사포그릴레이트 염산염을 함유하는 신규 OROS 정의 제제 설계 및 용출 거동

Abstract

Sarpogrelate hydrochloride (SGH) is a drug that improves ischemic symptoms such as ulcers, pain, and feeling of cold caused by chronic arterial occlusion, and has a short half-life of 0.6 to 0.8 hours. Also, reference drug (SarpodipilⓇ SR tablet) is affected by drug release depending on pH. To overcome this, the osmotic controlled release oral delivery system (OROS) utilizes push-pull osmotic pump (PPOP) technology that can achieve zero-order drug release over 24 hours by osmotic pressure. OROS tablet is double-layer tablet consisting of a drug layer (L200-PEO) and a push layer (H5,000- PEO). OROS tablet coated with a semi-permeable film has a orifice of a certain size made by a laser drill, so that the drug is released at a constant rate. The dissolution of the OROS tablet was not affected by the amount of sodium chloride in the drug layer and the number of orifice, but was affected by amount of coating, cellulose acetate (CA) : polyethylene glycol 3350 (PEG 3350) ratio and the size of orifice. Accordingly, as the amount of coating increased and PEG 3350 decreased, the dissolution rate decreased. The developed OROS tablet (formulation C), unlike the reference drug, is not affected by pH, showing high similarity factors of 76.0, 86.1, and 91.2 at pH 1.2, pH 4.0, and pH 6.8 when compared to distilled water. In conclusion, we developed OROS tablet containing SGH, showing zero-order release that continuously releases the drug for 24 hours regardless of pH, and confirmed the factors affecting dissolution.