KR20110032608A - Pharmaceutical composition comprising lacidipine tablet preparation - Google Patents

Abstract

PURPOSE: A pharmaceutical composition for lacidipine tablet is provided to formulate lacidipine into a tablet and to enhance elusion rate of lacidipine. CONSTITUTION: A pharmaceutical composition for lacidipine tablet contains co-precipitate compound of 1 weight part of lacidipine and 8.75-11.25 weight parts of polyvinyl pyrrolidone. A method for manufacturing the lacidicpine tablet comprises: a step of dissolving lacidipine and polyvinyl pyrrolidone in a solvent; a step of uniformly adding the solution into an excipient to form the co-precipitate compound and granulating; and a step of drying and tableting. The solvent is acetone, ehtnaol, methanol, chloroform, dichlomethane, or ether.

Description

Pharmaceutical composition of a tablet containing lacidipine {PHARMACEUTICAL COMPOSITION COMPRISING LACIDIPINE TABLET PREPARATION}

The present invention relates to a lacidipine tablet containing a lacidipine as an active ingredient, and more particularly to a lacidipine tablet prepared by using a coprecipitation compound of lacidipine and polyvinylpyrrolidine and a method for preparing the lasidipine. It is about.

Lacidipine, a calcium channel antagonist, is an antihypertensive drug that is widely used in hypertensive patients because of its low resistance, ease of administration once a day, and its effectiveness in atherosclerosis. However, since lacidipine is a poorly water-soluble drug, granules can be formed by using a disintegration aid commonly used to increase dissolution rate, by reducing the particles of lacidipine, or by adding polyvinylpyrrolidone as a binder to lacidipine. Formulation into tablets has limitations and product development has been difficult due to problems of poor absorption when applied to humans.

In addition, although there are prior arts to increase the solubility of water in water by increasing the solubility of a number of drugs, there are no prior arts to improve the poor water solubility of lacidipine.

An object of the present invention is to increase the dissolution rate by producing a water-soluble rashidipine effectively tablets.

In order to solve the above object, the present invention provides a pharmaceutical composition for the production of lacidipine tablets and a method for preparing the same comprising a compound in which the lacidipine co-precipitated to polyvinylpyrrolidone in the granulation step of formulating the lacidipine .

First, the present invention provides a pharmaceutical composition for lacidipine tablets comprising a coprecipitation compound of lacidipine and polyvinylpyrrolidone.

In the composition, polyvinylpyrrolidone is preferably used in an amount of 8.75 parts by weight to 11.25 parts by weight per 1 part by weight of lacidipine.

In another aspect, the present invention provides a lacidipine tablet prepared using the pharmaceutical composition.

In the present invention,

Dissolving lacidipine and polyvinylpyrrolidone in a solvent;

Homogeneously adding the lacidipine and polyvinylpyrrolidone solution to the excipient to form granulated co-precipitating compound together with lacidipine and polyvinylpyrrolidone;

Drying and sizing the granulated granules; And

It provides a method for producing lacidipine tablets comprising the step of tableting the granules to produce a tablet.

In the above production method, polyvinylpyrrolidone is preferably used in an amount of 8.75 to 11.25 parts by weight per 1 part by weight of lacidipine.

When polyvinylpyrrolidone is used in such an amount, the coprecipitation compound with lacidipine may well elute. When polyvinylpyrrolidone is used at less than 8.75 parts by weight per 1 part by weight of lacidipine, the coprecipitation compound is insufficient in dissolution rate in an aqueous solution such as water, and when used in an amount exceeding 11.25 parts by weight, There is no big problem, but the amount of solvent is increased, so it is inconvenient to apply in actual manufacturing sites.

In the above production method, the amount of the solvent used is preferably used in an amount of about 1 to 15 parts by weight per 1 part by weight of lacidipine, and the amount of the excipient is about 1 part by weight of the combined amount of lacidipine and polyvinylpyrrolidone. It is preferred to be used in an amount of 4 to 10 parts by weight, but is not limited to these ranges.

On the other hand, it may further comprise the step of mixing the granules established before the tableting after the formulation with the lubricant.

In the production method, the solvent may be acetone, ethanol, methanol, chloroform, dichloromethane or ether, etc., but is not limited to these, acetone or ethanol is preferred.

