Development of hot-melt pressure–sensitive adhesives for transdermal drug delivery

Styrene–isoprene–styrene (SIS) copolymer was epoxidized by in situ epoxidation to prepare a series of epoxidized SIS resins (ESIS). Their epoxidation degrees, phase structures, and compatibility with hydrocarbon resin were characterized with ¹H nuclear magnetic resonance spectroscopy, atomic force microscopy, and differential scanning calorimetry, respectively. These ESIS resins were melt-mixed with synthetic hydrocarbon resin, mineral oil, and antioxidants to fabricate a series of ESIS-based hot-melt pressure–sensitive adhesives (HMPSAs), which were used as carriers of transdermal drug delivery system. Their adhesive performances were measured, including holding power and 180^o peel strength. Geniposide and oleanic acid were representatively chosen as hydrophilic and lipophilic drug, respectively. Their in vitro release behaviors in ESIS-based HMPSAs were investigated using a modified Franz-type horizontal diffusion cells. Although the introduction of epoxide groups could alter the compatibility and phase structures between SIS resins and additives, the adhesive performances were slightly affected, as SIS resins had lower epoxidation degree (<15%). It is even more important that the cumulative release rate of both hydrophilic and lipophilic drugs is markedly enhanced with the increase of epoxidation degree in these ESIS-based HMPSAs. Therefore, this kind of HMPSAs has a promising future as a carrier of transdermal drug delivery system as their SIS resins are appropriately epoxidized.     

Hot-melt pressure-sensitive adhesives based on SIS-g-PB copolymer for transdermal delivery of hydrophilic drugs

SIS-g-PB copolymers were successfully synthesized by grafting living polybutadiene (PB) lithium macroanions onto epoxidized SIS copolymers. Their molecular structures and thermal properties were characterized by TGA, ¹H-NMR and DSC, respectively. SIS, epoxidized SIS (ESIS) and SIS-g-PB copolymers were melt-blended with tackifiers to develop hot-melt pressure-sensitive adhesives (HMPSAs), respectively (named of H-SIS, H-ESIS and H-SIS-g-PB). Their adhesive performances were measured in terms of 180° peel strength and holding power. A modified Franz type horizontal diffusion cell was used to carry out In vitro drug release experiments, in which geniposides were chosen as hydrophilic model drugs. The results showed that H-SIS-g-PB has two times as high a 180° peel strength as H-SIS. Meanwhile H-SIS-g-PB has a slightly lower drug cumulative release rate than H-ESIS. It is indicated that the PB branches not only could impart good adhesive performance to H-SIS-g-PB via improving the compatibility between the epoxidized main chains and tackifier resins but also provide release channels to hydrophilic drugs by retaining most of the epoxide groups in the SIS-g-PB copolymers.     

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.     

Epoxidation of Styrene-Isoprene-Styrene Block Copolymer and Its Use for Hot-Melt Pressure Sensitive Adhesives

The epoxidation of styrene-isoprene-styrene block copolymer (SIS) with performic acid generated in situ from hydrogen peroxide and formic acid was studied, and the hot-melt pressure sensitive adhesives (HMPSA) were prepared with epoxidized SIS (ESIS), SIS and the tackifier ESCOREZ-2203LC. The ¹H nucleal magnetic resonance and Fourier transform infrared spectra revealed that the epoxidation reaction mainly occurred in 1,4-isoprene units of SIS, and the reactivity of the cis-1,4-structure was higher than that of the trans-1,4-structure. Analysis by Gel Permeation Chromatography (GPC) showed that the molecular weight of SIS increased and the molecular weight distribution widened after epoxidation. Differential scanning calorimetry analysis showed that ESIS was compatible with SIS and ESCOREZ-2203LC. The addition of certain amount of polar ESIS in the HMPSA was beneficial to the improvement of 180° peel strength when the substrates were polar materials, such as PVC and steel. With the increase in peeling rate, the peel failure mode changed to adhesion failure from cohesion failure.     

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.     

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.     

