Enhancement of Drug Solubility and Absorption by Copolymers of 2-Methacryloyloxyethyl Phosphorylcholine and n-Butyl Methacrylate

Summary: Poly[2-methacryloyloxyethyl phosphorylcholine-co- n -butyl methacrylate]s (PMBs) are watersoluble solid copolymers of 2-methacryloyloxyethyl phosphorylcholine (MPC) and n -butyl methacrylate with a molecular weight of 30,000 (PMB50T) or 100,000 (PMB100T). Here, we characterized the solubilizing properties of PMBs using miconazole (MCZ), vidarabine (Ara-A) and griseofulvin (GRF), which are class 2, 3 and 4 compounds, respectively, in the Biopharmaceutics Classification System (BCS). Moreover, we evaluated the enhancement of gastric absorption of GRF dissolved in PMB solutions and the toxicity of PMBs in rats. PMB50T solution dramatically increased the solubility of GRF and MCZ compared with AraA, and these drugs became more soluble as the concentration of PMB50T was increased. The solubility of GRF in 10% PMB solutions was higher than with any other tested aqueous solubilizer. When a solution of GRF (20 mg/10 mL/kg) in 10% PMB was orally administered to rats, GRF absorption was greatly increased compared with that following administration of a suspension in water or Gelucire. After repeated oral administration of PMBs once daily for 14 successive days, no organ lesions or changes in biochemical parameters were observed. Thus, the polymers are expected to be useful and safe solubilizers and oral absorption enhancers for poorly soluble lipophilic drugs.