 The excipients may include, but are not limited to, lactose, sucrose, starch, calcium carbonate or gelatin, and lactose is preferred.

In addition, the present invention provides a lacidipine tablet produced by the above method.

In the present invention, in the granulation process for formulating lacidipine, by co-precipitating lacidipine in polyvinylpyrrolidone to increase the dissolution rate, it is possible to successfully prepare a tablet containing the active ingredient, recidipine, a poorly water-soluble drug.

The present invention includes preparing a tablet containing lacidipine by coprecipitation of lacidipine into polyvinylpyrrolidone, wherein the polyvinylpyrrolidone, which is a carrier of the lacidipine and the coprecipitation compound, is organic. After dissolving in a solvent, it is added to an excipient such as lactose, and then granulated, dried, and granulated to prepare tablet granules and tablets to prepare tablets.

The tablets prepared in the present invention had the same elution pattern as that of the reference drug Drax (Vaxar, GlaxoSmithKline) at pH 1.2, 4.0, 6.8 and water. It is a competitive product to replace Dr. Chung.

In addition, as a result of evaluating stability for 3 months at 40 ° C. acceleration condition, the lacidipine tablet prepared in the present invention was found to be stable enough for 2 years at room temperature during product development because there was no change in properties and no change in content.

Hereinafter, the present invention will be described in detail by the following Preparation Examples and Examples. The following Preparation Examples and Examples are merely illustrative of the present invention, but the scope of the present invention is not limited thereto.

Preparation Example 1 Preparation of Lacidipine Tablets (1)

Tablets are prepared from the following compositions.

Raw material name Weight (300mg)  Lacidipine     4.0mg  Lactose   255.0 mg  Polyvinylpyrrolidone    40.0mg  Magnesium stearate     1.0mg  Acetone     0.027ml  ethanol     0.020ml   300.0mg

Polyvinylpyrrolidone K-30 used as a coprecipitation dispersion carrier was swelled and dissolved in 0.027 ml of acetone and 0.020 ml of volatile organic solvent, followed by the addition of lassipine.

255.0 mg of lactose was added to a speed mixer, acetone and ethanol solution in which lacidipine and polyvinylpyrrolidone were dissolved by the weight of the table were added thereto, mixed homogeneously for 3 minutes, and dried at 45-55 ° C. for 3 hours. To remove the organic solvent.

The dried product was pulverized with a power mill, magnesium stearate was added, passed through an 80 mesh sieve, mixed for 15 minutes with a drum mixer, and compressed into 300 mg by weight.

Preparation Example 2 Preparation of Lacidipine Tablets (2)

Raw material name Weight (300mg)  Lacidipine    4.0mg  Lactose  260.0mg  Polyvinylpyrrolidone   35.0mg  Magnesium stearate    1.0mg  Acetone      0.023ml  ethanol      0.018ml  300.0mg

Lacidipine tablets were prepared in the same manner as in Preparation Example 1, except that the amount of the starting material was as shown in the above table.

After dissolving polyvinylpyrrolidone and lacidipine in the acetone and ethanol of the above capacity, it was added to lactose, granulated, dried and sintered. Magnesium stearate was added to the final mixture.

Preparation Example 3 Preparation of Lacidipine Tablets (2006.01)

Raw material name Weight (300mg)  Lacidipine     4.0mg  Lactose   250.0mg  Polyvinylpyrrolidone    45.0mg  Magnesium stearate     1.0mg  Acetone      0.030ml  ethanol      0.023ml   300.0mg

Lacidipine tablets were prepared in the same manner as in Preparation Example 1, except that the amount of the starting material was as shown in the above table.

After dissolving polyvinylpyrrolidone and lacidipine in the acetone and ethanol of the above capacity, it was added to lactose, granulated, dried and sintered. Magnesium stearate was added to the final mixture.

Example 1 Dissolution Experiment

Twelve tablets of each of the Lasidipine test drug and the control drug Dr. er tablet prepared in Preparation Example 1 were eluted at pH 1.2, 4.0, 6.8 and 4 conditions of water. The results are shown in Table 1 (pH 1.2) and Table 2 (pH). 4.0), Table 3 (pH 6.8) and Table 4 (water). The experimental method in each condition is as follows.

