CN106924223B - Meloxicam patch and preparation method and application thereof - Google Patents

Meloxicam patch and preparation method and application thereof Download PDF

Info

Publication number
CN106924223B
CN106924223B CN201710147676.7A CN201710147676A CN106924223B CN 106924223 B CN106924223 B CN 106924223B CN 201710147676 A CN201710147676 A CN 201710147676A CN 106924223 B CN106924223 B CN 106924223B
Authority
CN
China
Prior art keywords
meloxicam
patch
solvent
layer
sensitive adhesive
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN201710147676.7A
Other languages
Chinese (zh)
Other versions
CN106924223A (en
Inventor
孙英华
徐星星
陶明月
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Kangya Of Ningxia Pharmaceutical Co ltd
Shenyang Pharmaceutical University
Original Assignee
Kangya Of Ningxia Pharmaceutical Co ltd
Shenyang Pharmaceutical University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Kangya Of Ningxia Pharmaceutical Co ltd, Shenyang Pharmaceutical University filed Critical Kangya Of Ningxia Pharmaceutical Co ltd
Priority to CN201710147676.7A priority Critical patent/CN106924223B/en
Publication of CN106924223A publication Critical patent/CN106924223A/en
Application granted granted Critical
Publication of CN106924223B publication Critical patent/CN106924223B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/5415—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam

Landscapes

  • Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Dermatology (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention provides a meloxicam patch and a preparation method and application thereof, wherein the meloxicam patch comprises a back lining layer, a drug storage and an anti-sticking layer; the drug storage layer comprises an active component of meloxicam or pharmaceutically acceptable salt thereof, a pressure sensitive adhesive and a drug transdermal absorption enhancer, wherein the dosage of meloxicam or pharmaceutically acceptable salt thereof and the dosage of the transdermal absorption enhancer respectively account for 0.5-60% and 0.1-50% of the solid content of the drug storage layer. The preparation method of the meloxicam patch comprises the steps of dissolving meloxicam or medicinal salt thereof in a solvent, sequentially adding each medicinal auxiliary material, stirring, uniformly mixing, standing, degassing, coating, volatilizing the solvent, compounding a back lining layer, and cutting into the patch with proper size according to dosage requirements. The patch has strong adhesion and good flexibility, can avoid stimulation of oral administration to gastrointestinal tract, increase percutaneous penetration of medicine, and has lasting and stable curative effect, and can interrupt administration at any time.

