FI89457B - Foerfarande Foer framstaellning av ett preparat som somehaoller ett aluminiumsalt av en sackarossulfatester - Google Patents

Description

! 89457

The present invention relates to a preparation containing an aluminum salt of sucrose sulfate ester 5 (commonly known as sucralfate) and to a process for producing a sucralfate preparation. In the process of the present invention, sucralfate is mixed with polyethylene glycol to improve its degradability and dispersibility, and this makes sucralfate more useful as a drug.

Sucralfate is widely used as a treatment for gastrointestinal wounds and has the ability to protect the substrate protein (ability to protect the gastric mucosa) 25 and reduce the activity of pepsin in gastric fluid; in addition, it has antacid effects. It is generally believed that sucralfate binds strongly to the protein component of the wound bed and forms a layer that chemically protects the lesion area from the strong degradation effect of gastric fluid and thus promotes the healing process / iJazazawa, S. et al. Dig. Dis. Sci. 26 (1981) 297; and A. Ishimori et al., Igaku to Yakugaku 9 (1983) 25 /.

Sucralfate, on the other hand, is insoluble in water, and preparations containing it should readily disintegrate and disperse in order to effectively bind to the wound-damaged area.

The present inventors have conducted various studies to develop a sucralfate preparation having improved disintegration and dispersibility. As a result of the studies, the present inventors have found that this object can be achieved by mixing sucralfate with polyethylene glycol. The present invention has been made on the basis of this finding.

Figures 1 and 2 show disintegration and dispersion curves of sucralfate preparations and reference preparations prepared in accordance with the present invention.

According to the present invention, the sucralfate is mixed with polyethylene glycol in an amount of 0.1 to 5% by weight. The molecular weight of the polyethylene glycol to be mixed with sucralfate is not limited to any particular value. When administered orally, the sucralfate preparation of this invention allows for effective binding of sucralfate to the wound-damaged area. The sucralfate preparation of this invention can be formulated into various forms of administration, such as powders, granules, granules, tablets and capsules. Various additives such as binders, disintegrants, lubricants, extenders and colorants can be used for this purpose.

The following examples are provided to further illustrate this invention, but are not to be construed as limiting the invention in any way.

Example 1 The aluminum salt of sucrose sulfate ester (sucralate, 3920 g) was mixed well with an aqueous solution (2000 g) containing 4% polyethylene glycol (molecular weight 1500) in a mixer. The mixture was granulated in a drum-cooker equipped with a mesh with a mesh size (diameter) of 0.7 mm. The granules were dried for 3 hours at 60 ° C in a plate dryer. The dried granulation product was screened through a 16 mesh screen to give granules. Reference granules were otherwise prepared by the method described above, but an aqueous solution containing 4% polyethylene glycol was replaced with water.

The disintegration and dispersing ability of the two granule samples is shown as the change in turbidity in Figure 1, denoting the value measured for the reference suspension by 1. The reference suspension was prepared by dispersing well 3 g of with a layer thickness of 1 cm. The turbidity was measured 5 in more detail as follows: suspensions each containing 200 mg of sucralfate were placed in five auxiliary tubes of the degradation tester (test liquid: 1000 ml of water at 37 + 2 ° C) and turbidity was measured from liquid samples taken approximately 5 cm from the test below the surface of the liquids. Based on the results obtained, the specific turbidities of the individual samples were then determined.

The two grain samples were subjected to an aging acceleration test by maintaining them at 75 ° C and 75% relative humidity for 6 months and their dispersibility as a specific turbidity calculated as described above. The results are shown in Table 1.

Table 1 20 Change in specific turbidity due to accelerated aging (40 ° C, relative humidity 75%, 6 months) Sample__Time__2 min. 5 min. 20 min._

Invention Prior to Accelerated 0.93 0.95 0.96. . in accordance with the aging rskcpt

After accelerated obsolescence 0.85 0.92 0.95 2 5 in: Prior to accelerated obsolescence 0.28 0.33 0.41 ____; granules aging

After accelerated aging 0.16 0.18 0.19 Example 2

Sucralfate (4000 g) was mixed well with water. to a solution (2000 g) containing 10% polyethylene glycol (molecular weight 6000) in a mixer. The mixture was passed through a 16 mesh screen to prepare granules, which were dried at 60 ° C for 3 hours on a plate fiber and graded by passing them through a 10 mesh screen.

The obtained granules (4000 g) were mixed with crystalline cellulose (1376 g) and magnesium stearate (24 g), and the mixture was stirred for 5 min in a V-type mixer.

The obtained powder was placed in a rotary tableting machine equipped with nozzles and a perforating blade (diameter 12 mm) and compressed at a total pressure of about 2.5 tons into tablets each weighing 700 mg. Reference tablets were otherwise prepared as described above, but an aqueous solution containing 10% polyethylene glycol was replaced with an aqueous solution containing 10% hydroxypropylcellulose (Nisso HPC-L, Nippon Soda Co., Ltd).

The disintegration and dispersibility of the two tablet samples is shown in Figure 2 as the change in turbidity when the turbidity of the reference suspension was set to 1. The reference suspension was prepared by well dispersing 1000 mg sucralfate, 344 mg crystalline cellulose and 6 mg magnesium stearate in 1000 ml water. turbidity at 540 nm with a layer thickness of 1 cm in the detector cell. The turbidity measurement was performed as follows: each of the 25 tablets was placed in a disintegration tester (test liquid: 1000 ml of water at 37 + 2 ° C) and the turbidity of the liquid samples taken 5 cm below the surface of the test solutions was measured. Based on the results obtained, the specific turbidity of each sample was calculated.

The two tablet samples were subjected to an aging acceleration test by maintaining them at 40 ° C and 75% relative humidity for 6 months, and their dispersibility as a specific turbidity was evaluated, which was calculated as described above. The results are shown in Table 2.

5 89457

Table 2

Change in specific turbidity due to accelerated aging (40 ° C, relative humidity 75%, 6 months), Sample Time 2 min 5 min 20 min

Pre-accelerated tablets according to the invention 0.79 0.85 0.95 After accelerated aging 0.63 0.80 0.92

Comparative- Before accelerated 0.20 0.25 0.30 tablets aging

After accelerated aging 0.09 0.13 0.16

Claims (2)

6 39457 A process for producing a sucralfate preparation, characterized in that the aluminum salt of the sucrose sulfate ester is mixed with polyethylene glycol in a proportion of 0.1 to 10% by weight. Use of polyethylene glycol for improving the disintegration and dispersibility of a sucralfate preparation, wherein the proportion of polyethylene glycol is 0.1 to 10% by weight. 10 15 1. A mixture for the production of sucralfate preparations, which can be mixed with aluminum and a sulphate sulphate ester with polyethylene glycol, containing from 0.1 to 10% by weight. 2. Use of a polyethylene glycol in order to improve sönderdelningen Science 20 dispergerbarheten of a sukralfatpre-Parat, wherein the polyethylene glycol constitutes from 0.1 - 10% by weight.