1. Experimental conditions at pH 1.2

- Device ; Using paddle method of KEPCO (50 rpm)

-Test liquid temperature; 37 ± 0.5 ℃

-Test solution; Dissolve 7.0 ml of hydrochloric acid and water in 2.0 g of sodium chloride, and use it as a test solution.

-Method of analysis; UV at 284 nm [see British Pharmacopoeia Dissolution Section]

2. Experimental conditions at pH 4.0

Except for the test solution used, it is the same as the experimental condition of pH 1.2.

-Test solution; A 0.05 mol / L acetic acid solution and a 0.05 mol / L sodium acetate mixture (41: 9) were prepared and adjusted to pH 4.0 and used as a test solution.

3. Experimental conditions at pH 6.8

Same as pH 1.2 except for the test solution used.

-Test solution; 250 ml of 0.2 mol / L potassium dihydrogen phosphate solution was added to 118 ml of 0.2 mol / L sodium hydroxide solution and 1,000 ml of water to prepare a test solution.

4. Experimental conditions in water

Same as at pH 1.2, except that purified water was used as the test solution.

-Test solution; Purified water

5 minutes 10 minutes 15 minutes 30 minutes tween 20 u Absorbance
(284 nm) Dissolution rate Absorbance
(284 nm) Dissolution rate Absorbance
(284 nm) Dissolution rate Absorbance
(284 nm) Dissolution rate Test drug-1 0.0305 17.6 0.0922 51.8 0.1398 78.1 0.1799 99.9 Test drug-2 0.0300 17.3 0.0892 50.1 0.1333 74.5 0.1753 97.4 Test drug-3 0.0320 18.5 0.0920 51.7 0.1450 81.0 0.1789 99.4 Test drug-4 0.0291 16.8 0.0878 49.3 0.1362 76.1 0.1790 99.4 Test drug-5 0.0255 14.7 0.0800 44.9 0.1274 71.2 0.1724 95.8 Test about-6 0.0272 15.7 0.0794 44.6 0.1277 71.3 0.1733 96.3 Test drug-7 0.0216 12.5 0.0704 39.6 0.1157 64.6 0.1687 93.7 Test drug-8 0.0330 19.1 0.0904 50.8 0.1291 72.1 0.1733 96.3 Test Drug-9 0.0247 14.3 0.0634 35.6 0.1095 61.2 0.1681 93.4 Test about-10 0.0331 19.1 0.0851 47.8 0.1299 72.6 0.1719 95.5 Test Drug-11 0.0358 20.7 0.0970 54.5 0.1459 81.5 0.1741 96.7 Test Drug-12 0.0258 14.9 0.0768 43.1 0.1225 68.4 0.1764 98.0 at least 0.0216 12.5 0.0634 35.6 0.1095 61.2 0.1681 93.4 Average 0.0290 16.8 0.0836 47.0 0.1302 72.7 0.1743 96.8 maximum 0.0358 20.7 0.0970 54.5 0.1459 81.5 0.1799 99.9 Standard Deviation 0.0042 2.4 0.0099 5.6 0.0109 6.1 0.0038 2.1 5 minutes 10 minutes 15 minutes 30 minutes tween 20 u Absorbance
(284 nm) Dissolution rate Absorbance
(284 nm) Dissolution rate Absorbance
(284 nm) Dissolution rate Absorbance
(284 nm) Dissolution rate Reference Drug-1 0.0223 12.9 0.0791 44.4 0.1265 70.7 0.1785 99.2 Reference Drug-2 0.0327 18.9 0.0874 49.1 0.1308 73.1 0.1729 96.1 Reference Drug-3 0.0407 23.5 0.1012 56.9 0.1420 79.3 0.1774 98.6 Reference Drug-4 0.0388 22.4 0.0926 52.0 0.1383 77.3 0.1755 97.5 Antipsychotic-5 0.0458 26.5 0.0979 55.0 0.1479 82.6 0.1806 100.3 Antipsychotic-6 0.0355 20.5 0.0887 49.8 0.1274 71.2 0.1744 96.9 Counter Medicine-7 0.0345 19.9 0.0880 49.4 0.1358 75.9 0.1762 97.9 Counter Medicine-8 0.0376 21.7 0.0962 54.0 0.1476 82.5 0.1781 98.9 Reference Drug-9 0.0352 20.3 0.0843 47.4 0.1306 73.0 0.1768 98.2 Control drug-10 0.0291 16.8 0.0707 39.7 0.1135 63.4 0.1713 95.2 Reference Drug-11 0.0317 18.3 0.0872 49.0 0.1364 76.2 0.1727 95.9 Control Drug-12 0.0449 26.0 0.1064 59.8 0.1430 79.9 0.1800 100.0 at least 0.0223 12.9 0.0707 39.7 0.1135 63.4 0.1713 95.2 Average 0.0357 20.7 0.0900 50.5 0.1350 75.4 0.1762 97.9 maximum 0.0458 26.5 0.1064 59.8 0.1479 82.6 0.1806 100.3 Standard Deviation 0.0066 3.8 0.0098 5.5 0.0099 5.5 0.0029 1.6

