Factors influencing the release profile from a matrix tablet delivery system
Publication Date: 2003-Mar-27
The IP.com Prior Art Database
A sustained release matrix formulation of (±) 1-(isopropylamino)-3-[p-(β-methoxyethyl) phenoxy]-2-propanol succinate (2:1salt) with a dissolution profile of about 20 hour is disclosed. Different controlled release (CR) products based on a matrix principle, e.g. Betaloc SA® and Lopressor SR® have been developed and launched internationally. These preparations release about 80-100% of the dose within 8-10 hours. These products contain (±) 1-(isopropylamino)-3-[p-(β-methoxyethyl) phenoxy]-2-propanol tartarate (2:1salt) as an active b1-selective adrenoreceptor antagonist. The succinate salt is defined as a highly soluble active, although its solubility is less than the tartarate salt (257mg/ml vs. 700mg/ml). Integrating a medium dose (190 mg) highly soluble active into a matrix tablet with the purpose of a once daily delivery system is not an easy task. Upon exposure to the aqueous environment, the tablet releases the active ingredient by a conjunction of erosion and diffusion mechanisms. This dual release behavior yields in a relatively high drug release rate, which does not enable once daily dosing. The desired rate of drug release, i.e., 80-100% in approximately 20 hours could be achieved by adjusting the polyethylene oxide type polymer/ active material ratio to 1.2-1.8. The use of a single grade of polyethylene oxide or a combination of different grades can be employed. High molecular weight polyethylene types (MW 1,000,000 - 4,000,000), such as Polyox® WSRN-12K, Polyox ® WSRN-60K, Polyox® WSR-301 are preferred. The use of this polymer alone was found insufficient to mach the in vitro properties of the commercial product. A high amount of ethyl cellulose (20-30% of matrix components), serving both s a hydrophobic matrix builder and strong binder, had to be added. It was found that it i...