Study on Adhesion Properties of a Hot-Melt Pressure-Sensitive Adhesive Based on Epoxidized Styrene–Isoprene-Styrene Triblock Copolymers (ESIS) for Transdermal Drug Delivery Systems

Pressure sensitive adhesives are a critical component in transdermal drug delivery systems (TDDS). In this study, styrene-isoprene-styrene triblock copolymers (SIS) was epoxidized with peroxyformic acid generated in situ. The hot-melt pressure sensitive adhesive (HMPSA) of ESIS with hydrogenated rosin, epoxidized soybean oil, and antioxidant was prepared. The structure and properties of ESIS were characterized with infrared spectroscopy and dynamic mechanical analysis (DMA). Water content and water vapor transmission rate on ESIS membranes were determined. The adhesion properties of HMPSA of ESIS were investigated. The experimental results showed that the HMPSA of ESIS was superior to traditional HMPSA of SIS in 180°peel strength when the substrates were polar materials, such as PVC and steel.     

环氧化SDS型热熔压敏胶的制备及粘接性能研究

采用苯乙烯-丁二烯-苯乙烯(SBS)和苯乙烯-异戊二烯-苯乙烯(SIS)嵌段共聚物,并配合极性的环氧化SBS(ESBS)和环氧化SIS(ESIS)作为基体材料,制备了环氧化SDS(苯乙烯系热塑性弹性体)型热熔压敏胶。研究了ESBS和ESIS用量对压敏胶的初粘力、持粘力和在不同极性底材上剥离强度的影响。结果表明,随着ESBS和ESIS用量的增加,压敏胶的初粘力和持粘力下降,在聚乙烯(PE)上的剥离强度下降,但在聚氯乙烯(PVC)和不锈钢上的剥离强度先增加后下降。当ESBS和ESIS的质量份数均为20份时,压敏胶的初粘力和持粘力分别为23#和43.6 h,在PVC和不锈钢底材上的剥离强度分别达到0.82 N/mm和1.10 N/mm。     

环氧化SIS热熔型压敏胶的研究

利用过甲酸对热塑弹性体SIS进行环氧化改性，合成了环氧化SIS(ESIS)。与SIS相比，ESIS的内聚强度增加，弹性降低，永久形变变小。优选了与ESIS相容性好的增塑剂和增粘剂，并以环氧化SIS为基料，与增粘剂聚合松香、增塑剂环氧大豆油、软化剂及防老剂配合制成了环氧化SIS热熔型压敏胶。实验结果表明，同SIS热熔压敏胶相比，ESIS热熔压敏胶的剥离强度、持粘力、耐老化性均有提高，初粘力相差不大。     

PS热塑弹性体环氧化对胶粘剂性能的影响

通过对苯乙烯类热塑性弹体ＳＢＳ、ＳＩＳ、ＥＳＢＳ、ＥＳＩＳ的溶度参数进行估算入手，从理论上讨论了环氧化对苯乙烯热塑性弹性体胶粘剂的本体强度，增粘剂的互溶行为的影响，通过胶粘剂性能的测试探讨了ＳＢＳ环氧化后对胶接性能的影响。     

Rheological and physical characterization of pressure sensitive adhesives from bio‐derived block copolymers

Over the past decade, the development of various monomers and polymeric materials from renewable natural resources has received increasing attention. Soybean oil, as one of the most abundant vegetable oils, has been widely used in recent studies. To enhance the reactivity of pure soybean oil, it can undergo through different processes such as acrylation and epoxidation. In this article, we investigated the viability of polymerized acrylated epoxidized soybean oil (PAESO) in the composition of pressure sensitive adhesives (PSAs). We studied the physical and rheological properties of PSAs composed of poly(styrene‐b‐AESO), and five different tackifiers and three plasticizers. To verify the compatibility of the tackifiers with the biopolymer, a library of 15 PSAs was prepared through solvent blending method and tested by differential scanning calorimetry. The viable formulations were then prepared through hot‐melt blending and characterized using 180° peel tester, and advanced rheometric expansion system. Results showed that the combination of an ester of hydrogenated rosin and a high solvating plasticizer with the synthesized biopolymer indicated best performance relative to other formulations. The comparison of this candidate with its petroleum‐based counterpart containing SIS demonstrates promising potential of the material to perform as well as commercialized PSAs. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46618.     