Description

Meloxicam patch and preparation method and application thereof
Technical Field
The invention belongs to the technical field of medicines, and relates to a meloxicam patch with excellent stability and wide concentration range and a preparation method thereof.
Background
The meloxicam is used as a cyclooxygenase-2 (COX-2) inhibitor on the first market, and a large number of clinical tests show that the meloxicam has stronger analgesic and anti-inflammatory effects, has the treatment effects on patients with osteoarthritis, rheumatoid arthritis and sciatica comparable to those of the existing NSAIDs, and is even better, the daily dosage of the meloxicam is much lower than that of the piroxicam, diclofenac, indomethacin and naproxen, and the occurrence rate of gastrointestinal side effects is very low. Since the product was marketed in 1996, the product formulation developed very rapidly. Besides the commonly used 7.5mg/15mg tablets and capsules, 15mg suppositories and 15mg injections are also widely used. With the continued development of cyclooxygenase-2 inhibitors, recent studies have demonstrated that COX-2 plays an important role in regulating renal function, and plays an important role in maintaining renal hemodynamics and electrolyte balance, so COX-2 inhibitors may produce dangerous renal side effects, and should be used with caution in patients with renal insufficiency, the elderly, and patients with a history of recurrence of gastrointestinal disease. Because of no gastrointestinal protection effect and potential nephrotoxicity, the oral dosage forms such as meloxicam tablets and capsules and the application of injections and suppositories are limited due to the characteristics of long-term use and the like, and the injections can cause local pain and mild tissue necrosis at the injection part. The gel developed in China is affected by the water insolubility of meloxicam, so that the drug-loading rate of the local gel is small (about 1%), the administration frequency is frequent (3-4 times/day), and the gel is easy to pollute clothes, so the use is inconvenient. The meloxicam patch has the advantages of convenient use, stable percutaneous drug release, no pollution to clothes and the like, can increase suitable crowds for meloxicam, and obviously improves the safety and compliance of patients in medication. Indications are as follows: the anti-inflammatory analgesic drug is used for relieving swelling and pain of arthritis, and can also be used for relieving pain such as sprain, soft tissue contusion, etc.
Currently, there is no meloxicam patch on the market. The patents on meloxicam transdermal patches disclosed at present all use meloxicam as a main drug, such as patent 200410021122. However, the skin barrier mainly consists of a lipophilic stratum corneum and a hydrophilic active epidermis, which indicates that the drug with suitable lipophilicity can permeate the skin to be absorbed by the human body, and the meloxicam has higher lipid solubility and poorer solubility in common solvents, thereby limiting the percutaneous absorption of the meloxicam and increasing the preparation difficulty of the meloxicam external preparation. Therefore, the preparation of meloxicam organic salts is considered to solve the above problems.
Disclosure of Invention
The invention aims to provide a meloxicam patch and a preparation method thereof, overcomes the limitations in the prior art, and provides a local administration preparation with stronger stability, higher safety and better tolerance.
The invention aims to solve the problems by the following technical scheme:
the meloxicam transdermal patch provided by the invention is composed of a back lining layer, a drug storage layer and an anti-sticking layer, wherein the drug storage layer comprises a main drug meloxicam or a salt thereof, a pressure-sensitive adhesive and a percutaneous absorption enhancer, and the formula (weight percentage) is as follows:
meloxicam or its pharmaceutically acceptable salt 0.5-60%
10 to 98 percent of pressure-sensitive adhesive
Transdermal absorption enhancer 0.1-50%
Preferably, the drug reservoir layer comprises, based on the total weight of the drug reservoir layer:
1-45% of meloxicam or pharmaceutically acceptable salt thereof
50 to 98 percent of pressure-sensitive adhesive
1-45% of percutaneous absorption enhancer
Wherein the meloxicam salt is an organic amine salt which is acceptable to meloxicam in pharmacy, and is one or more of meloxicam diethylamine, meloxicam triethylamine, meloxicam monoethanolamine, meloxicam diethanolamine, meloxicam triethanolamine, meloxicam N-hydroxyethyl pyrrolidine, meloxicam N-hydroxyethyl piperidine, meloxicam dimethylaminoethanol and meloxicam tromethamine;
the matrix material selected by the pressure-sensitive adhesive is one or more compounds selected from silicone polymers, isobutylene polymers, acrylic polymers or celluloses and derivatives thereof, and the acrylic polymers are preferred.
The transdermal absorption enhancer is one or mixture of oleic acid, laurocapram, menthol esters, and N-methylpyrrolidone, preferably mixture of laurocapram and N-methylpyrrolidone. The weight ratio of laurocapram to N-methylpyrrolidone is selected from 1:0.1-1, preferably 1: 0.5-1.
The meloxicam patch also comprises a back lining layer and an anti-sticking layer, wherein the back lining layer is an aluminum-containing polyethylene composite film or elastic non-woven fabric; the anti-sticking layer is a polyester film or paper with the surface treated by silicon oil anti-sticking treatment or containing fluorine.
Another object of the present invention is to provide a method for preparing meloxicam patch, comprising the following steps:
(1) dissolving meloxicam or its pharmaceutically acceptable salt in solvent, sequentially adding pressure sensitive adhesive and medicinal transdermal absorption enhancer, dissolving, stirring, mixing, standing, and degassing;
(2) coating a film, volatilizing a solvent, compounding a back lining layer, and cutting into a patch with a proper size according to dosage requirements.
Wherein, the solvent in the step (1) is a mixed solvent of ethanol and acetone in a weight ratio of 2: 1.
