CN115444837B - Loxoprofen transdermal drug delivery system and preparation method thereof - Google Patents
Loxoprofen transdermal drug delivery system and preparation method thereof Download PDFInfo
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Abstract
The application provides a loxoprofen percutaneous administration system and a preparation method thereof, wherein the percutaneous administration system consists of a back lining material, a drug active layer and a cover lining material, the drug active layer comprises active drugs, polyethylene glycol, polyvinyl alcohol, polyvinylpyrrolidone and purified water, the active drugs are loxoprofen or medicinal salts thereof, and the drug active layer is formed by ultraviolet curing under the initiation of an initiating agent. The loxoprofen transdermal drug delivery system has the advantages of high water content, good air permeability, high drug loading capacity, strong water locking property, repeated adhesion, no tearing pain after being applied to skin, no skin mark, no peculiar smell and the like, and simultaneously effectively solves the defects of poor adhesive force and easy falling of a gel plaster (Cataplasts) agent.
Description
Technical Field
The application belongs to the technical field of medicines, and particularly relates to a loxoprofen percutaneous administration system and a preparation method of the loxoprofen percutaneous administration system.
Background
Loxoprofen sodium is a potent non-selective COX inhibitor, which is a precursor drug, not active per se, and is rapidly converted to trans-OH by the liver, and is first developed by japan Sanyo corporation, marketed in japan in 1986 as a tablet for anti-inflammatory and analgesic purposes of rheumatoid arthritis, osteoarthritis, lumbago, scapulohumeral periarthritis, shoulder-neck-wrist syndrome; pain relief and inflammation relief after surgery, post-traumatic extraction; antipyretic and analgesic effects of acute upper airway inflammation. Compared with similar clinical medicines, the medicine has the characteristics of faster (quick action) and stronger (strong anti-inflammatory action) clinically. Meanwhile, loxoprofen sodium can be converted into active metabolite trans-OH to play a role after being absorbed by skin, and the drug concentration in subcutaneous tissues and skeletal muscles is high, so that the characteristics determine that the loxoprofen sodium can be used as a good percutaneous absorption administration preparation. The loxoprofen sodium external preparation has the same curative effect as an oral preparation, has lower adverse reaction, lower systemic drug exposure, safe use and no toxic or side effect on important organs such as heart, brain, liver, kidney and the like, does not need to pass through the alimentary canal, is not influenced and destroyed by food and gastric juice, has high bioavailability, is suitable for patients unsuitable for oral administration due to various reasons, and is suitable for patients who are not suitable for oral administration due to the stimulation and damage of the gastrointestinal mucosa and the liver caused by common oral administration on the basis of quick acting.
Currently, the marketed loxoprofen sodium external preparation mainly comprises a gel plaster (Cataplasts) agent and a plaster (Tape), wherein the gel plaster has high water content, good air permeability, difficult skin allergy, high drug loading in clinical effect, high transdermal absorption rate, strong water locking property, repeated adhesion, no tearing and pain feeling after being applied to the skin, no skin mark, no peculiar smell, but slightly poor adhesion and easy falling. The patch has good adhesive force and is not easy to fall off, but the release of the patch is greatly influenced by the temperature of the external environment, and the release of the medicine in the patch can be increased due to heating.
Disclosure of Invention
One of the purposes of the present application is to overcome the defects of the prior art, and provide a loxoprofen transdermal drug delivery system, which has good adhesion to the skin, is not easy to fall off, and has little influence on drug release due to external temperature and environment.
Another object of the present application is to provide a method for preparing a transdermal loxoprofen delivery system, which provides a brand-new simple, economical and effective preparation scheme for a topical transdermal delivery preparation and improves the production efficiency.
According to one aspect of the present application there is provided a transdermal drug delivery system comprising a backing material, a pharmaceutically active layer comprising an active drug, polyethylene glycol, polyvinyl alcohol, polyvinylpyrrolidone and purified water, the active drug being loxoprofen or a pharmaceutically acceptable salt thereof, preferably loxoprofen sodium, and a cap material, the pharmaceutically active layer being cured by ultraviolet light under the initiation of an initiator.
Further, the components of the pharmaceutically active layer are as follows by weight percent:
loxoprofen or a pharmaceutically acceptable salt thereof 1-10%,
polyethylene glycol 2-20%,
1-10% of polyvinyl alcohol,
1-5% of polyvinylpyrrolidone,
60-94% of purified water.
