Synergistic effect of iontophoresis and chemical enhancers on transdermal permeation of tolterodine tartrate for the treatment of overactive bladder

Purpose The objective of the study was to evaluate the synergistic transdermal permeation effect of chemical enhancers and iontophoresis technique on tolterodine tartrate (TT) transdermal gel and to evaluate its pharmacokinetic properties. Materials and Methods Taguchi robust design was used for optimization of formulations. Skin permeation rates were evaluated using the Keshary-chein type diffusion cells in order to optimize the gel formulation. In-vivo studies of the optimized formulation were performed in a rabbit model and histopathology studies of optimized formulation were performed on rats. Results Transdermal gels were formulated successfully using Taguchi robust design method. The type of penetration enhancer, concentration of penetration enhancer, current density and pulse on/off ratio were chosen as independent variables. Type of penetration enhancer was found to be the significant factor for all the responses. Permeation parameters were evaluated when maximum cumulative amount permeated in 24 hours (Q24) was 145.71 ± 2.00µg/cm2 by CIT4 formulation over control (91.89 ± 2.30µg/cm2). Permeation was enhanced by 1.75 fold by CIT4 formulation. Formulation CIT4 containing nerolidol (5%) and iontophoretic variables applied (0.5mA/cm2 and pulse on/off ratio 3:1) was optimized. In vivo studies with optimized formulation CIT4 showed increase in AUC and T1/2 when compared to oral suspension in rabbits. The histological studies showed changes in dermis indicating the effect of penetration enhancers and as iontophoresis was continued only for two cycles in periodic fashion so it did not cause any skin damage observed in the slides. Conclusion Results indicated that iontophoresis in combination with chemical enhancers is an effective method for transdermal administration of TT in the treatment of overactive bladder. .

Statistically optimised ethosomes for transdermal delivery of tolterodine tartrate

The aim of the current investigation is to optimize ethosomes statistically for enhancing transdermal potential of Tolterodine Tartrate [TT]. Ethosomes bearing TT were prepared by cold method and characterized for various parameters like vesicle size, vesicle shape, surface morphology and% drug entrapment. Microscopic examinations suggest ethosomes as spherical unilamellar vesicles with a smooth surface. Optimized ethosomal vesicles were of 890 +/- 2.67nm size and showed 79.83 +/- 3.18% drug entrapment. Ex-vivo permeation studies across rat skin resulted in increased flux of 4.69 +/- 0.24 Micro g/cm[2]/hr and decreased lag time of 0.13 +/- 0.05 hr when compared with drug solution [0.546 +/- 0.05 Micro g/cm[2]/hr, 3 +/- 0.2 hr].This shows enhancement of transdermal delivery by 8.82 times. Anatomical changes in skin samples due to vesicle-skin interaction were observed on histological examination. Optimized formulation on storage at 4°C for 120 days showed insignificant growth in vesicular size revealing low aggregation of vesicles. The results collectively suggest ethosomes as carriers for accentuated transdermal delivery of TT

Development of ethosomes with taguchi robust design-based studies for transdermal delivery of alfuzosin hydrochloride.

In the present investigation efficiency of ethosomes as novel lipid carriers for transdermal delivery of Alfuzosin Hydrochloride (AH) has been evaluated. Taguchi robust design method was used for optimization of ethosomal formulations. Phospholipid type, concentration of phospholipid and concentration of ethanol was selected as independent variables and their effect on the dependent variables (entrapment efficiency and flux) was studied. Ethosomal formulation (EA8) with soya phosphatidylcholine (3%) and ethanol 20% were optimized. Vesicles were spherical, unilamellar with smooth surface. The optimized formulation exhibited vesicle size (6.85 ± 1.35μm), zeta potential (-8.14 ± 0.62mv), entrapment efficiency (91.86 ± 3.25%), flux (27.42 ± 0.04μg/cm2/hr), lag time (0.26±0.20hr) and skin deposition (298.01 ± 15.4μg/g). Transdermal flux was enhanced by 6.92 times over drug solution. Vesicle skin interaction studies showed fatty change in the dermis. The formulations were stable at 4°C for 120 days. Results suggested ethosomes as efficient carriers for AH transdermal delivery.

Development of ethosomes with taguchi robust design-based studies for transdermal delivery of alfuzosin hydrochloride.

In the present investigation efficiency of ethosomes as novel lipid carriers for transdermal delivery of Alfuzosin Hydrochloride (AH) has been evaluated. Taguchi robust design method was used for optimization of ethosomal formulations. Phospholipid type, concentration of phospholipid and concentration of ethanol was selected as independent variables and their effect on the dependent variables (entrapment efficiency and flux) was studied. Ethosomal formulation (EA8) with soya phosphatidylcholine (3%) and ethanol 20% were optimized. Vesicles were spherical, unilamellar with smooth surface. The optimized formulation exhibited vesicle size (6.85 ± 1.35μm), zeta potential (-8.14 ± 0.62mv), entrapment efficiency (91.86 ± 3.25%), flux (27.42 ± 0.04μg/cm2/hr), lag time (0.26±0.20hr) and skin deposition (298.01 ± 15.4μg/g). Transdermal flux was enhanced by 6.92 times over drug solution. Vesicle skin interaction studies showed fatty change in the dermis. The formulations were stable at 4°C for 120 days. Results suggested ethosomes as efficient carriers for AH transdermal delivery.