Controlled release of dexamethasone from fibrin sealant for intratympanic administration in inner ear therapy

The aim of the present work was to show the sustainability of fibrin sealant in releasing dexamethasone and adjust the protocol for clinical application of the novel method in the treatment of Meniere’s disease (MD) and sudden sensorineural hearing loss (SSHL).Gelation occurred shortly after mixing dexamethasone-containing fibrinogen with thrombin.Dexamethasone was constantly released for at least 16 d at a stable level after 7d in protocol 1 (low-dose),while it was robustly released within 4 d and slowed afterward until 10 d in protocol 2(high-dose).There were significant differences among the time points in Protocol 2 (p<0.01,ANOVA),and the exponential model with the formula y=15.299*e~(-0.483*t) fits the association.The estimated concentration of dexamethasone released on 7 d in protocol 2 was slightly lower than that observed in protocol 1.The fibrin sealant is capable of constantly releasing dexamethasone with adjustable dynamics.Targeted and minimally invasive administration of the material can be achieved in the clinic by sequential injections of the fluids using a soft-tipped catheter.

Assessment of the crucial factors influencing the responses of ammonia and nitrous oxide emissions to controlled release nitrogen fertilizer: A meta-analysis

Reducing ammonia(NH3) and nitrous oxide(N2O) emissions have great effects on mitigating nitrogen(N) nutrient loss and greenhouse gas emissions. Controlled release urea(CRU) can control the N release rate, which reduces reactive N loss and increases nitrogen use efficiency relative to conventional urea(CU). However, the crucial factors influencing the responses of NH3and N2O emissions to CRU relative to CU are still unclear. In this study, we evaluated the responses of NH3and N2O emissions to CRU based on collected field data with a meta-analysis. CRU reduced the NH3and N2O emissions by 32.7 and 25.0% compared with CU, respectively. According to subgroup analysis, CRU presented better mitigation of NH3and N2O emissions in soils with pH 6.5–7.5(–47.9 and –23.7%) relative to either pH<6.5(–28.5and –21.4%) or pH>7.5(–29.3 and –17.3%), and in the rice season(–34.8 and –29.1%) relative to the wheat season(–19.8 and –22.8%). The responses of NH3and N2O emissions to CRU increased from rainfed(–30.5 and –17.0%) to irrigated(–32.5 and –22.9%), and then to paddy(–34.8 and –29.1%) systems. In addition, the response of N2O emission mitigation increased with increases in soil total nitrogen(TN);however, soil TN did not significantly affect the response of NH3volatilization. The reduction in NH3emission was greater in sandy-textured soil(–57.7%) relative to loam-textured(–32.9%) and clay-textured(–32.3%) soils, whereas soil texture did not affect N2O emission. Overall, CRU was a good option for reducing the NH3and N2O emissions relative to CU in agricultural production. This analysis improves our understanding of the crucial environmental and management factors influencing the mitigation of NH3and N2O emissions under CRU application, and these site-specific factors should be considered when applying CRU to reduce reactive N loss and increase NUE.

Growth of tandem long-mat rice seedlings using controlled release fertilizers:Mechanical transplantation can be more economical and high yielding

The traditional soil-based rice seedling production methods for mechanical transplanting are resource-intensive,time consuming and laborious.The improvement and optimization of nutrient management in soil-less nursery raising methods like tandem long-mat seedlings(TLMS)are necessary for the resource-efficient cultivation of rice.In the present study,a controlled-release fertilizer(CRF)-polymer-coated compound fertilizer with 3 months release period(PCCF-3M)was applied as seedling fertilizer(SF),and five different dosages of SF(SF-0,SF-10,SF-20,SF-30,and SF-40)were compared with an organic substrate as the control(CK).Among all SF treatments,the best results were obtained with the application of 20 g/tray of SF(SF-20),as the seedling quality and machine transplanting quality were comparable to those of CK.In contrast,the lower dosages(SF-0 and SF-10)resulted in low nitrogen content and reduced shoot growth,while the higher dosages(SF-30 and SF-40)resulted in toxicity(increased malondialdehyde accumulation)and inhibited the root growth.Similarly,SF-20 increased panicle number(5.6-7.0%)and yield(4.3-5.3%)compared with CK,which might be related to the remaining SF entangled in the roots supporting the tiller growth of rice seedlings in the field.Moreover,SF-20 reduced the seedling block weight(53.1%)and cost of seedling production(23.5%)but increased the gross margin,indicating that it was easy to handle and economical.Taken together,our results indicate that SF-20 is a cost-effective way to promote the growth and transplanting efficiency of rice seedlings.To our knowledge,this study is the first to determine the optimum dosage of CRF for the soil-less production of rice seedlings.

