A polyethylene glycol-grafted pullulan polysaccharide adhesive improves drug loading capacity and release efficiency.

In this study, polyethylene glycol was grafted onto pullulan polysaccharides, resulting in the development of a novel adhesive termed PLUPE, offering superior drug loading capacity and rapid release efficiency. The efficacy of PLUPE was rigorously evaluated through various tests, including the tack test, shear strength test, 180° peel strength test, and human skin adhesion test. The results demonstrated that PLUPE exhibited a static shear strength that was 4.6 to 9.3 times higher than conventional PSAs, ensuring secure adhesion for over 3 days on human skin. A comprehensive analysis, encompassing electrical potential evaluation, calculation of interaction parameters, and FT-IR spectra, elucidated why improved the miscibility between the drug and PSAs, that the significant enhancement of intermolecular hydrogen bonding in the PLUPE structure. ATR-FTIR, rheological, and thermodynamic analyses further revealed that the hydrogen bonding network in PLUPE primarily interacted with polar groups in the skin. This interaction augmented the fluidity and free volume of PSA molecules, thereby promoting efficient drug release. The results confirmed the safety profile of PLUPE through skin irritation tests and MTT assays, bolstering its viability for application in TDDS patches. In conclusion, PLUPE represented a groundbreaking adhesive solution for TDDS patches, successfully overcoming longstanding challenges associated with PSAs.

Chromolaena odorata layered-nitrile rubber polymer transdermal patch enhanced wound healing in vivo.

The objective is to investigate the healing efficacy of a Chromolaena odorata layered-nitrile rubber transdermal patch on excision wound healing in rats. Wounds were induced in Sprague-Dawley rats and were later treated as follows: wound A, the negative control, received no treatment (NC); wound B, the negative control with an empty nitrile rubber patch (NC-ERP); wound C, treated with a C. odorata layered-nitrile rubber patch (CO-NRP); and wound D, the positive control with Solcoseryl gel with a nitrile rubber patch (PC-SG-NRP). After 1, 3, 6, 10, and 14 days, the rats were sacrificed and analyzed for wound contraction, protein content, hexosamine, and uronic acid levels. Macroscopic observation showed enhanced wound healing in wounds treated with CO-NRP with a wound contraction percentage significantly higher (p<0.05) on days 6 and 10 compared to those treated with NC-ERP. Similarly, protein, hexosamine, and uronic acid contents were also significantly higher (p<0.05) in CO-NRP-treated wounds when compared with wounds treated with NC-ERP. Histological findings showed denser collagen deposition and faster granulation tissue formation in wounds treated with CO-NRP. From the results obtained, it is concluded that the C. odorata layered-nitrile rubber transdermal patch was effective in healing skin wounds.

3D Printed Ion-Responsive Personalized Transdermal Patch.

Microneedle patches are easy-to-use medical devices for transdermal administration. However, the insufficient insertion of microneedles due to the gap between planar patches and contoured skin affects drug delivery. Herein, we formulate a prepolymer for high-fidelity three-dimensional (3D) printed personalized transdermal patches. With the excellent photoinitiation ability of 2-(4-methoxystyryl)-4,6-bis(trichloromethyl)-1,3,5-triazine (Tz), a high-fidelity and precise microneedle patch is successfully fabricated. Upon irradiation of the white illuminator, the doped gold nanoparticles (AuNPs) in the patch release heat and promisingly induce sweat production. With the introduction of Na+, the dominant component of sweat, the curvature of the produced transdermal patch is observed due to the ion-induced network rearrangement. The alkanethiol-stabilized AuNP with an end group of a carboxyl group causes controlled drug release behavior. Furthermore, the irradiation-induced photothermal heating of AuNP can facilitate the sustainability of drug release thanks to the substantially increased particle size of AuNP. These findings demonstrate that the developed prepolymer is a promising candidate for the production of transdermal patches fitting the curvature of the body surface.

