TW200418525A - Coated pharmaceutical tablets containing Tibolone - Google Patents

Abstract

The present invention relates to a stabilized pharmaceutical tablet comprising an amount of from 0.1 to 10% by weight of tibolone provided with a coating, such as a film coating, a sugar coating, a sugar film coating or a "wrap" coating. The invention further relates to the use of a coating for stabilizing a pharmaceutical tablet comprising tibolone. Preferably, the coating is a sugar coating or a sugar film coating. Preferably, the sugar comprises sucrose. These tablets were shown to have a lower amount of OM38, i.e. an isomerization degradation product of tibolone, after storage as compared to uncoated tibolone tablets.

Description

200418525 ⑴ 玖, Description of the invention [Technical field to which the invention belongs] The present invention relates to a medicinal tablet including Tibolon from 0.1 to 10% by weight. [Prior art] Including Tibolon, the chemistry of each is (7 a, 1 7 α) — 1 7 -hydroxyl 7 —methyl — 19 — norme 17 — pregnant 5 (10) — ene 20 — A combination of an alkyn-3-one (also known as Org OD 1 4) and a pharmaceutically acceptable solid carrier has been described in EP 3 8 9 03 5. One known formulation of Tiberium is a 1000 mg tablet containing 2.5 mg of Tiberium, a relatively small amount (e.g., about 1% by weight) of a pharmaceutically acceptable adjuvant, and a carrier to supplement the tablets. The carrier is typically about 10% by weight of starch, such as potato starch, and about 90% by weight of lactose. A 100 mg tablet containing 2.5 mg of Tiberium is available in the pharmaceutical industry under the name Li vial ®. During long-term storage of Tibolon-containing ingots, Tibolon degradation products may appear. The main degradation products are (7α, 17α) — 17 —hydroxy- 7 —methyl — 19 —nor-17 — progesterin — 4 —ene — 20 — alkyne — 3 —one (〇rg DM3 8). 0M3 8 differs from Tiburon in that the double bond system in the steroid backbone is located between positions 4 and 5, while in Tiburon, its system is located between positions 5 and 10. This isomerized product has been identified as a major impurity in Tiburon and Tibolon-containing ingots and will limit the identified shelf life of existing Livi al ® ingots to a maximum of two years (up to a maximum of 5% by weight) Below 0M 38). Significant advantages can be achieved in extending the shelf life of ingots containing Tibolon. Therefore, it is advantageous to find a way to reduce the formation of 0M 3 8 and to provide a more stable Tiberium ingot for the amount of OM 3 8 formed by (2) 200418525 after storage.

The solution to the problem of reducing the formation of OM 3 8 in Tiburon and products containing Tiburon was proposed earlier in WO 0 0/2 3 4 6 0 which contains less than 0.5% by weight OM 3 8 High-purity tibolon, and a composition including tibolon and a pharmaceutically acceptable carrier is proposed in W 0 9 8/4 7 5 1 7, the carrier has a high content of powder, that is, higher than 10%, preferably at least 40% by weight. Despite these contributions to the craftsmanship, there is still a need to further improve the shelf life of the Tiberium ingots and to W OO 0 0/2 3 4 6 0 and W 〇 Alternative to the solution proposed in 9 8/4 7 5 1 7 [Summary of the invention] According to the present invention, for the first time, a stabilized medicinal tablet is obtained, which comprises 0.1 to 10% by weight of Tiberium and plus There is a suit. Surprisingly, this tablet has a lower OM 3 8 content after storage, especially after months of storage, which is lower than similar tablets without coating. Unexpectedly, the coating can reduce the formation of the Tibellon-derived isomerization degradation product OM 3 8. The present invention further relates to the unexpected novel use of Yiyi for stabilizing medicaments including 0.1 to wt% tibolone. In the context of the present invention, the term `` stabilizing '' means ... stabilizing 〃 for the formation of OM 3 8 after storage. Therefore, clothing lines containing tibolon tablets are used to reduce the formation of OM 3 8 compared to uncoated tablets. In addition, in the context of the present invention, the term `` tablet '' means a `` solid dosage form '' which can be technically applied and is typically used for oral administration. As such, in addition to pressed or molded ingots, powders, granules, nonpareils, and capsules are also covered by the term '' ingots (3) 200418525. However, compressed tablets are the most commonly used solid dosage form.

