SI22850A - Quetiapine preparation - Google Patents

Abstract

A new pharmaceutical preparation with prolonged release, comprising quetiapine and keragenan, is described in the submitted invention.

Description

QUETIAPIN PREPARATION

FIELD OF THE INVENTION

The present invention relates to a novel extended release pharmaceutical composition comprising quetiapine and carrageenan.

BACKGROUND OF THE INVENTION

Quetiapine is an atypical antipsychotic with proven efficacy in the treatment of schizophrenia, demonstrating efficacy in the treatment of acute mania and depression associated with bipolar disorder. Quetiapine, either as monotherapy or in combination with lithium or divalproex sodium (seminodium valproate), is generally very well tolerated and effective in reducing manic symptoms in adults and adolescent patients with acute bipolar mania and is approved for use in adults for this indication. As monotherapy, the drug is also effective in reducing depressive symptoms in patients with bipolar depression.

Quetiapine and its hemifumarate salt were first described in EP 240228. Many more patent applications were subsequently published relating to quetiapine, such as: EP 282236, EP 907364, WO 9906381, EP 1218009, EP 1448169, EP 1482945, WO 2005028457, WO 2005041935, WO 2007036599, EP 1252151.

Carrageenan is a hydrocolloid obtained by extraction with water or aqueous alkali from some members of the class Rhodophyceae (red seaweed). Carrageenan consists mainly of potassium, sodium, calcium, magnesium and ammonium sulfate esters of galactose and 3,6-anhydrogalactose copolymers. These hexoses are alternately bound a-1,3 and b-1,4 in the polymer. The predominant copolymers in hydrocolloid are labeled capa-, iota- and lambda-carrageenan. Kappa-carrageenan is a largely alternating polymer of D-galactose-4-sulfate and 3,6-anhydro-D-galactose. Joto-carrageenan is similar except that 3,6-anhydrogalactose is sulfated at carbon 2. Between foz / ra-carrageenan and jotakaragenan there is a continuum of intermediate compositions that differ in the degree of sulfation at carbon 2. V / am / ii / a- carrageenan is an alternating monomeme unit mainly D-galactose-2-sulfate (1,3-bound) and D-galactose-2,6-disulfate (1,4-bound). The ester sulfate content for carrageenan ranges from 18% to 40%. In addition, it contains inorganic salts originating from seaweed and from the extraction process, λ-carrageenan (/ izmWa-carrageenan) is a non-negligible polymer containing about 35 wt. % of sulfate ester and zero 3,6-anhydrogalactose.

WO 97/45124 describes a sustained-release quetiapine formulation comprising a hydrophilic matrix comprising a gel agent. The disadvantage of such a preparation is that it is difficult to control the gel level of the preparation and, thus, its dissolution rate, since it also depends on physiological factors.

WO 03/000293 relates to an oral pharmaceutical formulation comprising iota-carrageenan, one or more gelling polymers and a basic pharmaceutical ingredient. Pharmaceutical formulations comprising quetiapine have not been described.

WO 03/039516 describes a process for improved dissolution of a poorly dispersible drug, e.g. quetiapine fumarate comprising mixing a poorly dispersible active substance with a Dotting Agent and granulating the mixture. Water-insoluble cellulose, sodium alginate, propylene glycol alginate, tragacanth in powder form, or xanthan gum are cited as the Grants.

DETAILED DESCRIPTION OF THE INVENTION

It is an object of the present invention to provide a pharmaceutical preparation to address the abovementioned disadvantages.

The present invention describes a pharmaceutical preparation and processes for its preparation comprising a solid matrix system of quetiapine or its salts and an non-invasive agent capable of prolonging the release of quetiapine from the preparation for at least 12 hours, preferably at least 16 hours, and most preferably at least 20 hours, such as carrageenan.

Preferably, carrageenan is / am / ii / a-carrageenan and quetiapine is preferably in the form of quetiapine hemifumarate.

The pharmaceutical composition of the present invention can be formulated into various dosage forms such as tablets or capsules. Preferably, the composition of the present invention is in the form of a tablet that can be made by direct tableting or granulation.

Additional excipients selected from fillers, binders, drug release rate modifiers, decomposers, gliders or lubricants can be used in the preparation.

Fillers may be selected from water-soluble fillers such as lactose, mannitol, dextran, or from water-insoluble fillers such as starch, starch derivatives such as pre-gelatinized starch, crystalline cellulose such as microcrystalline cellulose, alkaline earth salts of phosphoric acid, such as calcium hydrogen phosphate in anhydrous or hydrated form, etc.

The present invention is illustrated by reference to the following Examples. However, the Examples are not intended to limit the scope of claims in any way. It will be apparent to those skilled in the art that many modifications can be made to both materials and processes without departing from the purpose and interest of the present invention.

EXAMPLES

Procedure for Examples 1-4:

We mix the excipients. Add the active ingredient and mix with the excipients. Magnesium stearate was added to the resulting mixture, and the homogeneous mixture was finally mixed and compressed on a tablet machine.

Example 1

Ingredient mg / tablet core Quetiapine hemifumarate 400,0 Aaw0i / a-carrageenan 481,1 Magnesium stearate 8.9

Example 2

Ingredient mg / tablet core Quetiapine hemifumarate 400,0 Lam όί / α-carrageenan 240.55 Dicalcium phosphate dihydrate (CaHPO _4. 2H ₂ O, Bekapress) 240.55 Magnesium stearate 8.9

Example 3

Ingredient mg / tablet core Quetiapine hemifumarate 300,22 La m όί / ίζ-carrageenan 321,4 NaSDS 33.02 Magnesium stearate 13,36

Example 4

Ingredient mg / tablet core Quetiapine hemifumarate 300,22 ZizmZ? C / a-carrageenan 177.21 Lactose 177.21 Magnesium stearate 13,36

Claims (6)

PATENT APPLICATIONS A pharmaceutical composition comprising quetiapine or a salt thereof and carrageenan. The pharmaceutical composition of claim 1, wherein quetiapine is in the form of quetiapine hemifumarate. The pharmaceutical composition of claim 1, wherein the carrageenan / aza is ajafo-carrageenan. A pharmaceutical preparation according to claim 1, which is capable of prolonging the release of quetiapine from the preparation for at least 12 hours. 5. A pharmaceutical composition according to claim 4, which is capable of prolonging the release of quetiapine from the preparation for at least 16 hours. The pharmaceutical composition of claim 5, which is capable of prolonging the release of quetiapine from the preparation for at least 20 hours.