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Nicotine transdermal patches using
      polymeric natural rubber as the
    matrix controlling system : Effect of
      polymer and plasticizer blends
 Wiwat Pichayakorn, Jirapornchai Suksaeree, Prapaporn Boonme, Thanaporn Amnuaikit,
                       Wirach Taweepreda, Garnpimol C. Ritthidej

Department of Pharmaceutical Technology, Faculty of Pharmaceutical Science, Prince of Songkhla University,
Songkhla 90112, Thailand
Department of Material Science and Technology, Faculty of Science, Prince of Songkhla University, Songkhla 90112, Thailand
Department of Pharmaceutical and industrial Pharmacy, Faculty of Pharmaceutical Science, Chulalongkorn University, Bangkok
10330, Thailand




                         Present by
              Miss Nada Khattiyos 09520063
            Faculty of Engineering and Industrial
Introduction

                Objective
Outline
          Materials and Methods

          Results and Discussion

               Conclusion
                                   2
Introduction




               3
Objective
     This research is focused on the use of
deproteinized natural rubber latex (DNRL)
as a major polymer for preparing NCT
transdermal patches.
     Safe polymer blends, i.e. sodium
carboxymethyl cellulose (SCMC), methyl
cellulose (MC), or polyvinyl alcohol (PVA)
were used to improve the adhesive
properties. Either glycerin (GLY) or
                                              4
dibutylphthalate (DBP) is added as a
Materials
Deproteinized Natural Rubber Latex


         Nicotine (>99%)

 Sodium Carboxymethyl Cellulose
            (SCMC)

      Methyl Cellulose (MC)


      Polyvinyl alcohol (PVA)


          Glycerin (GLY)


     Dibutylphathalate (DBP)
                                     5
Preparation of patches
                                                     + DNRL
                                                  + DNRL + DBP
                   +
                                                  + DNRL + GLY


SCMS   MC    PVA
                                            Store at 5°C
                                             overnight.




                             Nicotine



                       At 70±2°C for 4 hours.
                                                                 6
Mechanical Properties

                        Young’s modulus

The tensile strength    Ultimate tensile strength

                        Elongation at break


                       peel strength (ASTM D1876)
The adhesiveness.
                       tack adhesion (ASTM D6195)

                                                    7
Moister uptake




              Silica gel

                       weigh specimens every
                       week until their weight
                            are constant
Calculate
%moisture
 uptake.
                           saturated NaCl,
                           75%RH.                8
swelling ratio and erosion studies



                  at 60±2°C           At room temperature
                  overnight                 48 hours



  Calculate
%swelling ratio
and %erosion.


                              at 60±2°C
                              overnight               9
Compatibility
    Fourier Transform Infrared (FT-IR)
              Spectroscopy.

 Differntial Scanning Calorimetry (DSC).

        X-ray Diffractometry (XRD).


Microscopic morphology
 Scanning Electron Microscope (SEM) -- the surface and
      cross section morphologies of the patches.
                                                         10
Porosity Determination
                   • After the membrane is
                     equilibrated
                     – Calculate %porosity




                                             11
Determination of the NCT content



5 mL of distilled water
                                                                        Collect 0.5 mL
                             sonication for 30 min



                                      Measure spectrometry

Compare with the validated
    calibration curve

                                                     Dilute with distilled water.   12
An in vitro NCT release study

                                          Fill 12 mL PBS, pH 7.4


                                         Stir constantly 100 rpm ,
                                                at 37±0.5°C


                                             Withdraw 1 mL




                                    The NCT concentrations -- HPLC

The modified Franz diffusion cell
                                                                   13
Newborn pig skin preparation             An in vitro skin
                                        permeation study
              Pig skin



         Stored at 4°C overnight.             Fill 12 mL PBS, pH 7.4


                                             Stir constantly 600 rpm ,
                                                    at 37±0.5°C


                                                 Withdraw 1 mL


Soak in PBS

                                        The NCT concentrations -- HPLC

    The modified Franz diffusion cell                                    14
Stability study

                             4 °C
  Store DNRL blend
  patches in a well   Ambient temperature
  closed container
                             45 °C




                                        5 mL of distilled water
  UV analysis                                              15
Results and Discussion
Table 1
The mechanical properties, moisture uptake, and swelling ratio of DNRL and its
blended patches.