5 minutes 10 minutes 15 minutes 30 minutes tween 20 u Absorbance
(284 nm) Dissolution rate Absorbance
(284 nm) Dissolution rate Absorbance
(284 nm) Dissolution rate Absorbance
(284 nm) Dissolution rate Test drug-1 0.0197 11.6 0.0670 37.7 0.1038 57.8 0.1605 88.7 Test drug-2 0.0171 10.0 0.0562 31.6 0.0950 52.9 0.1547 85.5 Test drug-3 0.0248 14.5 0.0699 39.3 0.1169 65.1 0.1614 89.2 Test drug-4 0.0205 12.0 0.0702 39.5 0.1062 59.1 0.1563 86.4 Test drug-5 0.0134 7.9 0.0529 29.8 0.0886 49.3 0.1548 85.5 Test about-6 0.0233 13.7 0.0644 36.2 0.1028 57.2 0.1611 89.0 Test drug-7 0.0216 12.7 0.0687 38.6 0.1058 58.9 0.1619 89.4 Test drug-8 0.0284 16.7 0.0781 43.9 0.1230 68.5 0.1727 95.4 Test Drug-9 0.0309 18.1 0.0708 39.8 0.1079 60.1 0.1659 91.7 Test about-10 0.0234 13.7 0.0693 39.0 0.1042 58.0 0.1599 88.3 Test Drug-11 0.0118 6.9 0.0572 32.2 0.0964 53.7 0.1586 87.6 Test Drug-12 0.0265 15.5 0.0730 41.1 0.1143 63.6 0.1605 88.7 at least 0.0118 6.9 0.0529 29.8 0.0886 49.3 0.1547 85.5 Average 0.0218 12.8 0.0665 37.4 0.1054 58.7 0.1607 88.8 maximum 0.0309 18.1 0.0781 43.9 0.1230 68.5 0.1727 95.4 Standard Deviation 0.0057 3.4 0.0075 4.2 0.0096 5.3 0.0049 2.7 5 minutes 10 minutes 15 minutes 30 minutes tween 20 u Absorbance
(284 nm) Dissolution rate Absorbance
(284 nm) Dissolution rate Absorbance
(284 nm) Dissolution rate Absorbance
(284 nm) Dissolution rate Reference Drug-1 0.0052 3.0 0.0478 26.9 0.0896 49.9 0.1571 86.8 Reference Drug-2 0.0290 17.0 0.0641 36.1 0.1098 61.1 0.1598 88.3 Reference Drug-3 0.0188 11.0 0.0564 31.7 0.1011 56.3 0.1664 91.9 Reference Drug-4 0.0208 12.2 0.0692 38.9 0.1126 62.7 0.1729 95.5 Antipsychotic-5 0.0153 9.0 0.0538 30.3 0.0929 51.7 0.1670 92.3 Antipsychotic-6 0.0188 11.0 0.0626 35.2 0.1019 56.7 0.1686 93.1 Counter Medicine-7 0.0148 8.7 0.0565 31.8 0.0922 51.3 0.1568 86.6 Counter Medicine-8 0.0239 14.0 0.0713 40.1 0.1181 65.8 0.1660 91.7 Reference Drug-9 0.0186 10.9 0.0648 36.4 0.1132 63.0 0.1746 96.5 Control drug-10 0.0182 10.7 0.0616 34.6 0.0957 53.3 0.1617 89.3 Reference Drug-11 0.0152 8.9 0.0568 31.9 0.1027 57.2 0.1659 91.7 Control Drug-12 0.0194 11.4 0.0666 37.5 0.1053 58.6 0.1627 89.9 at least 0.0052 3.0 0.0478 26.9 0.0896 49.9 0.1568 86.6 Average 0.0182 10.7 0.0610 34.3 0.1029 57.3 0.1650 91.1 maximum 0.0290 17.0 0.0713 40.1 0.1181 65.8 0.1746 96.5 Standard Deviation 0.0057 3.3 0.0069 3.9 0.0092 5.1 0.0056 3.1

