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Original Research Paper

Zingiber cassumunar blended patches for skinapplication: Formulation, physicochemicalproperties, and in vitro studies

Jirapornchai Suksaeree a,b,*, Laksana Charoenchai b, Fameera Madaka b,Chaowalit Monton b, Apirak Sakunpak b,c, Tossaton Charoonratana b,c,Wiwat Pichayakorn d,e

a Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Rangsit University, Muang, Pathum Thani 12000,

Thailandb Sino-Thai Traditional Medicine Research Center (Cooperation between Rangsit University, Harbin Institute of

Technology, and Heilongjiang University of Chinese Medicine), Faculty of Pharmacy, Rangsit University, Muang,

Pathum Thani 12000, Thailandc Department of Pharmacognosy, Faculty of Pharmacy, Rangsit University, Muang, Pathum Thani 12000, Thailandd Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University,

Hat-Yai, Songkhla 90112, Thailande Medical Products Innovations from Polymers in Clinical Use Research Unit, Prince of Songkla University, Hat-Yai,

Songkhla 90112, Thailand

a r t i c l e i n f o

Article history:

Received 15 December 2014

Received in revised form

16 February 2015

Accepted 3 March 2015

Available online 12 March 2015

Keywords:

Chitosan

Polyvinyl alcohol

Z. cassumunar patches

Blended patches

Skin application

* Corresponding author. Department of PharmThailand. Tel.: þ66 (2) 9972222x1502, þ66 (2)E-mail address: jirapornchai.s@rsu.ac.th (J. S

Peer review under responsibility of Shenyanhttp://dx.doi.org/10.1016/j.ajps.2015.03.0011818-0876/© 2015 Shenyang PharmaceuticalCC BY-NC-ND license (http://creativecommo

a b s t r a c t

Our work was to study the preparation, physicochemical characterization, and in vitro

characteristic of Zingiber cassumunar blended patches. The Z. cassumunar blended patches

incorporating Z. cassumunar Roxb. also known as Plai were prepared from chitosan and

polyvinyl alcohol with glycerin as plasticizer. They were prepared by adding all ingredients

in a beaker and homogeneously mixing them. Then, they were transferred into Petri-dish

and dried in hot air oven. The hydrophilic nature of the Z. cassumunar blended patches was

confirmed by the moisture uptake, swelling ratio, erosion, and porosity values. The FTIR,

DSC, XRD, and SEM studies showed revealed blended patches with amorphous region that

was homogeneously smooth and compact in both surface and cross section dimensions.

They exhibited controlled the release behavior of (E)-4-(30,40-dimethoxyphenyl) but-3-en-l-

ol (compound D) that is the main active compound in Z. cassumunar for anti-inflammation

activity. However, in in vitro skin permeation study, the compound D was accumulated in

newborn pig skin more than in the receptor medium. Thus, the blended patches showed

the suitable entrapment and controlled release of compound D. Accordingly, we have

aceutical Chemistry, Faculty of Pharmacy, Rangsit University, Muang, Pathum Thani 12000,9972222x4911; fax: þ66 (2) 9972222x1403, þ66 (2) 9972222x1508.uksaeree).

g Pharmaceutical University.

University. Production and hosting by Elsevier B.V. This is an open access article under thens.org/licenses/by-nc-nd/4.0/).

a s i a n j o u r n a l o f p h a rma c e u t i c a l s c i e n c e s 1 0 ( 2 0 1 5 ) 3 4 1e3 4 9342

demonstrated that such chitosan and polyvinyl alcohol formulated patches might be

developed for medical use.

© 2015 Shenyang Pharmaceutical University. Production and hosting by Elsevier B.V. This is

an open access article under the CC BY-NC-ND license (http://creativecommons.org/

licenses/by-nc-nd/4.0/).

