A glipizide controlled-release tablet

Abstract

The invention belongs to the field of pharmaceutical preparations, and specifically relates to a glipizide controlled-release tablet, which comprises a tablet core, a semipermeable membrane and a drug release hole. The tablet core comprises: glipizide, a penetration enhancer, an osmotic pressure active agent, a surfactant, a blocker, an adhesive, and a lubricant; the semipermeable membrane is polyvinyl alcohol, diethyl phthalate, and polyethylene glycol 400, all of which have good release effects. At the same time, the controlled-release tablet has stable performance, can be stored for a long time, and has a simple preparation process, and is suitable for industrial production.

Description

Technical Field

[0001] The present invention relates to the field of pharmaceutical preparations, and in particular to a glipizide controlled-release tablet and a preparation method thereof. Background Art

[0002] Glipizide is an oral hypoglycemic drug that can promote glucose-stimulated insulin secretion. The controlled-release tablets currently on the market under the trade name GLUCOTROL XL contain an "active" layer of the drug and a "boost" layer containing pharmacologically inert (but osmotically active) ingredients. Its prescription contains a water-soluble polymer ethylene oxide (PEO) as a matrix material, and its carrier has good miscibility with water. However, due to the low melting point of PEO, which is only 63°C-67°C, its thermal stability is poor, which is not conducive to large-scale production preparation and storage. Technicians in this field have made many attempts to improve the quality of glipizide controlled-release tablets. For example, CN110368372A discloses a dual-chamber osmotic pump type glipizide controlled-release tablet, CN104414992B discloses a glipizide osmotic pump controlled-release tablet, and CN103565774B discloses a glipizide controlled-release composition. The manufacturing cost is high, the controlled-release effect is not ideal, and there are problems such as too fast release speed, short duration, incomplete release, or unstable preparations that cannot be stored for a long time. In addition, the preparation process is complicated, which is not conducive to large-scale industrial production. Summary of the invention

[0003] The purpose of the present invention is to provide a glipizide controlled-release tablet in view of the above technical problems. The glipizide controlled-release tablet has mild and lasting release and can basically release completely within 24 hours. At the same time, the controlled-release tablet has stable performance, can be stored for a long time, has a simple preparation process, and is suitable for industrial production.

[0004] In order to solve the above technical problems, the technical solution adopted by the present invention is:

[0005] A glipizide controlled-release tablet comprises a tablet core, a semipermeable membrane and a drug-releasing hole. The tablet core is composed of the following excipients: glipizide, a penetration enhancer, an osmotic pressure active agent, a surfactant, a blocker, an adhesive and a lubricant; and the semipermeable membrane is composed of the following excipients: polyvinyl alcohol, diethyl phthalate and polyethylene glycol 400.

[0006] The weight ratio of the components in the glipizide controlled-release tablet core is: 5 parts of glipizide, 10-20 parts of penetration enhancer, 2-3 parts of osmotic pressure active agent, 3-5 parts of surfactant, 1-2 parts of retardant, 0.2-0.4 parts of adhesive, and 0.1-0.2 parts of lubricant.

[0007] The weight ratio of the components in the glipizide controlled-release tablet is: 10-20 parts of polyvinyl alcohol, 5-10 parts of diethyl phthalate, and 1-2 parts of polyethylene glycol 400.

[0008] The glipizide controlled-release tablets, the penetration enhancer is selected from one or more of hydroxypropyl methylcellulose, hydroxyethyl cellulose, methyl cellulose, non-cellulose polysaccharides, polyvinyl pyrrolidone, hydroxypropyl cellulose, carboxymethyl cellulose and its salts, alginic acid and its salts, polyethylene oxide, and hydroxymethyl cellulose.

[0009] In the glipizide controlled-release tablet, the osmotic pressure active agent is one or more of mannitol, xylitol, glucose, sorbitol, fructose, and sucrose; and the surfactant is sodium dodecyl sulfate.

[0010] In the glipizide controlled-release tablet, the blocker is one or more of beeswax, carnauba wax, hydrogenated vegetable oil, and stearyl alcohol; the binder is one or more of cellulose ether, polyvinyl pyrrolidone, and hydroxypropyl methylcellulose succinate; and the lubricant is one or more of stearic acid, magnesium stearate, and calcium stearate.

