41
Članek prispel / Received
30. 9. 2022
Članek sprejet / Accepted
15. 11. 2022
Abstract
Objective: Wound dressings are one 
of the most commonly used products 
in wound care. Various wound dres-
sings have been developed, containing 
different active ingredients and often 
drugs from different pharmacodynamic 
groups. Considering the changing envi-
ronment in each wound type, it is im-
portant that the experimental design for 
evaluating the in vitro drug release of 
such materials takes into account these 
varying conditions. Hence, this study ai-
med to examine the importance of Franz 
diffusion cell volume for in vitro drug 
release testing of wound dressings.
Methods: Franz diffusion cells were 
used for in vitro drug release testing, 
which not only simulated different con-
ditions during wound healing but also 
allowed a certain degree of possible 
changes in the experimental design (e.g., 
Izvleček
Namen: Obloge za oskrbo rane so med 
najbolj uporabljanimi izdelki na podro-
čju zdravljenja ran. V zadnjem času 
potekajo številne raziskave, v katerih se 
v obloge za oskrbo ran vključujejo različ-
ne aktivne substance, pogosto zdravilne 
učinkovine iz različnih farmakodina-
mičnih skupin. Ob upoštevanju spre-
menljivega in spreminjajočega se okolja 
v posameznih vrstah ran je nujno, da se 
pri in vitro vrednotenju učinkovitosti 
in varnosti takih naprednih materialov, 
simulira pogoje, ki so značilni za posa-
mezno vrsto rane.
Metode: Za ta namen je testiranje 
sproščanja v Francovih difuzijskih ce-
licah metoda izbire, saj ob sočasnem 
simuliranju pogojev v rani (temperatu-
ra, pH), omogoča določeno variabilnost 
tudi v smislu prilagajanja velikosti rane 
(velikost Franzevih difuzijskih celic). 
Ključne besede: 
in vitro testiranje sproščanja, 
Franzove difuzijske celice, 
simulacija, naproksen, alginat
Key words: 
alginate, Franz diffusion cells, in 
vitro drug release testing, naproxen, 
simulation
Pomen pravilne izbire volumna Franzove difuzijske 
celice za in vitro preizkušanje sproščanja zdravil pri 
oblogah za rane
Importance of Franz diffusion cell volume for in vitro 
drug release testing of wound dressings
Avtor / Author Tina Maver1,2, Uroš Maver1,2
Ustanova / Institute 1Univerza v Mariboru, Medicinska fakulteta, Inštitut za biomedicinske vede, Slovenia;  
2 Univerza v Mariboru, Medicinska fakulteta, Katedra za farmakologijo, Slovenia;
1University of Maribor, Faculty of Medicine, Institute of Biomedical Sciences, Slovenia; 
2University of Maribor, Faculty of Medicine, Department of Pharmacology, Slovenia; 
Naslov za dopisovanje /  
Correspondence
Doc. dr. Tina Maver
University of Maribor, Faculty of 
Medicine
Taborska ulica 8, 2000 Maribor, 
Slovenia
E-mail: tina.maver@um.si; 
Tel.: +386 2 23 45 878
Laboratorijska študija / Laboratory study
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2022; 15 (2): 41–48
https://doi.org/10.18690/actabiomed.241, CC BY 4.0
© 2022 Avtor(ji) / The Author(s)
42
INTRODUCTION
Wound healing is an essential part of survival skills 
and is thus crucial to the existence of life (1). It is 
often described as a complex process broadly divided 
into four distinct phases: hemostasis, inflammation, 
proliferation, and remodeling (2, 3). 
Although some processes overlap between phases, 
different combinations of inflammatory mediators and 
growth factors are known to orchestrate key processes 
in each phase (4). Consequently, novel pharmacological 
therapeutic approaches targeting wound healing are 
developed based on these specific drug targets (5).
Various wound dressings have been explored 
considering the aforementioned aspects and a wide 
range of clinical manifestations and complications 
associated with the healing of different wound types (6-
11). Many recent studies focus on developing wound 
dressings that allow the controlled release and delivery 
of drugs to the desired wound sites (12, 13).