Occasionally, it is mentioned in W 0 9 8/4 7 5 1 7 that it is possible to add a Tiberium spin coat with a film coat if needed (Daddy's 5th page, line 1 4-16). The ingots made according to W 0 9 8/4 7 5〗 7 utilize a pharmaceutically acceptable carrier containing more than 10%, preferably at least 40% by weight, starch. In this document, there is no mention or speculation of the technical impact of Yiyi on the formation of OM 3 8 in Tiburon-containing storage. In this document, 'Tiberon ingots stabilized by coating are not disclosed nor exemplified. Regarding the word "if required" in line 14, it should be mentioned in particular. The Livial ® tablets currently on the market are uncoated, also from the typical reasons for coating tablets No need for coaters (from Remington, p. 8 94, quoted below), that is, to separate the drug from its surroundings (especially for air, moisture and light), to shield offensive tastes or odors, The ease with which the product can be ingested by patients, improves the nature of the product, aids disposal, improves the appearance of the product, reduces the risk of interactions between incompatible ingredients, improves the mechanical integrity of the product, or the release of regulatory drugs. In addition, WO 98/4 75 1 7 only mentions film coats and does not mention any other type of coats. In the context of the present invention, '' coating '' means any garment that can achieve a stabilization effect of OM 3 8 after storage of the coated tablet relative to the uncoated tablet. Whether a garment can achieve a stabilization effect can be easily determined by those skilled in the art based on this specification. The amount of OM 3 8 contained in the ingot can be determined by HPLC analysis in a conventional manner. Suitable examples of clothing that can be used according to the present invention include film coatings, sugar coatings, sugar film coatings, for example, sugar film coatings according to US 2 002/0044 970, and according to -6- (4) 200418525

U S 5 1 4 6 7 3 0 '' wrapped jacket. The composition of these garments and the methods and equipment used to apply them to the ingots are well known to those skilled in the art, and they are, {Listed, Stuart C. Porter, Remington: The Science and Practice of Pharmacy; 20th ed., Chapter 46: Coating of pharmaceutical dosagd forms; Alfonso R. Ge naro, Editor, Lippincott Williams &Wilkins; Baltimore, USA; and in US 2002/0044970 and US 5146730 The person. Preferred are aqueous coating compositions, including water and organic solvents such as alcohols. The most preferred is the use of a coating composition containing water as the sole solvent or vehicle. In particular, the coat to be used according to the present invention is a satin coat, a sugar film coat, or a wrapper coat. In particular, the coat of the present invention is a film coat, a sugar coat, or a sugar film coat. In a preferred embodiment of the present invention, the coating is a sugar coating or a sugar film coating. The sugar coating can be with or without a seal coat and / or a subcoat.

With regard to film coatings, the inventors have found that not all film coatings can achieve the desired stabilization effect on Tiberone. In particular, Tiberium ingots coated with acrylic polymer coatings, such as Eudragit ® Ε ΡΟ and EUdi * agit® L100, which are used to prevent moisture, shield taste and odor, and to transport drugs in jejunum, After storage, it showed higher OM 38 content than uncoated tablets. Therefore, these film coats are not available. As explained in Remongton Chapter 46 (cited above), the main ingredients in any film coating formulation often include polymers, plasticizers, colorants, and solvents. According to the present invention, both the plasticizer and the colorant are optional ingredients and as described above-the solvent or vehicle is preferably an aqueous solvent or vehicle or most preferably water. (5) 200418525 Suitable examples of the polymer include cellulose ethers such as hydroxypropyl cellulose, methyl cellulose, and ethyl cellulose, and in particular, hydroxypropyl methyl cellulose. Suitable cellulose ether-containing coating compositions are commercially available under the names SepifilmTM, Opadry®, and Aquacoat®. Acrylic polymers such as methacrylate and methyl methacrylate copolymers, vinyl polymers such as polyvinyl alcohol and polyvinylpyrrolidone, gelatin or starch can also be used.