Development and Characterization of Transdermal Patches Using Novel Thymoquinone-L-Arginine-Based Polyamide Nanocapsules for Potential Use in the Management of Psoriasis.

Thymoquinone (TQ) is a phytochemical compound present in Nigella sativa and has potential benefits for treating dermatological conditions such as psoriasis. However, its clinical use is limited due to its restricted bioavailability, caused mainly by its low solubility and permeability. To overcome this, a new transdermal drug delivery system is required. Nanoparticles are known to enhance material solubility and permeability, and hence, this study aimed to synthesize TQ-loaded L-arginine-based polyamide (TQ/Arg PA) nanocapsules incorporated into transdermal patches for prolonged delivery of TQ. To achieve this, Eudragit E polymer, plasticizers, and aloe vera as penetration enhancer were used to develop the transdermal patch. Furthermore, novel TQ/Arg-PA was synthesized via interfacial polymerization, and the resultant nanocapsules (NCs) were incorporated into the matrix transdermal patch. The Arg-PA NCs' structure was confirmed via NMR and FTIR, and optimal TQ/Arg-PA NCs containing formulation showed high entrapment efficiency of TQ (99.60%). Molecular and thermal profiling of TQ/Arg-PA and the transdermal patch revealed the effective development of spherical NCs with an average particle size of 129.23 ± 18.22 nm. Using Franz diffusion cells and synthetic membrane (STRAT M®), the in vitro permeation profile of the prepared patches demonstrated an extended release of TQ over 24 h, with enhanced permeation by 42.64% when aloe vera was employed. In conclusion, the produced formulation has a potential substitute for corticosteroids and other drugs commonly used to treat psoriasis due to its effectiveness, safety, and lack of the side effects typically associated with other drugs.

Rhamnose-PEG-induced supramolecular helices: Addressing challenges of drug solubility and release efficiency in transdermal patch.

Transdermal drug delivery systems (TDDS) demand both high drug loading capacity and efficient delivery. In order to improve both simultaneously, this study aims to develop a novel rhamnose-induced pressure-sensitive adhesive (HPR) by dispersing the drug in the supramolecular helical structure. Ten model drugs, categorized as acidic and basic compounds, were chosen to understand the characteristics of the HPR and its inner mechanism. Notably, it enhanced drug loading by 1.41 to 5 times over commercially available pressure-sensitive adhesives Duro-Tak@ 87-4098 and Duro-Tak@ 87-2287, in addition to increasing drug release efficiency by a factor of about 5. Pharmacokinetic evaluation demonstrated that the HPR group had >4-fold (Tulobuterol TUL) and 3-fold (Diclofenac DIC) more area under the blood drug concentration curve (AUC) than the commercial TUL and DIC patches in the absence of added excipients and a significantly prolonged mean residence time (MRT) of >4-fold (TUL) and 3-fold (DIC), demonstrating the potential for highly efficacious and prolonged dosing. Furthermore, its safety and mechanical properties meet the requisite standards. Mechanistic inquiries unveiled that both acidic and basic drugs establish hydrogen bonds with HPR and become encapsulated within supramolecular helical structures. The supramolecular helical structures, significantly elevated both the enthalpy of the drug-HPR and entropy of the drugs release, thereby substantially enhancing drug delivery efficiency. In summary, HPR enabled a significant simultaneous enhancement of drug loading and drug delivery, which, together with its unique spatial structure, would contribute to the development of TDDS. In addition, the establishment of rhamnose-induced supramolecular helical structures would provide innovative pathways for different drug delivery systems.

Guidelines for Rational Clinical Use of Fentanyl Transdermal Patch.