Despite the immense potential of the aforementioned 
materials for more effective wound treatment, the data 
on the technical aspects of in vitro drug release of such 
controlled drug delivery systems are limited (9). Studies 
considering the actual wound environment, including 
its changing conditions over time, are particularly rare 
(9). The latter is an even more important feature of 
wound treatment, considering that various polymeric 
materials used in dressings (e.g., alginate, viscose, 
and carboxymethylcellulose) can be significantly (and 
differentially) affected by these changing conditions in 
the wound bed (14, 15). This requires careful planning 
of the in vitro evaluation of drug release from novel 
wound dressings, taking into account possible changes 
in the particular wound bed type (pH, T value, exudate 
volume, and so on) (16) (Fig. 1).
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Rezultati: V tej raziskavi smo primerjali dve Franzovi difu-
zijski celici z različnima volumnoma receptorskega medija, pri 
čemer smo iz alginatne obloge kot modelno učinkovino spro-
ščali naproksen. Z raziskavo smo potrdili, da volumen recep-
torskega medija ne vpliva le na količino sproščene zdravilne 
učinkovine, temveč ima tudi signifikanten vpliv na mehani-
zem sproščanja.
Zaklju~ek: Razlika v volumnu receptorskega dela Francovih 
difuzijskih celic omogoča simuliranje ran tako z večjim kot 
tudi z manjšim volumnom izločka. Zaključimo lahko, da je pri 
načrtovanju in vitro testiranj sproščanja zdravilnih učinkovin 
nujno potrebno določiti ciljno vrsto ran, za katere bo izdelek 
namenjen.
diffusion cell size).
Results: In this study, we compared two sets of Franz diffu-
sion cells with different volumes of the receptor medium to 
evaluate naproxen release from an alginate-based model 
wound dressing. We confirmed that the volume of the recep-
tor medium not only affected the amount of drug released in 
the selected time but also significantly influenced the release 
mechanism.
Conclusion: Different volumes of the Franz diffusion cell re-
ceptor compartments allowed the simulation of wounds with a 
higher and a lower degree of exudation. The experimental design 
for in vitro drug release testing based on Franz diffusion cells 
must thoroughly consider the targeted wound type for which the 
dressings are being developed.
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The drug release from polymer-based wound dressings 
is often controlled by one or more physical processes, 
including (a) hydration of the polymer, (b) swelling 
and gelation, (c) diffusion of the drug through the 
matrix, and (d) eventual erosion of the matrix (18, 19). 
Wounds exhibit varying degrees of exudation (with 
variable composition for different wounds). Hence, it is 
expected that targeted wound healing can be achieved 
by combining swelling, erosion, and subsequent drug 
diffusion kinetics as part of the controlled drug release 
mechanism (9, 20). This is also evident in some of the 
recently published studies, in which the reported drug 
release from the prepared wound dressings is explained 
by a combined mechanism of either two or three of the 
aforementioned principles (21, 22). 
Among the commonest methods for testing the in vitro 
drug release of topical and transdermal formulations 
is using Franz diffusion cells (23, 24). Such tests are 
useful for not only the design and development of 
novel formulations but also toxicity screening and 
quality control (25, 26). Static diffusion cells are of 
two types: vertical (Franz cells) and horizontal (side-by-
side) cells (27-29). Static diffusion cells are commonly 
used to test transitions through different membranes 
(e.g., skin and intestine) and the permeability of tissues 
and to determine the concentration of molecules in 
the receptor chamber, which can be used to estimate 
Figure 1. Overview of chemical and physical stimuli that influence drug release from wound dressing (17).
the time when dynamic equilibrium is reached  (8, 9, 
30-33). Hence, the purpose of using diffusion cells is 
to create in vitro conditions that resemble the actual 
physiological environment and then monitor the 
diffusion of test substances in a desired experimental 
setup (e.g., skin permeability and drug release) (34-36).
The proper choice of basic test equipment is important 
to reproduce the physiological conditions of the target 
organs. As our target in this study was the wound 
environment, we needed to appropriately select the 
release media and the type and size of Franz diffusion 
cells used. Our main focus was to show the effect of the 
size of the selected Franz diffusion cells on the release 
profile of a drug-loaded alginate-based model wound 
dressing and, thus, the impact on the interpretation of 
the release data. The drug used was naproxen (NPX), a 
common nonsteroidal anti-inflammatory drug.