1. Introduction

Topical and transdermal drug delivery systems are intended

for external use. They are often dermatologic products such as

sunscreens, local anesthetics, antiseptics and anti-

inflammatory agents intended for localized action on one or

more layers of the skin. Conversely, some transdermal drug

delivery systems are designed for percutaneous route of drug

delivery in which case skin is not the target. In such case, the

drug must be absorbed across the skin which is made up of

dermis and epidermis, especially the stratum corneum barrier

including sweat glands, sebaceous glands, and hair follicles

[1], and pass into deeper dermal layers to reach the systemic

blood circulation. Generally, substances intended for trans-

dermal delivery systems are low molecular weight (100-

500 Da), potent non-irritation and non-allergenic [2e4]. The

delivery system can be categorized as either i) drug in adhe-

sive or ii) drug in matrix systems. The drug is dispersed or

dissolved in a polymer matrix and attached to an adhesive

layer that contacts the skin. In some cases, the polymer ma-

trix can act as the adhesive layer. Polymer matrix layers and/

or the added adhesive layer act as a control of the rate of de-

livery [5,6].

Thai traditional medicines (herbal medicines) are popular

for the treatment of various symptoms and diseases and to

promote good health. Although the Western modern medi-

cines are increasingly popular, Thai traditionalmedicines are

still widely used especially among the rural Thais. Herbal

medicines may contain variations of active ingredients parts

of plants, other plant materials, or combinations that

included herbs, herbal materials, herbal preparations, and

finished herbal products. Zingiber cassumunar Roxb., also

known as Thai name “Plai”, is a medicinal plant widely

cultivated in Thailand and tropical Asia. It is frequently used

as an ingredient in marketed phytomedicines [7,8]. The

rhizome of Z. cassumunar Roxb. has an anti-inflammatory

activity. It has been the source of Thai traditional herbal

remedies and extracts for topical application to alleviate

inflammation [9e11]. The chemical composition of the

rhizome oils of Z. cassumunar Roxb. has been previously re-

ported [7,10,12e16]. The major constituents of the crude oils

are terpinen-4-ol, a- and b-pinene, sabinene, myrcene, a- and

g-terpinene, limonene, terpinolene, sabmene, and mono-

terpenes [12,17]. (E)-4-(30,40-dimethoxyphenyl) but-3-en-l-ol

(compound D) is the main active compound in Z. cassumunar

that exhibits anti-inflammatory [11,15,18], analgesic and

antipyrectic [11,15,16] activity in experimental models. It is

also used as topical treatment for sprains, contusions, joint

inflammations, muscular pain, abscesses, and similar

inflammation-related disorders [19e21]. Thus, this work

used the compound D as the marker compound for in vitro

study.

Herbal patches are adhesive patches that incorporate the

herbal medicines or extracted herb. When applied to the skin

the active compound is released at a constant rate. Such

patches are recommended for smoking cessation, herbal body

detox foot patch, relief of stress, to increase sexuality, as in-

sect repellants, as male energizer, to improve sleep, to post-

pone menopause, for rheumatoid arthritis, as herbal plasters

patches, etc. [22].

The aimof the current studywas to prepare a Z. cassumunar

containing product incorporating the crude Z. cassumunar oil

in blended patches that consisted of chitosan and polyvinyl

alcohol (PVA) polymer matrix combination using glycerin as

plasticizer. Similarly prepared blended patches without crude

Z. cassumunar oil served as control. The patches were evalu-

ated with regard to the physicochemical properties as mois-

ture uptake, swelling ratio, erosion, porosity, Fourier

transform infrared spectroscopy (FTIR), differential scanning

calorimetry (DSC), X-ray diffraction (XRD), scanning electron

microscope (SEM), and in vitro release and skin permeation

studies.

2. Materials and methods

2.1. Materials

The Z. cassumunar rhizome powder was purchased from

Charoensuk Osod, Thailand. The Z. cassumunar powder was

extracted in 95% ethanol and filtered through a 0.45 mm of

polyamide membrane to obtain crude Z. cassumunar oil. Chi-

tosan (degree of deacetylation ¼ 85%, mesh size 30) was pur-

chased from Seafresh Industry Public Co., Ltd, Thailand. PVA

and glycerin were purchased from SigmaeAldrich, USA. All

organic solvents were analytical grade obtained from Merck

KGaA, Germany.

