BG937U1 - Tablet medicinal form of diltiazem - Google Patents

Abstract

The tablet form of the medicinal substance diltiazem hydrochloride is used in the treatment of hypertonia of different origin, stenocardia, ischemic heart disease, for normalizing the heart rhythm, etc. It helps to ensure modified liberation of diltiazem hydrochloride that is in line with the modern pharmacopoeia requirements, as well as good stability. The medicinal form comprises diltiazem hydrochloride 30 to 60 mg in one tablet, and auxiliary agents: lactose monohydrate, microcrystalline cellulose, glyceryl behenat, hydroxypropylmethylcellulose, magnesium stearate, and colloidal silicium dioxide.

Description

Technical field

The useful model relates to a tablet form of the drug diltiazem hydrochloride, which is a benzodiazepine derivative and belongs to the group of so-called. calcium antagonists. It is used to treat hypertension of different origin, angina, ischemic heart disease, to normalize heart rhythm and others.

BACKGROUND OF THE INVENTION

There are known solid dosage forms of diltiazem hydrochloride with different active ingredient content - 30 and 60 mg tablets and retard forms 90, 120, 180 mg in one tablet or capsule.

From the group of tablet forms containing diltiazem hydrochloride 30 and 60 µg in one tablet are known:

- dosage form of diltiazem hydrochloride - tablet containing as excipients lactose monohydrate, methylhydroxypropyl cellulose, colloidal silica, povidone, magnesium stearate (leaflet Balkanpharma Dupnitsa);

- Diltiazem hydrochloride dosage form - 60 mg tablet containing as excipients carboxymethylcellulose-sodium, lactose monohydrate, magnesium stearate, hydrogenated castor oil, stearin palmitic acid. (Pharmaceutical Catalog of Medicinal Products Authorized in Bulgaria, 1998 p. 542);

- Diltiazem hydrochloride dosage form - 60mg tablet containing lactose monohydrate, hydroxypropyl methylcellulose, magnesium stearate, microcrystalline cellulose as excipients;

- Diltiazem hydrochloride dosage form - 60 mg tablet containing as adjuvants lactose, wheat starch, microcrystalline cellulose, talc, magnesium stearate, polyvidone 25 (Pharmaceutical Catalog of Medicinal Products authorized in Bulgaria,

1998, p. 541). This tablet composition does not provide a degree of dissolution of the drug substance in a dosage form that meets the requirements of the current US Pharmacopoeia 27 (ϋ $ Ρ 27), namely:

- stirrer speed - 75 g

- at 30 mm, not more than 60%

- at 180 mm, not less than 75%.

Changes in the rate for the “dissolution rate of the drug substance in the dosage form” set out in the US Pharmacopoeia were made in υδΡ 24 - 2000 and have not been changed.

The technical nature of the utility model

Modified release of diltiazem hydrochloride that meets current pharmacopoeial requirements is difficult to achieve due to the easy solubility of diltiazem hydrochloride in water. This technical problem is solved according to the utility model using excipients: magnesium stearate, anhydrous colloidal silica and lactose monohydrate and microcrystalline cellulose in a weight ratio of 1.5: 1 to 1: 1, glyceryl behenate in an amount of 3.0 to 4.0 wt. % by weight of tablet, and hydroxypropyl methylcellulose in an amount of 30 to 50 wt. % by weight of the drug substance, with an active substance content of 30 to 60 mg.

The composition according to the utility model provides a release of diltiazem hydrochloride of 30 mt, not more than 60% and 180 mt, not less than 75%. The dosage form is with good stability - 3 years.

Brief explanation of the attached figure

Figure 1 is a graphical representation of the comparative dissolution profiles of diltiazem hydrochloride, Table 1. 60 t§, part. No. 010701 and Shget® - “Ragke - Οανϊδ OOOOOKE AO” Table. 60 t§.

Exemplary embodiments of the utility model

The composition of the dosage form is illustrated without limitation by the following examples, where the amounts of the substances are given in (m).

