CN116327711A - Meloxicam Kang Nami crystal composition with high bioavailability and application thereof - Google Patents

Meloxicam Kang Nami crystal composition with high bioavailability and application thereof Download PDF

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CN116327711A
CN116327711A CN202310055184.0A CN202310055184A CN116327711A CN 116327711 A CN116327711 A CN 116327711A CN 202310055184 A CN202310055184 A CN 202310055184A CN 116327711 A CN116327711 A CN 116327711A
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meloxicam
sodium
nanocrystalline
less
nami
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郑爱萍
田阳
张慧
王增明
刘楠
高翔
高静
申辽
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Academy of Military Medical Sciences AMMS of PLA
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Abstract

The invention relates to a meloxicam nanocrystalline composition, which comprises 1-10% of meloxicam, 0.1-10% of stabilizer and 1-10% of suspending agent by mass volume ratio, wherein the grain diameter of meloxicam Kang Nami crystal is less than or equal to 80nm. The invention obviously improves the stability, bioavailability and the like of the meloxicam nanocrystalline, obviously shortens the analgesic onset time, prolongs the analgesic duration time, improves the medicine quality, improves the compliance of the patient for medication, and ensures the safety and effectiveness of clinical medication.

Description

Meloxicam Kang Nami crystal composition with high bioavailability and application thereof
Technical Field
The invention belongs to the field of pharmaceutical preparations, and particularly relates to a meloxicam Kang Nami crystal composition with high bioavailability, a preparation method and application thereof.
Background
Rheumatoid arthritis and osteoarthritis are common arthritic conditions. The incidence rate of rheumatoid arthritis in China is about 0.5%, the total suffering population is about 500 ten thousand people, and the rheumatoid arthritis has the incidence rate in all age groups. Osteoarthritis usually occurs over 40 years old, the incidence rate of people over 40 years old-60 years old is 10% -17%, the incidence rate of people over 60 years old is increased to 50%, and the incidence rate of people over 70 years old is up to 70%. The existing therapeutic drugs mainly comprise non-steroidal anti-inflammatory drugs, glucocorticoids, anti-rheumatoid drugs and the like, but the therapeutic pertinency and the curative effect of the drugs are all to be improved.
Meloxicam is enol non-steroidal anti-inflammatory drug with anti-inflammatory, analgesic and antipyretic effects, and is clinically used for treating short-term symptoms when osteoarthritis symptoms are aggravated, long-term symptoms of rheumatoid arthritis and ankylosing spondylitis, moderate and severe pain of rheumatoid arthritis and osteoarthritis, and the like. However, meloxicam has the defects of poor solubility, low bioavailability, complex process, high cost and the like. The prior art discloses meloxicam pharmaceutical compositions, but has the problems of larger nano-grain diameter, instability at normal temperature, large grain diameter change, low bioavailability and the like. Therefore, the stability and bioavailability of the medicine are required to be improved to meet clinical requirements.
Figure BDA0004060315750000021
Disclosure of Invention
The invention aims to provide a meloxicam nanocrystalline composition, which comprises 1-10% of meloxicam, 0.1-10% of stabilizer and 1-10% of suspending agent, wherein the grain diameter of meloxicam Kang Nami crystal is less than or equal to 80nm, the stabilizer is selected from any one or combination of hydroxypropyl methyl cellulose, polyvinylpyrrolidone PVPK12 PF, PVPK15, PVPK17 PF, lecithin, polyethylene glycol, poloxamer P l uron i cs F68, P l uron i cs F108, tween-80, sodium cholate, sodium deoxycholate, sodium docusate, sodium dodecyl sulfate and sodium dodecyl sulfonate, and the suspending agent is selected from any one or combination of sucrose, glycerol, povidone, hydroxypropyl cellulose, methyl cellulose, hydroxypropyl methyl cellulose, sodium carboxymethyl cellulose, polyvinyl alcohol, acacia gum and dextrin.
In the preferred technical scheme of the invention, the composition contains 1.5-8% of meloxicam, 0.2-5% of stabilizer, 2-8% of suspending agent and the balance of water in percentage by mass and volume, wherein the grain diameter of meloxicam nanocrystalline is less than or equal to 75nm.