Further, the addition amount of the initiator is 1-6% of the total weight of the materials of the drug active layer.
Further, the polyethylene glycol is at least one selected from polyethylene glycol 400, polyethylene glycol 600 and polyethylene glycol 800.
Further, the initiator is a photoinitiator, preferably at least one of photoinitiators 1173, 184, 907, 369, 1490, 1700, 1220, 1156.
Further, the weight ratio of the polyethylene glycol to the polyvinyl alcohol is 0.6-5: 1, under the condition, the prepared loxoprofen transdermal drug delivery system has better cohesion and adhesion state.
Further, the backing material is an external polyester non-woven fabric, and the weight of the backing material is 80-120 g/m 2 。
Further, the lining material is an external polypropylene embossing film, and the thickness of the lining material is 20-80 mu m.
Further, the weight of the pharmaceutically active layer is 71 g-710 g/m 2 。
According to another aspect of the present application, there is also provided a method for preparing the transdermal drug delivery system of loxoprofen, comprising the steps of:
dispersing polyethylene glycol, polyvinyl alcohol, polyvinylpyrrolidone, active drug and initiator in purified water, stirring to uniformly mix to obtain a mixture;
and uniformly coating the mixture on a backing material, then carrying out irradiation crosslinking curing under ultraviolet rays, coating the backing material, and rolling and cutting into corresponding specifications.
Further, the irradiation crosslinking time is 3-10 min, and the irradiation ultraviolet wavelength is 200-400 nm.
The application has the beneficial effects that:
1. the loxoprofen transdermal drug delivery system provided by the application has the advantages that the drug active layer comprises active drugs, polyethylene glycol, polyvinyl alcohol, polyvinylpyrrolidone and purified water, the drug active layer is formed by ultraviolet crosslinking and curing under the initiation action of an initiator, the curing reaction time is short, the prepared transdermal drug delivery system has the advantages of high water content, good air permeability, difficult allergy, high drug loading capacity, strong water locking property, repeated adhesion, no tearing pain feeling after being applied to skin, no skin mark, no peculiar smell and the like, and meanwhile, the defects of poor adhesive force and easy falling of a gel plaster (Cataplsms) agent are effectively solved.
2. The transdermal drug delivery system has stable release rate under different temperature conditions, and the in-vitro release rate has small change along with the temperature.
3. The application provides a brand-new simple, economical and effective preparation scheme for the local percutaneous administration preparation, and has high production efficiency.
Drawings
Fig. 1 is a schematic structural view of a transdermal loxoprofen delivery system according to the present application.
FIG. 2 is a schematic diagram showing the results of transdermal administration (32 ℃) of loxoprofen in vitro, according to an embodiment of the present application.
FIG. 3 is a schematic diagram showing the results of transdermal administration (30 ℃) of loxoprofen in vitro, according to an embodiment of the present application.
FIG. 4 is a schematic diagram showing the results of transdermal administration (35 ℃) of loxoprofen transdermal delivery system according to the embodiment of the present application.
Wherein the reference numerals are as follows:
1. transdermal drug delivery systems; 2. a backing material; 3. a pharmaceutically active layer; 4. and (5) covering and lining materials.
Detailed Description
The application is further illustrated by the following examples. The following examples are merely illustrative of the present application and should not be construed as limiting the application.
The reagents and raw materials used in the application are all commercially available.
The backing material consists of woven cloth or non-woven fabric of polyester fiber, and the weight of the backing material is 80-120g/m 2 。
The lining material is made of polypropylene material, and the thickness of the lining material is 20-80 mu m.
Example 1
The raw materials of the drug active layer are as follows:
| component (A) | Dosage (weight portions) |
| Loxoprofen sodium | 1 |
| Polyethylene glycol 400 | 2 |
| Polyvinyl alcohol | 1 |
| Polyvinylpyrrolidone | 1 |
| Purified water | 94 |
| 2-hydroxy-methylphenyl-propan-1-one (1173) | 1 |
The preparation method comprises the following steps:
(1) Dispersing polyethylene glycol 400, polyvinyl alcohol, polyvinylpyrrolidone, loxoprofen sodium and 2-hydroxy-methyl phenyl propane-1-ketone in purified water according to the composition and proportion of raw materials at room temperature, and stirring and mixing to obtain a uniform mixture;
(2) Applying the mixture to a backing material on a spreading machine;
(3) Irradiating and crosslinking the material obtained in the step (2) for 3-10 min under ultraviolet rays of 200-400 nm; and (5) covering the lining material, rolling and cutting into corresponding specifications.