Pain is one of the most common clinical symptoms of cancer patients, seriously affecting the quality of life of patients and bringing heavy mental and economic burden to families and society. The treatment of cancer pain in China is facing numerous challenges, one of which includes the irrational usage of analgesic drugs in clinical practice. As a strong opioid analgesic, transdermal fentanyl patch has been widely used due to its convenient clinical application and obvious therapeutic effect. Several basic-level hospitals and even general hospitals in China fail to appropriate the application of drugs in clinical application due to the lack of understanding of the pharmacological characteristics and clinical application of fentanyl transdermal patch by medical staff, seriously affecting the treatment quality. Therefore, it is imperative to strengthen the rational use and management of fentanyl transdermal patches. Accordingly, the initiation by the Cancer Rehabilitation and Palliative Treatment Professional Committee of the Hubei Anti-cancer Association launched the compilation of the "Guidelines for Rational Clinical Use of Fentanyl Transdermal Patch" (from now on referred to as the "Guidelines") in Hubei Province, China. The experts in the preparation group are experts in many disciplines, such as medicine, pharmacy, and nursing. The expert group determines the outline, prepares the required regulations, and revises it repeatedly. Moreover, these experts put forward suggestions for revision to strictly control the accuracy and scientific authenticity of the contents of the "Guide". Finally, all experts of the preparation team certify and finalize the draft. This "Guide" prepared by experts of the Cancer Rehabilitation and Palliative Treatment Professional Committee of the Hubei Anti-cancer Association and the expert advisory group with joint efforts, aims to play a positive role in promoting the rational clinical use of fentanyl transdermal patch, reducing the mental and economic burden of patients, and ensuring medical quality and medical safety.

Establishment and Validation of a Transdermal Drug Delivery System for the Anti-Depressant Drug Citalopram Hydrobromide.

To enhance the bioavailability and antihypertensive effect of the anti-depressant drug citalopram hydrobromide (CTH) we developed a sustained-release transdermal delivery system containing CTH. A transdermal diffusion meter was first used to determine the optimal formulation of the CTH transdermal drug delivery system (TDDS). Then, based on the determined formulation, a sustained-release patch was prepared; its physical characteristics, including quality, stickiness, and appearance, were evaluated, and its pharmacokinetics and irritation to the skin were evaluated by applying it to rabbits and rats. The optimal formulation of the CTH TDDS was 49.2% hydroxypropyl methyl cellulose K100M, 32.8% polyvinylpyrrolidone K30, 16% oleic acid-azone, and 2% polyacrylic acid resin II. The system continuously released an effective dose of CTH for 24 h and significantly enhanced its bioavailability, with a higher area under the curve, good stability, and no skin irritation. The developed CTH TDDS possessed a sustained-release effect and good characteristics and pharmacokinetics; therefore, it has the potential for clinical application as an antidepressant.

Pharmacodynamic Studies of Pravastatin Sodium Nanoemulsion Loaded Transdermal Patch for Treatment of Hyperlipidemia.

Pravastatin sodium (PVS) is a hypolipidemic drug with poor oral bioavailability due to the first-pass effect. Therefore, this study aims to formulate and evaluate transdermal patches containing PVS-loaded nanoemulsions (PVS-NEs) to increase PVS's hypolipidemic and hepatoprotective activities. PVS-NEs were prepared using the aqueous titration method, where oleic acid was chosen as an oil phase, and span 80 and tween 80 were used as surfactant and cosurfactant respectively. Droplet size (DS), polydispersity index (PDI), zeta potential (ZP), clarity, and thermodynamic stability of NEs were all characterized. Also, PVS-NEs (NE2) with 50% oil phase, 40% SC mix 2:1, and 10% water were selected as an optimum formula based on the results of DS (251 ± 16), PDI (0.4 ± 0.16), and ZP (-70 ± 10.4) to be incorporated into a transdermal patch, and PVS-NE2 loaded transdermal patches (PVS-NE2-TDPs) were prepared by solvent evaporation method. F1 patch with HPMC E15 and PVP K30 in a ratio of 3:1 represented satisfactory patch properties with good drug-excipients compatibility. Thus, it was selected as an optimum patch formula. The optimized F1 patch was characterized for thickness, moisture content, weight variation, and drug-excipients incompatibility. Therefore, it was subjected to ex vivo skin permeation and finally pharmacodynamic studies. Ex vivo permeation studies of F1 revealed that the cumulative amount of PVS permeated across rat skin was 271.66 ± 19 µg/cm2 in 72 h, and the pharmacodynamic studies demonstrated that the F1 patch was more effective in treating hyperlipidemia than PVS-TDP (control patch) based on both blood analysis and histopathological examination. .