Effects of Different Proportions of Controlled Release Urea and Ordinary Urea on Peanut Yield

[Objectives]To study the effects of different proportions of controlled release urea and ordinary urea on peanut yield.[Methods]A total of 5 treatments were set up according to different proportions of controlled release urea and ordinary urea,randomly arranged in blocks and repeated 3 times.[Results]The test results of field districts showed that different proportions of controlled release urea and conventional urea had different effects on peanut yield.On the basis of applying 50 kg/666.7 m^(2)of calcium superphosphate and 17 kg/666.7 m^(2)of potassium sulfate,13.34 kg/666.7 m^(2)of pure nitrogen was applied.The optimal ratio of controlled release urea to ordinary urea was 75:25,followed by 50:50.The output was 379.83 and 371.83 kg/666.7 m^(2),separately increased by 6.74%and 4.50%compared to the application of ordinary urea.[Conclusions]The combined application of controlled release urea and ordinary urea in peanuts can significantly increase peanut yield compared to just applying ordinary urea.

Effects of slow or controlled release fertilizer types and fertilization modes on yield and quality of rice

There is limited information about the influence of slow or controlled release fertilizer（S/CRF） on rice yield and quality. In this study, japonica rice cultivar Nanjing 9108 was used to study the effects of three different S/CRFs（polymer-coated urea（PCU）, sulfur-coated urea（SCU）, and urea formaldehyde（UF）） and two fertilization modes（both S/CRF and common urea（CU） as basal fertilizer, S/CRF as basal and CU as tillering fertilizer） on rice yield and quality. CU only was applied separately as control（CK）. Results showed that, rice grain yield, chalky kernel rate, chalky area, overall chalkiness, and the content of gliadin, glutenin, and protein, all showed the trends of UF〉PCU〉SCU within the same fertilization mode, and showed the trends of S/CRF as basal and CU as tillering fertilizer〉both S/CRF and CU as basal fertilizer within the same type of S/CRF. In contrast, the contents of amylose, amylopectin, and starch, as well as taste value, and peak and hot viscosity showed trends of SCU〉PCU〉UF, and the trends of both S/CRF and CU as basal fertilizer〉S/CRF as basal and CU as tillering fertilizer. Among S/CRF treatments and fertilization modes, taste values of cooked rice were positively correlated with amylose, amylopectin, and starch contents, as well as gel consistency, peak viscosity, hot viscosity, and cool viscosity, while negatively correlated with globulin, gliadin, glutenin, and protein contents. The types of S/CRF and fertilization modes are important for improving rice yield and quality. Compared to CK, higher yield and similar quality of rice was achieved with UF as basal and CU as tillering fertilizer, and similar yield with improved appearance and eating and cooking quality of rice was achieved with either both UF and CU as basal fertilizer, or PCU as basal and CU as tillering fertilizer.

Study of Dynamics of Floodwater Nitrogen and Regulation of Its Runoff Loss in Paddy Field-Based Two-Cropping Rice with Urea and Controlled Release Nitrogen Fertilizer Application