2.2. Analytical method

An Agilent 1260 Infinity system (Agilent Technologies, USA.)

was used for this experiment with detection at 260 nm, a

4.6 mm � 250 mm diameter, 5 mm particle size C18 column

(ACE 5, DV12-7219, USA.), a flow rate of 1 ml/min, and injec-

tion volume of 10 mL. Themobile phase was a gradient elution

of 2% acetic acid in ultrapure water (A) and methanol (B) of 60

to 50% of A, 50 to 30% of A, 30 to 20% of A, 20 to 50% of A,

50 to 60% of A, and 60% of A for 0e5 min, 5e15 min,

15e25 min, 25e30 min, 30e32 min, and 32e40 min, respec-

tively [23]. The HPLC validation method of compound D pro-

vided a limit of detection of 0.20 mg/ml, the limit of

a s i a n j o u rn a l o f p h a rma c e u t i c a l s c i e n c e s 1 0 ( 2 0 1 5 ) 3 4 1e3 4 9 343

quantification of 0.80 mg/ml, good accuracy (95.38e104.76%),

precision (less than 2%CV), and linearity with good correla-

tion coefficient (r2) > 0.9999 in the required concentration

range of 2e40 mg/ml. The separation method and validation

method of compound D from crude Z. cassumunar oil was

described in previous publication [23,24].

2.3. Z. cassumunar blended patches preparation

The chitosan was dissolved in 1% acetic acid in distilled water

in concentration of 3.5%w/v. The PVA was dissolved in

distilled water in concentration of 20%w/v. The blank blended

patches were prepared by 2 g of 3.5%w/v chitosan were mixed

together with 5 g of 20%w/v of PVA, and homogeneously

mixed with 2 g of glycerin as plasticizer to obtain clear poly-

mer blended solution. The Z. cassumunar blended patches

were prepared as 3 g of the crude Z. cassumunar oil completely

dissolved in absolute ethanol and continuously mixed in

polymer blend solution. They were transferred into Petri-dish

and dried in hot air oven at 70 ± 2 �C for 5 h. Finally, they were

peeled from Petri-dish and kept in desiccator until used.

2.4. Evaluation of blank and Z. cassumunar blendedpatches

2.4.1. SEM photographyThe surface and cross section of blank blended patches and Z.

cassumunar blended patcheswere placed onto copper stub and

then coated with gold in a sputter coater. They were photo-

graphed under SEM equipment (model: Quanta 400, FEI, Czech

Republic) with high vacuum and high voltage of 20 kV condi-

tion, with Everhart Thornley detector (ETD).

2.4.2. FTIR studyThe FTIR study employed the Attenuated Total Reflectance e

FTIR (ATR-FTIR) technique for the chitosan film, PVA film,

crude Z. cassumunar oil, blank blended patches, and Z. cassu-

munar blended patches. They were scanned at a resolution of

4 cm�1 with 16 scans over a wavenumber region of 400 e

4000 cm�1. The FTIR spectrometer (model: Nicolet 6700,

DLaTGS detector, Thermo Scientific, USA.) was used to

determine IR transmission spectra and record the character-

istic peaks.

2.4.3. DSC studyA DSC instrument (model: DSC7, Perkin Elmer, USA) was used

to investigate the endothermic transition of the substances

that also confirmed the compatibility of each ingredient. The 1

e 10 mg of sample was weighted in DSC pan, hermetically

sealed, and run in the DSC instrument at the heating rate of

10 �C/min under a liquid nitrogen atmosphere from 20 �C to

350 �C.

2.4.4. XRD studyThe XRD (model: X'Pert MPD, PHILIPS, Netherlands) was

employed to study the compatibility of the chitosan, PVA,

blank blended patches, and Z. cassumunar blended patches.

The generator operating voltage and current of X-ray source

were 40 kV and 45mA, respectively, with an angular of 5 e 40�

(2q), and a stepped angle of 0.02� (2q)/s.

2.4.5. Moisture uptake, swelling ratio, and erosion studiesFor determination of moisture uptake, swelling ratio and

erosion, 1 cm � 1 cm patch specimens were used. For mois-

ture uptake determination, the patch specimens were

weighed for their initial value (W0), then moved to a stability

chamber (model: Climate Chamber ICH/ICH L, Memmert

GmbH þ Co. KG, Germany) which controlled the temperature

at 25 ± 2 �C and 75% relative humidity environment. The

specimens were removed and weighed until constant (Wu).