Multi-material 3D printed eutectogel microneedle patches integrated with fast customization and tunable drug delivery.

Microneedle patches are emerging multifunctional platforms for transdermal diagnostics and drug delivery. However, it still remains challenging to develop smart microneedles integrated with customization, sensing, detection and drug delivery by 3D printing strategy. Here, we present an innovative but facile strategy to rationally design and fabricate multifunctional eutectogel microneedle (EMN) patches via multi-material 3D printing. Polymerizable deep eutectic solvents (PDES) were selected as printing inks for rapid one-step fabrication of 3D printing functional EMN patches due to fast photopolymerization rate and ultrahigh drug solubility. Moreover, stretchable EMN patches incorporating rigid needles and flexible backing layers were easily realized by changing PDES compositions of multi-material 3D printing. Meanwhile, we developed multifunctional smart multi-material EMN patches capable of performing wireless monitoring of body movements, painless colorimetric glucose detection, and controlled transdermal drug delivery. Thus, such multi-material EMN system could provide an effective platform for the painless diagnosis, detection, and therapy of a variety of diseases.

Treatment characteristics of chronic low back pain patients treated with buprenorphine buccal film or transdermal patch.

Aims: Retrospective insurance claims analysis exploring treatment characteristics in chronic low back pain patients prescribed buprenorphine buccal film (Belbuca®) or transdermal patches. Patients and methods: The first buprenorphine prescription (buccal film or transdermal patch) was an index event. Patients were observed over 6 month pre- and post-index periods. Propensity score matching minimized the selection bias. Results: Buccal film patients had a higher buprenorphine daily dose (501.7 vs 270.9 µg; p < 0.001). The patch-to-film switching rate was higher than vice versa (11.5 vs 3.8%; p < 0.001). The buccal film showed a greater reduction in opioid prescriptions (-1.1 vs -0.7; p = 0.012), daily morphine milligram equivalents (-12.6 vs -7.3; p < 0.001) and opioid treatment duration (-13.4 vs -7.6 days; p = 0.022). Conclusion: Buccal film was associated with higher buprenorphine doses and a greater reduction of opioid burden.

What is this article about? The analysis explored treatment patterns in chronic low back pain patients treated with different buprenorphine drugs. The use of other pain medications was also evaluated. Buprenorphine buccal film (Belbuca^®) was compared with transdermal patches. This study used commercial insurance data of US patients. What were the results? The most relevant findings were: Patients using buccal film had about two-times higher buprenorphine daily doses. About 12% of patch patients switched to film, while approximately 4% of film patients switched to patch. Initiation of both buprenorphine drugs led to reduced usage of opioids and other pain drugs. Despite a shorter buprenorphine treatment, the film was associated with a greater reduction in opioid use than the patch. What do the results of the study mean? The results showed that patients prescribed buprenorphine buccal film would be able to achieve higher daily doses required for appropriate chronic low back pain management. The buccal film will also lead to a great reduction in concomitant opioid use. These advantages may explain why more patients switched from buprenorphine transdermal patch to buccal film than the other way around.

Evaluation of wound healing active principles in the transdermal patch formulated with crude bio wastes and plant extracts against GSK-3 beta - an in silico study.