In the preferred technical scheme of the invention, the composition contains 2-5% of meloxicam, 0.3-2% of stabilizer, 4-6% of suspending agent and the balance of water in percentage by mass and volume, wherein the grain diameter of meloxicam nanocrystalline is less than or equal to 75nm.
In the preferred technical scheme of the invention, the composition contains, by mass volume percentage, 1-10% of meloxicam, 0.1-1% of PVPK17 PF, 0.1-1% of sodium deoxycholate and 1-10% of sucrose, and the balance is water, wherein the grain diameter of meloxicam nanocrystalline is less than or equal to 75nm.
In the preferred technical scheme of the invention, the composition contains 2-5% of meloxicam, 0.6-1% of PVPK17 PF, 0.3-0.5% of sodium deoxycholate, 2-8% of sucrose and the balance of water in percentage by mass and volume, wherein the grain diameter of meloxicam nanocrystalline is less than or equal to 75nm.
In the preferred technical scheme of the invention, the composition contains meloxicam 3%, PVPK17 PF 0.9%, sodium deoxycholate 0.3% and sucrose 6% by mass volume percentage, and the balance is water, wherein the grain diameter of meloxicam nanocrystalline is less than or equal to 75nm.
In a preferred embodiment of the present invention, the meloxicam nanocrystals have a PD I of 0.5 or less, preferably 0.4 or less, more preferably 0.35 or less.
In the preferable technical scheme of the invention, D10, D50 and D90 of the meloxicam nanocrystalline are less than or equal to 50nm, 100nm and 200nm respectively.
In a preferred embodiment of the present invention, the crystalline meloxicam Kang Nami composition has a particle size of not more than 100nm, preferably not more than 95nm, more preferably not more than 80nm when it is left at room temperature of 20-25 ℃ for 30 days.
In a preferred embodiment of the present invention, the meloxicam nanocrystalline composition has a particle size of not more than 120nm, preferably not more than 100nm, more preferably not more than 95nm when left at 40 ℃ for 40 days.
Another object of the present invention is to provide a method for preparing a meloxicam nanocrystalline composition, wherein the composition contains 1-10% meloxicam, 0.1-10% stabilizer, 1-10% suspending agent, wherein the grain size of meloxicam Kang Nami crystal is less than or equal to 100nm, the stabilizer is selected from any one of hydroxypropyl methylcellulose, polyvinylpyrrolidone PVPK12 PF, PVPK15, PVPK17 PF, lecithin, polyethylene glycol, poloxamer P l uron i cs F68 or P l uron i cs F108, tween-80, sodium cholate, sodium deoxycholate, sodium docusate, sodium dodecyl sulfate, or any one of combinations thereof, the suspending agent is selected from any one of sucrose, glycerin, povidone, hydroxypropyl cellulose, methylcellulose, hydroxypropyl methylcellulose sodium, carboxymethyl cellulose, polyvinyl alcohol, dextrin, or any one of combinations thereof, the method comprises the following steps:
(1) Weighing a required amount of stabilizer, dissolving the stabilizer in water, adding a required amount of meloxicam, stirring the mixture for 30 to 60min at a temperature of between 25 and 35 ℃ and a speed of between 500 and 1500rpm, and shearing the mixture for 1 to 10min at a high speed at a speed of between 1000 and 3500rpm to prepare a sheared mixed solution;
(2) Grinding the obtained shearing suspension at 25-35deg.C and 1500-3500rpm for 30-60min with 0.1-0.3mm particle size as grinding medium, adding stabilizer, grinding at 25-35deg.C and 1500-3500rpm for 30-60min, adding the suspending agent solution, and mixing, wherein the grinding speed is gradually increased from 1500rpm to 3500rpm and then decreased to 1500-3000rpm, and the increase or decrease speed of the grinding speed is increased or decreased by 500rpm every 5 min.
