KR100647901B1 - A pharmaceutical composition comprising sustained-releasing cefaclor and preparing process thereof - Google Patents

Abstract

The present invention relates to a sephacller-containing sustained-release drug composition and a method for preparing the same, more specifically, containing a certain amount of hydroxypropyl methyl cellulose and vinylpyrrolidone vinyl acetate copolymer, and has excellent stability. Rather, it relates to a sephacller-containing sustained release pharmaceutical composition which releases sephacler slowly and which is easy to manufacture, and a method for producing the same. According to the present invention, the hydroxypropyl methyl cellulose and vinylpyrrolidone vinyl acetate copolymer through a constant mixing to minimize the decomposition by the moisture of the sepacller not only excellent stability, but also sepacler constant without any deviation It is also advantageous industrially because it is possible to prepare the release agent, and the manufacturing process is easy and the manufacturing cost is low.

Description

Sephacller-containing sustained-release pharmaceutical composition and its preparation method {A PHARMACEUTICAL COMPOSITION COMPRISING SUSTAINED-RELEASING CEFACLOR AND PREPARING PROCESS THEREOF}             

1 is a graph showing the Sepacle sustained-release formulation in the present invention in 900ml of 0.1N hydrochloric acid solution in a basket method (rotational speed 100rpm) of the conventional method, the elution percent Sepacle eluted with time .

The present invention relates to a sephacller-containing sustained-release drug composition and a method for preparing the same, more specifically, containing a certain amount of hydroxypropyl methyl cellulose and vinylpyrrolidone vinyl acetate copolymer, and has excellent stability. Rather, it relates to a sephacller-containing sustained release pharmaceutical composition which releases sephacler slowly and which is easy to manufacture, and a method for producing the same.

In general, Sefar clutch (Cefaclor) is because it is resistant to beta-lactamase Staffordshire Philo Rhodococcus (staphylococcus), A Streptococcus (streptococcus), A morak cell Kata LAL-less (moraxelle catarrhalis), Haemophilus influenza (haemophylus influenzae ) And other Gram-negative bacteria. Absorption in animals is known to be caused by active transport in the small intestine and passive diffusion in the large intestine using a dipeptide transport system.In humans, drugs are detected in the blood within 1 hour after oral administration. It is known that the peak blood concentration is lowered and the time taken to reach the peak blood concentration is delayed.

A typical Sephacler is to take 250mg three times a day every eight hours, such a medication is difficult to keep the correct time, and if not do not expect sufficient antibiotic effect. In this regard, there is a need for a Sephacler sustained-release preparation that is taken every 12 hours twice daily to make it easier and safer for patients to receive Sephacler. Therefore, in order to improve this problem, studies have been conducted on sustained-release preparations containing Sephacller and a method for preparing the same, and the resultant conventional technology has been disclosed by the following patent publications and publications. Representative methods include Applicant Nos. 88-1974, such as Peter Lloyd Oren, Applicant Nos. 84-3359, such as Saccharomoderuo, Applicants No. 96-1997, such as Park Jin-kyu, etc.

The first method, US inventor Peterloid Oren, is a method using hydroxypropylmethylcellulose and methacrylic acid copolymer, which contains enteric methacrylic polymers in tablets, thus increasing the gastrointestinal retention time. If the pH in the gastrointestinal tract is changed by a plant, drug, or disease, there is a problem that the variation in body behavior of Sephacler may be increased by the preparation. This is because the formulation contains a polymer that melts when the pH is 5 or more.

The second method of Korean inventor Park Jin-kyu et al. Uses a saturated sodium chloride aqueous solution containing sugar as a dispersion medium using cetyl alcohol, which is a problem for sepaclo which is very anxious for moisture.

The last method, the invention of Japanese inventor Saromodo Teruo et al., Is a method of producing a sustained sepacler preparation by mixing fasteners and sustained-release preparations using methacrylic acid and methacrylic acid esters as a coating base, and mixing the two. This method has a problem in that the manufacturing method is complicated and the manufacturing time can be lengthened by making and mixing the fast-acting preparation and the slow-release preparation, respectively.

Therefore, the conventional sustained-release preparations have the above problems, and there is an urgent need for improvement thereof.

Accordingly, an object of the present invention is to provide a sepacler-containing sustained-release pharmaceutical composition excellent in the industrial ability to reduce the manufacturing cost as well as excellent stability to solve the problems of the prior art as described above. It's there.

In addition, the present invention includes a novel method for producing a sephacller-containing sustained-release drug composition having excellent stability by minimizing the decomposition of the sephacller by water during the manufacturing process.

Firstly, the present invention relates to a sephacller-containing sustained-release pharmaceutical composition comprising hydroxypropylmethylcellulose and vinylpyrrolidone vinyl acetate copolymer and a method for preparing the same. The Sephacller-containing sustained-release pharmaceutical composition is described in more detail as follows.