Suitable acrylic polymer-containing coating compositions are commercially available under the name Eli dragit®. Suitable coating compositions containing vinyl polymers are commercially available under the names Opaglos®, OpaiuxTM, and Opadry®. In particular, cellulose ethers, vinyl polymers or gelatins are used according to the present invention, and more particularly cellulose ethers or vinyl polymers. Typical plasticizers include glycerol (or propylene glycol), propylene glycol, polyethylene glycol glycerol diacetate (or glyceryl triacetate), ethylated glycerol monoester, and citrates (such as triethyl citrate Esters), and phthalates (such as

Diethyl phthalate). Preferred plasticizers are glycerol or glycerol, propylene glycol, and polyethylene glycol. As explained in Remington Chapter 46 (cited above), sugar coating typically includes a coating or sealing, a base coating and a sugar coating. The sugar coating described later is typically free of polymers. According to the present invention, the sealing coat and the undercoat white are used as a coat and do not need to be used in combination with a sugar coat to obtain the technical effects of the present invention. In particular, the stabilizing effect on OM 3 8 was observed in sugar-coated tablets without a coating and / or a base coating. The sugar used in the sugar coating is typically sucrose (sucrose or -8- (6) 200418525 saccharose), but other sugars such as glucose, fructose, and lactose or polyols such as sorbitol, mannitol, and xylitol It can also be used according to the invention. One or more sugars can be used according to the invention. Preferably, the sugar system includes sucrose. Sugar film coatings are coatings including polymers and sugars, as defined above. For example, the sugar film coating system according to US 2 002/00 44970 uses an aqueous sugar coating liquid,

It contains 30-50% by weight of sugar (preferably sucrose), 2-10% by weight of polyethylene glycol; and 0.2-2% by weight of polyvinylpyrrolidone to produce a single-layer sugar-coated tablet. . JP 2001026534 describes a sugar film coating comprising sucrose, pullulan, and hydroxypropyl methylcellulose. Using this as a basis, those skilled in the art can make appropriate variations in the sugar film coating without difficulty.

The `` wrapped jacket '' according to US 5 1 4 6 7 3 0 typically uses a water-based gelatin formulation with about 45% by weight of gelatin and about 9% by weight of a plasticizer (glycerin and / or sorbic acid) alcohol). In the method U S 5 1 4 6 7 3 0, the tablets are rolled or `` wrapped '' in a gelatin coat formed by applying an individual elastic gelatin layer to the opposite side of the tablets. The applied gelatin layer is tightly conformal to the surface of the ingot, and is firmly adhered to the ingot; and is basically sealed together at the sealing line in an edge-to-edge manner, the sealing line is wound around the desired point on the ingot The ingot extends. The garment is applied by feeding an ingot between a pair of molds in a mold cavity formed by two elastic self-adhesive films. The tablets enclosed in the two film envelopes in this manner are finally coated by sealing the films to each other along a line contacting the tablets. Instead of gelatin, (modified) starch, alginate, modified gelatin, acrylate, polyvinylpyrrolidone-9- (7) 200418525 'cellulose derivatives (including esters and ethers), and polysilicon Oxane. Details of this method and the '' wrapped '' coating composition are set out in US 5 1 4 6 7 30. The clothing to be used in accordance with the present invention typically also contains pharmaceutically acceptable adjuvants such as acacia, calcium carbonate, magnesium stearate, talc, porcelain clay, and / or titanium dioxide. These adjuvants can be used in customary amounts when needed. Colorants can also be used when needed.

