SISO-based hot-melt pressure-sensitive adhesives for transdermal delivery of hydrophilic drugs

A monomer-activated anionic polymerization approach was utilized to synthesize poly(styrene-b-isoprene-b-styrene-b-ethylene oxide) tetrablock terpolymers (SISO), which were melt-mixed with tackifiers and plasticizer to develop polar SISO-based hot-melt pressure-sensitive adhesives (HMPSAs) for transdermal delivery of hydrophilic drugs. Their hydrophilic performance was characterized using contact angle analysis. Their adhesive performances were measured in terms of 180° peel strength and holding power. In vitro drug release experiments were carried out using a modified Franz type horizontal diffusion cell, in which geniposide was chosen as a hydrophilic model drug. The results show that poly(ethylene oxide) (PEG) blocks exhibit substantial effects on adhesive performance and the release behavior of the model drug. The shorter PEG molecular chains enhance adhesive performance and the cumulative release rate of the model drug in the SISO-based HMPSAs. The longer PEG molecular chains tend to crystallize. Their crystallization structures have negative effects on adhesive performance and limit the dissolution and diffusion of drugs in the SISO-based HMPSAs. Therefore, appropriate PEG molecular chains are required to fabricate SISO-based HMPSAs with excellent adhesive performance for transdermal delivery of hydrophilic drugs.     

亲水性聚氨酯压敏胶经皮给药应用性能研究

针对目前经皮给药制剂发展急需性能优良的亲水性新型压敏胶基质,制备了亲水性聚氨酯压敏胶。对一些影响压敏胶贴剂力学性能的因素进行了考察,并重点研究了载药压敏胶贴剂经皮释放规律。结果表明,该聚氨酯压敏胶贴剂具有良好的药物控释能力,适用于经皮给药系统。     

Polyacrylate-N-vinyl lactam polymer or copolymer blends as pressure-sensitive adhesives

It has been previously shown that blends of a homopolymer or a copolymer of an N-vinyl lactam with an acrylate or a related copolymer containing a small proportion of acidic groups exhibit macroscale compatibility and a phase separated microstructure. This paper presents an application of this two-phase polymer system for the preparation of melt processable acrylic pressure-sensitive adhesives (PSA). 2-Ethylhexyl acrylate-acrylic acid copolymers, having molecular weights in the range of 50 000 to 115 000 were prepared by free-radical solution polymerization. These copolymers were tacky but possessed insufficient cohesive strength at ambient temperatures to be useful as PSAs. Blending such acrylate copolymers, having some acidic functionality, with minor proportions of a glassy homopolymer or a copolymer of an N-vinyl lactam resulted in materials having a balance of cohesive and adhesive characteristics required of a good PSA. Due to low molecular weights of the components of the polymer blend acrylic PSAs, they are amenable to hot melt processing. Some of the parameters affecting the pressure-sensitive adhesive properties of the polymer blend are: (a) fraction of the glassy polymer in the blend, (b) molecular weights of the polymeric components, (c) acidic functionality of the low molecular weight acrylate copolymer, and (d) N-vinyl lactam functionality of the glassy polymer.     

水性聚氨酯压敏胶的合成及其性能表征

以异佛尔酮二异氰酸酯(IPDI)、聚醚多元醇(N220、N210)、二羟甲基丙酸(DMPA)和三羟甲基丙烷(TMP)为主要原料制得了环保交联型水性聚氨酯(WPU)压敏胶,讨论了n(-NCO)/n(-OH)比值、交联剂用量以及聚醚相对分子质量大小对该压敏胶性能的影响。研究结果表明,由N220合成的WPU压敏胶的初粘力优于由N210合成的WPU压敏胶;随着n(-NCO)/n(聚醚中-OH)比值的减小,压敏胶的初粘力提高,持粘力呈先降后增再降的趋势;适度的交联可以提高压敏胶的粘接强度;当n(-NCO)∶n(聚醚中-OH)为2.5∶1、n(TMP中-OH)∶n(聚醚中-OH)为1∶3.0时,压敏胶的综合性能优异,初粘力达到13号钢球,持粘力达到23.1h,180°剥离强度达到20.14N/(20mm)。     