The percentage of moisture uptake was calculated by Equa-

tion (1) [25]

Moisture uptake ¼ ðWu �W0ÞW0

(1)

The swelling ratio and erosion study were also determined

by drying patch specimens at 60 ± 2 �C overnight. Then, they

were weighed (W0) and immersed in 5 ml of distilled water

and moved to stability chamber (model: Climate Chamber

ICH/ICH L, Memmert GmbH þ Co. KG, Germany) which

controlled the temperature at 25 ± 2 �C and 75% relative hu-

midity environment for 48 h. After removal of excess water,

the hydrated patches were weighed (Ws). They were then

dried again at 60± 2 �C overnight, andweighed again (Wd). The

percentage of swelling ratio and the percentage of erosion

were calculated by Equations (2) And (3), respectively.

%Swelling ratio ¼ ðWs �W0ÞW0

� 100 (2)

%Erosion ¼ ðW0 �WdÞW0

� 100 (3)

2.4.6. Porosity determinationAfter the patch specimens were equilibrated in water, the

volume occupied by the water and the volume of the mem-

brane in the wet state were determined. The porosity of patch

specimens was obtained by Equation (4).

%Porosity ¼ ðW1 �W2Þdwater

� 100w� l� t

(4)

where W1 and W2 ¼ the weights of the membranes in the wet

and dry states (g), respectively, dwater ¼ the density of pure

water at 20 �C, and w, l, t ¼ the width (cm), length (cm), and

thickness (cm) of the membrane in the wet state, respectively

[26,27].

2.5. The determination of compound D in patches

The blended patches were cut into 2 cm � 2 cm specimens

from different sites. Each Plai patch sample was soaked with

ethanol in 10 ml volumetric flask, and sonicated at 25 �C for

30 min. Then, the solution was sampled for 0.5 ml and

transferred into 100 ml volumetric flask and adjusted to vol-

ume of 100 ml with ethanol. The solution was filtered through

a 0.45 mm filter and analyzed with HPLC method.

2.6. In vitro release study of compound D

The modified Franz-type diffusion cell having effective diffu-

sion area of 1.77 cm2 was used for in vitro release and skin

a s i a n j o u r n a l o f p h a rma c e u t i c a l s c i e n c e s 1 0 ( 2 0 1 5 ) 3 4 1e3 4 9344

permeation study of compound D from the Z. cassumunar

blended patches. The receptor medium was 12 ml of isotonic

phosphate buffer solution pH 7.4: ethanol ¼ 80:20, thermo-

regulated with a water jacket at 37 ± 0.5 �C and stirred

constantly at 600 rpm with a magnetic stirrer. The crude Z.

cassumunar oil was applied on the cellulose membrane

(MWCO: 3500 Da, CelluSep® T4, Membrane Filtration Product,

Inc., USA) which was used as a barrier between the donor

compartment and the receptor compartment. The Z. cassu-

munar blended patch preparations were cut and placed

directly on the donor cells. The 1 ml of receptor solution was

withdrawn at 0, 0.5, 1, 2, 3, 4, 6, and 24 h intervals, and

immediately replaced with an equal volume of fresh receptor

medium. The compound D content in these samples was

determined by an HPLC method.

2.7. In vitro skin permeation study of compound D

The in vitro skin permeation of the compound D from the Z.

cassumunar blended patches was also carried out using a

modified Franz-type diffusion cell [28], and pig skin with

hair removed was an applied partitioning membrane [29,30].

The newborn pigs of 1.4e1.8 kg weight that had died by

natural causes shortly after birth were freshly purchased

from a local pig farm in Chachoengsao Province, Thailand.

The full thickness of flank pig skin was excised, hair was

surgically removed, and the subcutaneous fat and other

extraneous tissues were trimmed with a scalpel, cleaned

with isotonic phosphate buffer solution pH 7.4, blotted dry,

wrapped with aluminum foil and stored frozen. Before

permeation experiments, this isolated skin was soaked

overnight in isotonic phosphate buffer solution pH 7.4, and

mounted on the modified Franz-type diffusion cell with the

stratum corneum facing upward on the donor compart-

ment. The crude Z. cassumunar oil and Z. cassumunar

blended patches were laid onto the isolated skin in the same

way as for the release study. The receptor compartment was

12 ml of isotonic phosphate buffer solution pH 7.4:

ethanol ¼ 80:20 and stirred constantly at 600 rpm by a

magnetic stirrer, at a constant temperature of 37 ± 0.5 �C. A1 ml of the receptor solution was withdrawn at 0, 0.5, 1, 2, 3,

4, 6, and 24 h intervals and an equal volume of fresh re-

ceptor medium was immediately replaced. The compound D

content in these samples was determined by the HPLC

method.