As is known in the art of coating and is exemplified in the examples below, one or more layers may be used and if more than one layer is used, the layers may have the same or different compositions. In particular, a monolayer is used according to the present invention. Where necessary, the coated tablets of the present invention may be smoothed, polished, or printed, as known in the art.

The tablets to be used in accordance with the present invention may vary in weight and / or Tibolon content. In particular, there are currently 1000 mg tablets containing 2.5 mg of Tibolon (ie, 2.5% by weight) and 1.2 mg of Tibolon (ie, 1.9% by weight) on the market. The 65 mg tablet is under investigation. The results for both are presented in the examples given below. Pharmaceutically acceptable carriers may vary in composition and include about 10% by weight of starch and about 90% by weight of lactose, or may contain higher amounts of starch, such as at W 0 9 8/4 7 5 1 7 Contained in. In particular, the carrier contains less than 40% by weight, more specifically 10% by weight or less of starch. In a preferred embodiment of the present invention, a stabilized coating L i ν ia 1 ® | set. The invention is illustrated by the following examples. -10- (8) 200418525 Example 1 A purified Tiberium tablet was prepared with a total weight of 65 mg and containing 25 mg of Tiberium tablet. The Tiberone system is obtained according to the method described in W 0 0 0/2 3 4 60. It uses starch glue as a binding liquid to manufacture in a fluid bed granulator composed of 10% potato starch and 90% lactose. Base plasmid.

Uncoated tibolon tablets were prepared according to the following procedure: 65 mg tablets with the following composition: 1.25 mg tibolon, 6; 3.29 mg base plasmid, 0.13 mg ascorbyl palmitate, And 0.33 mg of magnesium stearate; the procedure was as follows: approximately 10% of the base plasmid was premixed with tebolone and ascorbyl palmitate. After sieving the premix through a 250 micron sieve, add the remaining base plasmids and continue mixing. Finally, magnesium stearate was incorporated and the final mixture was ingoted into 5 mm diameter ingots.

Film coating

A film coating (1.2 mg / tablet) having the following composition was added to the tablet prepared as described above: 0.75 mg of hydroxypropyl methylcellulose E1 5, 0.1 5 mg of polyethylene glycol 400, 0.1 1 mg of titanium dioxide, and 0.19 mg of talc. Using a standard film coating equipment (AccelaCotaTM 24 "), the coated excipient aqueous dispersion was spray-coated on the ingot at a 12.5 rpm coating pan speed, an inlet temperature of about 60 ° C, and an air flow rate of about 300 cubic meters per hour. Sugar coating I -11-200418525 〇) A batch of about 16 kg of film-coated tablets as described above (the film coating has the function of sealing) is further equipped with a sugar-containing base coat, sugar-containing layered powder, and One sugar coating. To apply the coating layers, the tablets are dosed with a sugar coating pan. The turntable has a diameter of about 0.7 meters and a rotational speed of 4 2 rp m. The indoor conditions are 2 1. (: and 46% relative humidity.

A base coat consisting of a 60.2 w / w% dispersion containing about 20% gelatin and about 80% sucrose was manually applied to the tablets in the sugar-coated pan step by step. After each addition, a total of several hundred grams of layered powder consisting of 6 4.3% talc, 21. 4% calcium carbonate, 7.1% sucrose, and 7.1% titanium dioxide was manually added. Between the base coat and the addition of the layered powder, the ingots were dried in open air without forced drying. After the completion of the base coat (about 21 mg per tablet of base coat layered powder), the sugar-coated dispersion having the composition shown in Table 1 was added in several sequential steps and the sugar-coated tablet batch was finally dried (sugar-coated about 3 9 Mg per tablet).

