Solubility and dissolution enhancement of flurbiprofen by solid dispersion using hydrophilic carriers

ABSTRACT The intent of the current work is to study the effect of polyethylene glycol 8000 and polyethylene glycol 10000 as hydrophilic carriers on dissolution behaviour of flurbiprofen. In the present study, solvent evaporation method was used to prepare flurbiprofen solid dispersions and evaluated for physico-chemical properties, drug-carrier compatibility studies and dissolution behaviour of drug. Solubility studies showed more solubility in higher pH values and formulations SD4 and SD8 were selected to prepare the fast dissolving tablets. FTIR and DSC study showed no interaction and drug was dispersed molecularly in hydrophilic carrier. XRD studies revealed that there was change in the crystallinity of the drug. The results of In vitro studies showed SD8 formulation confer significant improvement (p<0.05) in drug release, Q20 was 99.08±1.35% compared to conventional and marketed tablets (47.31±0.74% and 56.86±1.91%). The mean dissolution time (MDT) was reduced to 8.79 min compared to conventional and marketed tablets (25.76 and 22.22 min.) indicating faster drug release. The DE (% dissolution efficiency) was increased by 2.5 folds (61.63%) compared to conventional tablets (23.71%). From the results, it is evident that polyethylene glycol solid dispersions in less carrier ratio may enhance the solubility and there by improve the dissolution rate of flurbiprofen.

Effects of polyethylene glycols on intestinal efflux pump expression and activity in Caco-2 cells

The present study was planned to investigate the influence of polyethylene glycols (PEGs) on the activity and expression of P-glycoprotein (P-gp). Sub-toxic concentrations of PEGs in Caco-2 cells were determined using the MTT test assay. Then the measurement of Rhodamine-123 (Rho-123) uptake, a P-gp fluorescence substrate, in Caco-2 cells confronting PEG 400 (1% and 2% w/v), PEG 4000 (2% and 4% w/v), PEG 6000 (2% and 4% w/v), PEG 10000 (2% and 4% w/v), PEG 15000 (1% and 2% w/v), and PEG 35000 (2% and 4% w/v) overnight was taken to elucidate whether non-toxic concentrations of PEGs are able to impact P-gp activity. Furthermore, western blotting was carried out to investigate P-gp protein expression. The results showed that PEG 400 at concentrations of 1% (w/v) and 2% (w/v) and PEG 6000 at the concentration of 4% (w/v) are notably capable of blocking P-gp. Based on the obtained results it is concluded that the mentioned excipients could be used to obstruct P-gp efflux transporter in order to increase the bioavailability of co-administered substrate drug.

O presente estudo foi planejado para investigar a influência de polietileno glicóis sobre a atividade e expressão da P- glicoproteína (P-gp) . Concentrações sub-tóxicas de PGPs e em células Caco-2 foram determinadas por meio do ensaio de MTT. Em seguida, efetuou-se a a medida de captura de Rodamina-123 (Rho-123), um substrato fluorescente de P-gp, em células Caco-2, confrontando com PEG 400 (1% e 2% m/v), PEG 4000 (2% e 4% m/v) e PEG 6000 (2% e 4% m /v), PEG 10000 (2% e 4% w/v), PEG 15000 (1% e 2% m/v), e PEG 35000 (2% e 4% m/v). Essa medida foi efetuada durante a noite, para saber se as concentrações não tóxicas de excipientes são capazes de influenciar a actividade da P-gp. Além disso, realizou-se o western blotting para investigar a expressão da proteína P-gp. Os resultados mostraram que o PEG 400, nas concentrações de 1% (m/v) e 2% (m/v), e PEG 6000, na concentração de 4% (m/v) são capazes de bloquear P-gp. Com base nos resultados conclui-se que os excipientes mencionados poderiam ser utilizados para obstruir o efluxo por P-gp, a fim de aumentar a biodisponibilidade de do fármaco co-administrado.