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 byMiss Nada Khattiyos 09520063

Faculty of Engineering and Industrial Technology

Ou

tlin

eIntroduction

Objective

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 dibutylphthalate (DBP) is added as a plasticizer to provide satisfactory patches for

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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

At 70±2°C for 4 hours.

Store at 5°C overnight.

++ DNRL + DBP

+ DNRL + GLY

Nicotine

SCMS MC PVA

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Mechanical Properties

Young’s modulus

Ultimate tensile strength

Elongation at break

peel strength (ASTM D1876)

tack adhesion (ASTM D6195)

The adhesiveness.

The tensile strength

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Moister uptake

Silica gel

saturated NaCl, 75%RH.

weigh specimens every week until their weight

are constantCalculate

%moisture uptake.

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swelling ratio and erosion studies

at 60±2°C overnight

At room temperature 48 hours

at 60±2°C overnight

Calculate %swelling ratio and %erosion.

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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.

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Porosity Determination

• After the membrane is equilibrated– Calculate %porosity

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Dilute with distilled water.

Determination of the NCT content

5 mL of distilled water

sonication for 30 minCollect 0.5 mL

Measure spectrometry

Compare with the validated calibration curve

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An in vitro NCT release study

The modified Franz diffusion cell

Fill 12 mL PBS, pH 7.4

Stir constantly 100 rpm , at 37±0.5°C

Withdraw 1 mL

The NCT concentrations -- HPLC

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Newborn pig skin preparation

Pig skin

Stored at 4°C overnight.

Soak in PBS

Fill 12 mL PBS, pH 7.4

Stir constantly 600 rpm , at 37±0.5°C

Withdraw 1 mL

The NCT concentrations -- HPLC

An in vitro skin permeation study

The modified Franz diffusion cell 14

Stability study

Store DNRL blend patches in a well closed container

4 °C

Ambient temperature

45 °C

5 mL of distilled water

UV analysis 15

Results and Discussion

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

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

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Figure1. FT-IR spectra of DNRL, PVA, NCT, DBP, GLY, and their blended patches.

C=H

-OH

-OH

-OH

C=C

C=O C=C

C=N C=H pyridine

C=O

C-O

Aromatic ring bending band

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

-88.206°C

-64.794°C

-64.937°C

-70.896°C

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Figure3. XRD diffractograms of DNRL, PVA, NCT, and their blended patches

19.69°

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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).

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Figure5. (A)Water flux (B)percentage of porosity of various blended nicotine patches (n=3).

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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)

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

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

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

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

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Figure7. NCT permeation from DNRL/PVA patches with DBP or GLY compared with Nicotinell TTS-20(n=3) 30

Figure8. The percentage of NCT remaining in the DNRL/PVA matrix patches after storage in different conditions(n=6)

4°C 45°CAmbient Temperature

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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 GLY are siutable for developing NCT

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Thank you for your attention