Compared with the prior art, the invention has the following advantages: the transdermal penetration of meloxicam is effectively improved by salifying meloxicam, the administration dosage can be controlled by adjusting the administration area, the drug is released in a zero-order manner, and the drug is continuously and stably released within 24 hours, so that the curative effect is lasting and stable; the administration can be interrupted by removing the patch, and the use is convenient; the patch also has the advantages of good adhesion, flexibility and the like.
Detailed Description
The invention is illustrated in more detail by the following examples, which are intended to further illustrate the invention, but not to limit the scope of the invention.
Example 1
Adding 7.5g of meloxicam into a small beaker, adding 62.5g of ethanol and 31.25g of acetone, dissolving the medicine by ultrasonic treatment, adding 3.5g of laurocapram and 3.5g N-methyl pyrrolidone, stirring to dissolve, adding 300g of acrylate polymer, stirring to mix uniformly, standing and degassing, uniformly coating on an anti-sticking layer, volatilizing the solvent, then compounding by using a backing material comprising PVC or non-woven fabric, and punching to form 1000 patches.
Example 2
Adding 7.5g of meloxicam diethylamine into a small beaker, adding 62.5g of ethanol and 31.25g of acetone, dissolving the medicine by ultrasonic wave, adding 3.5g of laurocapram and 3.5g N-methyl pyrrolidone, stirring to dissolve, adding 300g of acrylate polymer, stirring to mix uniformly, standing and degassing, uniformly coating on an anti-sticking layer, volatilizing the solvent, then compounding by using a backing material comprising PVC or non-woven fabric, and punching into 1000 patches to obtain the patch.
Example 3
Adding 7.5g of meloxicam diethylamine into a small beaker, adding 62.5g of ethanol and 31.25g of acetone, ultrasonically dissolving the medicine, adding 7.0g of oleic acid, stirring to dissolve, adding 300g of acrylate polymer, stirring to mix uniformly, standing and degassing, uniformly coating on an anti-sticking layer, volatilizing the solvent, then compounding by using a backing material comprising PVC or non-woven fabric, and punching into 1000 patches to obtain the patch.
Example 4
Adding 7.5g of meloxicam diethylamine into a small beaker, adding 62.5g of ethanol and 31.25g of acetone, dissolving the medicine by ultrasonic wave, adding 7.0g of laurocapram and 3.5g N-methyl pyrrolidone, stirring to dissolve, adding 300g of isobutylene polymer, stirring to mix uniformly, standing and degassing, uniformly coating on an anti-sticking layer, volatilizing the solvent, then compounding by using a backing material comprising PVC or non-woven fabric, and punching into 1000 patches to obtain the patch.
Example 5
Adding 7.5g of meloxicam diethylamine into a small beaker, adding 62.5g of ethanol and 31.25g of acetone, ultrasonically dissolving the medicine, adding 25g of laurocapram, stirring to dissolve, adding 300g of silicone pressure-sensitive adhesive, stirring to mix uniformly, standing, degassing, uniformly coating on an anti-sticking layer, volatilizing the solvent, then compounding by using a backing material comprising PVC or non-woven fabric, and punching into 1000 patches to obtain the patch.
Example 6
Adding 7.5g of meloxicam diethylamine into a small beaker, adding 62.5g of ethanol and 31.25g of acetone, ultrasonically dissolving the medicine, adding 25g of menthol, stirring to dissolve, adding 200g of acrylate polymer, stirring to mix uniformly, standing and degassing, uniformly coating on an anti-sticking layer, volatilizing the solvent, then compounding by using a backing material comprising PVC or non-woven fabric, and punching into 1000 patches to obtain the patch.
Example 7
Adding 7.5g of meloxicam diethylamine into a small beaker, adding 62.5g of ethanol and 31.25g of acetone, dissolving the medicine by ultrasonic wave, adding 35g of laurocapram and 35g N-methylpyrrolidone, stirring to dissolve, adding 90g of acrylate polymer, stirring to mix uniformly, standing and degassing, uniformly coating on an anti-sticking layer, volatilizing the solvent, then compounding by using a backing material comprising PVC or non-woven fabric, and punching into 1000 patches to obtain the patch.
Example 8
Adding 7.5g of meloxicam into a small beaker, adding 62.5g of ethanol and 31.25g of acetone, ultrasonically dissolving the medicine, adding 25g of laurocapram and 25g N-methyl pyrrolidone, stirring to dissolve, adding 42.5g of acrylate polymer, stirring to mix uniformly, standing and degassing, uniformly coating on an anti-sticking layer, volatilizing the solvent, then compounding by using a backing material comprising PVC or non-woven fabric, and punching into 1000 patches to obtain the patch.
Comparative example 1
Adding 7.5g of meloxicam into a small beaker, adding 100g of chloroform, dissolving the medicine by ultrasonic treatment, adding 300g of acrylate polymer, stirring until the mixture is uniformly mixed, standing and degassing, uniformly coating on an anti-sticking layer, volatilizing the solvent, then compounding by using a backing material comprising PVC or non-woven fabric, and punching into 1000 patches.
Comparative example 2
Adding 7.5g of meloxicam diethylamine into a small beaker, adding 62.5g of ethanol and 31.25g of acetone, ultrasonically dissolving the medicine, adding 300g of pressure sensitive adhesive, stirring to mix uniformly, standing and degassing, uniformly coating on an anti-sticking layer, volatilizing the solvent, then compounding by using a backing material comprising PVC or non-woven fabric, and punching into 1000 patches to obtain the patch.
Transdermal absorption test:
the present invention employs a modified Franz horizontal diffusion cell, using rat abdominal skin as a barrier, with the test results as shown in table 1.
TABLE 1 permeation results for different formulations of patch
Q24(μg/cm2) Js(μg/cm2/h) Tlag(h)
Comparative example 1 10.79±0.31 0.2369 0.4756
Comparative example 2 11.10±2.49 0.2762 0.5173
Example 1 38.60±2.19 2.993 3.4980
Example 2 53.48±7.39 3.8756 4.2185
Example 3 41.08±7.44 3.1992 4.0606
Example 4 36.30±5.43 2.6661 2.9496
Example 5 36.10±2.49 2.7992 2.5573
Example 6 30.12±3.32 2.1147 2.0742
Example 7 27.60±2.19 1.8962 1.9606
Example 8 24.10±4.90 1.7563 1.8247

