Abstract

CHRONOPHARMACY AS POWERFUL INSTRUMENT FOR OPTIMIZATION OF ANTIPLATELET THERAPY WITH ACETYLSALICYLIC ACID

M. Dimitrov, T. Popova, V. Petkova*, Ch. Voycheva, A. Tsvetkova, A. Todorova, K. Andreevska and Nikolai Lambov

ABSTRACT

On the global market there are many solid dosage forms for antiplatelet therapy, containing low-dosed acetylsalicylic acid (ASA), but none of them comply with the chronophysiological rhythms of cardio-vascular diseases with peak of appearance during early morning hours, which leads to ineffective therapy. One of the ways to improve antiplatelet therapy, patient compliance and to reduce the undesirable complications is by creating chronopharmaceutical drug dosage system. By appropriate design this kind of systems can release the drug within a short/prolonged period of time, immediately after a predetermined lag-time (so called pulsatile-release drug delivery systems). Press-coating technology is appropriate method to obtain that kind of release profile. Depending on the polymers used in this system, they can deliver the drug after swelling and/or eroding of coating shell, obtaining pulsatile-release. For the purpose of the present study – creating a chronopharmaceutical system, which contains low-dosed ASA, a press coating technique with a little modification has been used. For establishing a release profile with 2-3 h lag-time and extended drug delivery within 6-8 h, eight different formulation double press coated tablets (A1-A8), based on PEO with different molecular weight (Mr), have been prepared and evaluated. The last two formulations A7 and A8 have a potential to be used as a chronopharmaceutical system. Because of the PEO 8000000 in their 2-nd outer layer and the lack of ASA, they protect the 1-st outer layer and core from entry of water and thereby slow the initial release to 9-12% within first 2 h (lag-time). On the other hand the presence of PEO with lower Mr in the 1-st outer layer and the core allows achieving almost constant release rate with peak of release at 9-10 h. Those systems are designed, by taken before bedtime, to cause minimal stomach irritation and to deliver ASA at the early morning hours when the cardio-vascular incidents are with the higher possible frequency.

Keywords: Press-coating technology, acetylsalicylic acid, chronopharmacy.