In a preferred embodiment of the present invention, the stabilizer in the step (1) is selected from any one of hydroxypropyl methylcellulose, polyvinylpyrrolidone PVPK12 PF, PVPK15, PVPK17 PF, lecithin, polyethylene glycol, poloxamer P l uron i cs F68, P l uron i cs F108, tween-80 or a combination thereof.
In a preferred embodiment of the present invention, the stabilizer in the step (2) is selected from any one of sodium cholate, sodium deoxycholate, sodium docusate, sodium dodecyl sulfate, sodium dodecyl sulfonate or a combination thereof.
In a preferred embodiment of the present invention, the stirring speed in step (1) is 600-1200rpm, preferably 800-1000rpm, the high-speed shearing speed is 2000-3000rpm, and the high-speed shearing is 3-10 min.
In a preferred embodiment of the present invention, the polishing speed in step (2) is increased from 1500rpm to 3500rpm, and then decreased to 1500rpm, and the increase or decrease speed of the polishing speed is increased or decreased by 500rpm every 5 min.
In a preferred embodiment of the present invention, the polishing speed in step (2) is increased from 1500rpm to 3500rpm, then decreased to 2000rpm, and the increase or decrease speed of the polishing speed is 500rpm at intervals of 5 min.
In a preferred embodiment of the present invention, the polishing speed in step (2) is increased from 1500rpm to 3500rpm and then decreased to 2500rpm, and the increase or decrease speed of the polishing speed is 500rpm at intervals of 5 min.
In a preferred embodiment of the present invention, the polishing speed in step (2) is increased from 1500rpm to 3500rpm, then decreased to 3000rpm, and the increase or decrease speed of the polishing speed is 500rpm at intervals of 5 min.
In the preferred technical scheme of the invention, the composition contains 1.5-8% of meloxicam, 0.2-5% of stabilizer, 2-8% of suspending agent and the balance of water in percentage by mass and volume, wherein the grain diameter of meloxicam nanocrystalline is less than or equal to 75nm.
In the preferred technical scheme of the invention, the composition contains 2-5% of meloxicam, 0.3-2% of stabilizer, 4-6% of suspending agent and the balance of water in percentage by mass and volume, wherein the grain diameter of meloxicam nanocrystalline is less than or equal to 75nm.
In the preferred technical scheme of the invention, the composition contains, by mass volume percentage, 1-10% of meloxicam, 0.1-1% of PVPK17 PF, 0.1-1% of sodium deoxycholate and 1-10% of sucrose, and the balance is water, wherein the grain diameter of meloxicam nanocrystalline is less than or equal to 75nm.
In the preferred technical scheme of the invention, the composition contains 2-5% of meloxicam, 0.6-1% of PVPK17 PF, 0.3-0.5% of sodium deoxycholate, 2-8% of sucrose and the balance of water in percentage by mass and volume, wherein the grain diameter of meloxicam nanocrystalline is less than or equal to 75nm.
In the preferred technical scheme of the invention, the composition contains meloxicam 3%, PVPK17 PF 0.9%, sodium deoxycholate 0.3% and sucrose 6% by mass volume percentage, and the balance is water, wherein the grain diameter of meloxicam nanocrystalline is less than or equal to 75nm.
In a preferred embodiment of the present invention, the meloxicam nanocrystals have a PD I of 0.5 or less, preferably 0.4 or less, more preferably 0.35 or less.
In the preferable technical scheme of the invention, D10 of the meloxicam nanocrystalline is less than or equal to 50nm, D10 is less than or equal to 100nm and D90 is less than or equal to 200nm.
In a preferred embodiment of the present invention, the crystalline meloxicam Kang Nami composition has a particle size of not more than 100nm, preferably not more than 95nm, more preferably not more than 80nm when it is left at room temperature of 20-25 ℃ for 30 days.
In a preferred embodiment of the present invention, the meloxicam nanocrystalline composition has a particle size of not more than 120nm, preferably not more than 100nm, more preferably not more than 95nm when left at 40 ℃ for 40 days.
Another object of the present invention is to provide the use of the crystalline meloxicam Kang Nami composition according to the present invention for the preparation of a medicament for the treatment of any one of rheumatoid arthritis or osteoarthritis, postoperative analgesia, antipyretic or complications thereof.