                                                                                 17
Table 1
The mechanical properties, moisture uptake, and swelling ratio of DNRL and
its blended patches(Cont.).




                                                                             18
C=C
  C=H

                                Figure1. FT-IR spectra
        C=O          C=C
                                of DNRL, PVA, NCT,
-OH
                                DBP, GLY, and their
                                blended patches.
-OH
               C=N     C=H pyridine




        C=O
                       Aromatic ring
                       bending band




        C-O
-OH



                                                    19
-64.937°C



                             -70.896°C




               -88.206°C




                                  -64.794°C




Figure2. DSC thermograms of DNRL, PVA, NCT, and their blended patches 20
19.69°




Figure3. XRD diffractograms of DNRL, PVA, NCT, and their blended patches 21
Figure4. SEM micrographs of (A)DNRL, (B)DNRL/PVA/DBP, and (C)DNRL/PVA/GLY patches
(a:surface of patches, b and c: cross section of a before and after the release study,
respectively)                                                                          22
Figure5. (A)Water flux (B)percentage of porosity of various blended nicotine patches (n=3).
                                                                                         23
Figure5. (A)Water flux (B)percentage of porosity of various blended nicotine patches (n=3).

                                                                                       24
Figure6. NCT release from DNRL
alone and (A)DNRL/SCMC,
(B)DNRL/MC and (C)DNRL/PVA
patches without and with DBP or
GLY compared with Nicotinell TTS-
20 (n=6)
                                25
Table2. The entrapment efficiency and in vitro release kinetics of NCT from
DNRL/polymer blended patches




                                                                              26
Table2. The entrapment efficiency and in vitro release kinetics of NCT from
DNRL/polymer blended patches(Cont.)




                                                                              27
Table3. The in vitro skin permeation kinetics of NCT from DNRL/polymer
blended patches.




                                                                         28
Table3. The in vitro skin permeation kinetics of NCT from DNRL/polymer
blended patches(Cont.).




                                                                         29
Figure7. NCT permeation from DNRL/PVA patches with DBP or GLY compared with
                                                                      30
Nicotinell TTS-20(n=3)
4°C                      Ambient                    45°C
                                     Temperature




Figure8. The percentage of NCT remaining in the DNRL/PVA matrix patches after
storage in different conditions(n=6)                                          31
Conclusions
• DNRL blended with PVA provided the
  best patch for delivery of the NCT to
  the skin.
• Moreover, the in vitro release and
  skin permeation study of the release
  of NCT are mainly affected by
  hydrophilicilty of the patches.
• The polymeric patches composed of
  DNRL/PVA blends with either DBP or      32
Thank you for
your attention