Progress on rubber-based pressure-sensitive adhesives

Rubber-based pressure-sensitive adhesives (PSAs), especially synthetic rubber-based PSAs, underwent deep and extensive development in the last 20 years because of their unique features such as high flexibility, good impact, and chemical resistance. Different rubbers and tackifiers; the PSA performance such as tack, peel strength, and shear strength; the affecting factors such as temperature, test rate, formulations, phase structure, and compatibility; rheological properties and bonding mechanism; as well as novel application in medical and electronic fields became the focus of many researchers. All of the relevant progress is summarized and reviewed in this article     

Solvent-based pressure-sensitive adhesives for PVC sign and marking films

This article shows the influence of parameters such as acrylic acid, initiator content, molecular mass, viscosity, content of methyl acrylate, content of ethyl acrylate, and content of N-vinyl caprolactam on such important parameters of pressure-sensitive adhesives as shrinkage, plasticity, adhesion to the steel, and deformation. Pressure-sensitive adhesives based on acrylic polymers and containing 2-ethylhexyl acrylate, methyl acrylate, acrylic acid, and N-vinyl caprolactam are used for production of self-adhesives containing polyvinyl chloride carrier. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 81: 3212–3219, 2001     

Preparation and characterization of polarity-modulated SIS-based hot-melt pressure-sensitive adhesives

In order to develop polarity-modulated hot-melt pressure-sensitive adhesives (HMPSAs), epoxidation of styrene-isoprene-styrene (SIS) copolymers, using in situ prepared per-formic acid was studied. The polymers were characterized with Fourier-transform infrared spectroscopy, ¹H nuclear magnetic resonance spectroscopy, differential scanning calorimetry, and contact angle tests. The epoxidation degree linearly increases with the epoxidation time without side reaction at low temperature. The polarity of the polymers increases with the epoxidation degree. At low epoxidation degree, the 180° peel strength of epoxidated-SIS-based HMPSA increases with the epoxidation degree. In epoxidated-SIS-based HMPSAs, ESIS plays the role of compatibilizer.     

Fabrication of Amphiphilic Hot-Melt Pressure Sensitive Adhesives for Transdermal Drug Delivery

Abstract

Styrene-isoprene-styrene (SIS) copolymer and tackifier resins can be utilized to prepare hot-melt pressure sensitive adhesives (HMPSAs) for the transdermal delivery of high lipophilic drugs. To meet the requirement of transdermal delivery of Chinese medicine (containing different ingredients including lipophilic, amphiphilic and hydrophilic drugs), amphiphilic HMPSAs were developed by melt-blending HMPSAs, poly(ethyl acrylate-co-methyl methacrylate-co-trimethylammonioethyl methacrylate chloride) (RLPO) and polyethylene glycol 2000 (PEG2000). Their morphological structures and miscibility were characterized with phase microscopy and differential scanning calorimetry. Their 180° peel strength and holding power were measured for their adhesive performances. In vitro drug release experiments were carried out using a modified Franz type horizontal diffusion cells, in which three ingredients of gardenia fruit (oleanic acid, luteolin and geniposide) were chosen as representatives of lipophilic, amphiphilic and hydrophilic drugs. It was found that amphiphilic phase structures were developed with the addition of RLPO and PEG2000. As the SIS/RLPO ratio was 1:1～1:2, the HMPSAs had miscible and amphiphilic phase structures. Drug release results showed that hydrophilic drugs could be released due to the existence of RLPO and PEG2000. Its release rate was rapidly enhanced with the increment of RLPO and PEG2000. Meanwhile, the release behavior of lipophilic and amphiphilic drugs and adhesive performance of HMPSAs were preserved in the experiment range. It was proposed that the addition of RLPO and PEG2000 did not destroy phase structures of SIS and tackifier, which insured appropriate adhesive performance and the amphiphilic polymer skeleton of SIS/RLPO/PEG2000 as release channels of various drugs.     

