Formulation having controlled, delayed release of active ingredient

Abstract

The present invention relates to novel pharmaceutical formulations which have controlled, delayed release of active ingredient, and to a process for the preparation of such formulations. The invention additionally relates to the use of these novel pharmaceutical administration forms as medicaments for the treatment of diseases which require delayed release of the active ingredient, such as hypertension, or asthmatic diseases.

Description

[0001]The present invention relates to novel pharmaceutical formulations which have controlled, delayed release of active ingredient, and to a process for the preparation of such formulations. The invention additionally relates to the use of these novel pharmaceutical administration forms as medicaments for the treatment of diseases which require delayed release of the active ingredient, such as hypertension, or asthmatic diseases.PRIOR ART[0002]Propranolol belongs to the active ingredient group of beta blockers having antihypertensive, anti-anginal and anti-arrhythmic properties. Although this active ingredient was introduced into therapy as the first β-receptor blocker as long ago as 1964, and in the meantime a multiplicity of different derivatives in diverse medicament forms are known, especially in order to avoid undesired effects and in order to achieve certain differences in action, propranolol continues to be a frequently administered beta blocker.[0003]The substance exhibits...

AI Technical Summary

Benefits of technology

[0012]Owing to the disadvantageous kinetic properties of propranolol, multiple doses per day are usually necessary, which frequently leads to inadequate patient compliance and consequently an unsatisfactory therapeutic result. The aim is thus to reduce the frequency with which the medication is taken to a single dose per day.

[0013]Thus, the administration form should ensure pharmacologically effective plasma concentrations of the active ingredient propranolol over an extended period, preferably for at least 12 hours, but in particular for 24 hours (controlled release), enabling the taking scheme to be simplified.

[0014]At the same time, it is an object of the present invention to provide a formulation having improved pharmacokinetic behaviour compared with comparative formulations, by means of which side effects, such as rapid dose dumping of active ingredient and a consequent considerable drop in blood pressure, can be reduced as far as possible. Furthermore, it is an object of the present invention to achieve improved patient compliance through the modified release of active ingredient.

Problems solved by technology

The substance exhibits good solubility and is absorbed virtually completely after oral administration, but, owing to a pronounced “first-pass” metabolism, has only limited bioavailability of about 25-30%.

In addition, the elimination half-life of 2-6 hours is quite short.

At the same time as the short elimination half-life of propranolol, the desired action cannot easily be guaranteed for 12 hours or more.

However, the necessity for multiple doses distributed over the day easily leads to errors in taking, and to undesired variations in the plasma concentration, which is detrimental to compliance and the therapeutic benefit.

However, side effects, which may be connected to the specific change in the plasma concentration over the day, have been found in connection with this formulation and the administration form [Warnke, A.; Blume, H.

Owing to the disadvantageous kinetic properties of propranolol, multiple doses per day are usually necessary, which frequently leads to inadequate patient compliance and consequently an unsatisfactory therapeutic result.

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