The prepared loxoprofen percutaneous administration system has a structure shown in figure 1 and comprises a backing material 2, a drug active layer 3 and a covering lining material 4. The prepared loxoprofen percutaneous administration system is subjected to paste content measurement, the measurement method refers to the second method measurement of 0122 (paste content) of the four general rules of the 2020 edition of Chinese pharmacopoeia, and the measured paste content is 710g/m 2 。
Example 2
The raw materials of the drug active layer are as follows:
| component (A) | Dosage (weight portions) |
| Loxoprofen sodium | 3 |
| Polyethylene glycol 400 | 8 |
| Polyvinyl alcohol | 2 |
| Polyvinylpyrrolidone | 2 |
| Purified water | 83 |
| 1-hydroxycyclohexyl phenyl ketone (184) | 2 |
The preparation method comprises the following steps:
(1) Dispersing polyethylene glycol 400, polyvinyl alcohol, polyvinylpyrrolidone, loxoprofen sodium and 1-hydroxy cyclohexyl phenyl ketone in purified water according to the composition and proportion of raw materials at room temperature, and stirring and mixing to obtain a uniform mixture;
(2) Applying the mixture to a backing material on a spreading machine;
(3) Irradiating and crosslinking the material obtained in the step (2) for 3-10 min under ultraviolet rays of 200-400 nm; and (5) covering the lining material, rolling and cutting into corresponding specifications.
The prepared loxoprofen percutaneous administration system has a structure shown in figure 1 and comprises a backing material 2, a drug active layer 3 and a covering lining material 4. The prepared loxoprofen percutaneous administration system is subjected to paste content measurement, the measurement method refers to the second method measurement of 0122 (paste content) of the four general rules of the 2020 edition of Chinese pharmacopoeia, and the measured paste content is 236g/m 2 。
Example 3
The raw materials of the drug active layer are as follows:
| component (A) | Dosage (weight portions) |
| Loxoprofen sodium | 5 |
| Polyethylene glycol 400 | 12 |
| Polyvinyl alcohol | 3 |
| Polyvinylpyrrolidone | 3 |
| Purified water | 75 |
| Methyl o-benzoyl benzoate (1156) | 2 |
The preparation method comprises the following steps:
(1) Dispersing polyethylene glycol 400, polyvinyl alcohol, polyvinylpyrrolidone, loxoprofen sodium and methyl o-benzoyl benzoate in purified water according to the composition and proportion of raw materials at room temperature, and stirring and mixing to obtain a uniform mixture;
(2) Applying the mixture to a backing material on a spreading machine;
(3) Irradiating and crosslinking the material obtained in the step (2) for 3-10 min under ultraviolet rays of 200-400 nm; and (5) covering the lining material, rolling and cutting into corresponding specifications.
The prepared loxoprofen percutaneous administration system has a structure shown in figure 1 and comprises a backing material 2, a drug active layer 3 and a covering lining material 4. The prepared loxoprofen percutaneous administration system is subjected to paste content measurement, the measurement method refers to the second method measurement of 0122 (paste content) of the four general rules of the 2020 edition of Chinese pharmacopoeia, and the measured paste content is 142g/m 2 。
Example 4
The raw materials of the drug active layer are as follows:
| component (A) | Dosage (weight portions) |
| Loxoprofen sodium | 7 |
| Polyethylene glycol 400 | 20 |
| Polyvinyl alcohol | 4 |
| Polyvinylpyrrolidone | 4 |
| Purified water | 62 |
| Benzophenone BP (1220) | 3 |
The preparation method comprises the following steps:
(1) Dispersing polyethylene glycol 400, polyvinyl alcohol, polyvinylpyrrolidone, loxoprofen sodium and benzophenone BP in purified water according to the composition and proportion of raw materials at room temperature, and stirring and mixing to obtain a uniform mixture;
(2) Applying the mixture to a backing material on a spreading machine;
(3) Irradiating and crosslinking the material obtained in the step (2) for 3-10 min under ultraviolet rays of 200-400 nm; and (5) covering the lining material, rolling and cutting into corresponding specifications.