In a preferred embodiment of the present invention, the condition is selected from any one of arthritis, inflammatory diseases, pain, fever, inflammation-related cardiovascular diseases, joint stiffness, bronchitis, allergic neuritis, and lumbago.
In a preferred embodiment of the present invention, the analgesia is selected from any one of the group consisting of an abdominal wall angioplasty, a colorectal surgery, a bunion excision, a total knee arthroplasty, and an analgesia after arthroscopic surgery.
Unless otherwise indicated, when the invention relates to a percentage between liquids, the percentages are volume/volume percentages; the invention relates to the percentage between liquid and solid, said percentage being volume/weight percentage; the invention relates to the percentage between solids and liquids, the percentage being weight/volume percentage; the balance being weight/weight percent.
Unless otherwise indicated, the invention was milled using a ball mill (WAB AK71M-2WKF, switzerland) and particle size was measured using a nanosized particle sizer (Nano-ZS 90, markov, UK).
Compared with the prior art, the invention has the following beneficial technical effects:
1. the invention scientifically screens the components, the proportion and the technological parameters of the meloxicam Kang Nami crystal composition, and the prepared meloxicam nanocrystalline composition (the grain diameter is less than or equal to 80 nm) has the advantages of no need of carrier materials, easy industrialization, diversified dosage forms, obvious improvement of the solubility and the bioavailability of insoluble medicines, obvious improvement of the stability and the bioavailability of meloxicam nanocrystalline, obvious shortening of the analgesic onset time, prolonged analgesic duration time, improved medicine quality, improved patient medication compliance, and ensured safety and effectiveness of clinical medication.
2. According to the wet medium grinding method (wet med ia mi l l i ng, WMM), the medicine particles are broken through high-energy shearing force generated by mutual collision among the medicine, the grinding medium and the grinding cavity, the prepared medicine has smaller particle size and narrower particle size distribution, and the wet medium grinding method has the advantages of simplicity and convenience in operation, obvious shortening of the production period, obvious cost benefit, suitability for industrial mass production and the like.
Drawings
Figure 1 stability study of crystalline composition of meloxicam Kang Nami according to the present invention;
fig. 2 bioavailability investigation of crystalline compositions of meloxicam Kang Nami according to the present invention.
Detailed Description
The present invention is described below with reference to examples, but the present invention is not limited to the examples.
Example 1Preparation of crystalline composition of meloxicam Kang Nami
Prescription of crystalline meloxicam Kang Nami composition:
Figure BDA0004060315750000081
the preparation of the meloxicam Kang Nami crystal composition comprises the following steps:
(1) Weighing PVPK17 PF with required amount, dissolving in 95ml water, adding meloxicam with required amount, and shearing at 25-35deg.C and 3000rpm for 3 min to obtain sheared mixed solution;
(2) Grinding the prepared shearing suspension at 25-35 ℃ and 1500-3500rpm by taking grinding beads with the particle size of 0.1mm as a grinding medium, wherein the grinding speed is gradually increased from 1500rpm to 3500rpm and then gradually decreased to 1500rpm, the lifting speed of the grinding speed is that every 5min is increased by 500rpm, then adding the required amount of sodium deoxycholate solution, grinding at 1500rpm for 60min, adding the required amount of sucrose solution, and adding water to fix the volume to 400ml to obtain the nano-crystalline sodium deoxycholate.
Example 2Preparation of crystalline composition of meloxicam Kang Nami
Prescription of crystalline meloxicam Kang Nami composition:
Figure BDA0004060315750000082
Figure BDA0004060315750000091
the preparation of the meloxicam Kang Nami crystal composition comprises the following steps:
(1) Weighing PVPK17 PF with required amount, dissolving in 95mL of water, adding meloxicam with required amount, and shearing at 25-35deg.C and 3000rpm for 3 min to obtain sheared mixed solution;
(2) Grinding the prepared shearing suspension at 25-35 ℃ and 1500-3500rpm by taking grinding beads with the particle size of 0.1mm as grinding media, wherein the grinding speed is gradually increased from 1500rpm to 3500rpm and then reduced to 2000rpm, the increasing or reducing speed of the grinding speed is increased or reduced by 500rpm every 5min, then adding sodium deoxycholate solution, continuously grinding for 60min at 2000rpm, adding sucrose solution with required amount, and adding water to fix the volume to 400m l.