Phase structure and adhesion properties of acrylic block copolymer/tackifier blends as nanocomposite-like pressure-sensitive adhesives

In a blend of acrylic block copolymer consisting of poly(methyl methacrylate) and poly(n-butyl acrylate) blocks and a special rosin ester resin (RE) tackifier as a model pressure-sensitive adhesive (PSA), RE exists in two states: as nm-sized agglomerated particles (A) and as dissolved molecules (B). The effect of A and B ratio on the PSA properties were investigated using REs with four different weight-average molecular weights (M_ws) in the range from 680 to 1700. The formation of A increased with increasing of M_w because of lowering of miscibility. The glass transition temperature increased with increasing of M_w. The tack at lower temperatures and the fracture energy were improved by B, whereas the tack at higher temperatures was improved by A. A and B enhanced the cohesive strength and the wettability of PSA, respectively. However, the improvement of cohesive strength by the RE with highest M_w was remarkably low. This seems to be caused by the larger size of agglomerated particles. ¹H pulse nuclear magnetic resonance analysis was useful for estimating the degree of A formation. The model PSA investigated in this study was nanocomposite-like.     

Adhesion properties of polyacrylic block copolymer pressure-sensitive adhesives and analysis by pulse NMR and AFM force curve

The adhesion strength of a pressure-sensitive adhesive (PSA) is influenced by two factors, the interfacial adhesion and the cohesive strength. A suitable method for the estimation of these two factors was investigated. Blends of triblock and diblock copolymers consisting of poly(methyl methacrylate) (hard) and poly(n-butyl acrylate) (soft) blocks (A) and blends of triblock copolymer and poly(n-butyl acrylate) oligomer (B), both with different blend ratios, were prepared as model PSAs. The peel strength decreased with an increase in the hard block content for B, whereas it was independent for A. The tack increased with a decrease in the hard block content for A, whereas it was independent for B. The influence of the hard block content on the peel strength and tack was thus different. The ¹H pulse nuclear magnetic resonance analysis and force curve analysis showed that the molecular mobility was higher for B than for A. The Young's modulus and adhesive energy calculated by the Johnson–Kendall–Roberts two-point method using the atomic force microscopy (AFM) force curve qualitatively reflected the cohesive strength and the interfacial adhesion, respectively. The Young's modulus and adhesive energy are found to be useful parameters to investigate the adhesion mechanism. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47791.     

The thermal degradation of acrylic pressure-sensitive adhesives based on butyl acrylate and acrylic acid

The thermal degradation of acrylic pressure-sensitive adhesives at 250 °C was investigated using pyrolysis-gas chromatography. Knowledge of the types and amounts of pyrolysis products will provide important information on the thermal degradation of acrylic adhesives and the mechanisms involved. Unsaturated monomers including butyl acrylate and butyl methacrylate were formed during thermal degradation of butyl acrylate–acrylic acid copolymers. As a result of side chain reactions in the thermal destruction of the butyl acrylate–acrylic acid-based self-adhesives, a remarkable amount of butyl alcohol was produced. The unsaturated monomers formed as a result of thermal degradation could potentially be used in a new polymerization process.     

Reusable dry adhesives based on ethylene vinyl acetate copolymer with strong adhesion

This work proposed the design and fabrication method for T-shaped dry adhesives based on stretchable ethylene-vinyl acetate (EVA) copolymer, with strong normal adhesion strength up to 70 N cm⁻². As fabricated adhesives based on the inexpensive soft replication process have comprehensive advantages including easy demolding applicable for various curable materials; self-cleaning characteristic based on excellent nonwetting characteristics to both water and oil; reversible adhere/detach cycling for reusability. The flexible and transparent EVA dry adhesive films were readily fabricated to be novel dry-adhesive coatings decorated on various substrates and shapes. We also explored the adhere and detach mechanism for the significantly enhanced adhesion of T-shaped EVA microstructures, which indicated the increased contact area and the friction dissipation between the undercut and the substrate contribute to the adhesion enhancement, while the excellent elastic deformation of EVA may play an important role for adhesion enhance during the pulling-off process. These results showed the great potential of high-performance T-shaped EVA-based polymer dry adhesives for practical applications. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47296.     