-12- 200418525 (10) Table 1 Ejiao 3.4 Sucrose 43.6 Calcium Carbonate 6.7 Talc 10.7 Titanium Dioxide 4.7 Polyethylene Glycol 0.7 Glucose 0.7 Glycerin 8 6.5 ° / 〇 0.1 Porcelain 6.7 Purified Water 22.7

The amounts of the ingredients are given in weight percent of the total weight of the composition. Sugared 11

A batch of 8 kg of film-coated tablets as described above was coated with sugar ' but there was no undercoat, as described above. The tablets prepared and coated as described above were loaded in open brown glass bottles and subjected to storage conditions of 25 ° C and 60% relative humidity (RH) or 40 ° C and ambient relative humidity. After 6 months, the amount of isomerized degradation product OM 38 in the ingot was measured by HPLC analysis and tabulated as the percentage of the amount of Tiberon declared in the table. The results are shown in Table 2. -13- (11) 200418525 Table 2 2 50 ° C, 60% R Η 1) 40 ° C, surrounding RH% 0 Μ 3 8 SD2)% OM 3 8 SD2) Uncoated tablets 2.83 0.02 6.53 0.02 Film coating Tablet 2.45 0.03 4.83 0.09 Sugar-coated I 2.32 0.02 3.19 0.04 Sugar-coated II 2.39 0.0 1 3.44 0.05

RH is the relative humidity of the environment. SD is the standard deviation of the mean value of three measurements from 10 ingots per pool (p 001) of the ingots. The results in Table 2 show that the coating of Tiberium according to the present invention results in a reduction in the formation of the isomerization degradation product OM 3 8 and thus results in stabilized Tiberium ingots. Sugar coating gave better results than film coating alone.

Example 2 Sugar-coated A batch of about 20 kg of uncoated tablets (65 mg, see Example 1) was sugar-coated. To apply sugar coating, add tablets to a conventional film-coated pan (Dumoulin IDA 30X) equipped with an air bypass. The turntable has a diameter of approx. 1 m and a rotation speed of 3 to 5 1 · p m. In several successive steps, add a sugar-coated dispersion with the composition shown in Table 3 until approximately 35 mg per milligram of sugar-coated is reached, and finally add the batch of sugar-14 · (12) 200418525 coated tablets and dry as per Analysis described in Example 1. The results after two months of storage are not shown in Table 4. Ejiao 1.8 sucrose 59.5 talc 3.0 carbon dioxide 0.9 s u n s e t yellow 0.002 purified water 34.8 total 100 carnauba " 0.1

Add after dressing for a shiny look. The amounts of the ingredients are given in weight percent of the total weight of the composition.

Table 4 40 ° C, J1% OM 3 8 RH SD]) Uncoated tablets 2.65 0.09 Sugar-coated tablets 1.66 0.02 1} SD is the standard of average radon measured three times from 10 tablets per pool deviation. -15- (13) (13) 200418525 The results in Table 4 show that the coating of the Tiberium tablets according to the present invention results in a reduction in the formation of isomerization degradation products OM 3 8 and thus results in stabilized Tiberium Ingots Example 3 The procedure described in Example 1 was used to prepare 1000 mg tablets with a total weight of 2.5 mg of Tiberium. An uncoated tibolon tablet was prepared as described in Example 1 into a 100 mg tablet having the following composition: 6 mm in diameter: 2.5 mg tibolon, 96.8 mg base plasmid, 0.2 mg ascorbyl palmitate, And 0.5 mg of magnesium stearate. Adding a film coat To a film coat prepared as described above (1.51 mg per tablet): 0.94 mg of hydroxypropyl methylcellulose E15, 0.19 mg of polyethylene glycol 400,000. · 4 mg of titanium dioxide, and 0.2 4 mg of talc. Using a standard film coating equipment (Accela CotaTM 24 "), spray the coating vehicle aqueous dispersion at an inlet temperature of 12.5 rpm at an inlet temperature of approximately 60 ° C and an air flow rate of approximately 300 m3 / h. On the tablets. Sugar-coated A batch of 14 kg of film-coated tablets as described above was added with sugar-coated (about 35 mg of the bottom of each tablet in the same manner as described in Example 1, `` Sugar-coated I ''). 16- (14) 200418525 coating and layered powder, and about 8 mg of sugar coating per tablet). The tablets were analyzed as described in the Examples and the results after 6 months storage are shown in Table 5. Table 5 2 50 ° C, 60% R Η 1) 4 ° C, surrounding RH% OM 3 8 o / oOM 3 8 uncoated tablets 3.07 6.0 5 film-coated tablets 2.74 4.88 sugar-coated tablets 2.72 3.83 RH is the relative humidity of the environment