[0011] The glipizide controlled-release tablets have the following weight ratios of the components in the tablet core: 5 parts of glipizide, 5-10 parts of sodium alginate, 5-10 parts of polyoxyethylene, 2-3 parts of mannitol, 3-5 parts of sodium lauryl sulfate, 1-2 parts of carnauba wax, 0.2-0.4 parts of polyvinyl pyrrolidone, and 0.1-0.2 parts of magnesium stearate.

[0012] The weight ratio of the components in the glipizide controlled-release tablet is: 15 parts of polyvinyl alcohol, 8 parts of diethyl phthalate, and 2 parts of polyethylene glycol 400.

[0013] The glipizide controlled-release tablets have the following weight ratios of the components in the tablet core: 5 parts of glipizide, 5 parts of sodium alginate, 10 parts of polyoxyethylene, 2 parts of mannitol, 4 parts of sodium lauryl sulfate, 1 part of carnauba wax, 0.3 parts of polyvinyl pyrrolidone, and 0.1 parts of magnesium stearate.

[0014] The preparation method of the glipizide controlled-release tablet comprises the following steps:

[0015] (1) Glipizide, a penetration enhancer, an osmotic pressure active agent, a surfactant, and a retardant are mixed uniformly, a binder is added to prepare a soft material, dried, granulated, a lubricant is added to mix, and tabletted to obtain a drug core;

[0016] (2) using an acetone-water solution as a coating solvent, adding polyvinyl alcohol, diethyl phthalate, and polyethylene glycol 400 to prepare a semipermeable membrane coating solution, and spraying the coating solution onto the drug tablet core obtained in step (1) to form a coated tablet;

[0017] (3) The coated tablets are aged and then punched with laser to obtain the product.

[0018] The present invention controls the rate at which water enters the tablet core through a membrane-controlled coating system. After water enters the tablet core, the osmotic pressure enhancer absorbs water to make the osmotic pressure in the tablet core higher than that of the external medium environment, thereby generating an osmotic pressure difference, further promoting the infiltration of water, the osmotic enhancer absorbs water and swells, and the drug forms a suspension and is pushed out from the drug release hole, thereby controlling the release of the drug. At the same time, the glipizide controlled-release tablet provided by the present invention has a mild and lasting release, and can basically release completely within 24 hours. The controlled-release tablet has stable performance, can be stored for a long time, and has a simple preparation process, which is suitable for industrial production. DETAILED DESCRIPTION

[0019] The beneficial effects of the present invention are further described below by way of examples. It should be correctly understood that the examples of the present invention are only given for illustrating the present invention, rather than for limiting the present invention. Therefore, simple improvements to the present invention based on the method of the present invention are all within the scope of protection claimed by the present invention.

[0020] Example 1

[0021] (1) Take 5 parts of glipizide, 5 parts of sodium alginate, 10 parts of polyoxyethylene, 2 parts of mannitol, 4 parts of sodium lauryl sulfate, 1 part of carnauba wax, 0.3 parts of polyvinyl pyrrolidone, and 0.1 parts of magnesium stearate, mix them evenly, add a binder to make a soft material, dry, granulate, add a lubricant to mix, and tablet press to obtain a drug core;

[0022] (2) using an acetone-water solution as a coating solvent, adding 15 parts of polyvinyl alcohol, 8 parts of diethyl phthalate, and 2 parts of polyethylene glycol 400 to prepare a semipermeable membrane coating solution, and spraying the coating solution onto the drug tablet core obtained in step (1) to form a coated tablet;

[0023] (3) The coated tablets are aged and then punched with laser to obtain the product.

[0024] Example 2

[0025] (1) Take 5 parts of glipizide, 10 parts of sodium alginate, 5 parts of polyoxyethylene, 2 parts of mannitol, 4 parts of sodium lauryl sulfate, 1 part of carnauba wax, 0.3 parts of polyvinyl pyrrolidone, and 0.1 parts of magnesium stearate, mix them evenly, add a binder to make a soft material, dry, granulate, add a lubricant to mix, and tablet press to obtain a drug core;

[0026] (2) using an acetone-water solution as a coating solvent, adding 15 parts of polyvinyl alcohol, 8 parts of diethyl phthalate, and 2 parts of polyethylene glycol 400 to prepare a semipermeable membrane coating solution, and spraying the coating solution onto the drug tablet core obtained in step (1) to form a coated tablet;

[0027] (3) The coated tablets are aged and then punched with laser to obtain the product.