First, hydroxypropyl methyl cellulose dissolves in water and organic solvents, and in particular, it is gelled without being affected by acids or alkalis, so it does not dissolve in the gastrointestinal tract for a long time and contains 1.0-16.0 wt% of the total content of the pharmaceutical composition. It is most desirable to control the release time of the Sephacle. In addition, vinylpyrrolidone vinyl acetate copolymer also has the property of gelling in both water and alcohol, and has the characteristic of forming a film without being affected by pH. The vinylpyrrolidone vinyl acetate copolymer most preferably contains 1.0-16.0% by weight of the total content of the pharmaceutical composition. Therefore, since both of the polymers are gelled regardless of pH, administration of a sustained release formulation using the two polymers will gel the irrespective of the acidity in the gastrointestinal tract, which can substantially eliminate the deviation of drug release caused by the preparation. Will be.

Next, the present invention includes a method for producing a sephacller-containing sustained-release drug composition, which will be described in more detail as follows.

First, a hydroxypropyl methyl cellulose and a vinylpyrrolidone vinyl acetate copolymer are dispersed in an organic solvent or a mixture of an organic solvent and water to prepare a dispersion. At this time, it is preferable to use 1.0-16.0 weight% of hydroxypropyl methyl cellulose: 1.0-16.0 weight% of vinylpyrrolidone vinyl acetate copolymer. In addition, in the production method, it is preferable not to use water, but considering the fluidity of the granules, the organic solvent may be used by mixing in an amount of 5-20 parts by weight to 80-95 parts by weight of the organic solvent. This is because, if used in excess of this, the target Sephacler may become unstable. In addition, it is preferable to use ethanol, methylene chloride, or isopropyl alcohol as the organic solvent, and in consideration of toxicity, ethanol is most preferable.

In the next step, the dispersion obtained in the above process is simply mixed with Sephacler and then crushed to make tablets, or the mixture is struck to prepare granules in a conventional manner and then compressed to prepare tablets, The tablets are coated using conventional pharmaceutically usable epidermis to prepare sustained release preparations for oral administration.

In addition, the present invention adds an organic solvent alone or a mixed solvent of water and an organic solvent to the mixture of Sepacle, hydroxypropyl methyl cellulose, vinylpyrrolidone vinyl acetate copolymer, to produce granules or tablets in the same manner as described above. In addition, the tablets are coated with a conventional pharmaceutically usable skin preparation to prepare a sustained release formulation for oral administration.

Forms of the preparations produced by such methods of the present invention include tablets, capsules, and coated tablets.

Hereinafter, the present invention will be described in more detail with reference to Examples and Experimental Examples. These Examples and Experimental Examples are only for illustrating the present invention more specifically, and the scope of the present invention is not limited by these Examples and Experimental Examples and various modifications are possible within the spirit and scope of the present invention. .

Example 1 :

As shown in Table 1, 30 g of hydroxypropyl methyl cellulose and 10 g of vinylpyrrolidone vinyl acetate copolymer were sufficiently dispersed in a solvent mixed with 720 g of ethanol and 80 g of water, and then added to Sepachlor Monohydrate 392.3 g to form granules immediately. It was dried for 5 hours in an oven. The mixture was granulated into No. 25 sieves, and 4 g of magnesium stearate was added thereto and tableted using a conventional tableting machine.

ingredient Weight (mg) / tablet weight (%) Sepacle Monohydrate Hydroxypropyl Methyl Cellulose Vinylpyrrolidone Vinyl Acetate Copolymer Magnesium Stearate 392.3 30 10 4 89.91 6.88 2.29 0.92

Example 2 :

30 g of hydroxypropyl methyl cellulose and 20 g of vinylpyrrolidone vinyl acetate copolymer were sufficiently dispersed in a solvent in which 720 g of ethanol and 80 g of water were mixed, and then granules were added to 392.3 g of Sephacler monohydrate. Immediately afterwards it was dried for 5 hours in a 50 ℃ oven. The mixture was granulated into No. 25 sieves, and 4 g of magnesium stearate was added thereto, followed by tableting using a conventional tableting machine.

Ingredient Name Weight (mg) / tablet weight (%) Sepacle Monohydrate Hydroxypropyl Methyl Cellulose Vinylpyrrolidone Vinyl Acetate Copolymer Magnesium Stearate 392.3 30 20 4 87.9 6.72 4.48 0.9

Example 3 :

As shown in Table 3 below, 30 g of hydroxypropylmethylcellulose and 30 g of vinylpyrrolidone vinyl acetate copolymer were dispersed in a solvent mixed with 720 g of ethanol and 80 g of water, and then added to Sepacle monohydrate 392.3 g to form granules immediately. It was dried for 5 hours in a 50 ℃ oven. The mixture was granulated into No. 25 sieves, and 4 g of magnesium stearate was added thereto, followed by tableting using a conventional tableting machine.