Example 3Preparation of crystalline composition of meloxicam Kang Nami
Prescription of crystalline meloxicam Kang Nami composition:
Figure BDA0004060315750000092
the preparation of the meloxicam Kang Nami crystal composition comprises the following steps:
(1) Weighing PVPK17 PF with required amount, dissolving in 95mL of water, adding meloxicam with required amount, and shearing at 25-35deg.C and 3000rpm for 3 min to obtain sheared mixed solution;
(2) Grinding 30min under the conditions of 25-35 ℃ and 1500-3500rpm by taking grinding beads with the particle size of 0.1mm as a grinding medium, wherein the grinding speed is gradually increased from 1500rpm to 3500rpm and is reduced to 2500rpm, the increasing or reducing speed of the grinding speed is increased or reduced by 500rpm every 5min, adding sodium deoxycholate solution, continuously grinding for 60min under the condition of keeping the rotating speed of 2500rpm, adding sucrose solution with the required amount, and adding water to fix the volume to 400ml to obtain the magnesium silicate glass.
Example 4Preparation of crystalline composition of meloxicam Kang Nami
Prescription of crystalline meloxicam Kang Nami composition:
Figure BDA0004060315750000101
the preparation of the meloxicam Kang Nami crystal composition comprises the following steps:
(1) Weighing PVPK17 PF with required amount, dissolving in 95mL of water, adding meloxicam with required amount, and shearing at 25-35deg.C and 3000rpm for 3 min to obtain sheared mixed solution;
(2) Grinding 25 min under the conditions of 25-35 ℃ and 1500-3500rpm by taking grinding beads with the particle size of 0.1mm as a grinding medium, wherein the grinding speed is gradually increased from 1500rpm to 3500rpm and then reduced to 3000rpm, the increasing or reducing speed of the grinding speed is increased or reduced by 500rpm every 5min, then adding sodium deoxycholate solution, continuously grinding 60min at the rotating speed of 3000rpm, adding sucrose solution with the required amount, and adding water to fix the volume to 400m l to obtain the nano-sized nano-particle.
Comparative example 1Preparation of crystalline composition of meloxicam Kang Nami
Prescription of crystalline meloxicam Kang Nami composition:
Figure BDA0004060315750000111
the preparation of the meloxicam Kang Nami crystal composition comprises the following steps:
(1) Weighing PVPK17 PF with required amount, dissolving in 95mL of water, adding meloxicam and sodium deoxycholate with required amount, and shearing at high speed of 3 min at 25-35deg.C and 3000rpm to obtain sheared mixed solution;
(2) Grinding 60min with grinding beads with particle size of 0.1mm as grinding medium at 25-35deg.C and 1500rpm, adding sucrose solution, and adding water to constant volume of 400m l.
Comparative example 2Preparation of crystalline composition of meloxicam Kang Nami
Crystalline composition of meloxicam Kang Nami:
Figure BDA0004060315750000112
Figure BDA0004060315750000121
the preparation of the meloxicam Kang Nami crystal composition comprises the following steps:
(1) Weighing PVPK17 PF with required amount, dissolving in 95mL of water, adding meloxicam with required amount, and shearing at 25-35deg.C and 3000rpm for 3 min to obtain sheared mixed solution;
(2) Grinding the prepared shearing suspension at 25-35deg.C and 1500rpm for 60min with grinding beads with particle diameter of 0.1-0.3mm as grinding medium, adding required amount of mixed solution (1.2 g sodium deoxycholate and 24g sucrose dissolved in 280mL water), and adding water to constant volume to 400 mL.