The prepared loxoprofen percutaneous administration system has a structure shown in figure 1 and comprises a backing material 2, a drug active layer 3 and a covering lining material 4. Determination of the amount of the ointment in the transdermal administration system of loxoprofen preparedThe method refers to the second method of "Chinese pharmacopoeia 2020 edition four general rules 0122" for measuring the ointment content, and the measured ointment content is 101g/m 2 。
Example 5
The raw materials of the drug active layer are as follows:
| component (A) | Dosage (weight portions) |
| Loxoprofen sodium | 10 |
| Polyethylene glycol 600 | 4 |
| Polyvinyl alcohol | 5 |
| Polyvinylpyrrolidone | 5 |
| Purified water | 72 |
| Methyl o-benzoyl benzoate (1156) | 4 |
The preparation method comprises the following steps:
(1) Dispersing polyethylene glycol 600, polyvinyl alcohol, polyvinylpyrrolidone, loxoprofen sodium and methyl o-benzoyl benzoate in purified water according to the composition and proportion of raw materials at room temperature, and stirring and mixing to obtain a uniform mixture;
(2) Applying the mixture to a backing material on a spreading machine;
(3) Irradiating and crosslinking the material obtained in the step (2) for 3-10 min under ultraviolet rays of 200-400 nm; and (5) covering the lining material, rolling and cutting into corresponding specifications.
The prepared loxoprofen percutaneous administration system has a structure shown in figure 1 and comprises a backing material 2, a drug active layer 3 and a covering lining material 4. The prepared loxoprofen percutaneous administration system is subjected to paste content measurement, the measurement method refers to the second method measurement of 0122 (paste content) of the four general rules of the 2020 edition of Chinese pharmacopoeia, and the measured paste content is 71g/m 2 。
Example 6
The raw materials of the drug active layer are as follows:
| component (A) | Dosage (weight portions) |
| Loxoprofen sodium | 7 |
| Polyethylene glycol 600 | 6 |
| Polyvinyl alcohol | 6 |
| Polyvinylpyrrolidone | 4 |
| Purified water | 73 |
| Benzophenone BP (1220) | 4 |
The preparation method comprises the following steps:
(1) Dispersing polyethylene glycol 600, polyvinyl alcohol, polyvinylpyrrolidone, loxoprofen sodium and benzophenone BP in purified water according to the composition and proportion of raw materials at room temperature, and stirring and mixing to obtain a uniform mixture;
(2) Applying the mixture to a backing material on a spreading machine;
(3) Irradiating and crosslinking the material obtained in the step (2) for 3-10 min under ultraviolet rays of 200-400 nm; and (5) covering the lining material, rolling and cutting into corresponding specifications.
The prepared loxoprofen percutaneous administration system has a structure shown in figure 1 and comprises a backing material 2, a drug active layer 3 and a covering lining material 4. The prepared loxoprofen percutaneous administration system is subjected to paste content measurement, the measurement method refers to the second method measurement of 0122 (paste content) of the four general rules of the 2020 edition of Chinese pharmacopoeia, and the measured paste content is 101g/m 2 。
Example 7
The raw materials of the drug active layer are as follows:
| component (A) | Dosage (weight portions) |
| Loxoprofen sodium | 5 |
| Polyethylene glycol 600 | 8 |
| Polyvinyl alcohol | 7 |
| Polyvinylpyrrolidone | 3 |
| Purified water | 72 |
| Methyl o-benzoyl benzoate (1156) | 5 |
The preparation method comprises the following steps:
(1) Dispersing polyethylene glycol 600, polyvinyl alcohol, polyvinylpyrrolidone, loxoprofen sodium and methyl o-benzoyl benzoate in purified water according to the composition and proportion of raw materials at room temperature, and stirring and mixing to obtain a uniform mixture;
(2) Applying the mixture to a backing material on a spreading machine;
(3) Irradiating and crosslinking the material obtained in the step (2) for 3-10 min under ultraviolet rays of 200-400 nm; and (5) covering the lining material, rolling and cutting into corresponding specifications.
