CS251847B1 - Coated tablets containing 2.5 mg or 5.0 mg of glycerol trinitrate and its controlled release - Google Patents

Abstract

Film-coated tablets containing 2.5 mg or 5.0 mg of glycerol trinitrate containing a base compact with the active ingredient, coated with a film of a mixture of hydroxypropylmethylcellulose and ethylcellulose in a mutual weight ratio of 27 to 33:35 in an amount of 1.7 to 2.3 based on the weight of the base compact.

Description

The invention relates to the composition of controlled release tablets of 2.5 mg or 5.0 mg glycerol trinitrate.

Glycerol trinitrate (hereinafter nitroglycerin) still maintains a leading position among vasodilators for the treatment and prevention of angina attacks. The development of a controlled-release nitnoglycerin product aims to eliminate the benefits of short-acting nitroglycerin when administered orally due to its rapid absorption, but also the very rapid elimination and degradation.

Adverse reactions after ingestion of a controlled-release dosage form are the same as those in the conventional formulation, but the frequency is lower and less than the intensity described with conventional formulations. In the case of controlled controlled release of nitroglycerin, the preparation can also be used for prophylaxis by prolonged administration.

This can be achieved in several ways, in particular by administering solid-release controlled-release dosage forms, e.g., so-called scaffold tablets or micropellets in hard gelatin capsules. Because it is a preparation produced in large quantities, it is desirable that the technology be as simple and inexpensive as possible and that the preparation produced reliably releases a sufficient amount of the active ingredient at regular intervals for at least 8 hours.

Systematic research has succeeded in designing a suitable composition and developing a simple technology providing nitroglycerin tablets of corresponding properties.

The invention therefore relates to a composition of nitroglycerin film-coated tablets containing 2.5 mg and 5.0 mg of active ingredient and its controlled release, characterized in that the basic active ingredient compact is coated with a layer of hydroxypropyl methylcellulose containing not less than 19% and not more than 30%. % of methoxy groups and not less than 3% and not more than 12% of hydroxypropoxyakupin and ethylcellulose containing not less than 44% and not more than 51% of ethoxy groups, calculated on the dried basis, at a mass ratio of 27 to 33: 35 in an amount of 1,7 up to 2.3% by weight based on the caliper of the basic compact.

Surprisingly, following possible technological variations of the described process, it was surprisingly found that greater deviations from these values result in a substantial deterioration in the linear course of the active substance release and a substantial increase in the non-released residue of the active substance,

Monitoring in vitro the amount of total active substance released gave values of the released amount: 1 h 15%, 2 h 26%, 4 h 55%, 8 h 86%, which gives prerequisites for very good in vivo release. The invention is illustrated by the following non-limiting examples.

Example 1

250 g of lactose with 10% nitroglycerin content (25 g) is mixed with 32.4% polyvinylpyrrolidone, 13.5 g of powdered methacrylate polymer and 2350 g of pure lactose in a high shear granulator. After complete homogenization, 1,300 ml of a mixture of ethanol (450 parts by weight) and methylene chloride (200 parts by weight) are added successively, and the resulting mixture is granulated and dried at a temperature not exceeding 45 ° C.

The dry granulate is homogenized with 54 g of calcium stearate and tableted to cores weighing 270 mg. The kernels are then circulated on a suitable fluidized bed device by spraying a solution containing 24.9 g of hydroxypropyl methyl cellulose and 29.1 g of ethyl cellulose in 1000 ml of ethanol and 1000 ml of dichloromethane at 40 ° C.

Example 2

500 g of lactose and 10% nitroglycerin (50 g) were mixed with 45.9 g of polyvinylpyrrolidone and 2100 g of pure lactose. After complete homogenization, 1300 ml of a 4.5: 2 mixture of ethanol in methylene chloride was added and the resulting mixture was granulated and dried. 54 g of calcium stearate are added to the sieved granulate and tableted to cores weighing 270 mg.

The cores were then circulated on a suitable fluidized bed apparatus by spraying a solution containing 24.9 g of hydroxypropylmethylcellulose and 29.1 g of ethylcellulose in 1000 ml of ethanol and 1000 ml of dichloromethane at 40 ° C.

Claims (1)

SUBJECT OF THE INVENTION Film-coated tablets containing 2,5 mg or 5,0 µg of glycerol trinitrate and its controlled release, characterized in that the base molding of the active ingredient is coated with a layer of hydroxypropyl methylcellulose containing not less than 19% and not more than 30% of methoxy groups and not less than 3 % and not more than 12% of hydrohypropoxy and ethylcellulose, containing by weight not less than 44% and not more than 51% of ethoxy, calculated on the dried basis, in a ratio by mass of 27 to 33: 35 to 1.7 to 2.3% by weight to the weight of the basic molding.