MATERIALS AND METHODS
Materials
Commercially available alginate wound dressing 
material was purchased from Tosama, Slovenia. NPX 
was purchased from Sigma-Aldrich (St. Louis, MO, 
USA). All materials were used as obtained without 
further modification before sample preparation or 
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assay. Ultrapure water (18.2 MΩ cm 
at 25°C) from an ELGA PureLab 
water purification system (Veolia 
Water Technologies, UK) was used 
to prepare all solutions. 
Incorporation of the drug into the 
wound dressing material
The wound dressing samples were 
cut into squares of size 1 × 1 cm2 
and impregnated with NPX (dis-
solved in EtOH, 1 mg/mL) for 30 The drug-loaded samples were cut into squares 
of size 1 × 1 cm2 and placed on top of a rare woven 
polyethylene terephthalate membrane. The receptor 
compartment was filled with ultrapure water, and its 
temperature was maintained at 37°C. The medium 
was continuously stirred with a magnetic bar at 50 
rpm during the dissolution experiment. The samples 
were collected at various time intervals (1, 5, 10, 20, 
30, 60, 120, 180, 240, 300, 360, and 1,440 min) for 
24 h. The released/dissolved NPX concentration in 
the receptor medium was determined by quantifying 
the absorption band at 232 nm using an ultraviolet–
visible (UV-Vis) spectrophotometer (Cary 60 UV-Vis 
Spectrophotometer, Agilent).  
The collected sample volumes were replaced with fresh 
ultrapure water. The sink conditions were ensured by 
sampling and subsequent dilution of the samples by 
replacing the medium. This dilution was considered 
when calculating concentrations using the Beer–
Lambert law. All release studies were performed in 
triplicate.
RESULTS 
Morphological evaluation using optical microscopy
First, we used optical microscopy to observe the 
morphological changes in alginate fibers after adding 
the drug NPX (Fig. 3). 
Figure 2. Franz diffusion cell with a volume of 5 mL (left) and 15 
mL (right). 
min. The samples were then dried in an oven at 50°C 
for 5 min, cooled to room temperature, and finally 
purged with nitrogen gas. The as-prepared samples 
were immediately used for the in vitro release assay 
and/or other characterization methods.
Optical microscopy
The wound dressing morphology before and after 
NPX incorporation was observed using a Zeiss Axio 
T25 upright high definition optical microscope (Zeiss, 
Germany).
Attenuated total reflectance infrared spectroscopy
The attenuated total reflectance infrared spectroscopy 
(ATR-IR) spectra of NPX, alginate, and NPX-loaded 
alginate were acquired using an Agilent Cary 630 
Fourier-transform infrared spectroscopy (FTIR) 
spectrometer (Agilent, Santa Clara, CA, USA) equipped 
with a diamond crystal (ATR module, measurement 
range 400–650 cm–1). The scans were performed at 
three different places in 24 scan repetitions on each 
sample surface before and after impregnation (37, 38). 
In vitro drug release testing
The in vitro drug release test was performed using an 
automated transdermal diffusion cell collection system 
(Logan System 912-6; Somerset, NJ, USA). The size 
of the diffusion cells varied (two sizes were used for 
comparison, such as 5 and 15 mL) (Fig. 2).
 
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Figure 3. (a) Chemical structures of alginate and NPX. (b) Optical micrograph of alginate fibers before NPX 
attachment. (c) Optical micrograph of alginate fibers after NPX incorporation.
Conformation of the drug incorporated into the wound 
dressing material
ATR-IR spectra of the NPX and alginate with and 
without NPX were acquired to confirm the successful 
incorporation of the drug into the wound dressing 
material (Fig. 4). After an initial observation of the 
spectra, we could confirm that no chemical changes 
occurred in the drug during its incorporation.  
The absorption bands of about 1610 and 1416 cm-1 were 
attributed to the stretching vibrations of asymmetric 
and symmetric bands of the carboxylate anions of 
the alginate, respectively. For the NPX, the bands of 
Figure 4. ATR-IR spectra of woven alginate, di-
luted NPX, and alginate samples loaded with the 
drug.
stretching vibration v(C=O) of carboxyl groups at 1260 
cm-1 were attributed to the presence and vibrations of 
NPX v(C–H) at about 900 cm-1. A broad peak between 
3700 and 3000 cm-1 corresponded to the stretching 
vibration v(O–H). 