The prepared loxoprofen percutaneous administration system has a structure shown in figure 1 and comprises a backing material 2, a drug active layer 3 and a covering lining material 4. The prepared loxoprofen percutaneous administration system is subjected to paste content measurement, the measurement method refers to the second method measurement of 0122 (paste content) of the four general rules of the 2020 edition of Chinese pharmacopoeia, and the measured paste content is 142g/m 2 。
Example 8
The raw materials of the drug active layer are as follows:
| component (A) | Dosage (weight portions) |
| Loxoprofen sodium | 3 |
| Polyethylene glycol 600 | 10 |
| Polyvinyl alcohol | 8 |
| Polyvinylpyrrolidone | 2 |
| Purified water | 72 |
| Benzophenone BP (1220) | 5 |
The preparation method comprises the following steps:
(1) Dispersing polyethylene glycol 600, polyvinyl alcohol, polyvinylpyrrolidone, loxoprofen sodium and benzophenone BP in purified water according to the composition and proportion of raw materials at room temperature, and stirring and mixing to obtain a uniform mixture;
(2) Applying the mixture to a backing material on a spreading machine;
(3) Irradiating and crosslinking the material obtained in the step (2) for 3-10 min under ultraviolet rays of 200-400 nm; and (5) covering the lining material, rolling and cutting into corresponding specifications.
The prepared loxoprofen percutaneous administration system has a structure shown in figure 1 and comprises a backing material 2, a drug active layer 3 and a covering lining material 4. The prepared loxoprofen transdermal drug delivery system is subjected to paste content measurement, and the measurement method refers to Chinese pharmacopoeia 2020 edition four general rules 0122 (paste content) the second method measurement shows that the paste content is 236g/m 2 。
Example 9
The raw materials of the drug active layer are as follows:
| component (A) | Dosage (weight portions) |
| Loxoprofen sodium | 3 |
| Polyethylene glycol 800 | 6 |
| Polyvinyl alcohol | 9 |
| Polyvinylpyrrolidone | 1 |
| Purified water | 79 |
| 2-methyl-1- (4-methylsulfanylphenyl) -2-morpholinyl-1-propanone (907) | 2 |
The preparation method comprises the following steps:
(1) Dispersing polyethylene glycol 800, polyvinyl alcohol, polyvinylpyrrolidone, loxoprofen sodium and 2-methyl-1- (4-methylthiophenyl) -2-morpholinyl-1-acetone in purified water according to the composition and proportion of raw materials at room temperature, and stirring and mixing to obtain a uniform mixture;
(2) Applying the mixture to a backing material on a spreading machine;
(3) Irradiating and crosslinking the material obtained in the step (2) for 3-10 min under ultraviolet rays of 200-400 nm; and (5) covering the lining material, rolling and cutting into corresponding specifications.
The prepared loxoprofen percutaneous administration system has a structure shown in figure 1 and comprises a backing material 2, a drug active layer 3 and a covering lining material 4. The prepared loxoprofen percutaneous administration system is subjected to paste content measurement, the measurement method refers to the second method measurement of 0122 (paste content) of the four general rules of the 2020 edition of Chinese pharmacopoeia, and the measured paste content is 236g/m 2 。
Example 10
The raw materials of the drug active layer are as follows:
| component (A) | Dosage (weight portions) |
| Loxoprofen sodium | 5 |
| Polyethylene glycol 800 | 10 |
| Polyvinyl alcohol | 10 |
| Polyvinylpyrrolidone | 2 |
| Purified water | 67 |
| 2-methyl-1- (4-methylsulfanylphenyl) -2-morpholinyl-1-propanone (907) | 6 |
The preparation method comprises the following steps:
(1) Dispersing polyethylene glycol 800, polyvinyl alcohol, polyvinylpyrrolidone, loxoprofen sodium and 2-methyl-1- (4-methylthiophenyl) -2-morpholinyl-1-acetone in purified water according to the composition and proportion of raw materials at room temperature, and stirring and mixing to obtain a uniform mixture;
(2) Applying the mixture to a backing material on a spreading machine;
(3) Irradiating and crosslinking the material obtained in the step (2) for 3-10 min under ultraviolet rays of 200-400 nm; and (5) covering the lining material, rolling and cutting into corresponding specifications.