5 minutes 10 minutes 15 minutes 30 minutes tween 20 u Absorbance
(284 nm) Dissolution rate Absorbance
(284 nm) Dissolution rate Absorbance
(284 nm) Dissolution rate Absorbance
(284 nm) Dissolution rate Test drug-1 0.0357 18.9 0.0819 44.2 0.1198 64.8 0.1754 94.9 Test drug-2 0.0239 12.7 0.0657 35.5 0.1030 55.7 0.1581 85.5 Test drug-3 0.0270 14.3 0.0724 39.1 0.1127 61.0 0.1614 87.3 Test drug-4 0.0178 9.4 0.0592 32.0 0.0993 53.7 0.1587 85.8 Test drug-5 0.0224 11.9 0.0652 35.2 0.1085 58.7 0.1654 89.5 Test about-6 0.0400 21.2 0.0838 45.3 0.1262 68.3 0.1662 89.9 Test drug-7 0.0244 12.9 0.0672 36.3 0.1126 60.9 0.1589 85.9 Test drug-8 0.0288 15.3 0.0772 41.7 0.1201 65.0 0.1761 95.2 Test Drug-9 0.0310 16.4 0.0804 43.4 0.1268 68.6 0.1710 92.5 Test about-10 0.0291 15.4 0.0705 38.1 0.1123 60.8 0.1651 89.3 Test Drug-11 0.0412 21.8 0.0873 47.2 0.1305 70.6 0.1713 92.6 Test Drug-12 0.0302 16.0 0.0740 40.0 0.1187 64.2 0.1712 92.6 at least 0.0178 9.4 0.0592 32.0 0.0993 53.7 0.1581 85.5 Average 0.0293 15.5 0.0737 39.8 0.1159 62.7 0.1666 90.1 maximum 0.0412 21.8 0.0873 47.2 0.1305 70.6 0.1761 95.2 Standard Deviation 0.0070 3.7 0.0086 4.6 0.0096 5.2 0.0064 3.5 5 minutes 10 minutes 15 minutes 30 minutes tween 20 u Absorbance
(284 nm) Dissolution rate Absorbance
(284 nm) Dissolution rate Absorbance
(284 nm) Dissolution rate Absorbance
(284 nm) Dissolution rate Reference Drug-1 0.0366 19.4 0.0855 46.2 0.1310 70.9 0.1711 92.5 Reference Drug-2 0.0356 18.9 0.0838 45.3 0.1320 71.4 0.1791 96.9 Reference Drug-3 0.0229 12.1 0.0725 39.2 0.1122 60.7 0.1668 90.2 Reference Drug-4 0.0288 15.3 0.0763 41.2 0.1116 60.4 0.1684 91.1 Antipsychotic-5 0.0250 13.2 0.0713 38.5 0.1166 63.1 0.1699 91.9 Antipsychotic-6 0.0205 10.9 0.0623 33.7 0.0942 51.0 0.1634 88.4 Counter Medicine-7 0.0320 17.0 0.0774 41.8 0.1142 61.8 0.1726 93.3 Counter Medicine-8 0.0181 9.6 0.0636 34.4 0.0989 53.5 0.1663 89.9 Reference Drug-9 0.0275 14.6 0.0715 38.6 0.1124 60.8 0.1738 94.0 Control drug-10 0.0249 13.2 0.0670 36.2 0.1051 56.9 0.1737 93.9 Reference Drug-11 0.0220 11.7 0.0779 42.1 0.1061 57.4 0.1732 93.7 Control Drug-12 0.0329 17.4 0.0819 44.2 0.1339 72.5 0.1826 98.8 at least 0.0181 9.6 0.0623 33.7 0.0942 51.0 0.1634 88.4 Average 0.0272 14.4 0.0743 40.1 0.1140 61.7 0.1717 92.9 maximum 0.0366 19.4 0.0855 46.2 0.1339 72.5 0.1826 98.8 Standard Deviation 0.0060 3.2 0.0076 4.1 0.0128 6.9 0.0054 2.9