For the alginate samples loaded with the drug, the 
presence of NPX in the samples was indicated by the 
bands of stretching vibration between 3700 and 3000 
cm–1 for v(O–H) and the vibrations of NPX v(C–H) at 
about 900 cm-1. This showed that NPX was successfully 
incorporated into alginate.
Comparison of drug release performance using Franz 
diffusion cells of different sizes
After confirming that the drug was bound to the fibers, 
we evaluated the effects of the Franz diffusion cell size on 
the actual release results. As discussed in the Materials 
and Methods section, two sizes of Franz diffusion cells 
were used for this purpose (5 and 15 mL). The release 
performance was presented in the form of three graphs 
to provide a better overview, showing drug release as 
concentration, mass, and percentage of NPX released 
as a function of time (Fig. 5). 
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Figure 5. Comparison of release performance between the two differently sized Franz diffusion cells: (a) 
concentration of NPX released as a function of time, (b) mass of NPX released as a function of time, and 
(c) percentage of NPX released as a function of time.
DISCUSSION
An optical microscope was used to confirm the actual 
binding of the drug to the fibers of the alginate wound 
dressing material (Fig. 3). The figure shows that most 
of the drug was in the form of crystals. The alginate 
material was suitable for NPX incorporation because 
the fibers were almost invisible after attachment. The 
successful incorporation of NPX was additionally 
confirmed using FTIR. The latter confirmed that the 
incorporation did not affect the chemical composition 
of the drug. 
Figure 5 shows that the compartment volume of the 
used Franz diffusion cells significantly influenced 
the in vitro drug release outcome. The release curves 
corresponding to different cell volumes differed in all 
three result representation types. This was true even 
though they showed the evaluation of samples prepared 
by the same process (the alginate wound dressings with 
the incorporated NPX were prepared the same way for 
all performed release studies). Although the difference 
in the concentration of released NPX was expected (a 
larger volume meant a lower concentration; Fig. 5a), 
the other two graphs were more surprising. Figure 5b 
shows the released NPX mass as a function of time. 
The graphs for the two cell volumes not only showed 
different masses at the respective time points, but 
also had completely different curve shapes, indicating 
different release kinetics. The same was true for the 
third graph, which showed the percentage of NPX 
released as a function of time (Fig. 5c). 
Several possible explanations existed for these drastic 
changes. First, the size of the Franz diffusion cells might 
affect the extent of wetting of the samples. The size of 
the entry point changed for both cell sizes, and hence 
might have a huge impact, especially in the initial 
minutes of release. This might explain the difference 
in the first 30 min of release, where the release curve 
for the larger cell showed a burst-like release while the 
release for the smaller cell showed a slower release. 
The second possible explanation for the changes in 
the rest of the release curve was most likely related to 
the wetting, as previously discussed. This could lead 
to more rapid degradation of the alginate wound 
dressing material over a longer period. The resulting 
increased degradation might lead to an increase in the 
surface area of the portions of the material exposed to 
the release medium. A larger surface area and a larger 
number of NPX molecules exposed to the medium 
could significantly improve the release behavior (as 
observed in this study).
In this study, we compared the in vitro drug release 
of NPX from a model alginate-based wound dressing 
from two Franz diffusion cells of different volumes. 
The different volumes of their receptor compartments 
allowed the simulation of wounds with higher and 
lower levels of exudation. We confirmed that the 
volume of the receptor medium not only affected the 
amount of drug released in the selected time period 
but also significantly influenced the release kinetics 
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REFERENCES
1. Lima TPL, Passos MF. Skin wounds, the healing 
process, and hydrogel-based wound dressings: A 
short review. Journal of Biomaterials Science Poly-
mer edition. 2021;32(14):1910–25.
2. Maver T, Maver U, Stana Kleinschek K, Smrke DM, 
Kreft S. A review of herbal medicines in wound 
healing. Int J Dermatol. 2015;54(7):740–51.
3. Muse ME, Crane JS. Physiology, epithelialization. 
StatPearls. Treasure Island (FL): StatPearls Pub-
lishing Copyright © 2022, StatPearls Publishing 
LLC.; 2022.
4. Gantwerker EA, Hom DB. Skin: histology and 
physiology of wound healing. Clinics in Plastic 
Surgery. 2012;39(1):85–97.
5. Oliva N, Almquist BD. Spatiotemporal delivery of 
bioactive molecules for wound healing using stim-
uli-responsive biomaterials. Adv Drug Deliv Rev. 