The prepared loxoprofen percutaneous administration system has a structure shown in figure 1 and comprises a backing material 2, a drug active layer 3 and a covering lining material 4. The prepared loxoprofen percutaneous administration system is subjected to paste content measurement, the measurement method refers to the second method measurement of 0122 (paste content) of the four general rules of the "Chinese pharmacopoeia" 2020 edition, and the measured paste content is 355g/m 2 。
Example 11
The raw materials of the drug active layer are as follows:
| component (A) | Dosage (weight portions) |
| Loxoprofen sodium | 7 |
| Polyethylene glycol 800 | 14 |
| Polyvinyl alcohol | 5 |
| Polyvinylpyrrolidone | 3 |
| Purified water | 67 |
| 1-hydroxycyclohexyl phenyl ketone (184) | 4 |
The preparation method comprises the following steps:
(1) Dispersing polyethylene glycol 800, polyvinyl alcohol, polyvinylpyrrolidone, loxoprofen sodium and 1-hydroxy cyclohexyl phenyl ketone in purified water according to the composition and proportion of raw materials at room temperature, and stirring and mixing to obtain a uniform mixture;
(2) Applying the mixture to a backing material on a spreading machine;
(3) Irradiating and crosslinking the material obtained in the step (2) for 3-10 min under ultraviolet rays of 200-400 nm; and (5) covering the lining material, rolling and cutting into corresponding specifications.
The prepared loxoprofen percutaneous administration system has a structure shown in figure 1 and comprises a backing material 2, a drug active layer 3 and a covering lining material 4. The prepared loxoprofen percutaneous administration system is subjected to paste content measurement, the measurement method refers to the second method measurement of 0122 (paste content) of the four general rules of the 2020 edition of Chinese pharmacopoeia, and the measured paste content is 236g/m 2 。
Example 12
The raw materials of the drug active layer are as follows:
| component (A) | Dosage (weight portions) |
| Loxoprofen sodium | 10 |
| Polyethylene glycol 800 | 18 |
| Polyvinyl alcohol | 4 |
| Polyvinylpyrrolidone | 4 |
| Purified water | 60 |
| 2-hydroxy-methylphenyl-propan-1-one (1173) | 4 |
The preparation method comprises the following steps:
(1) Dispersing polyethylene glycol 800, polyvinyl alcohol, polyvinylpyrrolidone, loxoprofen sodium and 2-hydroxy-methyl phenyl propane-1-ketone in purified water according to the composition and proportion of raw materials at room temperature, and stirring and mixing to obtain a uniform mixture;
(2) Applying the mixture to a backing material on a spreading machine;
(3) Irradiating and crosslinking the material obtained in the step (2) for 3-10 min under ultraviolet rays of 200-400 nm; and (5) covering the lining material, rolling and cutting into corresponding specifications.
The prepared loxoprofen transdermal delivery system has a structure shown in figure 1 and comprises a backingA material 2, a pharmaceutically active layer 3 and a cap material 4. The prepared loxoprofen percutaneous administration system is subjected to paste content measurement, the measurement method refers to the second method measurement of 0122 (paste content) of the four general rules of the 2020 edition of Chinese pharmacopoeia, and the measured paste content is 178g/m 2 。
Adhesion study
Taking the products prepared in examples 1-12 and the preparation (1) on the market: the loxoprofen sodium gel plaster (manufacturer: LEADCHEMICALCO., LTD. lot number: G018N 2) is subjected to adhesion test comparison, and the adhesion measurement method adopts a first method (primary adhesion measurement) of an adhesion measurement method of "Chinese pharmacopoeia 2020" 0952.
The adhesion test results are shown in table 1.
Table 1: adhesion test results
。
As is clear from the data in Table 1, the adhesion of the transdermal drug delivery systems of loxoprofen of examples 1 to 12 was significantly better than that of the marketed formulation (1) (G018N 2).
The loxoprofen transdermal drug delivery system can be repeatedly stuck, and can be torn off after being stuck to the skin for several hours, so that the loxoprofen transdermal drug delivery system still has no tearing off pain, has no skin mark and no peculiar smell, and the defects of poor adhesive force and easy falling off of a gel plaster (Cataplasts) are effectively overcome.
The loxoprofen transdermal drug delivery system has high water content, good air permeability, high drug loading capacity and strong water locking property, and is not easy to be allergic when being applied to the skin.
In vitro transdermal studies
The products of example 1, example 4, example 6, example 8, example 9, example 12 were chosen as marketed formulation (1): loxoprofen sodium gel plaster (manufacturer: LEADCHEMICALCO., LTD. lot number: G018N 2), marketed formulation (2): loxoprofen sodium patch (manufacturer: LEADCHEMICALCO., LTD. lot: M170R) was subjected to SD rat ex vivo skin transdermal test comparison.
