Investigation of crystallinity and dissolution rate of poorly water soluble drugs with swellable polymers in peg 6000-based solid dispersion

Abstract

Poor bioavailability and low dissolution rate of drug are challenging issues for scientists. Curcumin and isradipine were used as model drugs due to their low bioavailability, short elimination half-life and high light sensitiveness. Polyethylene glycol (PEG 6000) and other polymer carriers, such as hydroxylpropyl methylcelluloses (HPMCs) and polyethylene oxide (PEO), were applied to investigate crystallinity, improved dissolution rate and sustained drug release. Solid dispersions (SDs) in different ratio were prepared by hot melting method. Specially, the effectiveness of PEG and HPMC combination on drug dissolution rate was evaluated by two combining methods differentiated by the order of HPMC and drug adding into the melted PEG solution. The SDs were dissolved in simulated gastric fluid (buffer pH 1.2) and simulated intestinal fluid (buffer pH 6.8). High-performance liquid chromatography (HPLC) method was used to determine concentration of curcumin and isradipine after dissolution test. Fourier transform infrared spectroscopy (FTIR) and Powder X-ray diffraction (PXRD) were used to analyze the physicochemical characteristics of drug. The dissolution rate of curcumin was enhanced by the incorporation into a hydrophilic carrier (e.g. PEG 6000, HPMC 4000, HPMC 6, and PEO). The best percentage drug release of curcumin was observed at ratio 1:8:4 of curcumin: PEG 6000: HPMC 4000, method II in which the combination between polymer PEG 6000 and carrier HPMC 4000 has occurred before the drug was dispersed into the molten mixture. Therefore, method II was applied for the next model drug – isradipine to enhance drug dissolution rate and investigate the capability of sustaining drug release. The optimal sustained release of isradipine was observed at 1:4:8 ratio of isradipine: PEG 6000: HPMC 4000 during 24 hours. Results from FTIR and PXRD showed that there was a transformation from crystalline state into amorphous state via formulating intermolecular hydrogen bond or creating a new chemical group between drug and carriers, resulting in an increased drug dissolution rate of curcumin and isradipine and the formation of a sustained drug release system.