2020;161–162:22–41.
6. Maver T, Gradišnik L, Kurečič M, Hribernik S, 
Smrke DM, Maver U, et al. Layering of different ma-
terials to achieve optimal conditions for treatment 
of painful wounds. Int J Pharmaceut. 2017;529(1–
2):576–88.
7. Maver T, Kurečič M, Smrke DM, Kleinschek KS, 
Maver U. Electrospun nanofibrous CMC/PEO as a 
part of an effective pain-relieving wound dressing. 
J Sol-Gel Sci Techn. 2016;79(3):475–86.
8. Maver T, Maver U, Mostegel F, Grieser T, Spirk 
S, Smrke D, et al. Cellulose based thin films as a 
platform for drug release studies to mimick wound 
dressing materials. Cellulose. 2015;22(1):749–
61.
9. Maver T, Hribernik S, Mohan T, Smrke DM, Maver 
U, Stana-Kleinschek K. Functional wound dressing 
materials with highly tunable drug release proper-
ties. RSC Advances. 2015;5(95):77873–84.
10. Buote NJ. Updates in wound management and 
dressings. Vet Clin North Am Small Anim Pract. 
2022;52(2):289–315.
11. Milojević M, Harih G, Vihar B, Vajda J, Gradišnik 
L, Zidarič T, et al. Hybrid 3D printing of advanced 
hydrogel-based wound dressings with tailorable 
properties. Pharmaceutics. 2021;13(4):564.
12. Khan MUA, Razaq SIA, Mehboob H, Rehman S, 
Al-Arjan WS, Amin R. Antibacterial and hemocom-
patible pH-responsive hydrogel for skin wound 
healing application: In vitro drug release. Polymers 
(Basel). 2021;13(21).
13. Moazzami Goudarzi Z, Soleimani M, Ghasemi-
Mobarakeh L, Sajkiewicz P, Sharifianjazi F, Es-
maeilkhanian A, et al. Control of drug release 
from cotton fabric by nanofibrous mat. Interna-
tional Journal of Biological Macromolecules. 
2022;217:270–81.
14. Boateng JS, Matthews KH, Stevens HNE, Ec-
cleston GM. Wound healing dressings and 
drug delivery systems: A review. J Pharm Sci. 
2008;97(8):2892–923.
15. Alven S, Peter S, Mbese Z, Aderibigbe BA. Poly-
mer-based wound dressing materials loaded 
with bioactive agents: Potential materials for the 
treatment of diabetic wounds. Polymers (Basel). 
2022;14(4).
16. Powers JG, Higham C, Broussard K, Phillips TJ. 
Wound healing and treating wounds: Chronic 
wound care and management. Journal of the Amer-
ican Academy of Dermatology. 2016;74(4):607–
25.
17. Harrison IP, Spada F. Hydrogels for atopic derma-
titis and wound management: A superior drug de-
and thus the drug release performance. Based on these 
results, we concluded that the experimental design of 
in vitro drug release tests based on Franz diffusion cells 
must thoroughly consider the targeted wound type for 
which the dressings were developed.
ACKNOWLEDGMENTS
The authors acknowledge the financial support from 
the Slovenian Research Agency for research core No. 
P3-0036 and project numbers J3-1762 and L7-4494.
ACTA MEDICO-BIOTECHNICA
2022; 15 (2): 41–48
48
Laboratorijska študija / Laboratory study
livery vehicle. Pharmaceutics. 2018;10(2):71.
18. Weiser JR, Saltzman WM. Controlled release for 
local delivery of drugs: barriers and models. J Con-
trol Release. 2014;190(0):664–73.
19. Altun E, Yuca E, Ekren N, Kalaskar DM, Ficai D, 
Dolete G, et al. Kinetic release studies of antibiotic 
patches for local transdermal delivery. Pharmaceu-
tics. 2021;13(5).
20. Mogrovejo-Valdivia A, Rahmouni O, Tabary N, Ma-
ton M, Neut C, Martel B, et al. In vitro evaluation of 
drug release and antibacterial activity of a silver-
loaded wound dressing coated with a multilayer 
system. Int J Pharm. 2019;556:301–10.
21. Huang Y, Wang L, Liu Y, Li T, Xin B. Drug-loaded 
PLCL/PEO-SA bilayer nanofibrous membrane for 
controlled release. Journal of Biomaterials Sci-
ence Polymer Edition. 2021;32(18):2331–48.