The article deals with the effects of urea and controlled release nitrogen fertilizer （CRNF） on dynamics of pH, electronic conductivity （EC）, total nitrogen （TN）, NH4^＋-N and NO3 -N in floodwater, and the regulation of runoff TN loss from paddy field-based two-cropping rice in Dongting Lake, China, and probes the best fertilization management for controlling N loss. Studies were conducted through modeling alluvial sandy loamy paddy soil （ASP） and purple calcareous clayey paddy soil （PCP） using lysimeter, following the sequence of the soil profiles identified by investigating soil profile. After application of urea in paddy field-based two-cropping rice, TN and NHa＋-N concentrations in floodwater reached peak on the 1st and the 3rd day, respectively, and then decreased rapidly over time; all the floodwater NO3--N concentrations were very low; the pH of floodwater gradually rose in case of early rice within 15 d （late rice within 3 d） after application of urea, and EC remained consistent with the dynamics of NH4^＋-N. The applied CRNF, especially 70% CRNF, led to significantly lower floodwater TN and NH4^＋ concentrations, pH, and EC values compared with urea within 15 d after application. The monitoring result for N loss due to natural rainfall runoff indicated that the amount of TN lost in runoff from paddy field- based two-cropping rice with urea application in Dongting Lake area was 7.47 kg ha^-1, which accounted for 2.49% of urea- N applied, and that with CRNF and 70% CRNF application decreased 24.5 and 27.2% compared with urea application, respectively. The two runoff events, which occurred within 20 d after application, contributed significantly to TN loss from paddy field. TN loss due to the two runoffs in urea, CRNF, and 70% CRNF treatments accounted for 72, 70, and 58% of the total TN loss due to runoff over the whole rice growth season, respectively. And the TN loss in these two CRNF treatments due to the first run-off event at the 10th day after application to early rice decreased 44.9 and 44.2% compared with urea, respectively. In conclusion, the 15-d period after application of urea was the critical time during which N loss occurred due to high floodwater N concentrations. But CRNF decreased N concentrations greatly in floodwater and runoff water during this period. As a result, it obviously reduced TN loss in runoff over the whole rice growth season.

Release Characteristics of Different N Forms in an Uncoated Slow/Controlled Release Compound Fertilizer

This study examined the release characteristics of different N forms in an uncoated slow/controlled-release compound fertilizer （UCRF） and the N uptake and N-use efficiency by rice plants. Water dissolution, soil leaching, and pot experiments were employed. The dynamics of N release from the UCRF could be quantitatively described by three equations： the first-order kinetics equation [N1=N0 （1-e^-kt）], Elovich equation （N1=a ＋ blnt）, and parabola equation （N1=a ＋ bt^0.5）, with the best fitting by the first-order kinetics equation for different N （r= 0.9569^＊＊-0.9999^＊＊）. The release potentials （No values estimated by the first-order kinetics equation） of different N in the UCRF decreased in the order of total N 〉 DON 〉 urea-N 〉 NH4^＋-N 〉 NO3^-N in water, and total N 〉 NH4^＋-N 〉 DON 〉 urea-N 〉 NO3^--N in soil, respectively, being in accordance with cumulative amounts of N release. The constants of N release rate （k values and b values） for different N forms were in decreasing order of total N 〉 DON 〉 NH4^＋-N 〉 NO3^--N in water, whereas the k values were urea- N 〉DON 〉 NH4^＋-N 〉 total N 〉 NO3^--N, and the b values were total N 〉 NH4^＋-N 〉 DON 〉 NO3^--N 〉 urea-N in soil. Compared with a common compound fertilizer, the N-use efficiency, N-agronomy efficiency, and N-physiological efficiency of the UCRF were increased by 11.4%, 8.32 kg kg^-1, and 5.17 kg kg^-1, respectively. The ratios of different N to total N in the UCRF showed significant correlation with N uptake by rice plants. The findings showed that the first-order kinetics equation [Nt=N0 （l-e^kt）] could be used to describe the release characteristics of different N forms in the fertilizer. The UCRF containing different N forms was more effective in facilitating N uptake by rice compared with the common compound fertilizer containing single urea-N form.

Synthesis and Performance of Polyurethane Coated Urea as Slow/controlled Release Fertilizer

Polyurethane coated urea slow/controlled release fertilizer was prepared based on urea granules, isocyanate, polyols and paraffin. Isocyanate reacted with polyols to synthesize the polyurethane skin layer on urea granules surface. Paraffin serves as a lubricant during syntheses of polyurethane skin layers. The structure and nutrient release characteristics of the polyurethane skin layers were investigated by FTIR, SEM and TG. Urea nitrogen slow-release behavior of the polyurethane coated urea was tested. The experimental results indicated that compact and dense polyurethane skin layers with a thickness of 10-15 lam were formed on urea surface, the urea nitrogen slow-release time can reach 40-50 days. Paraffin proves to play a key role in inhibiting water to penetrate into urea, but excessive addition would decrease the polyurethane crosslinking density.