The results in Table 5 show that coating of a Tibolon tablet according to the present invention can lead to a reduction in the formation of the isomerization degradation product OM 38 and thus results in a stabilized Tibelon tablet.

Example 4 Tablets having a total weight of 65 mg and 0.625 mg of Tiberon were prepared using the procedure described in Example 1. Uncoated tibolone tablets 65 mg tablets with the following composition: gram-based plasmid, 0.13 mg magnesium palmitate aspartate. Bad 0.625 mg of tibolone, 63.9 mmol of hematyl ester, and 0.325 mg of adipose as described in Example 1 -17- (15) 200418525

Film coating I

The tablets prepared as described above were coated with a film having the following composition: 5.2 mg of Opadry ® A MB, including polyethylene glycol, fluorite, talc, iron oxide yellow, lecithin, xanthan gum, and Iron oxide red. Using a standard film coating equipment (Glatt® GC3 0 0), the coating vehicle aqueous dispersion (approximately 15 rpm), the inlet temperature of about 60, and the air flow rate of about 100 cubic meters per hour ( Solid content of 15 w / w%) was sprayed on the ingot. Film coating Π The film coating prepared as described above was added with a film coating having the following composition: 5.2 mg of SepifilmTM LP 7 70, including hydroxypropyl methylcellulose, stearic acid 'and talc. The coat is applied using a standard film coating equipment (G 1 a 11 ® GC 300) at a plate speed of about 15 rpm, an inlet temperature of about 60 ° C, and an air flow rate of about 1000 cubic meters per hour. The aqueous vehicle dispersion (solid content 8 w / w%) was sprayed on the ingot_h. Φ The ingots were analyzed as described in Example 1 and the results after 6 months of storage are shown in Table 6. (16) 200418525 Table 6 2 5t, 6% 0 Μ 3 0 0% RH " SD2) 4 0 ° C,% OM 3 8 40% RH SD2) Uncoated tablet 4.84 0.08 17.10 0.60 Film-coated tablet I 3.57 0.02 10.69 0.14 Film-coated tablets 11 3.5 1 0.06 5.77 0.05

RH is the relative temperature of the environment and SD is the standard deviation of the average radon obtained from three measurements of 10 ingots per pool. The results in Table 6 show that coating of the Tibelon ingots according to the present invention can lead to a reduction in the formation of the isomerization degradation product OM 3 8 and thus to the stabilized Tibelon ingots.

Example 5 Tiberium tablets without coating

Using the procedure described in Example 1, 65 mg ingots having a diameter of 5 mm and having the following composition were prepared: 0.644 mg of Tiberone, 63.9 mg of plasmid, 0.13 mg of ascorbyl palmitate, and 0.3 2 5 mg of hard Magnesium stearate. Adding film coating I To the tablets prepared as described above, 5.2 mg of each film coating having the following composition was added: 3.07 mg of £ 13 (^ 8 "© £ ?, 0.31 mg of sodium lauryl sulfate-19- (17) 200418525, 0.78 mg of stearic acid 'and .04 mg of magnesium stearate. Using a standard film coating equipment (GUU⑧GC 300 0) at a plate speed of about 15 rpm, about 45. (: At the inlet temperature and at an air flow rate of about 100 cubic meters / hour, a coating vehicle aqueous dispersion (solid content: 6 w / w%) was sprayed onto the tablets. Film coating was performed on the tablets prepared as described above. Add 5.2 mg of film coating per tablet, using a film coating dispersion (based on λν / λν% of total dispersion) with the following composition: 1 1 · 1% Eudragit ® L 1 〇〇, 5 · 6 % Triethyl citrate, 3.7% 1 NN Η 3, 74% purified water, and 5.6% talc. Using a standard film coating equipment (Glatt ® GC3 00) at a plate speed of about 20rpm, about This aqueous dispersion was sprayed onto the urn with an inlet temperature of 45 ° C and an air flow rate of about 80 m3 / h. Film coating IΠ

