POLYETHYLENE GLYCOL CONJUGATES OF PACLITAXEL AS PRODRUGS BY SIMPLE TECHNIQUE SUCH AS SOLVENT EVAPORATION

Abstract

Paclitaxel (PACL) is an anti-cancer drug used to treat breast cancer, lung cancer, ovarian cancer etc. It is available as IV infusion and not as oral formulation. It is practically insoluble in water and hence possesses problems for development as oral or per oral formulations. Hence in the present research work, polyethylene glycol conjugates of PACL were prepared by simple technique such as solvent evaporation technique using high molecular weight polyethylene glycols such as PEG15000 and PEG35000 without linking agents. Eight compositions in drug to PEG15000/PEG35000 ratio of (1:10), (1:20) (1:25) and (1:50) were prepared. The prepared conjugates were evaluated by solubility studies, drug content uniformity and analysis by FTIR and DSC. Solubility of paclitaxel was enhanced in case of all prepared PACL-PEG conjugates. PACL: PEG35000(1:50) exhibited 0.317±0.081 mg/ml and all other PACL: PEG35000 conjugates of ratios (1:10), (1:20) (1:25) and (1:50) also evidenced same values with slight variation.The low c.v. values in percent drug content values of all conjugates ensured the uniformity of drug in prepared conjugates. FTIR spectra of paclitaxel PACL:PEG35000 evidenced disappearance of –N-H vibrational stretch at 3311.35 cm-1indicating conjugation of this end hydroxyl group with amine group of paclitaxel. The shift in the endothermic peak of the PEG conjugate (67.290 C) compared to the respective pure drug (221.570 C) confirmed the formation of drug-PEG conjugate. This work indicates PEG conjugates of paclitaxel will act as prodrugs and upon dissolution of polyethylene glycol moieties they parent drug in body fluids without effecting required therapeutic effect of paclitaxel.