Study on the Rapid Method to Predict Longevity of Controlled Release Fertilizer Coated by Water Soluble Resin

The study discussed the rapid method to test and predict the longevity of controlled release fertilizers （CRFs） coated by water soluble resin by using the short-term leaching under higher temperature. Pure water dissolving incubation and higher temperature leaching were used to study the patterns of the nutrient release of the CRFs. The correlation analysis between the days at 25℃ and the hours at 80℃ of Trincote 1 and Trincote 2 for the same cumulative release rates were conducted. Patterns of cumulative nutrient release curve followed one factor quadratic regression equation at each given temperatures, and each of relative coefficient was bigger than 0.995. As the temperature increased, nutrients release of the CRFs increased. The longevity of resin coated CRFs were predicted by use of both the cumulative nutrients release equation at 80℃ and the regression equation of release time needed for the same cumulative release rates between 25 and 80℃. There were only 0.3-6.9% relative errors between the tested longevity and predicted one. In conclusion, the longevity of resin coated CRFs could be predicted more quickly and precisely by use of the higher temperature short-term leaching method than that of the traditional differential release rate. The longevity of resin coated CRF could be rapidly and precisely predicted in a few hours by application of the higher temperature shortterm leaching method.

Alginate-based complex fibers with the Janus morphology for controlled release of co-delivered drugs

Hydrogels are soft materials consisting of a three-dimensional network of polymer chains.Over the years,hydrogels with different compositions have been developed as drug carriers for diverse biomedical applications,ranging from cancer therapy and wound care to the treatment of neurodegenerative and inflammatory diseases.Most of these carriers,however,are designed only to deliver single agents.Carriers based on hydrogels for co-delivery of multiple agents,with the release rate of each of the co-delivered agents tunable,are lacking.This study reports a one-pot method of fabricating alginate-based complex fibers with the Janus morphology,with carboxymethyl cellulose sodium functioning as a polymeric modifier of the properties of each of the fiber compartments.By using malachite green and minocycline hydrochloride as model drugs,the generated fibers demonstrate the capacity of enabling the release profile of each of the co-delivered drugs to be precisely controlled.Along with their negligible toxicity and the retention of the activity of the loaded drugs,the complex fibers reported in this study warrant further development and optimization for applications that involve co-delivery of multiple agents.

CONTROLLED RELEASE FROM PDMAEMA GELS PREPARED BY GAMMA RADIATION

Poly(N,N-dimethylaminoethyl methacrylate) (polyDMAEMA) hydrogels prepared by gamma-irradiation showed obvious temperature-sensitivity in a temperature range of 38-40degreesC and pH-sensitivity at pH=2.5. They also showed electric response behavior although it was not typical. The hydrogels were used in controlled release at different pH, temperature, and electric voltage. The release rates of methylene blue (MB) from the gels at 52degreesC and pH=1.24 were faster than those at 20degreesC and pH=10.56, respectively. In addition, the release rate at a field voltage of 5.0 was also faster than that without electric field.

Nitrogen Release Characteristics of a Bag Controlled Release Fertilizer

Slow release fertilizers are designed to enhance crop yield and minimizing the loss of nitrogen(N)to environment.However,N release in leaching and loss in ammonia emission from bag controlled release fertilizers have not been previously evaluated under the standardized conditions in soil.Accordingly,a laboratory study was conducted to evaluate the characteristics of N release from a bag controlled fertilizer with 1,3,5 and 7 rows of hole(B-1,B-3,B-5,B-7)and a kraft bag without hole(B-W).The results showed that the amount of N leaching of B-1,B-3,B-5,B-7 and B-W were significantly lower than urea fertilizer without bag(U).The maximum N release from the fertilizers followed the order:U(83.16%)>B-7(54.61%)>B-5(54.02%)>B-W(51.51%)>B-3(48.87%)>B-1(38.60%)during the experimentation.Compared with U treatment,ammonia volatilization losses were significantly decreased by B-1,B-3,B-5,B-7 and B-W treatments.Based on N release and loss,a suitable bag with holes should be considered in practice when using the bag controlled fertilizer to meet an environment good objective.The evaluation method merits further study combined with field experiment.