5 minutes 10 minutes 15 minutes 30 minutes tween 20 u Absorbance
(284 nm) Dissolution rate Absorbance
(284 nm) Dissolution rate Absorbance
(284 nm) Dissolution rate Absorbance
(284 nm) Dissolution rate Test drug-1 0.0243 12.1 0.0677 35.7 0.1049 55.9 0.1604 85.8 Test drug-2 0.0308 15.3 0.0713 37.6 0.1042 55.5 0.1619 86.6 Test drug-3 0.0271 13.5 0.0769 40.6 0.1246 66.4 0.1699 90.9 Test drug-4 0.0281 14.0 0.0724 38.2 0.1186 63.2 0.1585 84.8 Test drug-5 0.0333 16.6 0.0827 43.6 0.1213 64.7 0.1668 89.2 Test about-6 0.0188 9.4 0.0595 31.4 0.0952 50.7 0.1601 85.6 Test drug-7 0.0271 13.5 0.0716 37.8 0.1239 66.0 0.1657 88.6 Test drug-8 0.0249 12.4 0.0714 37.7 0.1069 57.0 0.1644 87.9 Test Drug-9 0.0309 15.4 0.0779 41.1 0.1206 64.3 0.1705 91.2 Test about-10 0.0318 15.8 0.0771 40.7 0.1233 65.7 0.1642 87.8 Test Drug-11 0.0170 8.5 0.0752 39.7 0.1035 55.2 0.1574 84.2 Test Drug-12 0.0351 17.5 0.0769 40.6 0.1303 69.5 0.1716 91.8 at least 0.0170 8.5 0.0595 31.4 0.0952 50.7 0.1574 84.2 Average 0.0274 13.6 0.0734 38.7 0.1148 61.2 0.1643 87.9 maximum 0.0351 17.5 0.0827 43.6 0.1303 69.5 0.1716 91.8 Standard Deviation 0.0055 2.7 0.0059 3.1 0.0111 5.9 0.0048 2.6 5 minutes 10 minutes 15 minutes 30 minutes tween 20 u Absorbance
(284 nm) Dissolution rate Absorbance
(284 nm) Dissolution rate Absorbance
(284 nm) Dissolution rate Absorbance
(284 nm) Dissolution rate Reference Drug-1 0.0308 15.2 0.0809 42.7 0.1280 68.2 0.1847 98.8 Reference Drug-2 0.0269 13.3 0.0743 39.2 0.1113 59.3 0.1742 93.2 Reference Drug-3 0.0244 12.0 0.0705 37.2 0.1147 61.1 0.1760 94.1 Reference Drug-4 0.0140 6.9 0.0566 29.9 0.0939 50.1 0.1719 91.9 Antipsychotic-5 0.0262 12.9 0.0721 38.0 0.1158 61.7 0.1767 94.5 Antipsychotic-6 0.0247 12.2 0.0670 35.4 0.1064 56.7 0.1709 91.4 Counter Medicine-7 0.0186 9.2 0.0620 32.7 0.1057 56.3 0.1692 90.5 Counter Medicine-8 0.0212 10.4 0.0681 35.9 0.1079 57.5 0.1797 96.1 Reference Drug-9 0.0227 11.2 0.0658 34.7 0.1128 60.1 0.1770 94.7 Control drug-10 0.0257 12.7 0.0706 37.3 0.1141 60.8 0.1782 95.3 Reference Drug-11 0.0333 16.4 0.0802 42.3 0.1268 67.6 0.1813 97.0 Control Drug-12 0.0216 10.6 0.0728 38.4 0.1070 57.0 0.1780 95.2 at least 0.0140 6.9 0.0566 29.9 0.0939 50.1 0.1692 90.5 Average 0.0242 11.9 0.0701 37.0 0.1120 59.7 0.1765 94.4 maximum 0.0333 16.4 0.0809 42.7 0.1280 68.2 0.1847 98.8 Standard Deviation 0.0052 2.5 0.0069 3.7 0.0093 4.9 0.0044 2.4