IVPT simulates the percutaneous permeation process of percutaneous administration preparations (including skin topical preparations and percutaneous absorption preparations) under physiological conditions, and provides references and guarantees for evaluating the safety and effectiveness of the preparations. IVPT is mainly an in vitro skin and a proper analysis method, and the drug quantity penetrating through the skin within a specific time after administration is dynamically monitored, so that the in vitro percutaneous penetration behavior of the drug and the preparation thereof is examined.
SD rats (200+ -20 g) were selected and carefully shaved with a suitable hair removal device such as an animal shaver, and the hair removal process was not performed without scratching or damaging the skin cuticle, nor with scalding water and chemicals which could damage the skin barrier. The whole ring of the skin on the abdomen, the side face and the back is cut off by using a scalpel, and the skin can be taken by adopting an electric skin taking machine to set a certain thickness. After taking the skin, washing the outer surface of the skin with pure water or normal saline, carefully scraping off residual subcutaneous fat, capillaries and other tissues with forceps, a blade and the like, repeatedly washing with pure water or normal saline, and preserving at low temperature (storing in a refrigerator at-20 ℃ or-80 ℃) for one week.
The temperature control is consistent in the experimental process, and the skin surface temperature is stabilized at (32+/-1). The stirring or agitating speed is controlled so that the interface trough leakage condition can be maintained.
Phosphate buffer with pH 7.4 is selected as the receiving medium, and the receiving medium needs to be degassed before use. Test duration 24 h, sampling time points were 7.
The results of the in vitro transdermal test are shown in Table 2 and FIG. 2.
Table 2: in vitro transdermal contrast test
。
In vitro transdermal studies at different temperature conditions
Test methods in vitro transdermal studies the products of example 1, example 6, example 8, example 12 were selected with the commercial formulation (2): loxoprofen sodium patch (manufacturer: LEADCHEMICALCO., LTD. batch: M170R) is subjected to SD rat in vitro skin transdermal test contrast, test temperature is adjusted, and body surface temperature measurement difference under different environments after different crowds are simulated. The results of the in vitro skin transdermal comparative tests of SD rats at 30℃and 35℃are shown in tables 3 and 4 and FIGS. 3 and 4.
Table 3: in vitro transdermal comparison test (test temperature 30 ℃ C.)
。
Table 4: in vitro transdermal comparison test (test temperature 35 ℃ C.)
。
As is clear from the above comparison test, the in vitro skin transdermal test results of the commercial preparation (2) are very sensitive to temperature, and the effect of temperature on the transmittance is remarkable, while the transdermal drug delivery systems of the present application, examples 1, 6, 8 and 12, have relatively stable release rates under different temperature conditions and have small temperature variation.
The foregoing is a further detailed description of the application in connection with specific embodiments, and it is not intended that the application be limited to such description. It will be apparent to those skilled in the art that several simple deductions or substitutions may be made without departing from the spirit of the application, and these should be considered to be within the scope of the application.
Claims (8)
1. The transdermal drug delivery system of loxoprofen consists of a backing material, a drug active layer and a cover lining material, and is characterized in that the drug active layer mainly comprises active drugs, polyethylene glycol, polyvinyl alcohol, polyvinylpyrrolidone, purified water and an initiator, wherein the active drugs are loxoprofen or medicinal salts thereof, and the drug active layer is formed by ultraviolet curing under the initiation of the initiator;
the components of the drug active layer are as follows by weight percent:
loxoprofen or a pharmaceutically acceptable salt thereof 1-10%,
polyethylene glycol 2-20%,
1-10% of polyvinyl alcohol,
1-5% of polyvinylpyrrolidone,
60-94% of purified water,
1-6% of an initiator.
2. The transdermal loxoprofen delivery system according to claim 1, wherein,
the active medicine is loxoprofen sodium.
3. The transdermal loxoprofen delivery system according to claim 1 or 2, wherein,
the weight ratio of the polyethylene glycol to the polyvinyl alcohol is 0.6-5: 1.
4. the transdermal loxoprofen delivery system according to claim 1 or 2, wherein,
the polyethylene glycol is at least one selected from polyethylene glycol 400, polyethylene glycol 600 and polyethylene glycol 800.
