الفهرس 
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Abstract
The aim of the present study was to investigate the influence of iontophoretic electrical parameters (current frequency) and physicochemical factors (donor drug concentration, donor ionic strength, electrode material) on the transdermal delivery of tryptophane (high Mwt, essential amino-acid) and Glycine (low Mwt, non-essential aminoacid) using iontophoresis .
In this work passive diffusion experiments and all iontophoresis diffusion experiments of the two amino acids through mouse skin was done in a modified Franz type glass diffusion cell using a home made two-compartment horizontal glass diffusion cell with a surface area of ~ 2 cm2. The volumes of the donor and receptor chambers were ~ 5o ml. The excised rat skin was mounted between the two half cells with stratum corneum facing the donor chamber. During experimentation the diffusion cells was immersed in a thermostated water-bath maintained at 37ºC (to simulate normal human physiological temperature) and the receptor chamber was continuously stirred using a small magnetic stirrer bar to ensure adequate mixing of the receptor medium. The skin was equilibrated for 1 h in phosphate buffer saline (pH 7.4) before each experimentation. Diffusion experiments were carried out for a period of 2 h and the number of experiments in each investigation will be 3-4. Samples of 1 ml were withdrawn from the receptor compartment at regular intervals (~30 min.) and were immediately replaced by same volume of drug-free buffer.
The effect of concentration of drug in donor solution was studied for both passive and iontophoretic delivery. The concentration of drug (i.e. Gly or tryptophan ) was varied from 1-10 mg/ml. During iontophoresis experiments, pulsed dc square wave of 50% duty cycle and 1 KHz freqency. was used with maximum current density kept at 0.5 mA/cm2 . When compared to passive drug delivery significant enhancement effect was achieved using inotophoretic delivery of both glycine and tryptophan at pulsed dc square wave of 50% duty cycle and frequency of 1000 Hz with current density at 0.5 mA/cm2 for different concentrations of both glycine and tryptohan in donor solution. For different concentrations of both glycine and tryptophan, the total drug accumulated amount permeated through skin was increased by increasing the duration of current applied in iontophoretic drug delivery. Also, for different concentrations of both glycine and tryptophan, the total drug accumulated amount permeated through skin was increased by increasing the initial dug donor concentrations at 0.2, 0.4, 0.8 and 1 g/ml compared with 0.1 g/ml.
The effect of ionic strength on the skin permeation of drug was studied by varying the concentration of NaCl form 0.07 to 0.5 M in the donor solution at pulsed dc square wave of 50% duty cycle and frequency of 1000 Hz with maximum current density of 0.5 mA/cm2 using 1 g/ml donor drug concentration. By varying the donor ionic strength for both glycine and tryptophan, the drug permeation amount increased by increasing the duration of current applied in iontophoretic drug delivery. Within 2 hrs of permeation study, there were significant decreased amount of both glycine and tryptophan permeation through skin by increasing the donor ionic stength for the pulsed dc square wave of 50% duty cycle and frequency of 1000 Hz with maximum current density at 0.5 mA/cm2 using 1 g/ml donor drug concentration .
The effects of variation of frequency of the pulsed dc square wave of 50% duty cycle with current density at 0.5 mA/cm2 on drug permeation using 1 g/ml donor drug concentration were evaluated using in vitro Franz cell diffusion model on rat skin. At all frequencies used both glycine and tryptophan permeation amount increased by increasing the duration of current applied in iontophoretic drug delivery. Within 2 hrs of permeation study, there were significant increased amount of both glycine and tryptophan permeation through skin by increasing frequency of the pulsed dc square wave of 50% duty cycle with current density at 0.5 mA/cm2 using 1 g/ml donor drug concentration.
The effect of electrode material on the iontophoretic delivery of both glycine and tryptophan was studied by comparing SS (stainless steel) and Ag/AgCl electrodes using in vitro Franz cell diffusion model on rat skin at pulsed AC square wave of 50% duty cycle and frequency of 1000 Hz with maximum current density of 0.5 mA/cm2 using 1 g/ml donor drug concentration. Both glycine and tryptophan showed increased drug permeation with Ag/AgCl electrodes at pulsed AC square wave of 50% duty cycle and frequency of 1000 Hz with maximum current density of 0.5 mA/cm2 using 1 g/ml donor drug concentration compared with stainless steel elctrodes.
Conclusion
from the present study we could conclude that
1. The transport of glycine and tryptophan delivery depends on the duration of current applied in iontophoretic drug delivery. The iontophoretic accumulative permeation of glycine and tryptophan linearly increased with increasing application time.
2. The glycine and tryptophan cumulative amount permeated through rat skin significantly increased with the use of iontophoresis when compared to passive diffusion.
3. As the drug concentration increase, the iontophoretic accumulative permeation of drug linearly increased. Therefore, depending on purpose, higher glycine and tryptophan concentrations can dramatically increase the mode of action while low concentrations can be more suitable for sustained drug release.
4. The transport of drug delivery depends on the frequency of current applied in iontophoretic drug delivery. The iontophoretic accumulative permeation of drug linearly increased with increasing frequency of applied current.
5. The iontophoretic accumulative permeation of drug was inversely proportional to the drug ionic strength.
6. Both glycine and tryptophan showed increased drug permeation with Ag/AgCl electrodes compared with stainless steel elctrodes.
7. The molecular size of the solute is a major factor governing its feasibility for iontophoretic delivery and hence the amount transported. Transport of compounds decreased with increase in molecular weight. Therfore glycine permeation through rat skin was significantly higher compared with that of tryptophan.