from step S2 inside and press it to obtain polyprepared zinc gastric floating tablets.

[0057] Dissolution experiments were conducted on the gastric floating tablets prepared in this embodiment. The dissolution results are shown in Table 6 and... Figure 3 As shown:

[0058] Table 6 Dissolution results of Example 3

[0059]

[0060] From Table 6 and Figure 3 The results show that the outermost layer of the present invention dissolves rapidly, the shell layer dissolves almost completely in 5 hours, and the tablet core dissolves completely in 14 hours, meeting the requirements of the formulation design.

[0061] In other embodiments, the following can achieve the desired effect: the core layer consists of 75-85 parts of polymethyl methacrylate (PMMA), 18-20 parts of slow-release material A, 0.02-0.06 parts of colorant, and 0.4-0.6 parts of lubricant A, totaling 100 parts; the shell layer consists of 250-260 parts of slow-release material B, 60-70 parts of inhibitor, and 1-2 parts of lubricant B, totaling 320 parts; and the outermost layer consists of 68-72 parts of PMMA, 10-14 parts of disintegrant, 10-14 parts of binder, 190-210 parts of filler, and 1-3 parts of lubricant C, totaling 300 parts. Studies have shown that when preparing polyprednisolone gastric floating tablets using the formulation of Example 3, each gastric floating tablet contains 150mg of effective polyprednisolone. Because it can effectively prolong the time the drug acts in the stomach, it has high bioavailability, and only needs to be taken once a day to meet the needs.

[0062] The present invention has been described in detail above through specific embodiments and examples, but these are not intended to limit the invention. Many modifications and improvements can be made by those skilled in the art without departing from the principles of the invention, and these should also be considered within the scope of protection of the present invention.

Claims

1. A polyprene zinc gastric floating tablet, characterized in that, The gastric floating tablet consists of a core layer, a shell layer, and an outermost layer from the inside out. The core layer comprises zinc polymethyl methacrylate (PMMA), sustained-release material A, a colorant, and lubricant A. The shell layer comprises sustained-release material B, a retardant, and lubricant B. The outermost layer comprises PMMA, a disintegrant, a binder, a filler, and lubricant C.

2. The polyprene zinc gastric floating tablet as described in claim 1, characterized in that, The core layer comprises 75-85 parts of polymethyl methacrylate (PMMA), 18-20 parts of slow-release material A, 0.02-0.06 parts of colorant, and 0.4-0.6 parts of lubricant A, totaling 100 parts. The shell layer comprises 250-260 parts of slow-release material B, 60-70 parts of inhibitor, and 1-2 parts of lubricant B, totaling 320 parts. The outermost layer comprises 68-72 parts of PMMA, 10-14 parts of disintegrant, 10-14 parts of binder, 190-210 parts of filler, and 1-3 parts of lubricant C, totaling 300 parts.

3. The polyprene zinc gastric floating tablet as described in claim 2, characterized in that, The core layer consists of 80 parts of polymethyl methacrylate (PMMA), 19.45 parts of slow-release material A, 0.05 parts of colorant, and 0.5 parts of lubricant A, totaling 100 parts. The shell layer consists of 254.4 parts of slow-release material B, 64 parts of inhibitor, and 1.6 parts of lubricant B, totaling 320 parts. The outermost layer consists of 70 parts of PMMA, 12.5 parts of disintegrant, 12.5 parts of binder, 203.75 parts of filler, and 1.25 parts of lubricant C, totaling 300 parts.

4. The polyprene zinc gastric floating tablet as described in claim 1, characterized in that, The weight ratio of the core layer, shell layer, and outermost layer is 100:320:

300.

5. The polyprene zinc gastric floating tablet as described in claim 1, characterized in that, In the core layer, the sustained-release material A is one or a mixture of two of hydroxypropyl methylcellulose and hydroxypropyl cellulose.

6. The polypyrimethanil zinc gastric floating tablet as described in claim 5, characterized in that, In the core layer, the sustained-release material A is hydroxypropyl methylcellulose, which is one or both of the types K4M and K15M; the colorant is red iron oxide; and the lubricant A is magnesium stearate.

7. The polypyrimethanil zinc gastric floating tablet as described in claim 1, characterized in that, In the shell layer, the sustained-release material B is hydroxypropyl cellulose, specifically HPC-LFP and HPC-MFP, and the ratio of the two is 6:

1.

8. The polypyrimethanone zinc gastric floating tablet as described in claim 1, characterized in that, In the shell, the retardant is Eutech, and its type is selected from one or two of L100-55 and RS PO, preferably L100-55 and RS PO are mixed in a 1:1 weight ratio; the lubricant B is magnesium stearate.

9. The polypyrimethanil zinc gastric floating tablet as described in claim 1, characterized in that, In the outermost layer, the disintegrant is crospovidone; the binder is hydroxypropyl methylcellulose E5; the filler is microcrystalline cellulose pH101; and the lubricant C is magnesium stearate.

10. The method for preparing polyprene zinc gastric floating tablets according to any one of claims 1-8, characterized in that, Includes the following steps: S1. Preparation of tablet core: Mix polymethyl methacrylate zinc, red iron oxide, HPMC-K4M and magnesium stearate evenly; compress to obtain tablet core, and use a 7mm circular flat angled punch for tableting. S2, Shell: All excipients are mixed and compressed into tablets. An 11mm circular shallow concave die is used to wrap the tablet core layer with the shell excipients and compress the tablets to prepare the shell structure that wraps the tablet core layer. S3, Outermost layer: First, sieve and mix all raw and auxiliary materials together; use water as a binder, wet granulate, wet granulate through a 24-mesh sieve; dry at 60℃, dry granulate through a 20-mesh sieve; add auxiliary materials and mix evenly; wrap the shell layer from step S2 inside and press to obtain polyprepared zinc gastric floating tablets.

Images