Transcript Microwave non-destructive testing technique for

Microwave non-destructive testing
technique for characterization of
HPMC-PEG 3000 films
Nor Khaizan Anuar1,3, Wong Tin Wui1,3*, Mohd Nasir Taib2,3 and
Deepak K. Ghodgaonkar4
1Particle
Design Research Group, Faculty of Pharmacy,
Universiti Teknologi MARA, 40450, Shah Alam, Selangor,
Malaysia
2Faculty of Electrical Engineering, Universiti Teknologi MARA,
40450, Shah Alam, Selangor, Malaysia
3Non-Destructive Biomedical and Pharmaceutical Research
Centre, Universiti Teknologi MARA, 40450, Shah Alam,
Selangor, Malaysia
4Dhirubhai Ambani Institute of Information and
Communication Technology, DA-IICT Near Indroda Circle,
Gandhinagar, 382007, Gujarat, India
* [email protected]
CONTENT
1.0 INTRODUCTION
2.0 EXPERIMENTAL
2.1 Materials
2.2 Sample preparation
2.3 Physicochemical characterization
3.0 RESULTS AND DISCUSSION
4.0 CONCLUSION
ACKNOWLEDGEMENT
REFERENCES
1.0 INTRODUCTION
• Transdermal drug delivery system
(TDDS) utilizes the skin for the
delivery of drug molecules from the
surface of the skin, through its
layers, to the circulatory system.
• Quality
control
of
matrix
characteristics, such as state of
polymer-polymer and drug-polymer
interaction, is essential with respect
to the therapeutic effectiveness of a
TDDS.
• In the pharmaceutical industry, the
analytical
techniques
such
as
differential scanning calorimetry
(DSC) and Fourier transform infra-red
spectroscopy (FTIR) have long been
employed to determine the matrix
characteristics of a TDDS.
• However, these techniques result in
sample being unrecoverable from
test and restrict the analysis to
statistically selected samples.
• The present study sets to explore the
applicability of microwave NDT
technique as an optional tool to
characterize the matrix property of
polymer film for use as a transdermal
drug delivery system.
2.0 EXPERIMENTAL
2.1 Materials
• Hydroxypropylmethylcellulose
(HPMC, Dow Chemical Company,
USA) – matrix polymer.
• Loratadine (Morepen Laboratories,
India) – model drug.
• Polyethylene glycol (PEG 3000,
Merck, Germany) – plasticizer.
2.2 Sample preparation
• The films were prepared using
solvent evaporation method.
• The films were conditioned in a
desiccator at 25  1 °C and at three
different levels of relative humidity
(25  5 %, 50  5 % and 75  5 %) for
at least 5 days prior to the
physicochemical characterization.
Sample
HPMC
(mg)
PEG 3000
(mg)
Loratadine
(mg)
H0
37.5
0
0
P0
37.5
3.75
0
P1
37.5
3.75
5
P2
37.5
3.75
20
Table 1: Theoretical contents of HPMC, PEG 3000 and loratadine in films.
2.3 Physicochemical characterization
• The formed film was subjected to
drug content assay using UV
spectrophotometry technique, DSC,
FTIR and microwave NDT analysis.
Fig. 1: Rectangular dielectric waveguide (RDWG) measurement system.
3.0 RESULTS AND DISCUSSION
i) Drug content analysis:
Sample
Film thickness
(mm)
Relative humidity (%)
25
50
75
Loratadine content (%w/w)
H0
0.031  0.006
0
0
0
P0
0.036  0.003
0
0
0
P1
0.064  0.015
12.15  0.32
13.59  0.36
13.06  0.16
P2
0.114  0.033
39.06  0.93
35.06  1.14
38.04  1.34
Table 2: Drug content of films measured using the UV spectrophotometry technique.
The drug content of films
was not affected by the
level of relative humidity in
the
storage
chamber
(ANOVA: p > 0.05).
A flat film was formed.
A thicker film was formed in sample
containing a higher content of drug load.
ii) DSC analysis:
PEG 3000
HPMC
film
=
Tm = Polymer-plasticizer interaction was effected.