Claims (3)

1. The meloxicam transdermal patch consists of a back lining layer, a medicine storage layer and an anti-sticking layer, and is characterized in that the medicine storage layer contains active ingredient meloxicam medicinal salt, pressure-sensitive adhesive and a medicine transdermal absorption enhancer, and the weight percentage is as follows:
1-45% of meloxicam medicinal salt
50 to 98 percent of pressure-sensitive adhesive
Transdermal absorption enhancer 1-about 2.23%
The matrix material selected by the pressure-sensitive adhesive is an acrylate polymer;
the transdermal absorption enhancer is a mixture of laurocapram and N-methylpyrrolidone in a weight ratio of 1: 1;
the medical salt of the meloxicam is meloxicam diethylamine.
2. The transdermal meloxicam patch according to claim 1, wherein the backing layer is an aluminum-containing polyethylene composite film or an elastic non-woven fabric; the anti-sticking layer is a polyester film or paper with the surface treated by silicon oil anti-sticking treatment or containing fluorine.
3. A method of preparing a meloxicam transdermal patch according to claim 1, characterized in that it comprises the following steps:
(1) dissolving medical meloxicam salt in solvent, adding pressure sensitive adhesive and transdermal absorption promoter successively, dissolving, stirring, mixing, standing and degassing;
(2) coating a film, volatilizing a solvent, compounding a back lining layer, and cutting into a patch with a proper size according to dosage requirements;
wherein, the solvent in the step (1) is a mixed solvent of ethanol and acetone in a weight ratio of 2: 1.
CN201710147676.7A 2017-03-13 2017-03-13 Meloxicam patch and preparation method and application thereof Active CN106924223B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201710147676.7A CN106924223B (en) 2017-03-13 2017-03-13 Meloxicam patch and preparation method and application thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201710147676.7A CN106924223B (en) 2017-03-13 2017-03-13 Meloxicam patch and preparation method and application thereof

Publications (2)

Publication Number Publication Date
CN106924223A CN106924223A (en) 2017-07-07
CN106924223B true CN106924223B (en) 2021-11-12

Family

ID=59432371

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201710147676.7A Active CN106924223B (en) 2017-03-13 2017-03-13 Meloxicam patch and preparation method and application thereof

Country Status (1)