[0028] Example 3

[0029] (1) Take 5 parts of glipizide, 10 parts of sodium alginate, 10 parts of polyoxyethylene, 2 parts of mannitol, 4 parts of sodium lauryl sulfate, 1 part of carnauba wax, 0.3 parts of polyvinyl pyrrolidone, and 0.1 parts of magnesium stearate, mix them evenly, add a binder to make a soft material, dry, granulate, add a lubricant to mix, and tablet press to obtain a drug core;

[0030] (2) using an acetone-water solution as a coating solvent, adding 15 parts of polyvinyl alcohol, 8 parts of diethyl phthalate, and 2 parts of polyethylene glycol 400 to prepare a semipermeable membrane coating solution, and spraying the coating solution onto the drug tablet core obtained in step (1) to form a coated tablet;

[0031] (3) The coated tablets are aged and then punched with laser to obtain the product.

[0032] Example 4

[0033] (1) Take 5 parts of glipizide, 10 parts of polyoxyethylene, 2 parts of mannitol, 4 parts of sodium lauryl sulfate, 1 part of carnauba wax, 0.3 parts of polyvinyl pyrrolidone, and 0.1 parts of magnesium stearate, mix them evenly, add a binder to make a soft material, dry, granulate, add a lubricant to mix, and tablet press to obtain a drug core;

[0034] (2) using an acetone-water solution as a coating solvent, adding 15 parts of polyvinyl alcohol, 8 parts of diethyl phthalate, and 2 parts of polyethylene glycol 400 to prepare a semipermeable membrane coating solution, and spraying the coating solution onto the drug tablet core obtained in step (1) to form a coated tablet;

[0035] (3) The coated tablets are aged and then punched with laser to obtain the product.

[0036] Example 5

[0037] (1) Take 5 parts of glipizide, 10 parts of sodium alginate, 2 parts of mannitol, 4 parts of sodium lauryl sulfate, 1 part of carnauba wax, 0.3 parts of polyvinyl pyrrolidone, and 0.1 parts of magnesium stearate, mix them evenly, add a binder to make a soft material, dry, granulate, add a lubricant to mix, and tablet press to obtain a drug tablet core;

[0038] (2) using an acetone-water solution as a coating solvent, adding 15 parts of polyvinyl alcohol, 8 parts of diethyl phthalate, and 2 parts of polyethylene glycol 400 to prepare a semipermeable membrane coating solution, and spraying the coating solution onto the drug tablet core obtained in step (1) to form a coated tablet;

[0039] (3) The coated tablets are aged and then punched with laser to obtain the product.

[0040] Example 6

[0041] (1) Take 5 parts of glipizide, 2 parts of mannitol, 4 parts of sodium lauryl sulfate, 1 part of carnauba wax, 0.3 parts of polyvinyl pyrrolidone, and 0.1 parts of magnesium stearate, mix them evenly, add a binder to make a soft material, dry, granulate, add a lubricant to mix, and tablet press to obtain a drug tablet core;

[0042] (2) using an acetone-water solution as a coating solvent, adding 15 parts of polyvinyl alcohol, 8 parts of diethyl phthalate, and 2 parts of polyethylene glycol 400 to prepare a semipermeable membrane coating solution, and spraying the coating solution onto the drug tablet core obtained in step (1) to form a coated tablet;

[0043] (3) The coated tablets are aged and then punched with laser to obtain the product.

[0044] Example 7

[0045] (1) Take 5 parts of glipizide, 5 parts of sodium alginate, 10 parts of polyoxyethylene, 2 parts of mannitol, 1 part of carnauba wax, 0.3 parts of polyvinyl pyrrolidone, and 0.1 parts of magnesium stearate, mix them evenly, add a binder to make a soft material, dry, granulate, add a lubricant to mix, and tablet press to obtain a drug tablet core;

[0046] (2) using an acetone-water solution as a coating solvent, adding 15 parts of polyvinyl alcohol, 8 parts of diethyl phthalate, and 2 parts of polyethylene glycol 400 to prepare a semipermeable membrane coating solution, and spraying the coating solution onto the drug tablet core obtained in step (1) to form a coated tablet;

[0047] (3) The coated tablets are aged and then punched with laser to obtain the product.