环氧化SIS的合成及表征

在甲苯中,利用过甲本酸对ＳＩＳ进行了环氧化反应,并通过红外光谱、核磁共振、凝胶渗透色谱、透射电镜等分析方法对环氧化ＳＩＳ的结构进行了表征,同时也对环氧化ＳＩＳ的力学性能进行了测试。结果表明,在ＳＩＳ环氧化过程中伴随有副反应发生,分子链炭生了部分降解;异戊二烯链段上双键的反应活性大小依次为：顺－１,４－结构,反－１,４－结构,由于环氧基团的引入,环氧化ＳＩＳ的极性增强,内聚强度增加。     

Cure kinetics and thermal stability of micro and nanostructured thermosetting blends of epoxy resin and epoxidized styrene‐block‐butadiene‐block‐styrene triblock copolymer systems

The compatibility of styrene‐block‐butadiene‐block‐styrene (SBS) triblockcopolymer in epoxy resin is increased by the epoxidation of butadiene segment, using hydrogen peroxide in the presence of an in situ prepared catalyst in water/dichloroethane biphasic system. Highly epoxidized SBS (epoxy content SBS >26 mol%) give rise to nanostructured blends with epoxy resin. The cure kinetics of micro and nanostructured blends of epoxy resin [diglycidyl ether of bisphenol A; (DGEBA)]/amine curing agent [4,4′‐diaminodiphenylmethane (DDM)] with epoxidized styrene‐block‐butadiene‐block‐styrene (eSBS 47 mol%) triblock copolymer has been studied for the first time using differential scanning calorimetry under isothermal conditions to determine the reaction kinetic parameters such as kinetic constants and activation energy. The cure reaction rate is decreased with increasing the concentration of eSBS in the blends and also with the lowering of cure temperature. The compatibility of eSBS in epoxy resin is investigated in detailed by Fourier transform infrared spectroscopy, optical and transmition electron microscopic analysis. The experimental data of the cure behavior for the systems, epoxy/DDM and epoxy/eSBS(47 mol%)/DDM show an autocatalytic behavior regardless of the presence of eSBS in agreement with Kamal's model. The thermal stability of cured resins is also evaluated using thermogravimetry in nitrogen atmosphere. POLYM. ENG. SCI., 2012. © 2012 Society of Plastics Engineers     

Synthesis of Bio-based Polyurethane from Modified Prosopis juliflora Oil

Studies on the epoxidation of Prosopis juliflora seed oil were carried out to evaluate the optimum level of oxirane formation. On optimization of epoxidation of Prosopis juliflora oil (PJO), it was observed that at 60 °C and the mole ratio of double bond to the hydrogen peroxide to the acetic acid was 1:1.1:0.5 and at 2 wt% catalyst loading gave the maximum oxirane conversion. Further, epoxidized Prosopis juliflora oil (EPJO) was reacted with aminopropyltrimethoxysilane. Aminopropyltrimethoxysilanated Prosopis juliflora oil (ASPJO) was used as a polyol and was allowed to react with varying concentrations of isophorone diisocyanate resulting in polyurethane. The polyurethane films biodegradability was studied using phosphate buffer and proteinase K. The epoxidized oil was characterized by its epoxy value and FT-IR spectroscopy. Similarly, ASPJO was characterized by its amine value, FT-IR and ¹H-NMR spectroscopy. Whereas the polyurethane coating was characterized by gel content, FT-IR spectroscopy, scanning electron microscopic analysis and also evaluated for its chemical resistance, optical and mechanical properties.     