937 υι

Example 1 2 3 4 Diltiazem hydrochloride 60.0 60.0 60.0 60.0 Lactose monohydrate 98.5 121,0 116.0 111,0 Microcrystalline cellulose 98.5 81,0 88,0 90,0 Hydroxypropyl methylcellulose 30.0 23,0 20,0 25,0 Glyceryl behenate 9.0 11,0 12,0 10,0 Magnesium stearate 3.0 3.0 3.0 3.0 Colloidal silica anhydrous 1.0 1.0 1.0 1.0

an example 5 6 7 Diltiazem hydrochloride 45.0 45.0 45.0 Lactose monohydrate 74,0 84,0 90.75 Microcrystalline cellulose 73,8 67.5 60.75 Hydroxypropyl methylcellulose 22,4 18,0 17,25 Glyceryl behenate 6,8 7.5 8.25 Magnesium stearate 2.2 2.25 2.25 Colloidal silica anhydrous 0.75 0.75 0.75

an example 8 9 10 Diltiazem hydrochloride 30.0 30.0 30.0 Lactose monohydrate 49,3 60.5 58,0 Microcrystalline cellulose 49,2 40.5 44,0 Hydroxypropyl methylcellulose 15.0 11.5 10,0 Glyceryl behenate 4.5 5.5 6.0 Magnesium stearate 1.5 1.5 1.5 Colloidal silica anhydrous 0.5 0.5 0.5

937 υι

A parallel study was performed to determine the release rate of the active substance diltiazem hydrochloride, calculated as% of the declared content. Tested according to Table 1 and Table 2 diltiazem 5 hydrochloride Table. 60 t§, lot No 010701 and ONGet® - “Ragke - OaU18 OOOOOK AO”, Table. 60 t§ and their comparative profiles according to FIG. 1 with a similarity factor of 66.62%.

Table 1

Diltiazem hydrochloride, table 60 t§, part no 010701

The tank 15 ηώι% 30 wt% 60 vol% 90 vols% 120 vols% 150tt % 180 vols% 1 16,82 29.68 51.78 69.09 80.37 88.09 92.05 2 16.01 28.19 49.84 67.63 80.85 89.58 91,60 3 17.24 29.35 51.07 65.30 81,82 90.39 93.30 4 17,38 31,65 51.03 69.07 82.31 93.38 98.95 5 17.02 28,20 47.55 66.40 79.76 86.93 88.78 6 17.11 28,85 51.03 68.65 79.73 86.90 91,86 7 17,44 30.15 50.68 69,10 83.34 91,26 89.68 8 17,87 29.77 47.68 71.18 78.89 90.14 91.70 9 17,27 29.84 51.24 68.24 82.21 87,99 93.35 10 16,84 31,26 50.13 71.15 81,15 88.84 94.15 11 18,25 27.78 50.44 70.44 80.40 89.15 92.22 12 18,78 28,83 48.26 67.78 81,35 91.37 92.45 Average 17,34 29.46 50.06 68.67 81.02 89,50 92.51 Κ8ϋ% 4:14 4.04 2.89 2.59 1.57 2.16 2.72

Table 2

IIGet® - “Ragke OaU15 OOOOOK AO”, Table. 60 pc

Tank 15 vols% 30 Vol% 60 vol% 90 vols% 120 vols% 150 vols% 180 vols% 1 21,88 34.58 51.31 65.37 74,60 86.17 91.37 2 23,37 38.66 46.90 61.12 73.44 83.05 93,40 3 24.11 38.01 46,96 68.90 70,22 82.21 96.58 4 24,82 33.63 50.43 64.90 76,27 88.56 91.74 5 22,12 35.41 53.89 68.97 77.81 86.55 91.01 6 22,25 40.92 49.73 62.70 74.12 83,74 92.41 7 22,22 35.57 46.90 68.91 75.71 86.37 91.31 8 22,85 37.01 46.40 68.73 76.18 82.48 93.45 9 23,54 34.63 47.78 64.78 76,25 86.41 95.58 10 25.15 36.61 49.81 64.40 75.36 88.75 92.28 11 21,72 38.92 51.10 66.37 77.15 88.23 94.37 12 21,44 39.41 51.11 67.74 74.27 85.45 90.70 Average 22,96 36.95 49.36 66.07 75,12 85.66 92.85 % 5.39 6.12 4.77 3.99 2.67 2.71 2.02

Claims (1)

Claims A tablet formulation of diltiazem hydrochloride comprising excipients: magnesium stearate, anhydrous colloidal silica, lactose monohydrate, microcrystalline cellulose, characterized in that it contains lactose monohydrate and microcrystalline cellulose in a weight ratio of 1.5: 1 1: 1, as well as glyceryl behenate in an amount of from 3.0 to 4.0 wt. % by weight of tablet, and hydroxypropyl methylcellulose in an amount of 30 to 50 wt. % by weight of drug substance, with diltiazem hydrochloride content of 30 to 60 mg per tablet. Attachment: 1 figure FIG. 1. I 100 h {80; 70 ί 60 50. 40 30 20 10 - -, - 1 -, -, -—— τ ' 30 60 90 120 150 180 ₀ 4—