All in vitro release and skin permeation studies were per-

formed in triplicate and the means of all measurements

calculated. The results were presented in terms of cumulative

percentage release or skin permeation as a function of time

using the following formula:

Cumulative percentage release or skin permeation

¼ Dt

Dl� 100 (5)

where Dt was the amount of compound D released or

permeated from the Z. cassumunar blended patches at time t

and Dl was the amount of compound D loaded into the Z.

cassumunar blended patches.

3. Results and discussion

3.1. Evaluation of blank and Z. cassumunar blendedpatches

Generally, the Z. cassumunar rhizomes were of deep yellow

color possessing a strong camphoraceous smell, warm, spicy,

and bitter taste [12,17,31]. The extraction of the Z. cassumunar

rhizome powder yielded a clear, high viscosity, yellow-orange

crude Z. cassumunar oil. The solvent extraction of plant ma-

terials likely produced oleoresin, which contained not only the

volatile compounds but also waxes and color pigments [32]. In

addition, Sukatta et al. 2009 reported two pathways for Z.

cassumunar rhizome extraction-hydro distillation and hexane

extraction. They confirmed that hydro distillation produced

the yellowish, low viscosity crude Z. cassumunar oil, while the

crude Z. cassumunar oil from the hexane extraction was

yellow-orange in color and had high viscosity. Commonly, our

work could confirm from its appearance that crude Z. cassu-

munar oil was obtained. Therefore, when crude Z. cassumunar

oil was added in blank blended patches, it produced the dark

yellow patches referred to as Z. cassumunar blended patches.

The photographs of blank blended and Z. cassumunar blended

patches were shown in previous reports by our research group

[33].

The SEM technique was used to photograph the high res-

olution morphology of the surface and cross section of blank

blended patches and Z. cassumunar blended patches (Fig. 1).

The surface of blank blended patches was homogeneously

smooth and dense with no visual pores (Fig. 1A). The surface

of Z. cassumunar blended patches became rough and uneven

as a result of widely distributed conglomeration and aggre-

gation in the matrix of Z. cassumunar blended patches (pho-

tographed by digital camera and presented in previous

publication [33]) (Fig. 1B).

Recorded spectra are shown in Fig. 2. For the chitosan film,

the absorption peaks of stretching vibrations of eOH groups

broadly overlapped the stretching vibration of NeH ranging

from 3750 to 3000 cm�1. The broad stretching vibrations of

CeH bond were observed at 2920e2875 cm�1. The bending

vibrations of methylene and methyl groups were also absor-

bed at 1375 cm�1 and 1426 cm�1, respectively. The spectrum

bands in the range of 1680e1480 cm�1 were identified as vi-

brations of carbonyl bonds of the amide group and vibrations

of protonated amine group. The vibrations of CO group

occurred in the range from 1160 cm�1e1000 cm�1. In addition,

the spectrum band located at around 1150 cm�1 related to

asymmetric vibrations of CO in the oxygen bridge resulting

from deacetylation of chitosan. The spectrum bands at

1080e1025 cm�1 were attributed to eCO of the ring COH, COC,

and CH2OH. Finally, the small spectrum peak at ~890 cm�1

corresponded to wagging of the saccharide structure of chi-

tosan [34]. Furthermore, the spectrum of acetic acid were

found at 3050, 1720, and 1432 related toeOH bond in carbox-

ylic acid, CeO bond, and CeO bond, respectively. In addition,

the PVA spectrum showed both OeH stretching and CeO

stretching at 3449 and 1637 cm�1, respectively [35,36].