5. The transdermal loxoprofen delivery system according to claim 1 or 2, wherein,
the initiator is selected from at least one of photoinitiators 1173, 184, 907, 369, 1490, 1700, 1220, 1156.
6. The transdermal loxoprofen delivery system according to claim 1 or 2, wherein,
the backing material is an external polyester non-woven fabric, and the weight of the backing material is 80-120 g/m 2 ；
The lining material is an external polypropylene embossing film, and the thickness of the lining material is 20-80 mu m;
the weight of the drug active layer is 71 g-710 g/m 2 。
7. The method for preparing a transdermal loxoprofen delivery system according to any one of claim 1 to 6, wherein,
dispersing polyethylene glycol, polyvinyl alcohol, polyvinylpyrrolidone, active drug and initiator in purified water, stirring to uniformly mix to obtain a mixture;
and uniformly coating the mixture on a backing material, then irradiating and crosslinking the backing material under ultraviolet rays until the backing material is solidified, and winding and cutting the backing material into corresponding specifications after covering the backing material.
8. The method for preparing a transdermal loxoprofen delivery system according to claim 7, wherein,
the irradiation crosslinking time is 3-10 min, and the irradiation ultraviolet wavelength is 200-400 nm.
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Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6248350B1 (en) * | 1996-08-26 | 2001-06-19 | Lead Chemical Co., Ltd. | External formulation containing loxoprofen |
| JP2014224111A (en) * | 2013-04-25 | 2014-12-04 | 第一三共ヘルスケア株式会社 | External preparation composition containing loxoprofen |
| JP2015042665A (en) * | 2014-10-28 | 2015-03-05 | 帝國製薬株式会社 | Non-steroid antiinflammatory patches |
| WO2019143114A1 (en) * | 2018-01-18 | 2019-07-25 | 대화제약 주식회사 | Hydrogel-patch-type pharmaceutical composition for transdermal administration |
| CN110946846A (en) * | 2018-09-27 | 2020-04-03 | 湖南九典制药股份有限公司 | Loxoprofen sodium gel cream matrix without transdermal penetration enhancer and preparation method thereof |
| CN112190568A (en) * | 2019-07-08 | 2021-01-08 | 大化制药株式会社 | Preparation method of hydrogel patch containing loxoprofen or pharmaceutically acceptable salt thereof |
| CN113069437A (en) * | 2020-12-29 | 2021-07-06 | 北京湃驰泰克医药科技有限公司 | External gel emplastrum containing loxoprofen and medicinal salt thereof and preparation method thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20120107153A (en) * | 2011-03-15 | 2012-10-02 | 아이큐어 주식회사 | Transdermal patch for delivery of fentanyl |
| KR101717699B1 (en) * | 2016-02-11 | 2017-03-17 | 아이큐어 주식회사 | UV-curable hydrogel resin for Cataplasma , Hydrogel curing the same and Cataplasma containning the same |
-
2022
- 2022-10-13 CN CN202211250782.5A patent/CN115444837B/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6248350B1 (en) * | 1996-08-26 | 2001-06-19 | Lead Chemical Co., Ltd. | External formulation containing loxoprofen |
| JP2014224111A (en) * | 2013-04-25 | 2014-12-04 | 第一三共ヘルスケア株式会社 | External preparation composition containing loxoprofen |
| JP2015042665A (en) * | 2014-10-28 | 2015-03-05 | 帝國製薬株式会社 | Non-steroid antiinflammatory patches |
| WO2019143114A1 (en) * | 2018-01-18 | 2019-07-25 | 대화제약 주식회사 | Hydrogel-patch-type pharmaceutical composition for transdermal administration |
| CN110946846A (en) * | 2018-09-27 | 2020-04-03 | 湖南九典制药股份有限公司 | Loxoprofen sodium gel cream matrix without transdermal penetration enhancer and preparation method thereof |
| CN112190568A (en) * | 2019-07-08 | 2021-01-08 | 大化制药株式会社 | Preparation method of hydrogel patch containing loxoprofen or pharmaceutically acceptable salt thereof |
| CN113069437A (en) * | 2020-12-29 | 2021-07-06 | 北京湃驰泰克医药科技有限公司 | External gel emplastrum containing loxoprofen and medicinal salt thereof and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 洛索洛芬钠凝胶膏治疗强直性脊柱炎的疗效;迟宏伟;孙雪;王小楠;齐炳洁;;中国继续医学教育(01);全文 * |
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