Country Link
CN (1) CN106924223B (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109125733A (en) * 2018-10-30 2019-01-04 成都先手生物科技有限公司 A kind of composition for the treatment of of arthritis and its application
CN111135087A (en) * 2020-01-09 2020-05-12 范小玲 Industrialized preparation method of solvent type transdermal patch

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1557320A (en) * 2004-02-09 2004-12-29 沈阳药科大学 Meloxicam containing skin topical paste formulation
CN104447313A (en) * 2015-01-07 2015-03-25 河北联合大学 Alpha-terpineol aliphatic ester derivative and application

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100835074B1 (en) * 2006-09-27 2008-06-03 조선대학교산학협력단 Preparation and composition of meloxicam transdermal drug delivery system

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1557320A (en) * 2004-02-09 2004-12-29 沈阳药科大学 Meloxicam containing skin topical paste formulation
CN104447313A (en) * 2015-01-07 2015-03-25 河北联合大学 Alpha-terpineol aliphatic ester derivative and application

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Influence of ion-pairing and chemical enhancers on the transdermal delivery of meloxicam;Jing-Ying Zhang等;《Drug Development and Industrial Pharmacy》;20090519;第35卷(第6期);摘要，第668页右栏第1段，表4、表6 *
美洛昔康二乙胺盐贴剂的制备及渗透性和释放度的考察;王金兰等;《中国药剂学杂志》;20170115;第15卷(第1期);摘要，第1页正文第1段，第2.1.2、2.5、2.6、2.7.1、2.7.2小节，表1-2 *

Also Published As

Publication number Publication date
CN106924223A (en) 2017-07-07

Similar Documents

Publication Publication Date Title
JP6434104B2 (en) Diclofenac formulation
EP0974350B1 (en) External preparation containing tranilast and process for producing the same
US11607407B2 (en) Dermal pharmaceutical compositions of 1-methyl-2′,6′-pipecoloxylidide and method of use
CN103394091A (en) Analgesic anti-inflammatory preparation for external application
WO2007070679A2 (en) Compositions and methods for dermally treating pain
CN104546803A (en) Flurbiprofen hydrogel plaster and composition thereof
WO1993009768A1 (en) Fomentation containing ketorolac
CN101530401A (en) Compound transdermal patch used for curing acute and chronic inflammatory pain
CN106924223B (en) Meloxicam patch and preparation method and application thereof
CN111825548B (en) Pharmaceutical composition containing aryl propionic acid compound
CN1180770C (en) Transdermal plaster of aryl propionic non-steroid antiphlogistic
WO2018141661A1 (en) Pharmaceutical patch comprising lidocaine and diclofenac for treating neuropathic pain
JP4620168B2 (en) Ito-liquefied etodolac tape
CN110693860B (en) Gel plaster containing ketoprofen and preparation method thereof
WO2006025516A1 (en) Medicinal composition for percutaneous perospirone administration
CN1694699A (en) Percutaneous absorption preparations containing 3-methyl-phenyl-2-pyrazolin-5-one
CN106806893A (en) Skin external used patch containing calcium-sensing receptor activator
CN111789832B (en) Deketoprofen trometamol gel plaster and preparation method thereof
WO2018141662A1 (en) Administration regimen for a pharmaceutical patch comprising lidocaine and diclofenac
CN109481423B (en) Diclofenac salt transdermal patch and preparation method thereof
US20240100042A1 (en) Brucine gel plaster and preparation method and use thereof
CN105327351A (en) Anti-inflammatory analgesic preparation for external application
US20040197397A1 (en) Drug delivery system for treatment of urinary incontinence
CN1075372C (en) Indomethacin adhesive plaster
US20070197483A1 (en) External preparation for treating painful skin wound

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
CB02 Change of applicant information
CB02 Change of applicant information

Address after: 110016 Shenhe province Shenyang District Cultural Road, No. 103, No.

Applicant after: Shenyang Pharmaceutical University

Applicant after: Ningxia Kang Ya pharmaceutical Limited by Share Ltd

Address before: 110016 Shenhe province Shenyang District Cultural Road, No. 103, No.

Applicant before: Shenyang Pharmaceutical University

Applicant before: Kangya Pharmaceutical Industry Co., Ltd., Ningxia

GR01 Patent grant
GR01 Patent grant