复合填料/聚丙烯酸酯导电压敏胶的制备与性能

针对导电胶黏剂（ECA）在实用中所遇到填料组分单一、易团聚、对基体力学性能影响较大等问题,本文利用不同组分填料间的架桥、插层等“协同”效应,将一定比例的碳黑（CB）、碳纤维（CF）、碳纳米管（CNTs）、纳米石墨微片（NanoG）复合作为导电填料加入到聚丙烯酸酯压敏胶（PSA）中,采用溶液共混法超声分散,得到填料添加量小、导电性能和力学性能良好的导电PSA。运用多种检测手段对导电PSA的电学性质、微观结构、热稳定性和力学性能进行了分析。结果表明,复合填料组成为CF 3%、NanoG 5%、CNTs 5%（均为质量分数）时,导电PSA的电导率达到3.0×10?2S/cm,180°剥离强度为0.38kN/m。     

Synthesis of SIS-based hot-melt pressure sensitive adhesives for transdermal delivery of hydrophilic drugs

A series of epoxidized styrene–isoprene–styrene (SIS) copolymer was obtained with in situ epoxidation. Their epoxidation degrees were analyzed by ¹H nuclear magnetic resonance spectroscopy and Fourier transform infrared spectroscopy. SIS, Epoxidized SIS (ESIS), C5 resin, mineral oil and antioxidants were melt-blended to prepare SIS/ESIS-based hot-melt pressure sensitive adhesives (HMPSAs). Their compatibility was studied with differential scanning calorimetry (DSC). The adhesive performances of the HMPSAs were measured, including holding power and 180° peel strength. Geniposide was chosen as a representative hydrophilic drug and it’s in vitro release behavior in the HMPSAs was investigated using a modified Franz type horizontal diffusion cells. It was shown that SIS was successfully epoxidized without side reactions. Although the epoxidation impaired the compatibility between ESIS and other additives, the 180° peel strength increased with the epoxidation degrees of ESIS. Furthermore, the in vitro release behavior of hydrophilic drugs was obviously enhanced with the increment of epoxidation degrees.     

用均匀设计和正交设计研究水性PU压敏胶配方

为制得环保、交联型水性聚氨酯压敏胶,以IPDI、聚醚多元醇、DMPA、TMP为主要原料进行乳液聚合.用红外光谱表征合成材料的结构,测定其初粘性、持粘性、180°剥离强度.运用均匀设计筛选配方,并用正交图表分析较优值,通过正交试验确定了压敏胶的最佳配方.当n-NCO/n聚醚-OH=2.5:1,TMP/N220的-OH物质的量比为1:3时,压敏胶综合性能最好,初粘性为13号钢球,持粘性为23.1 h,180°剥离强度为20.14 N/20 mm.     

Controlled co‐delivery of hydrophilic and hydrophobic drugs from thermosensitive and crystallizable copolymer nanoparticles

Functionalized amphiphilic block copolymers poly(N‐isopropyl acrylamide)‐b‐poly(stearyl methacrylate) (PNIPAM‐PSMA) are synthesized. Their self‐assembled core‐shell nanoparticles have the hydrophilic thermosensitive shell and hydrophobic crystallizable core. Nanoparticles exhibit volume phase transition at temperature of 38 °C and its poly(stearyl methacrylate) (PSMA) moiety could form nano size crystals to retain drugs, making them good carriers for drug co‐delivery system. Thermosensitivity and crystallinity of nanoparticles are characterized with dynamic light scattering (DLS), differential scanning calorimetry (DSC), small‐angle X‐ray scattering (SAXS), and atomic force microscopy (AFM). The interactions and relationship between chemical structures of copolymer nanoparticles and loading drugs are discussed. Different loading techniques and combined loading of hydrophobic/hydrophilic drugs are studied. Nanoparticles show a good and controllable drug loading capacity (DL) of hydrophilic/hydrophobic drugs. The drugs release kinetics is analyzed with Fick's law and Weibull model. A general method for analyzing drug release kinetics from nanoparticles is proposed. Weibull model is well fitted and the parameters with definite physical meaning are analyzed. PNIPAM‐PSMA nanoparticles show a quite different thermal response, temporal regulation, and sustained release effect of hydrophilic and hydrophobic drugs, suggesting a promising application in extended and controlled co‐delivery system of multi‐drug. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 44132.     