Polar polystyrene‐isoprene‐styrene copolymers with long polybutadiene branches

Polar polystyrene‐isoprene‐styrene (SIS) copolymers having epoxide groups and long polybutadiene (PB) branches were synthesized via the combination of in situ epoxidation, anionic polymerization and graft‐onto reaction. They were characterized with ¹H NMR, GPC, FT‐IR, DSC, and contact angle test. Their polarity was determined by the epoxidation degree and graft efficiency. The epoxidation degree linearly increased with the epoxidation time. The graft efficiency decreased with the branch length, but increased with the epoxidation degrees. Although their glass transition temperature (T_g) of diene blocks and flexibility properties had been negatively affected by in situ epoxidation, they could be modulated by the epoxidation degree, branch length, and branch density. Their T_g could be tailored by the branch length and branch density since they fitted the Fox equation very well, especially as the longer branches were grafted. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40303.     

Role of epoxidation on segmental motion of polyisoprene as studied by broadband dielectric spectroscopy

In this article, the broadband dielectric spectroscopy (BDS) is used to investigate the relaxation behavior of polyisoprene (PI) epoxidized to various levels and the special consideration is devoted to the effect of epoxidation degree on segmental relaxation. To associate segmental relaxation with molecular structure, several empirical equations are used to fit experimental data. Furthermore, we want to discuss the origin of the change of segmental relaxation. Thermal measurement reveals that glass transition temperature of epoxidized PI (EPI) increase with the increase of epoxidation degrees. The epoxidation modification increases the breadth of the dielectric dispersion. Oxirane groups as steric interference enhance the cooperativity of segmental relaxation process and retard the relaxation process, which results in the increase of coupling parameter. Specifically, Vogel–Fulcher–Tammann equation shows the relationship between correlation length and temperature. These results further illustrate the effect of epoxidation group on segmental motion of PI. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43879.     

热熔压敏胶的粘接性能和流变行为的关系

研究了热熔压敏胶初粘性、剥离强度与流变学行为之间的关系。研究发现,用温度扫描方法得到的流变曲线与压敏胶主曲线较为一致,因此可以将其转化为不同弛豫时间下的流变行为。通过调整液体树脂含量,设计出一系列橡胶平台模量保持相对不变的同时,具有不同玻璃化温度的压敏胶配方,其中玻璃化温度相同的压敏胶配方,具有基本相同的环形初粘力和剥离强度。     

Shear creep resistance of styrene–isoprene–styrene (SIS)‐based hot‐melt pressure‐sensitive adhesives

The effects of the properties of substrates and tackifier on the shear creep of SIS‐based HMPSAs were investigated. The holding power (t_b) and shear adhesion failure temperature (SAFT) were measured. The relationship between the complex viscosity and the holding power was examined. The holding power and SAFT values of the triblock SIS blends were higher than those of the diblock‐containing SIS blends, perhaps because blends using triblock SIS have higher crossover temperature and complex viscosity than those using diblock‐containing SIS. Higher levels of aromatic resin‐modified aliphatic tackifier and rosin ester were found to decrease the holding power of the HMPSAs. This maybe due to the fact that rosin ester and aromatic‐modified aliphatic resin are compatible with both the ends and midblocks of SIS. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 825–831, 2006     

中药贴片用ESIS热熔压敏胶的制备与性能研究

以ESIS(环氧化苯乙烯-异戊二烯-苯乙烯嵌段共聚物)为基体树脂、环氧大豆油为增塑剂和高度氢化松香为增黏树脂,制备出一种ESIS型HMPSA(热熔压敏胶)。以ESIS、增塑剂和增黏树脂用量作为试验因素,HMPSA的初粘力、剥离强度和持粘力作为考核指标,采用正交试验和载药量试验法优选出制备中药贴片用ESIS型HMPSA的最佳配方。结果表明:当m(ESIS)∶m(环氧大豆油)∶m(高度氢化松香)∶m(抗氧剂1010)=100∶80∶100∶1.4时,ESIS型HMPSA的综合性能满足中药贴片的使用要求,并且其最大载药量(34%)和水蒸气透过率[1.297 g/(m2.d)]均高于同类产品(医用SIS型压敏胶和传统天然橡胶膏)。