22. Hu B, Gao M, Boakye-Yiadom KO, Ho W, Yu W, 
Xu X, et al. An intrinsically bioactive hydrogel with 
on-demand drug release behaviors for diabetic 
wound healing. Bioact Mater. 2021;6(12):4592–
606.
23. Franz TJ. Percutaneous absorption on the 
relevance of in vitro data. J Invest Dermatol. 
1975;64(3):190–5.
24. Salamanca CH, Barrera-Ocampo A, Lasso JC, 
Camacho N, Yarce CJ. Franz Diffusion cell ap-
proach for pre-formulation characterisation of ke-
toprofen semi-solid dosage forms. Pharmaceutics. 
2018;10(3).
25. Ng SF, Rouse JJ, Sanderson FD, Meidan V, Ec-
cleston GM. Validation of a static Franz diffusion 
cell system for in vitro permeation studies. AAPS 
PharmSciTech. 2010;11(3):1432–41.
26. Alberti M, Dancik Y, Sriram G, Wu B, Teo YL, Feng 
Z, et al. Multi-chamber microfluidic platform for 
high-precision skin permeation testing. Lab Chip. 
2017;17(9):1625–34.
27. Karande P, Mitragotri S. High throughput screen-
ing of transdermal formulations. Pharmaceut Res. 
2002;19(5):655–60.
28. Ng S-F, Rouse JJ, Sanderson FD, Meidan V, Ec-
cleston GM. Validation of a static Franz diffusion 
cell system for in vitro permeation studies. Aaps 
Pharmscitech. 2010;11(3):1432–41.
29. Patel D, Chaudhary SA, Parmar B, Bhura N. Trans-
dermal drug delivery system: a review. The Pharma 
Innovation. 2012;1(4).
30. Maver T, Gradisnik L, Kurecic M, Hribernik S, 
Smrke DM, Maver U, et al. Layering of different ma-
terials to achieve optimal conditions for treatment 
of painful wounds. Int J Pharmaceut. 2017;529(1-
2):576–88.
31. Maver T, Kurecic M, Smrke DM, Kleinschek KS, 
Maver U. Electrospun nanofibrous CMC/PEO as a 
part of an effective pain-relieving wound dressing. 
J Sol-Gel Sci Techn. 2016;79(3):475–86.
32. Maver T, Gradisnik L, Smrke DM, Stana Klein-
schek K, Maver U. Systematic evaluation of a di-
clofenac-loaded carboxymethyl cellulose-based 
wound dressing and its release performance with 
changing pH and temperature. AAPS PharmSci-
Tech. 2019;20(1):29.
33. Maver T, Mastnak T, Mihelič M, Maver U, Finšgar 
M. Clindamycin-based 3D-printed and electrospun 
coatings for treatment of implant-related infec-
tions. Materials. 2021;14(6):1464.
34. Seo JE, Kim S, Kim BH. In vitro skin absorption 
tests of three types of parabens using a Franz dif-
fusion cell. Journal of Exposure Science & Environ-
mental Epidemiology. 2017;27(3):320–5.
35. Miller MA, Kasting G. A measurement of the un-
stirred aqueous boundary layer in a Franz diffusion 
cell. Pharmaceutical Development and Technol-
ogy. 2012;17(6):705–11.
36. Venter JP, Muller DG, du Plessis J, Goosen C. A 
comparative study of an in situ adapted diffusion 
cell and an in vitro Franz diffusion cell method for 
transdermal absorption of doxylamine. Eur J Pharm 
Sci. 2001;13(2):169–77.
37. Maver U, Xhanari K, Žižek M, Korte D, Gradišnik 
L, Franko M, et al. A combination of interdisciplin-
ary analytical tools for evaluation of multi-layered 
coatings on medical grade stainless steel for 
biomedical applications. Eur J Pharm Biopharm. 
2018;128:230–46.
38. Maver U, Xhanari K, Žižek M, Gradišnik L, Repnik 
K, Potočnik U, et al. Carboxymethyl cellulose/di-
clofenac bioactive coatings on AISI 316LVM for 
controlled drug delivery, and improved osteogenic 
potential. Carbohyd Polym. 2020;230:115612.
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2022; 15 (2): 41–48