The wound-healing process is accelerated by inhibiting proteins that decelerate the wound-healing pathway. One of the active proteins involved in enhancing healing at the nuclear level and in gene expression is catenin. Inhibition of Glycogen Synthase Kinase 3ß (GSK3 ß) phosphorylates and degrades catenin via the downstream Wnt signalling pathway, thereby stabilizing catenin. A medicated wound dressing transdermal patch designed with fusion of bio wastes, viz. physiologically clotted fibrin, fish scale collagen, and the ethanolic extract of Mangifera indica (L.) and spider web, was analysed against GSK3ß to enhance healing. In our earlier studies, the compounds present in the transdermal patch were identified using GC-MS analysis; 12 compounds exhibiting the wound healing mechanism were analyzed using PASS software and filtered out. From these 12 compounds, 6 compounds that possessed drug-likeness were screened by SwissADME and vNN-ADMET to dock against GSK3ß in the present work. The PyRx results confirmed the binding of the six ligands to the active site of the target protein. Though the remaining filtered ligands also exhibited inhibitory activity, Molecular dynamics simulation studies were carried out with 100 ns on a complex of 10,12 Tricosadiyonic acid, Nopyl acetate and 2 Methyl 4 Heptanol as they showed binding affinity of -6.2Kcal/mol, -5.7Kcal/mol and -5.1Kcal/mol respectively. The stability of the complex was validated using MD simulation parameters RMSD, RMSF, Rg, and Number of Hydrogen bonds. These results implied that the transdermal patch would be efficient in accelerating the wound healing process through the inactivation of GSK3ß.Communicated by Ramaswamy H. Sarma.

Generic selection criteria for safety and patient benefit [â «]: Comparing the physicochemical and pharmaceutical properties of brand-name and generic tulobuterol tape.

Physicochemical properties (drug release, peel strength, adhesion, and stiffness) of Hokunalin® Tape (Hokunalin) and 13 generic transdermal bronchodilator patches containing tulobuterol were characterized and evaluated for comparison. Drug-release studies evaluating sustained release behavior demonstrated better performance by the drug Hokunalin, than the generics MED, YP, Sawai, and Teikoku. Hokunalin yield a 16.2% release 1 hour after initiation, 30.1% at 3 hours, 50.0% at 8 hours. In comparison, the generics MED, YP, Sawai, and Teikoku showed an intermediate release behavior to that of Hokunalin, with more than 80% release after 8 hours. A 90-degree peel adhesion test for tape peel strength demonstrated that the generic MED (4.99 N), YP (3.26 N), Sawai (4.17 N), and Teikoku (4.37 N) tapes yielded significantly higher values compared to Hokunalin (2.66 N). Probe tack tests, evaluating adhesive strength, yielded significantly higher values for the generics HMT (4.89 N)and Towa (4.25 N) compared to Hokunalin (3.66 N). Furthermore, for the stiffness-softness test, a significantly higher value was obtained for each generic yielded compared to Hokunalin (3.7-degree). These factors are important components of product qualities that affect treatment efficacy, including "ease of application" and other usability factors.

Fabrication and characterization of coated microneedle patches based on PEGDA for transdermal administration of metformin.

Type 2 diabetes is one of the major challenges that the world is facing today. However, metformin (MET) as most type 2 diabetics' first-line oral hypoglycemic drug may cause serious side effects such as gastrointestinal irritation and nausea which reduce the patients' medication compliance. Therefore, the aim of the study was to design a safe and effective self-treatment device for the delivery of MET. Here, a kind of coated microneedle (MN) patches based on poly(ethylene glycol)diacrylate (PEGDA) were prepared by a two-step casting method and photopolymerization process for transdermal administration of MET. The needles wrapped with drug-loaded hyaluronic acid (HA) coating showed promising mechanical properties and drug delivery ability that allowed them to penetrate the skin barrier for rapid drug delivery, and they had no skin irritancy. The in vivo experiment of type 2 diabetic rats showed a satisfying hypoglycemic effect of the coated MN patches. The study shows that the prepared MN patches will be a potential method for the treatment of type 2 diabetes in the future.

