Browse Prior Art Database

Process for the synthesis of new stable polymorphic form of naltrexone hydrochloride from ethanol / water mixture

IP.com Disclosure Number: IPCOM000187843D
Publication Date: 2009-Sep-18
Document File: 2 page(s) / 36K

Publishing Venue

The IP.com Prior Art Database

Abstract

The synthesis of a new stable anhydrous polymorphic form of Naltrexone Hydrochloride is described. Properties and identity were confirmed by HPLC purity, melting point, XRD- and Raman spectra.

This text was extracted from a PDF file.
This is the abbreviated version, containing approximately 58% of the total text.

Page 1 of 2

IPCOM article - New polymorphic form of naltrexone hydrochloride

Alexander Franz, 18.09.2009

Process for the synthesis of new stable polymorphic form of
naltrexone hydrochloride from ethanol / water mixture

Naltrexone Hydrochloride is an opioid receptor antagonist used
primarily in the management of alcohol dependency and opioid
dependency. It is marketed in generic form as its hydrochloride salt
or as the free base. The indication of Naltrexone Hydrochloride is
longer-term dependency control. Naltrexone hydrochloride is known to
form several polymorphs, solvates and hydrates. In patent WO
2008/127618 A1 eleven forms are published and claimed.

In this publication, a process for the synthesis of a new, so far
unknown, stable polymorphic form of naltrexone hydrochloride is
described. The identity thereof was investigated and characterized
by melting point, XRD- and Raman spectra (see graphic 1 and 2).

Naltrexone base (11.0 g, 32.2 mmol) and butylated hydroxytoluene
(0.35 g, 1.6 mmol) are dissolved in a mixture of 55.0 g ethanol and
8.8 g water at 70°C. The solution is cooled to 60°C and hydrochloric
acid 37% (3.81 g, 38.7 mmol) is added. The mixture is heated to 70°C
till a clear solution is obtained. Crystallisation is initiated by
addition of naltrexone hydrochloride anhydrate (0.1 g) at 70°C. The
mixture is gradually cooled to 0°C and stirred over night. The
crystalls are filtered off, washed with ethanol (9.0 g) and ethyl
acetate (...