Effect of the rheological properties of industrial hot-melt and pressure-sensitive adhesives on the peel behavior

Three factors govern the adhesion properties of hot-melt and pressure-sensitive adhesives: (1) thermodynamic interfacial properties (Dupré adhesion energy); (2) interfacial losses due to specific interactions; and (3) viscoelastic losses in the bulk related to the rheological properties of the adhesive. In the present paper, we focus on the main factor in the adhesion properties, which is the viscoelastic factor. We extend in this paper the results obtained on a series of model adhesives to the case of industrial formulations: one SIS triblock copolymer-based PSA formulation and one EVA copolymer-based hot-melt formulation. After studying the rheological properties of these adhesives over a wide frequency range using time-temperature equivalence, we present data obtained on peel tests at various temperatures. As with model adhesives, the peel rate-temperature equivalence leads to the same shift factors as rheology. The experiments demonstrate that there is a one-to-one relationship between the cohesive fracture domain and the terminal region of relaxation exhibited in rheological testing. The first interfacial fracture mode is related to the rubbery plateau, and the brittle interfacial fracture mode observed at high peel rates to the glassy behavior exhibited at very high frequencies in rheological measurements.     

Incorporation of cellulose nanocrystals and reactive surfactants for improved pressure-sensitive adhesive performance

Pressure-sensitive adhesives (PSAs), which achieve instantaneous adhesion with the application of light pressure, are used in a large range of commodity applications. In this work, PSAs enriched with cellulose nanocrystals (CNCs) and stabilized with a reactive surfactant (Hitenol AR-1025, AR) were synthesized via in situ emulsion polymerization. Incorporation of CNCs into AR-stabilized PSAs lead to improvements of peel strength, shear strength, and loop tack with significant increases observed at a CNC concentration of 0.75 parts per hundred monomer (phm). A comparative investigation of PSAs stabilized with reactive (AR) and non-reactive (sodium dodecyl sulfate) surfactant revealed that the enhanced performance can be attributed to the synergistic combination of CNCs and reactive surfactant, as only modest improvements can be attributed to surfactant type. In contrast to previous studies that report a trade-off in adhesive properties, we present a well-rounded PSA with exceptional peel strength, shear strength, and loop tack.     

Heat resistance of acrylic pressure-sensitive adhesives based on commercial curing agents and UV/heat curing systems

The development of adhesive tapes that can be applied at high temperature is a major challenge for pressure-sensitive adhesives (PSAs). To date, the heat resistance of PSAs has not been investigated in sufficient details. In this study, based on the relationship between curing structures and properties, a series of acrylic PSAs with excellent heat resistance were prepared. Commercial zirconium acetylacetonate (ZrACA), desmodur L75 (L75), and N,N,N′,N′-tetrakis(2,3-epoxypropyl)-m-xylene-α,α′-diamine (GA240) were employed as heat-curing agents. Trimethylolpropane triacrylate (TMPTA) was used as ultraviolet (UV)-curing agent to form semi-interpenetration polymer network structures after UV exposure. The influences of different curing agents on the thermal stability, adhesion performance, gel fraction, and viscoelastic of PSAs were explored. The results showed that the PSAs cured by L75, GA240, and TMPTA exhibited excellent heat resistance. Especially, when the content of L75 was 1.0 wt %, the PSAs could be peeled off substrate without residues on substrate surface after treatment at 170 °C for 4 h, while the nonmodified acrylic PSAs possessed residues after treatment from 110 °C. The cured PSAs adhesive performance was evaluated showing maximum 180° peel strength of 16.7 N/25 mm comparable to current PSAs. These resulting PSAs showed high heat resistance and they are suitable for a broad range of special fields. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47310.     

Miscibility and fracture energy of probe tack for acrylic pressure-sensitive adhesives: acrylic copolymer/tackifier resin systems

The relationship between the miscibility of acrylic pressure-sensitive adhesive (PSA) and the fracture energy (W) (Jm⁻²) of the probe tack was investigated, wherein the master curve of W was compared with that of the maximum force (σ_max) (gf) of the probe tack. It was ascertained that W of acrylic PSA was closely related to the miscibility between the components (acrylic copolymer and tackifier resin). In the case of the miscible blend system, the master curve of W shifted toward the lower rate side and, at the same time, the magnitude decreased as the tackifier resin content increased. The degree of the shift of W was extremely smaller than that of σ_max. In the case of the immiscible blend system, the master curve of W remarkably decreased as the tackifier resin content increased, which suggests the fact that W of the PSA depended on the dynamic mechanical properties of the matrix phase and that the resin-rich phase acted as a kind of filler, thus reducing the practical performance. © 1998 John Wiley & Sons, Inc. J Appl Polym Sci 69: 581–587, 1998