Test example 1Stability investigation of meloxicam Kang Nami crystalline compositions
After 10ml of the crystalline meloxicam Kang Nami composition prepared in examples 1-2 and comparative examples 1-2 was taken and put into a test tube, the crystalline meloxicam Kang Nami composition was observed by a Nano-ZS90 particle sizer and left to stand naturally at room temperature of 20-25 ℃ for 0 days (see Table 1), 3 days, 7 days, 15 days, 30 days, and the particle size, PD I and the change (see FIG. 1). The crystalline compositions of meloxicam Kang Nami prepared in examples 1-2 all have no delamination and no crystallization phenomenon, and the particle size and PD I are stable.
TABLE 1 nanocrystalline grain size on day 0
Figure BDA0004060315750000122
Figure BDA0004060315750000131
Test example 2Stability investigation of meloxicam Kang Nami crystalline compositions
After 10m l of the crystalline meloxicam Kang Nami composition prepared in example 1 was put into a test tube, the crystalline meloxicam Kang Nami composition was observed by a Nano-ZS90 particle sizer and left at 40 ℃ for 0 day, 10 day, 20 day, and 40 day of particle size change. The meloxicam nanocrystalline composition prepared in example 1 has no delamination and no crystallization phenomenon. The results are shown in Table 2.
TABLE 2 nanocrystalline grain diameter variation
Time (d) Particle size/nm
0 72.83
10 84.03
20 92.87
40 93.60
Test example 3Bioavailability study of crystalline meloxicam Kang Nami compositions
20 male SD rats weighing 200g + -5 g were divided into 2 groups of 10 animals each. Trial tail intravenous injection of crystalline meloxicam Kang Nami composition of example 1; the control group was given tail vein injection of commercially available meloxicam nanocrystals (300 nm particle size). After tail vein injection is completed, 0.5ml of blood is taken from the eye sockets at 1min,5min,15min,30min, 1h, 2h, 4h, 6h, 8h, 12h, 24h, 48h and 72h respectively, and the blood is placed in a refrigerated centrifuge for centrifugation at 4000rpm for 10min, and supernatant is taken for refrigeration and preservation; the drug concentration in plasma was measured by LC-MS. The results are shown in Table 3 and FIG. 2. The crystalline composition of meloxicam Kang Nami of the present invention has significantly better bioavailability.
TABLE 3 Table 3
Figure BDA0004060315750000141
The above description of the embodiments of the present invention is not intended to limit the present invention, and those skilled in the art can make various changes or modifications according to the present invention without departing from the spirit of the present invention, and shall fall within the scope of the claims of the present invention.

Claims (10)

1. The meloxicam nanocrystalline composition comprises, by mass and volume percentage, 1-10% of meloxicam, 0.1-10% of a stabilizer and 1-10% of a suspending agent, wherein the grain diameter of meloxicam Kang Nami crystals is less than or equal to 80nm, the stabilizer is selected from any one or combination of hydroxypropyl methylcellulose, polyvinylpyrrolidone PVPK12 PF, PVPK15, PVPK17 PF, lecithin, polyethylene glycol, pluronic F68 of poloxamer, pluronic F108, tween-80, sodium cholate, sodium deoxycholate, docusate sodium, sodium dodecyl sulfate and sodium dodecyl sulfonate, and the suspending agent is selected from any one or combination of sucrose, glycerol, povidone, hydroxypropyl cellulose, methylcellulose, hypromellose, carboxymethylcellulose sodium, polyvinyl alcohol, acacia and dextrin.
2. The nanocrystalline composition according to claim 1, wherein the composition comprises, by mass volume percentage, meloxicam 1.5-8%, stabilizer 0.2-5%, suspending agent 2-8%, and water in balance, the meloxicam nanocrystalline particle size is less than or equal to 75nm.
3. The nanocrystalline composition according to any one of claims 1-2, wherein the composition comprises meloxicam 2-5%, stabilizer 0.3-2%, suspending agent 4-6%, and balance water, wherein the grain diameter of meloxicam nanocrystalline is less than or equal to 75nm.
