A comparative study on the effects of amphiphilic and hydrophilic polymers on the release profiles of a poorly water-soluble drug

Abstract

This paper reports the use of two crystalline polymers, an amphiphilic Pluronic® F-127 (PF-127) and a hydrophilic poly(ethylene glycol) (PEG6000) as drug delivery carriers for improving the drug release of a poorly water-soluble drug, fenofibrate (FEN), via micelle formation and formation of a solid dispersion (SD). In 10% PF-127 (aq.), FEN showed an equilibrium solubility of ca. 0.6 mg/mL, due to micelle formation. In contrast, in 10% PEG6000 (aq.), FEN only exhibited an equilibrium solubility of 0.0037 mg/mL. FEN-loaded micelles in PF-127 were prepared by direct dissolution and membrane dialysis. Both methods only yielded a highest drug loading (DL) of 0.5%. SDs of FEN in PF-127 and PEG6000, at DLs of 5-80%, were prepared by solvent evaporation. In-vitro dissolution testing showed that both micelles and SDs significantly improved FEN's release rate. The SDs of FEN in PF-127 showed significantly faster release than crystalline FEN, when the DL was as high as 50%, whereas SDs of PEG6000 showed similar enhancement in the release rate when the DL was not more than 20%. The DSC thermograms of SDs of PF-127 exhibited a single phase transition peak at ca. 55-57 °C when the DL was not more than 50%, whereas those in PEG6000 exhibited a similar peak at ca. 61-63 °C when the DL was not more than 35%. When the DL exceeded 50% for SDs of PF-127 and 35% for SDs of PEG6000, DSC thermograms showed two melting peaks for the carrier polymer and FEN, respectively. FT-IR studies revealed that PF-127 has a stronger hydrophobic-hydrophobic interaction with FEN than PEG6000. It is likely that both dispersion and micelle formation contributed to the stronger effect of PF-127 on enhancing the release rate of FEN in its SDs.

Dissolution study and thermal analysis of fenofibrate–Pluronic F127 solid dispersions

“…In addition, improvements in the FEN dissolution property were observed for solid dispersions of the drug with Poloxamer 407 and Poloxamer 407 microprepared using a physical mixing technique [19]. Irwan et al [20] prepared the FEN solid dispersions with Poloxamer 407 using a solvent evaporation method and observed a significantly faster release of the drug when the fenofibrate loading was not greater than 50 %.…”

Oromucosal Alginate Films with Zein Nanoparticles as a Novel Delivery System for Digoxin

“…This could be due to the poorly water-soluble character of digoxin. Besides, hydrophobic polymers (zein) do not allow for quick hydration upon contact with simulated saliva and, hence, delay the dissolution time of the films [93].…”

Formulation and Characterization of Fenofibrate Loaded Solid Dispersion with Enhanced Dissolution Profile

“…previous studies[21] [39] [40]. The anticipated mechanism for increased wettability of the drug might be noticed as a strong interaction of silica with PEG-4000 and formation of reversible chemical bonding by FF with Carplex-80, suggesting the improvement of wettability property of the drug, which resulted its improved dissolution[41] [42][43].…”

“…To overcome this limitation, large number of investigations had been conducted. Some reported approaches are development of self-microemulsifying drug delivery system [11] [12], impregnation of drug into various silica [13] [14] [15], impact of fillers [16], oral push-pull osmotic pump [17], electrosprayed nanospherules [18], nanosuspension [19], solid dispersion [10] [20] [21], nanoparticles formations [22], anti-solvent precipitation technique [23], a pair of side by side diffusion cells [24], holt-melt extrusion [25], core shell dual mesoporous silica nanoparticles [28], nanocomposites [26] [27], dry suspension and dry emulsion [28], controlled release matrix [29], lipidic dispersion [30] and co-crystals formation [31]. Among these physi- Although many SD approaches using various carriers have been examined, but there is no report regarding the use of blend of silica and PEG on dissolution property of FF.…”