[0048] Example 8

[0049] (1) Take 5 parts of glipizide, 5 parts of sodium alginate, 10 parts of polyethylene oxide, 2 parts of mannitol, 4 parts of sodium lauryl sulfate, 0.3 parts of polyvinyl pyrrolidone, and 0.1 parts of magnesium stearate, mix them evenly, add a binder to make a soft material, dry, granulate, add a lubricant to mix, and tablet press to obtain a drug core;

[0050] (2) using an acetone-water solution as a coating solvent, adding 15 parts of polyvinyl alcohol, 8 parts of diethyl phthalate, and 2 parts of polyethylene glycol 400 to prepare a semipermeable membrane coating solution, and spraying the coating solution onto the drug tablet core obtained in step (1) to form a coated tablet;

[0051] (3) The coated tablets are aged and then punched with laser to obtain the product.

[0052] Example 9

[0053] (1) Take 5 parts of glipizide, 5 parts of sodium alginate, 10 parts of polyoxyethylene, 2 parts of mannitol, 4 parts of sodium lauryl sulfate, 1 part of carnauba wax, 0.3 parts of polyvinyl pyrrolidone, and 0.1 parts of magnesium stearate, mix them evenly, add a binder to make a soft material, dry, granulate, add a lubricant to mix, and tablet press to obtain a drug core;

[0054] (2) using an acetone-water solution as a coating solvent, adding 15 parts of polyvinyl alcohol and 2 parts of polyethylene glycol 400 to prepare a semipermeable membrane coating solution, and spraying the coating solution onto the drug tablet core obtained in step (1) to form a coated tablet;

[0055] (3) The coated tablets are aged and then punched with laser to obtain the product.

[0056] Example 10

[0057] (1) Take 5 parts of glipizide, 5 parts of sodium alginate, 10 parts of polyoxyethylene, 2 parts of mannitol, 4 parts of sodium lauryl sulfate, 1 part of carnauba wax, 0.3 parts of polyvinyl pyrrolidone, and 0.1 parts of magnesium stearate, mix them evenly, add a binder to make a soft material, dry, granulate, add a lubricant to mix, and tablet press to obtain a drug core;

[0058] (2) using an acetone-water solution as a coating solvent, adding 8 parts of diethyl phthalate and 2 parts of polyethylene glycol 400 to prepare a semipermeable membrane coating solution, and spraying the coating solution onto the drug tablet core obtained in step (1) to form a coated tablet;

[0059] (3) The coated tablets are aged and then punched with laser to obtain the product.

[0060] Verification Example 1: In vitro release evaluation

[0061] The chromatographic conditions for the release determination are: C18 column, mobile phase: phosphate buffer (13.8 g of sodium dihydrogen phosphate was dissolved in water and diluted to 1000 mL, and the pH was adjusted to 6.0 with 2 mol / L sodium hydroxide)-methanol (55:45); detection wavelength: 225 nm. The release rate was determined by the standard curve method. According to the release rate determination method (Chinese Pharmacopoeia Part II, Appendix XD Method 1), the dissolution method method 2 apparatus was used, with phosphate buffer (6.8 g of potassium dihydrogen phosphate was dissolved in an appropriate amount of water, 190 mL of 0.2 mol / L sodium hydroxide solution was added, water was added to about 900 mL, the pH was adjusted to 7.5 with 0.2 mol / L sodium hydroxide solution, water was added to 1000 mL, and mixed) 900 mL was used as the dissolution medium, the rotation speed was 50 rpm, and the determination was carried out according to the method. 9 mL of the solution was taken at 2, 4, 8, 12, 16, 20, and 24 hours, and 9 mL of phosphate buffer preheated to 37°C was immediately added, filtered, and the release rate was determined, as shown in Table 1.