Controlled Release of Construction Chemicals by Encapsulation

Encapsulation and controlled release of active agents is a common practice to improve processing and properties of materials and final products in different industries. Today, a large variety of chemical admixtures are used in construction materials, the performance of which could be improved by a better dosage control. This work presents investigations on the controlled release of encapsulated construction chemicals for future applications in construction materials. The high shear mixing technology was used to produce matrix based encapsulations by agglomeration applied to commercially available construction materials. The agglomeration process was varied by the use of different agitator types, the variation of the agitator speed and the application of additional coating materials. The particle size distribution as well as the particle shape of the produced agglomerates was analyzed by automatic image evolution and scanning electron microscopy. The release behavior of the capsules in aqueous solutions was investigated by UV spectroscopy. The obtained results confirmed a theoretical model for the encapsulation and release of admixtures, which was derived from pharmaceutical drug release concepts and adapted to construction materials. The results indicate that the matrix based encapsulation is a promising technique for future applications in the field of construction materials.

An emerging terpolymeric nanoparticle pore former as an internal recrystallization inhibitor of celecoxib in controlled release amorphous solid dispersion beads:Experimental studies and molecular dynamics analysis

Solid oral controlled release formulations feature numerous clinical advantages for drug candidates with adequate solubility and dissolution rate.However,most new chemical entities exhibit poor water solubility,and hence are exempt from such benefits.Although combining drug amorphization with controlled release formulation is promising to elevate drug solubility,like other supersaturating systems,the problem of drug recrystallization has yet to be resolved,particularly within the dosage form.Here,we explored the potential of an emerging,non-leachable terpolymer nanoparticle(TPN)pore former as an internal recrystallization inhibitor within controlled release amorphous solid dispersion(CRASD)beads comprising a poorly soluble drug(celecoxib)reservoir and insoluble polymer(ethylcellulose)membrane.Compared to conventional pore former,polyvinylpyrrolidone(PVP),TPN-containing membranes exhibited superior structural integrity,less crystal formation at the CRASD bead surface,and greater extent of celecoxib release.All-atom molecular dynamics analyses revealed that in the presence of TPN,intra-molecular bonding,crystal formation tendency,diffusion coefficient,and molecular flexibility of celecoxib were reduced,while intermolecular H-bonding was increased as compared to PVP.This work suggests that selection of a pore former that promotes prolonged molecular separation within a nanoporous controlled release membrane structure may serve as an effective strategy to enhance amorphicity preservation inside CRASD.

Controlled-Release of Plant Volatiles:New Composite Materials of Porous Carbon-Citral and Their Fungicidal Activity against Exobasidium vexans

Citral(Eo)exhibits excellent fungicidal activities.However,it is difficult to maintain long-term fungicidal activity due to its strong volatility.Herein,a controlled-release strategy by using biomass-derived porous carbon(BC)was developed to overcome the drawback of Eo.New composite materials were prepared by loading Eo on tea stem porous carbon(BC@Eo),and their controlled-release fungicidal activity against Exobasidium vexans was assessed.BC with a large specific surface area of 1001.6 m2/g and mesoporous structure was fabricated through carbonization tempera-ture of 700℃.The BC@Eo materials were characterized using Fourier-transform infrared spectroscopy and X-ray powder diffraction.The results suggested that chemical and physical interactions occurred in BC@Eo.The Eo release profile suggested a biphasic pattern with an initial fast release on days 1–14 and a subsequent controlled phase on days 14–30.The in vitro cumulative release percentage of Eo from BC@Eo was 51%during one month,and this result was significantly lower than that from free Eo(cumulative release percentage of Eo of 82%in one week).The anti-fungal activities of Eo and BC@Eo against E.vexans were determined using the inhibition zone method.The results indicated that Eo and BC@Eo formed large inhibition zones of 19.66±0.79 and 21.92±0.77 mm,respectively.The influence on the hyphal structure of E.vexans was observed by scanning electron microscopy on day 30.The hyphal structure of E.vexans treated with BC@Eo was more shrunken than that treated with Eo at 30 days,suggesting that BC@Eo prolongs the fungicidal activity against E.vexans.This study demonstrated that the encapsulation of Eo in BC for developing the BC@Eo materials could be a promising strategy to inhibit volatility and maintain the fungicidal activity of Eo and provide a potential alternative for the reuse of abundant tea biomass waste resources.