Co-delivery of drugs by adhesive transdermal patches equipped with dissolving microneedles for the treatment of rheumatoid arthritis.

In this study, a dosage form consisting of dissolving (D) microneedles (M) and an adhesive (A) transdermal patch (P; DMAP) was designed and pre-clinically evaluated for the treatment of rheumatoid arthritis (RA). The tip of the dissolving microneedles (DMNs) was loaded with the macromolecular drug melittin (Mel@DMNs), this to treat joint inflammation and bone damage, while the adhesive transdermal patches contained the low molecular weight drug diclofenac sodium (DS; DS@AP) for pain relief. Mel@DMNs and DS@AP were ingeniously connected through an isolation layer for compounding Mel-DS@DMAP for the simultaneous delivery of the drugs. In vitro and in vivo experiments showed that DS@AP did not affect the mechanical properties and dissolution process of Mel@DMNs while the pores formed by the microneedles promoted the skin penetration of DS. Treatment of rats suffering from RA with Mel-DS@DMAP reduced paw swelling and damage of the synovium, joint and cartilage, suggesting that the 'patch-microneedle' dosage form might be promising for the treatment and management of RA.

MAP-box: a novel, low-cost and easy-to-fabricate 3D-printed box for the storage and transportation of dissolving microneedle array patches.

Research on the use of microarray patches (MAPs) has progressed at an unprecedented rate over the years, leading to the development of many novel drug delivery systems. As the technology approaches patients, there are several key aspects that ought to be addressed in order to facilitate the smooth translation of MAPs from bench to bedside. One integral factor includes the choice of devices and packaging for the storage of MAPs. In the current work, a slide-and-seal box, MAP-box, was developed for the storage of dissolving MAPs, using fused-deposition modelling. The device has been designed to act as a pill-box for MAPs not only to provide protection for MAPs from the environment, but also to improve patient's adherence to treatment. The overall design of the MAP-box was simple, yet offers the capability of sealing and protecting dissolving MAPs up to 30 days. Donepezil HCl was formulated into a dissolvable MAP, which was used to treat dementia related to Alzheimer's disease. This compound was used as a model formulation to evaluate the utility of the 3D printed MAP-box when placed under three storage conditions: 5 °C and ambient humidity, 25 °C and 65% relative humidity and 40 °C and 75% relative humidity. It was shown that the slide-and-seal box was able to confer protection to MAPs for up to 30 days under accelerated stability study conditions as the drug loading, mechanical properties and insertion properties of MAPs remained unaffected when compared to the unpackaged MAPs stored under these same parameters. These preliminary data provide evidence that the MAP-box prototype may be of great utility for the storage of single or multiple MAPs. Nevertheless, future work will be needed to evaluate their patient usability and its application to different types of MAP systems to fully validate the overall robustness of the prototype.

The efficacy of a transdermal hydrogel patch containing betamethasone dipropionate for treatment of chronic hand eczema: A single-blind, randomized and controlled trial.

BACKGROUND: Topical corticosteroids under occlusion have been used to enhance the treatment of eczema. However, no study has investigated the efficacy of a steroid-containing transdermal patch for the treatment of chronic hand eczema. METHODS: We conducted a randomized, controlled, assessor-blinded trial to determine the efficacy of a transdermal patch containing betamethasone dipropionate compared to topical betamethasone dipropionate ointment in the treatment of mild to moderate chronic hand eczema. The patients were included and assigned to receive either the transdermal patch once daily at night or the ointment twice daily for a period of 8 weeks. The outcomes were assessed using the Hand Eczema Severity Index (HECSI), Physical Global Assessment (PGA) score, self-reported compliance, level of patient satisfaction, quality of life, and side effects. RESULTS: Fifty-six patients completed this study. At 8 weeks, there was a significant reduction in the HECSI scores in both the transdermal patch and topical ointment groups compared to those measured at baseline (14.61 to 1.86, p < 0.001; 18.46 to 3.43, p < 0.001, respectively) without a statistically significant difference between the two groups. Similarly, the two groups did not show any significant difference in the PGA scores, quality of life and side effects. However, the transdermal patch group reported better compliance and a higher level of patient satisfaction than the topical ointment group. CONCLUSION: The transdermal corticosteroid patch has proven to be a safe and effective treatment, comparable to topical corticosteroids, after 8 weeks of use. Its sustained-release properties, along with once-daily use, can improve patient satisfaction and promote greater adherence to the treatment. TRIAL REGISTRATION: This study was registered with the Thai Clinical Trials Registry (www. CLINICALTRIALS: in.th) under registration number TCTR20220413003.

