Lovastatin (LVS) is a well-known compound for lowering plasma cholesterol levels. After oral administration, the inactive parent lactone is hydrolyzed to the corresponding hydroxyacid form. The hydroxyacid is the principal metabolite and a potent inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA) reductase. This enzyme catalyzes the conversion of hydroxymethylglutarate to mevalonate, which is an early and rate-limiting step in cholesterol biosynthesis (1, 2).
LVS is white crystalline powder that is insoluble in water (0.4 g/mL). At room temperature, the partition coefficient of LVS in n-octanol/water system is approximately: Ko/w = 1.2 × 104 (3). Low aqueous solubility of LVS leads to inadequate dissolution in gastrointestinal fluids and, hence, poor absorption, distribution, and targeted organ delivery. The improvement of aqueous solubility in such a case is a valuable goal to improve therapeutic efficacy.
β-CD has ideal dimensions to complex a range of commonly used drugs. Unfortunately, it has the limitation of a high affinity for cholesterol, which may lead to crystallization of a poorly water-soluble β-CD–cholesterol complex in the kidney. This complex could cause nephrotoxicity. HPβ-CD, a chemical derivative of β-CD, similarly improves the aqueous solubility of many drugs, but it is more hydrophilic than β-CD, forms a less-stable complex with cholesterol, and, therefore, is less toxic (13).