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Seminar presentation

  • 1. Nicotine transdermal patches using polymeric natural rubber as the matrix controlling system : Effect of polymer and plasticizer blends Wiwat Pichayakorn, Jirapornchai Suksaeree, Prapaporn Boonme, Thanaporn Amnuaikit, Wirach Taweepreda, Garnpimol C. Ritthidej Department of Pharmaceutical Technology, Faculty of Pharmaceutical Science, Prince of Songkhla University, Songkhla 90112, Thailand Department of Material Science and Technology, Faculty of Science, Prince of Songkhla University, Songkhla 90112, Thailand Department of Pharmaceutical and industrial Pharmacy, Faculty of Pharmaceutical Science, Chulalongkorn University, Bangkok 10330, Thailand Present by Miss Nada Khattiyos 09520063 Faculty of Engineering and Industrial
  • 2. Introduction Objective Outline Materials and Methods Results and Discussion Conclusion 2
  • 4. Objective This research is focused on the use of deproteinized natural rubber latex (DNRL) as a major polymer for preparing NCT transdermal patches. Safe polymer blends, i.e. sodium carboxymethyl cellulose (SCMC), methyl cellulose (MC), or polyvinyl alcohol (PVA) were used to improve the adhesive properties. Either glycerin (GLY) or 4 dibutylphthalate (DBP) is added as a
  • 5. Materials Deproteinized Natural Rubber Latex Nicotine (>99%) Sodium Carboxymethyl Cellulose (SCMC) Methyl Cellulose (MC) Polyvinyl alcohol (PVA) Glycerin (GLY) Dibutylphathalate (DBP) 5
  • 6. Preparation of patches + DNRL + DNRL + DBP + + DNRL + GLY SCMS MC PVA Store at 5°C overnight. Nicotine At 70±2°C for 4 hours. 6
  • 7. Mechanical Properties Young’s modulus The tensile strength Ultimate tensile strength Elongation at break peel strength (ASTM D1876) The adhesiveness. tack adhesion (ASTM D6195) 7
  • 8. Moister uptake Silica gel weigh specimens every week until their weight are constant Calculate %moisture uptake. saturated NaCl, 75%RH. 8
  • 9. swelling ratio and erosion studies at 60±2°C At room temperature overnight 48 hours Calculate %swelling ratio and %erosion. at 60±2°C overnight 9
  • 10. Compatibility Fourier Transform Infrared (FT-IR) Spectroscopy. Differntial Scanning Calorimetry (DSC). X-ray Diffractometry (XRD). Microscopic morphology Scanning Electron Microscope (SEM) -- the surface and cross section morphologies of the patches. 10
  • 11. Porosity Determination • After the membrane is equilibrated – Calculate %porosity 11
  • 12. Determination of the NCT content 5 mL of distilled water Collect 0.5 mL sonication for 30 min Measure spectrometry Compare with the validated calibration curve Dilute with distilled water. 12
  • 13. An in vitro NCT release study Fill 12 mL PBS, pH 7.4 Stir constantly 100 rpm , at 37±0.5°C Withdraw 1 mL The NCT concentrations -- HPLC The modified Franz diffusion cell 13
  • 14. Newborn pig skin preparation An in vitro skin permeation study Pig skin Stored at 4°C overnight. Fill 12 mL PBS, pH 7.4 Stir constantly 600 rpm , at 37±0.5°C Withdraw 1 mL Soak in PBS The NCT concentrations -- HPLC The modified Franz diffusion cell 14
  • 15. Stability study 4 °C Store DNRL blend patches in a well Ambient temperature closed container 45 °C 5 mL of distilled water UV analysis 15
  • 17. Table 1 The mechanical properties, moisture uptake, and swelling ratio of DNRL and its blended patches. 17
  • 18. Table 1 The mechanical properties, moisture uptake, and swelling ratio of DNRL and its blended patches(Cont.). 18
  • 19. C=C C=H Figure1. FT-IR spectra C=O C=C of DNRL, PVA, NCT, -OH DBP, GLY, and their blended patches. -OH C=N C=H pyridine C=O Aromatic ring bending band C-O -OH 19
  • 20. -64.937°C -70.896°C -88.206°C -64.794°C Figure2. DSC thermograms of DNRL, PVA, NCT, and their blended patches 20
  • 21. 19.69° Figure3. XRD diffractograms of DNRL, PVA, NCT, and their blended patches 21
  • 22. Figure4. SEM micrographs of (A)DNRL, (B)DNRL/PVA/DBP, and (C)DNRL/PVA/GLY patches (a:surface of patches, b and c: cross section of a before and after the release study, respectively) 22
  • 23. Figure5. (A)Water flux (B)percentage of porosity of various blended nicotine patches (n=3). 23
  • 24. Figure5. (A)Water flux (B)percentage of porosity of various blended nicotine patches (n=3). 24
  • 25. Figure6. NCT release from DNRL alone and (A)DNRL/SCMC, (B)DNRL/MC and (C)DNRL/PVA patches without and with DBP or GLY compared with Nicotinell TTS- 20 (n=6) 25
  • 26. Table2. The entrapment efficiency and in vitro release kinetics of NCT from DNRL/polymer blended patches 26
  • 27. Table2. The entrapment efficiency and in vitro release kinetics of NCT from DNRL/polymer blended patches(Cont.) 27
  • 28. Table3. The in vitro skin permeation kinetics of NCT from DNRL/polymer blended patches. 28
  • 29. Table3. The in vitro skin permeation kinetics of NCT from DNRL/polymer blended patches(Cont.). 29
  • 30. Figure7. NCT permeation from DNRL/PVA patches with DBP or GLY compared with 30 Nicotinell TTS-20(n=3)
  • 31. 4°C Ambient 45°C Temperature Figure8. The percentage of NCT remaining in the DNRL/PVA matrix patches after storage in different conditions(n=6) 31
  • 32. Conclusions • DNRL blended with PVA provided the best patch for delivery of the NCT to the skin. • Moreover, the in vitro release and skin permeation study of the release of NCT are mainly affected by hydrophilicilty of the patches. • The polymeric patches composed of DNRL/PVA blends with either DBP or 32
  • 33. Thank you for your attention