4. The nanocrystalline composition according to any one of claims 1 to 3, wherein the composition comprises, in mass volume percentage, meloxicam 1 to 10%, PVPK17 PF 0.1 to 1%, sodium deoxycholate 0.1 to 1% and sucrose 1 to 10%, the balance being water, and the meloxicam nanocrystalline has a particle size of 75nm or less.
5. The nanocrystalline composition according to any one of claims 1 to 4, wherein the composition comprises meloxicam 2 to 5% by mass volume percentage, PVPK17 PF 0.6 to 1%, sodium deoxycholate 0.3 to 0.5% and sucrose 2 to 8% by mass volume percentage, the balance being water, and the grain size of meloxicam nanocrystalline is less than or equal to 75nm.
6. The nanocrystalline composition according to any one of claims 1-5, which crystalline composition of meloxicam Kang Nami has a particle size of less than or equal to 100nm, preferably less than or equal to 95nm, more preferably less than or equal to 80nm, when left at room temperature of 20-25 ℃ for 30 days.
7. The nanocrystalline composition according to any one of claims 1-6, which has a particle size of 120nm or less, preferably 100nm or less, more preferably 95nm or less, when left at 40 ℃ for 40 days.
8. The method for preparing a meloxicam Kang Nami crystal composition according to any one of claims 1 to 7, which comprises meloxicam 1 to 10 percent, stabilizer 0.1 to 10 percent and suspending agent 1 to 10 percent by mass and volume ratio, wherein the meloxicam Kang Nami crystal has a particle diameter less than or equal to 100nm, the stabilizer is selected from any one of hydroxypropyl methylcellulose, polyvinylpyrrolidone PVPK12 PF, PVPK15 and PVPK17 PF, lecithin, polyethylene glycol, pluronic F68 or Pluronic F108 of poloxamer, tween-80, sodium cholate, sodium deoxycholate, sodium docusate, sodium dodecyl sulfate or any one of combinations thereof, the suspending agent is selected from any one of sucrose, glycerin, povidone, hydroxypropyl cellulose, methylcellulose, hydroxypropyl methylcellulose sodium, carboxymethyl cellulose, polyvinyl alcohol, dextrin or any one of combinations thereof, the method for preparing the same comprises the following steps:
(1) Weighing required amount of stabilizer, dissolving in water, adding required amount of meloxicam, stirring at 25-35deg.C and 500-1500rpm for 30-60min,
then placing the mixture in a condition of 1000-3500rpm for shearing at high speed for 1-10min to prepare a sheared mixed solution;
(2) Grinding with 0.1-0.3mm particle size as grinding medium, grinding the obtained shearing suspension at 25-35deg.C and 1500-3500rpm for 30-60min, adding stabilizer, grinding at 25-35deg.C and 1500-3500rpm for 30-60min, adding suspending agent solution, mixing, wherein the grinding speed gradually increases from 1500rpm to 3500rpm, then decreases to 1500-3000rpm, the speed of increase or decrease of grinding speed is 500rpm every 5min,
preferably, the stabilizing agent in step (1) is selected from any one or combination of hydroxypropyl methylcellulose, polyvinylpyrrolidone PVPK12 PF, PVPK15, PVPK17 PF, lecithin, polyethylene glycol, pluronic F68, pluronic F108, tween-80 of poloxamer,
preferably, the stabilizer in the step (2) is selected from any one or a combination of sodium cholate, sodium deoxycholate, docusate sodium, sodium dodecyl sulfate and sodium dodecyl sulfonate.
9. The method according to claim 8, wherein the polishing rate of step (2) is increased from 1500rpm to 3500rpm and then decreased to 1500rpm, and the increase or decrease rate of the polishing rate is 500rpm every 5 minutes.
10. Use of a crystalline meloxicam Kang Nami composition according to claims 1-7 or a crystalline meloxicam Kang Nami composition according to any one of claims 8-9 for the manufacture of a medicament for the treatment of any one of rheumatoid arthritis or osteoarthritis, post-operative analgesia, antipyretic disorders or complications thereof.
CN202310055184.0A 2022-01-18 2023-01-13 Meloxicam Kang Nami crystal composition with high bioavailability and application thereof Pending CN116327711A (en)

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