[0062] Table 1: In vitro release (%)

[0063] Group 2h 4h 8h 12h 16h 20h 24h Example 1 39.5 75.2 95.4 96.1 98.2 99.3 99.9 Example 2 27.8 56.4 72.8 87.5 91.4 96.8 97.3 Example 3 32.8 61.4 85.6 89.8 94.5 97.4 98.2 Example 4 19.7 45.7 65.5 76.5 78.5 82.4 90.1 Example 5 26.5 38.5 55.6 69.4 73.5 83.8 92.3 Example 6 29.4 45.8 50.9 56.7 68.7 79.5 89.2 Example 7 36.6 45.8 55.8 66.9 78.4 89.2 93.5 Example 8 49.5 95.2 99.4 99.3 99.2 99.5 99.1 Example 9 34.8 64.7 75.5 86.9 91.3 94.6 95.8 Example 10 31.3 55.8 68.9 76.8 81.3 90.3 94.9

[0064] According to Table 1, by selecting the treatment ingredients, ratios and contents of Example 1, the obtained glipizide controlled-release tablets have a mild and sustained release and the highest release rate. When the ratio of sodium alginate and polyethylene oxide is changed to prepare Examples 2-5, the release is slow, while Examples 6-8 lacking a penetration enhancer, or lacking a surfactant and a retardant, the release is slow or too fast; in addition, the prescription of the semipermeable membrane can also affect the release rate, so only a specific ratio of excipients can produce a beneficial effect. Verification Example 2: Release stability study

[0065] The samples of Example 1 and Example 2 were placed under accelerated conditions (40°C / relative humidity RH75%) and long-term conditions (25°C / relative humidity RH65%) for one month, respectively. The change trend of the in vitro release was investigated according to the above-mentioned release evaluation method. The release conditions are shown in Table 2.

[0066] Table 2: In vitro release (%)

[0067] Group 2h 4h 8h 12h 16h 20h 24h Example 1 39.5 75.2 95.4 96.1 98.2 99.3 99.9 Example 1 (Acceleration) 37.8 74.3 94.5 97.2 98.9 99.5 99.3 Example 1 (Long-term) 39.8 70.5 93.8 98.2 98.9 99.8 99.7 Example 2 27.8 56.4 72.8 87.5 91.4 96.8 97.3 Example 2 (acceleration) 29.5 59.7 75.9 80.4 86.7 90.7 90.5 Example 2 (Long-term) 30.6 45.5 65.7 76.8 78.9 89.3 91.3

[0068] According to Table 2, the release of the glipizide controlled-release tablets of Example 1 of the present invention under accelerated conditions and long-term conditions is compared with the release of the glipizide controlled-release tablets under 0-month conditions, and the release trend does not change significantly. It can be seen that the glipizide controlled-release tablets of Example 1 of the present invention have good stability and do not change significantly under accelerated conditions and long-term storage conditions. The release of the glipizide controlled-release tablets of Example 2 under accelerated conditions and long-term conditions is compared with the release of the glipizide controlled-release tablets under 0-month conditions. It is not completely released, indicating that the prescription ratio of Example 1 is more reasonable.

[0069] 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 glipizide controlled-release tablet, characterized in that: The controlled-release tablet comprises a tablet core, a semipermeable membrane and a drug release hole. The tablet core is composed of the following excipients: glipizide, a penetration enhancer, an osmotic pressure active agent, a surfactant, a blocker, an adhesive, and a lubricant. Specifically, the weight ratio of each component in the tablet core is: 5 parts of glipizide, 5 parts of sodium alginate, 10 parts of polyoxyethylene, 2 parts of mannitol, 4 parts of sodium lauryl sulfate, 1 part of carnauba wax, 0.3 parts of polyvinyl pyrrolidone, and 0.1 parts of magnesium stearate; the weight ratio of each component in the semipermeable membrane is: 15 parts of polyvinyl alcohol, 8 parts of diethyl phthalate, and 2 parts of polyethylene glycol 400.

2. The glipizide controlled-release tablet according to claim 1, characterized in that: The preparation method comprises the following steps: (1) mixing glipizide, a penetration enhancer, an osmotic pressure active agent, a surfactant, and a retardant uniformly, adding a binder to prepare a soft material, drying, granulating, adding a lubricant to mix, and tableting to obtain a drug core; (2) using an acetone-water solution as a coating solvent, adding polyvinyl alcohol, diethyl phthalate, and polyethylene glycol 400 to prepare a semipermeable membrane coating solution, and spraying the coating solution onto the drug tablet core obtained in step (1) to form a coated tablet; (3) The coated tablets are aged and then punched with laser to obtain the product.