Patent ID: 6159501
Filing Date: 2000-12-12
Classification: A61K,A61P

Abstract:
An oral pharmaceutical modified release multiple-units composition for the administration of analgesically effective amount of an opioid to obtain both a relatively fast onset of the analgesic effect and the maintenance of an analgesically active plasma concentration for at least 12 hours, a unit dosage of the composition comprising at least two fractions of multiple-units as follows:a first fraction of modified release coated multiple-units that comprise a coating of a substantially water insoluble material for relatively fast release in vivo of an opioid to obtain a therapeutically active plasma concentration within a relative short period of time, anda second fraction of modified release coated multiple-units for delayed release in vivo of an opioid to maintain an analgesically active plasma concentration for a period of at least 12 hours,the formulation of the first and the second fractions, with respect to modified release therefrom and with respect to the ratio between the first and the second fraction in the unit dosage, being adapted so as to obtain:i) a relative fast in vitro release of the opioid from the first fraction of modified release multiple-units, as measured by a dissolution method employing a USP/Ph.Eur. dissolution apparatus equipped with a paddle, a rotation speed of 1000 rpm and 0.1 N HCl as dissolution medium,ii) a delayed in vitro release of the opioid from the second fraction of modified release multiple-units relative to the in vitro release of the first fraction of the opioid, as measured by said dissolution method,the fast release and the delayed in vitro release being adapted so that the first fraction is substantially released when the release from the second fraction is initiated corresponding to at least 50% release of the opioid contained in the first fraction at the time when 10% of the opioid contained in the second fraction is released as measured by said dissolution method, the ratio between the first and the second fraction of modified release multiple-units in the composition being in the range of 1:20-1:2 calculated on the weight of the fractions.