Page 525 - IJB-10-4

International Journal of Bioprinting 3D printed substrate for adhesion tests

1. Introduction skin surface. Moreover, the model skin surface has not been
tested in stability studies, which are essential for ensuring
While transdermal system (TDS) patches have been in the reproducibility of adhesion results. Kowalski et al.
the market for decades, concerns about their ability to reported a study measuring the tack properties of acrylic
1–5
adhere securely to the skin, efficacy, and safety persist. PSAs crosslinked with materials such as polyethylene
Additionally, current methods to characterize the adhesion (PE), polypropylene, polytetrafluorethylene, SS, glass,
properties of TDS patches fail to correlate in vitro and polycarbonate (PC), and poly(methyl methacrylate).
16
1,6
in vivo performance. Hence, marketed TDS products Although they demonstrated the relationship between tack
with poor adhesive properties may require an additional and SE, the study did not include the United States Food and
overlay. Many marketed TDS patches have reported patch Drug Administration (FDA)-approved PSAs, including
1,7
adhesion failure (i.e., detach earlier than their prescribed silicone, acrylate, and polyisobutylene, commonly used in
time), including clonidine (1-week patch), fentanyl (72- marketed transdermal patches.
h patch), rivastigmine (24-h patch), and rotigotine (24-
h patch). 1,4,7–10 As per the manufacturer’s guidelines, Drugs and excipients (e.g., penetration enhancers, drug
fentanyl transdermal patches should be reapplied every 3 crystallization inhibitors, antioxidants, or preservatives)
days (72 h). However, a study conducted at the St. Clara can be incorporated to alter the rheological and adhesive
Hospital Cancer Center (Switzerland) observed that properties of PSAs. 1,3,17–23 It was reported that adding
fentanyl patches were replaced every 2 days for nearly all isopropyl myristate into a silicone-based PSA improved
patients (739 total patients), resulting in increased drug drug permeation and facilitated smooth spreading of the
side effects and failure to deliver the prescribed dose. The matrix, thereby promoting rapid skin contact, enhancing
early reapplication of the patches is mainly due to the the initial peel strength, and decreasing the cohesion
24
loss of adhesion between the skin and the transdermal strength. Conversely, adding the same substance to a
patch. Clonidine patches are sold in the market for the poly(amino methylmethacrylate) (PAMA)-based matrix
11
1,25
treatment of hypertension and the prevention of stroke, reduced peel adhesion strength. Taghizadeh et al.
heart attack, and kidney abnormalities. These patches are reported a decrease in the peel adhesion of acrylic-based
3
usually applied for 1 week and reapplied if the patch starts PSAs on the use of oleic acid, a permeation enhancer. On
loosening from the skin or detaching completely, as per the the other hand, an opposite effect was reported in the case
17
manufacturer’s guidelines. When removing a patch from a of PAMA-based PSA. In a study by Lin et al., loading
7
surface, four types of failure can occur: piroxicam into a PAMA-based PSA led to a reduction in
peel adhesion strength, most likely due to drug-induced
(i) Adhesive failure that occurs when the adhesive elevation of the polymer’s glass transition temperature. To
comes off completely and leaves no residue, which is mitigate this effect, the quantity of plasticizers incorporated
the only acceptable outcome for patches when they into the PAMA matrix was increased accordingly. 17
are removed from a surface;
Several studies have addressed adhesion failure caused
(ii) Complete transfer of the pressure-sensitive adhesive by PSA–excipient interaction. However, a systematic study
(PSA) from the backing layer to the adhered surface; of the effect of intrinsic factors, including coat weight,

(iii) Cohesive failure that occurs when the adhesive viscosity of PSAs, and backing membrane, on the adhesion
material has good adhesion but lacks cohesive properties of PSAs using skin-mimetic substrates is lacking
strength; in the literature. Therefore, there is an urgent need to study
the effect of various factors on the adhesion properties of
(iv) Simultaneous adhesive and cohesive failure.
TDS products to overcome the patch adhesion failure issue
The transition between these failure types is influenced and avoid extensive in vivo studies. Our research aims to:
by factors such as additives and the rate at which the patch (i) evaluate the effect of various intrinsic factors, including
is peeled. 1,12,13 coat weight, viscosity of silicone-based PSAs, and backing
Currently, transdermal patches are evaluated with membrane, on the adhesion properties of TDS consisting
adhesion testing using a stainless steel (SS) probe. of silicone-based PSAs; and (ii) improve the in vitro
However, the surface properties of SS (surface energy adhesion testing of TDS products by developing probes
[SE] > 700 mN/m) are different from that of the skin (SE or plates (skin-mimetic substrates) that mimic the human
= 25–56 mN/m), depending on its hydrolipidic balance. skin SE using three-dimensional (3D) printing technology.
14
Charkoudian developed model skin surfaces using gelatin . In this study, FDA-approved materials used in the
15
for testing adhesive patches. However, it was not tested on manufacturing of TDS formulations, including silicone-
marketed transdermal patches or adopted by the industry based adhesives, backing membranes, and release liner,
due to the complexity involved in developing the model were selected to formulate the transdermal patches,

Volume 10 Issue 4 (2024) 517 doi: 10.36922/ijb.3735