THE DEVELOPMENT OF DELAYED-THEN-EXTENDED-RELEASE LOVASTATIN TABLET

Niacin and lovastatin are lipid-altering agents but differ in physicochemical properties. Niacin (nicotinic acid, pKa of 2.17) is a BCS class 1 drug with the plasma half-life about 20 to 48 min, while lovastatin (pKa 13.49) is classified as BCS class 2 with half-life 4.5 h. This project was originally set to design a tablet containing 250 mg niacin and 20 mg lovastatin. The in vitro dissolution methodology for Niacin ER/Lovastatin tablet was adopted from FDA Dissolution Method Database. During the early formulation stages, lovastatin was found unstable in the acidic medium. When the solvents were prepared as 0.1 N HCl to simulate gastric medium or phosphate buffer pH 4.5 as duodenum medium, unidentified chromatographic peak in addition to the lovastatin peak was recorded in Agilent HPLC software. Since niacin is a rather acidic compound, we felt that from product storage stability viewpoint these two drugs are not to be compounded together. This led to the development of a delayed- then extended-release 20 mg tablet (without niacin) in order to target the release of lovastatin in the small intestine.