Phenomenological Analysis of Drug Transport through Stratum Corneum

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Phenomenological Analysis of Drug Transport
through Stratum Corneum

• Wang Hong

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Purpose

• To illustrates the phenomenological relationship
  of drug permeable process through SC and provides
  theory and method for research of transdermal
  drug delivery (TDD).

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Results

• (1) Not only drug transdermal permeation, but
  also volume loss of solution occurs in the system
• (2) According to experimental data,
  phenomenological coefficient is time variable,
  the action of surface force on mass flow and
  physical force on physical flow decreases as time
  expands
• (3) Volume flow may be generated by velocity
  gradient arising from solution convection on the
  surface of stratum corneum (SC)

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Conclusion

• The permeation chamber is a non-linear and
  time-variable system.

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INTRODUCTION

• advances in biotechnology
• A lot of therapeutic macromolecules are reaching
  the clinical application
• bioactive macromolecules limited
• A novel delivery system needed
• Transdermal drug delivery (TDD)

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TDD (Transdermal drug delivery)

• TDD is that patching the drug on the skin, the
  drug molecules permeate through the skin into the
  subcutaneous capillary vessels
• TDD is an alternative method of drug delivery
  that draws peoples attention as a potential
  administration of biological pharmacy.

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Exist diffculty

• very few drugs can be administered transdermally
  at therapeutic levels to the barrier of stratum
  corneum (SC), the skins outer layer.

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Method to enhance

• iontophoresis
• electroporation
• photomechanical wave
• sonophoresis
• magnetophoresis
• chemical enhancers

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Non-equilibrium theory of permeation cell

• System of permeation cell and its hypothesis
  Permeation cell
• Phenomenological equation of permeation cell

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System of permeation cell

• Permeation cell, the basic equipment of TDD
  experiment in vitro is composed of a donor
  compartment and a receptor compartment, among
  which SC sample is loaded and a couple of
  electrodes were put at their sides
• The solution in donor is saturated liquid
  containing solute, while the solution in receptor
  is physiological saline

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System hypothesis

• The system is constant temperature there is no
  heat flow between donor compartment and receptor
  compartment.
• There is no chemical reaction in the system.
• The physiological saline or buffer solution is
  not viscous fluid.
• The species in the system are no more than
  pattern drug and physiological saline or buffer
  solution.
• The subsystems of donor and receptor are local
  equilibrium, i.e. it is equilibrium in the volume
  element, but non-equilibrium between one volume
  element and other.

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Phenomenological equation of permeation cell
here L11?L12?L21?L22 are phenomenological
coefficient, zs electrovalence of molecule or
ion, cs concentration of molecule or ion, F
96500 Faraday constant, k gaseity constant, T
absolute temperature. On the basis of Onsager
reciprocity relations, L12 L21 .
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Materials

• Chemicals Tinidazole
• Skin preparation heat separately in 60oC water
  for 2 min and gently removing the SC.
• Equipments side-by-side permeation chambers,
• Multi-Pulse Generator for Electroporation,
  oscilloscope
• Pulse protocols table 1

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Fig 1 experiment system
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Table 1Pulse protocols
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Methods

• Prepared SC sample was loaded into the
  permeation orifice between donor and receptor,
  outer surface of SC face to donor and inner
  surface face to receptor.
• Adding Tinidazole saturated solution into donor
  and physiological saline (0.9 NaCl) into
  receptor. Electrical pulses were applied to
  side-by-side permeation chambers by Multi-Pulse
  Generator for Electroporation of TDD according to
  determined pulse protocols.
• Each group consisted of one control test (passive
  permeation) and three pulse tests (electrical
  pulse permeation) with different pulse protocols.
  The receptor was sampled periodically i.e. 0,
  0.33, 0.67, 1.0, 1.5, 2hr after pulse by emptying
  its contents and replacing it with fresh
  physiological saline (0.9 NaCl).
• The concentration of samples was measured after
  filtration by HPLC with measure limit of 0.01
  µg/ml and sampling injection of 20µl. The
  retention time of Tinidazole was 10.42 min.
  Tinidazole permeation flux across SC at every
  sampling time was calculated.

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Results and discussion

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Determination of Thermodynamic Force and Flow

• Tinidazole mass flow Js came into being from
  donor to receptor in the permeation cell no
  matter in passive or electric pulse permeation.
• Volume loss of donor in both groups was observed
  simultaneously, it occurred in control and pulse
  group for 7/17 41.1 and 11/33 33.3 ,
  respectively, the control was greater than the
  pulse.
• High level of Tinidazole permeation through SC
  went with great volume loss, but great volume
  loss not always meant high level of permeation
  through SC. In fact, volume loss in donor was
  observed at each sampling time .

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table 2receptor tinidazole
concentration ci(µg/ml) and donor volume loss
V(µl) at sampling times(control test and
protocol M1, L2, SL3)
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Fig 2 tinidazole cumulative(mg/cm3) and volume
loss V(ml) after 2 hours.
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Experiential Formula of Phenomenological
Coefficient

• phenomenological coefficient is time dependent.
  Supposing phenomenological coefficient L11, L12,
  L21and L22 are exponential function
• where a0,a1,k1,b0,b1,k2,c0,c1,k 3 are
  experimentally fitted coefficient, fitted
  function is supposed as

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• Data function is
• Criterion function that evaluates fitting degree
  is

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Table 3 Phenomenological Coefficients
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thank you!!