The chitosan film, blank blended, and Z. cassumunar

blended patches weighed 1.662, 8.747, and 8.821 mg,

Fig. 1 e Surface (£500 (A), £1000 (B), and £1500 (C)) and cross section morphology (£1000 (D), £1500 (E), and £5000 (F)) of

blank blended patches (upper) and Z. cassumunar blended patches (bottom) under SEM technique.

a s i a n j o u rn a l o f p h a rma c e u t i c a l s c i e n c e s 1 0 ( 2 0 1 5 ) 3 4 1e3 4 9 345

respectively. They were run with DSC instrument to study the

thermal behavior. The thermogram of chitosan film, blank

blended, and Z. cassumunar blended patches showed an initial

broad peak at 70.33 �Cwith 231.35 J/g of enthalpy of peak (DH),

99.34 �C with 188.307 J/g of DH, and 92.37 �C with 78.76 J/g of

DH, respectively, which was attributed to evaporation of

moisture and represented the required energy to vaporize

water present in their samples. Moreover, the degradation

DSC peak of chitosan film broadly occurred at 323.67 �C with

127.30 J/g of DH. In addition, the blank blended patches and Z.

cassumunar blended patches revealed high broad endothermic

peaks at 257.00 �C with 363.24 J/g of DH and 261.00 �C with

606.41 J/g of DH, respectively. Although the observed endo-

thermic peaks in blank blended patches and Z. cassumunar

blended patches were slightly changed, there were no new

exo- or endo-thermic peaks in any experimental ranges indi-

cating compatibility of all ingredients (Fig. 3).

The XRD technique was used to identify and characterize

crystalline and amorphous form of chitosan film, PVA film,

blank blended patches, and Z. cassumunar blended patches

that had been studied in range of 5e40� (2q values) (Fig. 4). TheX-ray diffraction profile of chitosan film showed peaks at ~10�

Fig. 2 e FTIR spectra of chitosan, PVA, blank blended

patches, and Z. cassumunar blended patches.

and ~23� (2q). The intensity result of PVA film was 19.69�

representing their semi-crystalline characters because of the

strong intermolecular interaction between PVA chains

through intermolecular hydrogen bonding [37]. Thus, the

chitosan and PVA film exhibited the semi-crystalline charac-

teristics, but the XRD patterns of blank blended patches and Z.

cassumunar blended patches had broad diffraction halo of

amorphous region.

From above experimentals, the FTIR, DSC and XRD results

showed that therewere no chemical interactions between any

components in blank blended patches or Z. cassumunar

blended patches.

Limpongsa and Umprayn (2008) reported that moisture

uptake, swelling ratio, erosion, and porosity values play

important roles for the release behavior of active compound in

matrix type patches [38]. Thus, this research evaluated these

variables as show in Fig. 5.We found that themoisture uptake,

swelling ratio, erosion, and porosity of blank blended patches

were 28.85 ± 4.17, 21.01 ± 5.38, 2.39 ± 0.41, and 1.92 ± 0.22%,

respectively.When crude Z. cassumunar oil was added in blank

blended patches, the moisture uptake, swelling ratio, erosion,

and porosity of blank blended patches were 28.51 ± 0.78,

Fig. 3 e DSC thermograms of chitosan, blank blended

patches, and Z. cassumunar blended patches.

Fig. 4 e XRD patterns of chitosan, PVA, blank blended

patches, and Z. cassumunar blended patches.

a s i a n j o u r n a l o f p h a rma c e u t i c a l s c i e n c e s 1 0 ( 2 0 1 5 ) 3 4 1e3 4 9346

20.93 ± 5.88, 2.42 ± 0.98, 1.86 ± 0.24%, respectively, which

were not significantly different from blank blended patches.

These results are due to the fact that hydrophilic parts of in-

gredients could be dissolved and eroded from the blended

patches. The chitosan and PVA could swell and immediately

had the hydrated blended patches contents. The chains

Fig. 5 e The moisture uptake, swelling ratio, erosion, and poro

blended patches.

mobility of chitosan and PVA increased, therefore, increasing

the hydrodynamic volume of the polymer compact.

3.2. In vitro release study of compound D

In vitro release of the crude Z. cassumunar oil released com-

pound D calculated as cumulative percentage release

90.43 ± 19.28% after 24 h (Fig. 6). The almost 100% release of

compound D in 24 h might be due to rapid diffusion in the

receptor medium as a fast, initial burst during the first 6 h.