Ingredient Name Weight (mg) / tablet weight (%) Sepacle Monohydrate Hydroxypropyl Methyl Cellulose Vinylpyrrolidone Vinyl Acetate Copolymer Magnesium Stearate 392.3 30 30 4 85.97 6.57 6.57 0.89

Experimental Example 1 Dissolution Test

In order to observe the dissolution behavior of the sustained-release tablets prepared in Examples 1, 2, and 3, evaluation was performed according to the dissolution test item in Sepacle Sustained Release Criteria and Test Method Examination (notified on Sept. 10, 1994) of antibiotic drug notification. It was. The commercially available Sephacller sustained-release tablet (L Pharmaceutical) was also tested. Take 1 tablet of this solution and test it with 900 ml of 0.1 N hydrochloric acid solution as a test solution at 100 revolutions per minute according to the Dissolution Test No. 1 method. 30 minutes after the start of the dissolution test, a certain amount of the eluate was accurately taken and supplemented with the same volume of test solution warmed to 37 ± 0.5 ° C. The eluate was filtered using a 0.45 um filter, and a certain amount of this solution was accurately taken and diluted to contain about 20-30 ug (titer) per ml with 0.1 N hydrochloric acid solution to prepare a sample solution. Subsequently, the dissolution test was carried out and the same procedure was carried out after 60 and 240 minutes, and the obtained solution was used as the sample solution. In addition, a separate commercial standard Sephacler was diluted with 0.1 N hydrochloric acid solution to prepare a commercial standard solution. The dissolution rate was determined by measuring the absorbance of each sample with 0.1 N hydrochloric acid at 265 nm with the sample solution and the commercial standard solution. And the result is shown in FIG.

As a result, as shown in FIG. 1, Sepacle sustained-release tablets prepared using hydroxypropyl cellulose and vinylpyrrolidone vinyl acetate copolymers according to Examples 1, 2, and 3 are commercially available products. As such, it can be seen that the dissolution rate criteria are higher than 5.0-30.0% after the start of dissolution, 20.0-50.0% after 60 minutes, and 80.0% after 240 minutes.

Experimental Example 2 : Stability Test

The sustained release formulations of Examples 1 to 3 using hydroxypropylmethylcellulose and vinylpyrrolidone vinylacetate copolymer were placed in an HDPE container and stored at room temperature for 24 months, whereby the sustained release formulation was taken every 3 months. The stability of Sephacller was evaluated.

As shown in Table 5, after the preparation of the sustained-release preparation, the titer of Sepacle can be seen that the titer of Sepacle hardly falls. In addition, even after 24 months after preparation, the dissolution rate of Sephacller in the formulation did not change with time.

Stability test results of Sephacller sustained-release tablet division Example 1 Example 2 Example 3 Initial 3 months 6 months 9 months 12 months 15 months 18 months 21 months 24 months 110.2% 109.3% 109.1% 108.7% 108.6% 108.6% 108.5% 107.6% 107.8% 110.3% 109.4% 109.6% 109.5% 109.4% 108.5% 108.3% 108.1% 107.1% 110.2% 109.6% 109.5% 109.4% 108.6% 107.8% 107.4% 107.2% 106.7%

As described above, the present invention is a sephacler sustained-release preparation using hydroxypropylmethylcellulose and vinylpyrrolidone vinyl acetate copolymer and a method for preparing the same. Sephacle sustained release formulations excellent in stability can be prepared.

In addition, according to the present invention, it is possible to gradually release the sephacller from the preparation made through various combination ratios of hydroxypropylmethylcellulose and vinylpyrrolidone vinylacetate copolymer, and in the preparation of a sustained release formulation because the preparation method is easy. It is possible to achieve uniformity by overcoming the problem of sustained deviation, and to produce a very advantageous effect industrially because of low manufacturing cost.

Claims (5)

Sephacler-containing sustained-release pharmaceutical composition comprising 1.0-10.0% by weight of hydroxypropyl methyl cellulose and 1.0-10.0% by weight of vinylpyrrolidone vinyl acetate copolymer. delete Preparing a dispersion by dispersing 1.0-10.0 wt% of hydroxypropyl methyl cellulose and 1.0-10.0 wt% of vinylpyrrolidone vinyl acetate copolymer in an organic solvent or a mixture of organic solvent and water; Preparing a granule or tablet by simply mixing the dispersion with Sephacle; And, A method for producing a sephacller-containing sustained release pharmaceutical composition comprising coating the granule or tablet with a coating agent. The method of claim 3, wherein the mixture is an organic solvent: water in the ratio of 80 to 95% by weight: 5 to 20% by weight of the method for producing a sephacller-containing sustained-release pharmaceutical composition. The method of claim 3 or 4, wherein the organic solvent is at least one selected from ethanol, methylene chloride and isopropyl alcohol.

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