STABLE FORMULATION OF AMORPHOUS PERINDOPRIL SALTS, A PROCESS FOR THEIR PREPARATION, ESPECIALLY INDUSTRIAL PREPARATION, AND THEIR USE IN THE THERAPY OF HYPERTENSION

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STABLE FORMULATION OF AMORPHOUS PERINDOPRIL SALTS, A PROCESS FOR THEIR PREPARATION, ESPECIALLY INDUSTRIAL PREPARATION, AND THEIR USE IN THE THERAPY OF HYPERTENSION
Publication Number: WO/2007/058634 International Application No.: PCT/SI2006/000034
Publication Date: 24.05.2007 International Filing Date: 08.11.2006

Int. Class.: A61K 38/55 (2006.01), A61K 31/401 (2006.01), A61K 9/16 (2006.01), A61P 9/12 (2006.01), C07D 209/42 (2006.01)
Applicants: DIAGEN SMARTNO PRI LJUBLJANI, D.O.O. [SI/SI]; Spodnje Gameljne 72, 1211 Smartno Pri Ljubljani (SI) (All Except US).
RUCMAN, Rudolf [SI/SI]; Spodnje Gameljne 72, 1211 Smartno Pri Ljubljani (SI) (US Only).
ZUPET, Pavel [SI/SI]; Mlinarska Pot 15, 8000 Novo Mesto (SI) (US Only).
Inventors: RUCMAN, Rudolf [SI/SI]; Spodnje Gameljne 72, 1211 Smartno Pri Ljubljani (SI).
ZUPET, Pavel [SI/SI]; Mlinarska Pot 15, 8000 Novo Mesto (SI).
Agent: PATENTNA PISARNA, D.O.O.; Copova 14, Pob 1725, 1001 Ljubljana (SI).
Priority Data: P-200500314 17.11.2005 SI
P-200600177 31.07.2006 SI
Abstract: There is disclosed a stable formulation of amorphous perindopril erbumine of the formula which is obtained in such a way that perindopril erbumine, which may also be prepared in situ from perindopril and tert-butylamine, or perindopril erbumine hydrate is dissolved in demineralized water or in a mixture of demineralized water and alcohol, to this solution a solution of sodium hydrogen carbonate is added for stabilization, inert ingredients for tabletting are wetted therewith, dried in vacuo by lyophilization or at normal pressure with a stream of warm air at not more than 40?C, hydrophobic additives to facilitate tabletting are added, it is homogenized and the granulate is tabletted. Disclosed is also a stable formulation of amorphous perindopril sodium salt obtained by modification of the drying procedure in the process of preparing the granulate. X-ray powder diffraction investigations show that perindopril erbumine is present in amorphous form and does not contain crystal &agr;, &bgr; and ϝ forms.