A ROS-Sensitive Diselenide-Crosslinked Polymeric Nanogel for NIR Controlled Release

Here we report a novel polymeric nanogel with stable loading cargo and near-infrared(NIR) controlled release properties.The nanogels are crosslinked by quaternization reactions of biocompatible poly(β-amino esters) and diselenide-bonded crosslinker(DSe DCl) in microemulsions.The hydrophobic cavities of the nanogels have the property of stably encapsulating the hydrophobic guest molecules,resulted from the crosslinked network structure.Due to the redox responsiveness of the diselenide bonds on the DSe DCl crosslinker,the nanogels can respond to oxidant H_(2)O_(2) causing the disintegration of the crosslinked network structure,thus the encapsulated guest cargo molecules will be released.It is noted that,upon loading the photosensitizer IR780,the nanogels can generate reactive oxygen species(ROS) under NIR irradiation to release the cargo.The advantages of encapsulated cargo stability enhanced by chemical cross-linking and remote stimulation response performance via NIR offer great potential of nanogels for applications of cargo controlled release.

A matrix metalloproteinase-responsive hydrogel system controls angiogenic peptide release for repair of cerebral ischemia/reperfusion injury

Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in vivo.Therefore,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke.Matrix metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ischemia.Herein,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel PA-TIMP-QK.PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro.The results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor function.These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.

Design of a gastroretentive mucoadhesive dosage form of furosemide for controlled release

The aim of the present study was to develop and characterize a gastroretentive dosage form suitable for controlled drug release.It consists of a drug loaded polymeric film made up of a bilayer of immediate(IR)and controlled release(CR)layers folded into a hard gelatin capsule.Gast roretention results from unfolding and swelling of the film and its bioadhesion to the gastric.mucosa.Furosemide,a drug with a narrow absorption window,was selected as the model drug.Inclusion of hydroxypropyl β-cyclodextrin in both layers and Carbopol■ 971P NF in the CR layer of the bilayer film resulted in optimum drug release,bioadhesion and mechanical properties.The film with zig-zag folding in the capsule was shown to unfold and swell under acidic conditions and provide IR of drugover 1 hand CR for up to 12 h in acidic medium.X-ray diffraction,differential scanning calorimetry and scanning electron microscopy revealed uniform dispersion of furosemide in the polymeric matrices.The results indicate the dosage form is gastroretentive and can provide controlled release of drugs with narrow therapeutic wind ows.

Mechanistic insights of the controlled release capacity of polar functional group in transdermal drug delivery system:the relationship of hydrogen bonding strength and controlled release capacity

Background:Hydrogen bonding interaction was considered to play a critical role in controlling drug release from transdermal patch.However,the quantitative evaluation of hydrogen bonding strength between drug and polar functional group was rarely reported,and the relationship between hydrogen bonding strength and controlled release capacity of pressure sensitive adhesive(PSA)was not well understood.The present study shed light on this relationship.Methods:Acrylate PSAs with amide group were synthesized by a free radical-initiated solution polymerization.Six drugs,i.e.,etodolac,ketoprofen,gemfibrozil,zolmitriptan,propranolol and lidocaine,were selected as model drugs.In vitro drug release and skin permeation experiments and in vivo pharmacokinetic experiment were performed.Partial correlation analysis,fourier-transform infrared spectroscopy and molecular simulation were conducted to provide molecular details of drug-PSA interactions.Mechanical test,rheology study,and modulated differential scanning calorimetry study were performed to scrutinize the free volume and molecular mobility of PSAs.Results:Release rate of all six drugs from amide PSAs decreased with the increase of amide group concentrations;however,only zolmitriptan and propranolol showed decreased skin permeation rate.It was found that drug release was controlled by amide group through hydrogen bonding,and controlled release extent was positively correlated with hydrogen bonding strength.Conclusion:From these results,we concluded that drugs with strong hydrogen bond forming ability and high skin permeation were suitable to use amide PSAs to regulate their release rate from patch.