As shown in Table 1 to Table 4, the lacidipine test drug made of cocipitating compound in the polyvinylpyrrolidone rashidipine in the granulation process is a dissolution test in the reference drug (Ph.D.) and pH 1.2, 4.0, 6.8 and water. The results were consistent.

This shows that in the bioequivalence experiments, the Lassidipine test drug and the reference drug may be equivalent at Cmax and AUC, and as a result of experimenting with the actual bioequivalence as shown in Example 2, the Lassidipine test drug is biologically equivalent to the control drug. Result.

Example 2. Bioequivalence Experiment

The tablet prepared in Preparation Example 1 The test drug was used as a control drug by GlaxoSmithKline, Inc., and as a reference, 9 out of 46 healthy adult volunteers were dropped out according to the 2 x 2 crossover test.

The test was performed on the bioavailability parameters of blood concentration-time curve area (AUC) and peak blood concentration (Cmax) obtained from oral administration of each tablet of the test drug or control drug. The bioequivalence between the two formulations was evaluated.

Variance equations for the logarithmic values of the two comparative endpoints showed that the 90% confidence interval of the logarithmic difference between the reference and test drug for AUC was log 0.8402 to log 1.0563, and for the Cmax value, for control and test drug. Both formulations were considered to be biologically equivalent, satisfying the biological equivalence test criteria that the 90% confidence interval of the logarithmic difference of the logarithm of the difference was between log 0.8507 and log 1.0769, both items being within log 0.8 and log 1.25.

Example 3. Stability Test

In order to find out the stability of the lacidin test drug prepared in Preparation Example 1, the result of the stability test for 3 months at 40 ℃ packed in a PE sealed container, PE hermetic container and lactic acid paper is shown in Table 5 below.

Sample Name Early 1 month 3 months content Leading substance content Leading substance content Leading substance PE sealed container 102.310 1.087 95.880 1.291 101.564 1.152 PE hermetic container 103.587 1.160 103.796 1.152 Heritage 89.888 6.434 87.420 8.413

As shown in Table 5, the lacidipine test drug prepared according to the present invention was unstable in a packaging capable of convention without being shielded like lactic acid paper, but stable in a sealed or airtight container that was shielded.

Particularly, in the shading hermetic container, since there is no decrease in content, when packaged in a shading hermetic container during commercial production, the lassidipine tablet prepared by the present invention is considered to be a very stable formulation without a decrease in the content of racidipine in circulation.

Claims (9)

Lacidipine tablet pharmaceutical composition comprising a coprecipitation compound of lacidipine and polyvinylpyrrolidone. The method according to claim 1, Polyvinylpyrrolidone is a pharmaceutical composition for the use of lacidipine tablets is used in 8.75 parts by weight to 11.25 parts by weight per 1 part by weight of lacidipine. Lacidipine tablets prepared using the pharmaceutical composition of claim 1. Dissolving lacidipine and polyvinylpyrrolidone in a solvent; Homogeneously adding the lacidipine and polyvinylpyrrolidone solution to the excipient to form and assemble a coprecipitation compound together with the lacidipine and the polyvinylpyrrolidone; Drying and granulating the granulated granules; And Tableting the granules to produce a tablet comprising the step of preparing a tablet. The method according to claim 4, Polyvinylpyrrolidone is used in an amount of 8.75 to 11.25 parts by weight per 1 part by weight of lacidipine. The method according to claim 4, And further comprising the step of mixing the granulated granules with the lubricant after the formulation and before tableting. The method according to claim 4, The solvent is at least one selected from the group consisting of acetone, ethanol, methanol, chloroform, dichloromethane and ether. The method according to claim 4, The excipient is at least one selected from the group consisting of lactose, sucrose, starch, calcium carbonate and gelatin. Lacidipine tablets prepared by the process of claim 1.