The amount of compound D in the Z. cassumunar blended

patches was 2.19 ± 0.16 mg/cm2. When the Z. cassumunar

blended patches were studied in in vitro, the cumulative per-

centage release of compound D was 81.49 ± 10.92% after 24 h

(Fig. 6). The release behavior was similar to the compound D

release behavior from crude Z. cassumunar oil that had a fast

initial burst release during the first 6 h. This behavior was

likely due to the compound D on the surface of patches might

be rapid diffusion. However, the effect may be attributed to

the moisture uptake, swelling ratio, erosion, and porosity

whereby the patch could absorb the moisture, and create a

space and a large free volumewithin the blended patches that

enhanced compound D diffusion [38]. Moreover, Guo et al.

2011 reported enhanced drug diffusion with amorphous ma-

trix type patches [39] which supports our results in in vitro

study. The in vitro release kinetics model of compound D

provided a better fit to first-ordermodel than to the zero-order

and Higuchi's model (Fig. 6).

3.3. In vitro skin permeation study of compound D

The in vitro skin permeation studywas carried out in amodified

Franz-type diffusion cell using newborn pig skin as a partition

sity values of blank blended patches and Z. cassumunar

Fig. 6 e In vitro release of compound D content from crude Z. cassumunar oil and Z. cassumunar blended patches and in vitro

release kinetics of zero order model (A), first order model (B), and Higuchi's model (C).

Fig. 7 e In vitro skin permeation of compound D content from crude Z. cassumunar oil and Z. cassumunar blended patches

and in vitro skin permeation kinetics of zero order model (A), first order model (B), and Higuchi's model (C).

a s i a n j o u rn a l o f p h a rma c e u t i c a l s c i e n c e s 1 0 ( 2 0 1 5 ) 3 4 1e3 4 9 347

a s i a n j o u r n a l o f p h a rma c e u t i c a l s c i e n c e s 1 0 ( 2 0 1 5 ) 3 4 1e3 4 9348

membrane. The mean cumulative amount of compound D

permeated from crude Z. cassumunar oil and Z. cassumunar

blended patches were 38.55 ± 18.48% and 36.72 ± 11.29% after

24 h, respectively (Fig. 7). Although another publication re-

ported that glycerine could enhance drug permeability [40,41],

the Z. cassumunar blended patches contained only a small

amount of glycerin as plasticizer which was unlikely to affect

drug permeation. Moreover, compound D was only slightly

detected in the receptor medium. Because of its structure,

compound D exhibits less hydrophilicity than hydrophobicity

[11,13,15]. The in vitro skin permeation kinetics model of com-

pound D provided a better fit to a first-order model than zero-

order and Higuchi's model (Fig. 7).

Thus, the newborn pig skins were removed from modified

Franz-type diffusion cell apparatus. They were cut into small

pieces and homogenized, and then were extracted in absolute

ethanol. These solutions were analyzed for the remaining

compound D content by HPLC method. They contained

60.54 ± 39.55% and 46.77 ± 17.93% compound D content in

crude Z. cassumunar oil and Z. cassumunar blended patches,

respectively. Thus, the compound D was highly accumulated

in newborn pig skin layer minimum permeation into receptor

medium. However, the underlying mechanisms for this effect

was never reported and will be further studied.

4. Conclusion

In the currentwork prepared the Z. cassumunarblended patches

made from chitosan and PVA polymer blends incorporating the

crude Z. cassumunar oil. The surface and cross section were

photographed for morphology study under SEM technique and

the physicochemical properties evaluated by FTIR, DSC, XRD,

moisture uptake, swelling ratio, erosion, and porosity. The re-

sults revealed compatible, homogeneous, smooth, and

compact blended ingredients. The blended patches could

absorb the moisture that resulted in swelling of blended

patches. They were eroded which increased the number of

porous channels homogenously to pass compound D from Z.

cassumunar blended patches. The blended patches provided a

controlled release and skin permeation of compound D when

studied by modified Franz-type diffusion cell apparatus. Thus,

the blended patches could be suitably used for herbal medicine

application.

Acknowledgment

The authors reported no declaration of interests. The authors

are thankful to the Faculty of Pharmacy and the Research

Institute of Rangsit University (Grant No.74/2555) for financial

supports.

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