H0, P0, P1 & P2
25, 50, 75% RH
Tm
Tm
H
H
Similar exotherm was not
found in the thermograms of
films stored at the higher
levels of relative humidity, as it
was probably masked by the
melting endotherms of the
same thermogram.
An exotherm was found in
the thermogram of film P0
stored at the relative
humidity of 25%.
iii) FTIR analysis:
PEG 3000
HPMC
film
= induced polymerplasticizer interaction via
O-H moiety
H0
P0
RH (%)
25
50
75
O-H & C-H
O-H & C-H
Functional
group
Sample
P1
P2
aC=C
C-H
O-H
O-H
iv) Microwave NDT analysis:
Frequency
25
H0
P0
8 GHz
12 GHz
RH (%)
RH (%)
50
nPAC ; nPTC
nPAC ; nPTC
75
25
50
nPAC ; nPTC
nPAC ; nPTC
75
O-H & C-H
O-H & C-H
Sample
P1
nPAC ; nPTC
nPAC ; nPTC
O-H & aC=C
P2
nPAC ; nPTC
nPAC ; nPTC
O-H & C-H
• From the previous study of our laboratory,
it was found that the measurement of
microwave NDT test at 8 GHz was
sensitive to the chemical environment
involving polar moiety such as O-H
functional group, while it was greatly
governed by the less polar C-H moiety in
test conducted at 12 GHz.
• The present findings indicated that the
changes of both polar and apolar
environments of HPMC-PEG 3000 films
were reflected accordingly by the
microwave NDT measurements conducted
at the frequency bands of 8 and 12 GHz
respectively.
4.0 CONCLUSION
• The measurements of microwave NDT test
at 8 and 12 GHz were sensitive to the
changes of chemical environment in
matrix involving polar functional group
such as O-H moiety and less polar
functional group such as C-H and
aromatic C=C moieties.
• The present investigation verified that the
microwave NDT technique has the
capacity to evaluate the state of
interaction between polymer, plasticizer
and/or drug of a binary polymeric matrix,
in addition to the existing DSC and FTIR
techniques.
ACKNOWLEDGEMENT
• The authors wish to express their
heart-felt gratitude to Institute of
Research,
Development
and
Commercialization, UiTM for financial
support
and
motivation
given
throughout the research project.
REFERENCES
[1] S.T. Narisetty and P. Ramesh, “Transdermal Delivery of Zidovudine: Effect
of Vehicles on Permeation Across Rat Skin and their Mechanism of
Action,” Euro. J. Pharm. Sc., vol. 18, pp. 71-79, 2003.
[2] N.K. Pramila and R.V. Pradeep, “Eudragits: Role as Crystallization
Inhibitors in Drug-In-Adhesive Transdermal Systems of Estradiol,” Euro. J.
Pharm. and Biopharm., vol. 52, pp. 173–180, 2001.
[3] K.J. Amit, S.T. Narisetty and P. Ramesh, “Transdermal Drug Delivery of
Imipramine Hydrochloride. I. Effect of Terpenes,” J. Cont. Rel., vol. 79, pp.
93–101, 2002.
[4] X. Yu, X. Bai and G. Yunhua, “Controlled Transdermal Delivery of Model
Drug Compounds by MEMS Microneedle Array,” Nanomedicine:
Nanotechnology, Biology, and Medicine, vol. 1, pp. 184-190, 2005.
[5] C.W. Robert, J.A. Melvin and H.B. William, CRC Handbook of Chemistry
and Physics, 69th Ed., CRC Press, Inc., Florida, 1989.
[6] A. Zulkifly, D.P. Roger and W.K. Robert, “Determination of the Dielectric
Constant of Materials from Effective Refractive Index Measurements,”
IEEE Trans. on Inst. & Meas., vol. 47, pp. 148-152, 1998.
[7] A. Nor Khaizan, T.W. Wong, D.K. Ghodgaonkar and T. Mohd Nasir,
“Characterization of Hydroxypropylmethylcellulose Films using Microwave
Non-Destructive Testing Technique,” Journal of Pharmaceutical and
Biomedical Analysis, vol. 43, pp. 549–557, 2007.