Controlled release pharmaceutical compositions based on one or more pharmaceutically acceptable salts of gamma hydroxy-butyric acid

A process for the preparation of controlled release pharmaceutical compositions, administrable by oral route, containing as active principle at least one salt of gamma-hydroxy-butyric acid with a pharmaceutically acceptable cation, consisting of:

• (a) a nucleus in the form of granules or tablets comprising said active principle dispersed in from 2.5 to 75% by weight based on the active principle weight of a cellulosic matrix consisting of a mixture of ethylcellulose and hydroxy-propyl-methyl-cellulose having a viscosity of 100,000 cps, and wherein the weight ratio between ethylcellulose and hydroxy-propyl-methyl-cellulose is comprised between 5 and 50%,
• (b) from 2.5 to 20% by weight based on the total nucleus weight of a filming coating consisting of a mixture of two water insoluble acrylic and methacrylic acid ester copolymers in a weight ratio comprised between 0.5:10 and 10:0.5, these copolymers containing the following repeating units:
• ##STR3## wherein R.sub.1 is H or methyl, R.sub..sub.2 is methyl or ethyl, R.sub.3 is methyl, R.sub.4 is --CH.sub.2 CH.sub.2.sup.(+) N(CH.sub.3).sub.3.sup.(-) Cl,
• the first copolymer containing 5% by weight of the second repeating unit, and the second copolymer containing 10% by weight of the second repeating unit said process comprising the following steps:
• (i) the active principle is dry mixed with hydroxy-propyl-methyl-cellulose and optionally with a portion of ethylcellulose and the remaining part of ethylcellulose is added in the form of a solution, suspension or dispersion in an alcoholic solvent, the mixture is granulated under wet condition, then the obtained granulate is dried thus obtaining the controlled release pharmaceutical composition, in the form of granules wherein the nucleus (a) contains the active principle dispersed in the cellulosic matrix;
• (ii) the granulate from step (i), optionally added with excipients selected from antisticking agents, lubricating agents and moisture protecting agents or their mixture, is subjected to compression in order to obtain the corresponding tablets;
• (iii) the tablets from the step (ii) are submitted to a filming coating by spraying a dispersion containing:
• from 2 to 10% by weight of a mixture of said acrylic or methacrylic acid ester copolymers, containing the above mentioned repeating units, wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4 have the above defined meanings, in said mixture in weight ratio comprised between 0.5:10 and 10:0.5;
• a mixture of one or more alcoholic solvents and/or one or more ketonic solvents in order to have on said nucleus a polymer coating ranging from 2.5 to 20% by weight based on the total nucleus weight.

A process for the preparation of controlled release pharmaceutical compositions, administrable by oral route, containing as active principle at least one salt of gamma-hydroxy-butyric acid with a pharmaceutically acceptable cation, consisting of:

• (a) a nucleus in the form of granules or tablets comprising said active principle dispersed in from 2.5 to 75% by weight based on the active principle dispersed in from 2.5 to 75% by weight based on the active principle weight of a cellulosic matrix consisting of a mixture of ethylcellulose and hydroxy-propyl-methyl-cellulose having a viscosity of 100,000 cps, and wherein the weight ratio between ethylcellulose and hydroxy-propyl-methyl-cellulose is comprised between 5 and 50%,
• (b) from 2.5 to 20% by weight based on the total nucleus weight of a filming coating consisting of a mixture of two water insoluble acrylic and methacrylic acid ester copolymers in a weight ratio comprised between 0.5:10 and 10:0.5, these copolymers containing the following repeating units:
• ##STR4## wherein R.sub.1 is H or methyl, R.sub.2 is methyl or ethyl, R.sub.3 is methyl, R.sub.4 is --CH.sub.2 Ch.sub.2.sup.(+) N(CH.sub.3).sub.3 Cl.sup.(-), the first copolymer containing 5% by weight of the second repeating unit, and the second copolymer containing 10% by weight of the second repeating unit said process comprising the following steps:
• (i) the active principle is dry mixed with hydroxy-propyl-methyl-cellulose and optionally with a portion of ethylcellulose and the remaining part of ethylcellulose is added in the form of a solution, suspension or dispersion in an alcoholic solvent, the mixture is granulated under wet condition, then the obtained granulate is dried thus obtaining the controlled release pharmaceutical composition, in the form of granules wherein the nucleus (a) contains the active principle dispersed in the cellulosic matrix;
• (ii) the granules from step (i) are submitted to a filming coating by spraying a dispersion containing:
• from 2 to 10% by weight of a mixture of said acrylic or methacrylic acid ester copolymers, containing the above mentioned repeating units, wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4 have the above defined meanings, in said mixture in weight ratio comprised between 0.5:10 and 10:0.5;
• a mixture of one or more alcoholic solvents and/or one or more ketonic solvents
• in order to have on said nucleus a polymer coating ranging from 2.5 to 20% by weight based on the total nucleus weight.