Preparation, characterization, and pharmacokinetic assessment of metformin HCl loaded transfersomes co-equipped with permeation enhancer to improve drug bioavailability via transdermal route

Metformin Hydrochloride (MF HCl), an anti-diabetic drug, has compromised oral absorption due to low permeability resulting in lower bioavailability. Therefore, transfersomes (TFs) were explored as a novel strategy in an attempt to address permeation limitations. MF HCl loaded transfersomes (MF-TFs) were prepared using a modified thin film hydration technique. Prepared MF-TFs were then embedded in Carbopol gel containing permeation enhancer (PE) to improve the drug bioavailability with the potential to combat type 2 diabetes mellitus (DM-II) through the transdermal route. To assess the glucose control of MF-TFs, a glucose tolerance test was performed. The optimized formulation was further characterized by in vitro and as well as ex vivo skin studies. In addition, in vivo studies were also performed in healthy mice to determine the pharmacokinetic parameters of the formulation. The resulting formulation showed smooth and spherical MF-TFs particles with a size of 185.3 +/- 3.2 nm, a zeta potential of -12.5 +/- 0.12 mV, PDI of 0.16 +/- 0.01, and encapsulation efficiency (EE) of 88 +/- 1.4%, whereas, the drug release from the MF-TFs particles displayed sustained drug release profile. Moreover, physicochemical characterization techniques such as FTIR and XRD showed the optimal fabrication of MF-TFs. Furthermore, skin permeation studies showed superior permeation of MF-TFs gel with PE (1041.7 +/- 7.53 mu g/cm2) compared to the pure drug. Skin irritation study indicated formulation compatibility with negligible signs of erythema or edema. Glucose tolerance test demonstrated that MF-TFs significantly reduced blood glucose levels in test animals as compared to pure drug embedded in gel and oral drug solution. While in vivo pharmacokinetic evaluation demonstrated increased MF HCl bioavailability with increased AUC0-alpha (42.336 +/- 1.115 ng h/ml) and Cmax of 2.195 mu g/ml by MF-TFs gel with PE in comparison to oral drug solution. Based on the study findings, MF-TFs gel can be considered a feasible alternative to oral MF HCl therapy with enhanced bioavailability and the potential to manage DM-II via transdermal application.

Automated summary

In this study, transfersomes were used to improve the oral absorption of Metformin Hydrochloride (MF HCl), an anti-diabetic drug, and increase its bioavailability. The MF-TFs were prepared using a modified thin film hydration technique and embedded in Carbopol gel containing a permeation enhancer. The resulting formulation showed smooth and spherical MF-TFs particles with sustained drug release. Skin permeation studies demonstrated superior permeability of MF-TFs gel compared to the pure drug. Glucose tolerance test and in vivo pharmacokinetic evaluation further confirmed the potential of MF-TFs gel for transdermal application in the management of type 2 diabetes mellitus (DM-II).