Transdermal Rotigotine at End-of-Life for Parkinson's Disease: Association With Measures of Distress.

BACKGROUND: End-of-life (EOL) care for Parkinson's disease (PD) can be challenging when oral medications are no longer tolerated. MEASURES: To assess EOL prescribing for people with PD (PWP), focusing on rotigotine dosing and proxy measures of distress: benzodiazepine and opioid use. INTERVENTION: A retrospective audit of patient records from PWP who died between January 2019 and May 2022 at the Royal Hobart Hospital (RHH), Australia, was conducted. Data was systematically collated on demographics, symptoms, levodopa equivalent daily dose (LEDD) and rotigotine, oral morphine equivalent (OME) and benzodiazepine doses in the last 72 hours of life . OUTCOMES: Pain (72%), respiratory secretions (66%) and agitation (66%) were the most documented EOL symptoms. 83% (n = 52) of PWP were eligible for rotigotine and, of those, 13% (n = 7) received the correct dose, 38% (n = 20) a lower dose, 12% (n = 6) a higher dose and 37% (n = 19) did not receive any. Rotigotine dose was positively associated with total (P = 0.016) and PRN (P = 0.037) benzodiazepine dose. LEDD was positively associated with total benzodiazepine (P = 0.018) and total OME dose (P = 0.046). Contraindicated dopamine antagonists were prescribed for 43% of PWP and administered in 31% of those cases. CONCLUSIONS: Rotigotine dose and admission LEDD were both associated with proxy measures of distress in the last 72 hours of life. This suggests cautious use of rotigotine at EOL. LEDD may help identify patients at risk of distress. Rates of inappropriate prescribing and symptom prevalence were high, indicating a need for further staff education to optimize the care of PWP.

Design of a tulobuterol patch with improved mechanical properties: effect of transdermal permeation enhancers on the release process of metal ligand-based acrylic pressure-sensitive adhesives.

The aim of this study was to design a tulobuterol (TUL) patch with good penetration behavior and mechanical properties. Particular attention was paid to the effect of transdermal permeation enhancers on the release process of metal ligand-based acrylic pressure-sensitive adhesive (AA-NAT/Fe3+). The type and dosage of the enhancers were screened by in vitro transdermal penetration in rat skin. The optimized formulation was evaluated in a pharmacokinetic study in rats. Furthermore, the molecular mechanism by which Azone (AZ) improves the release rate of TUL from AA-NAT/Fe3+ was investigated by FT-IR, shear strength test, rheological study, and molecular simulation. As a result, the optimized formula using AA-NAT/Fe3+ showed better mechanical properties compared to commercial products. Meanwhile, the AUC0-t and Cmax of the optimized patch were 1045 ± 89 ng/mL·h and 106.8 ± 28.5 ng/mL, respectively, which were not significantly different from those of the commercial product. In addition, AZ increased the mobility of the pressure-sensitive adhesive (PSA) rather than decreasing the drug-PSA interaction, which was the main factor in enhancing TUL release from the patch. In conclusion, a TUL transdermal drug delivery patch was successfully developed using metal-coordinated PSA, and a reference was provided for the design of metal-coordinated acrylic PSA for transdermal patch delivery applications.