5.2 mg of film coating per tablet was added to the tablets prepared as described above, wherein a film coating water dispersion (based on w / w% of the total dispersion) having the following composition was used: 3 9 · 2% E udragit ® RL 3 0 D, 2.4% triethyl citrate, 5 2.5% purified water, and 5.9% talc. Use a standard film coating equipment (G1 at t ® GC 3 0 0) to spray the aqueous dispersion at a plate speed of about 15 rpm, an inlet temperature of about 45 ° C ', and an air flow rate of about 80 cubic meters per hour. On sharp

Add film coating IV-20- (18) 200418525 Add 5 · 2 mg of film coating to each tablet prepared as described above, using a film coating water dispersion (the total dispersion w / w%): 4 1 · 7% E ud 1 · agit ⑧ NE 3 0 D, 4 5 · 8% purified water, and i 2.5 ° / 〇 talc. This aqueous dispersion was spray-coated using a standard film coating equipment (Glatt ® GC 300) at a plate speed of about 20 rpm, an inlet temperature of about 45 ° C ', and an air flow rate of about 80 m3 / hour. On the ingot.

The ingots were analyzed as described in Example 1 and the results after two months of storage are shown in Table 7. Table 7 2 50 ° C, t% OM 3 8; 0% R Η 1) sd2) 4 0 ° C,% OM 3 8 4 0% RH SD2) Uncoated tablets 1.72 0.0 1 4.27 0.02 with film coating Ingot I 2.65 0.03 6.7 1 0.0 7 Film-coated tablet II 3.05 0.06 8.89 0.33 Film-coated tablet III 1.27 0.0 1 4.06 0.05 Film-coated tablet IV 1.70 0.02 4.86 0.02 RH is the relative humidity of the environment SD is 10 pairs of tablets per pool The standard deviation of the average tritium obtained from three measurements of the polypyridine ingot. The results in Table 7 show that not all coatings of Tiberium lead to a decrease in the formation of the isomerization degradation product OM 3 8, especially when using Eudragit® EPU or Eudragit® L100, compared to uncoated tablets The results are worse. -twenty one -

Claims (1)

(1) 200418525, scope of patent application] · A stabilized medicinal tablet Boron with a coating. It includes from 0.1 to 10% by weight 2. The key of item i of the patent scope 'wherein the coating is a film coating, a sugar coating, a sugar film coating, or a' wrap coating '. 3. If a patent is applied for the second item, the coating is a sugar coating or a sugar film coating. 4. The tablet according to item [2] or [2], wherein the film coating contains cellulose ether, vinyl polymer or gelatin. 5. The tablet according to item 3 of the patent application, wherein the sugar comprises sucrose. 6. The tablet according to item 1 or 2 of the scope of patent application, wherein the coating contains a plasticizer selected from the group consisting of glycerin, diethylene glycol, and polyethylene glycol. 7. A method for stabilizing a tablet comprising 0.1 to 10% by weight of Tibolon, wherein a coating is used. 8. The method according to item 7 of the application for a patent, wherein the coating is a film coating, a sugar coating, a sugar film coating, or a wrapper coating. 9. The method according to item 8 of the patent application, wherein the coating is a sugar coating or a sugar film coating. 1 0 · If the method of claim 9 of the scope of the patent application, wherein the sugar includes sucrose 0 -22- 200418525 柒, (a), the representative representative of this case is: the first (two), the representative symbol of the element Note: Μ j \ \\ 捌, if there is a chemical formula in this case, please disclose the chemical formula that best shows the characteristics of the invention =