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1.
A membrane permeation-controlled transdermal delivery system (MC-TDS) of isosorbide dinitrate (ISDN), a model drug, was prepared from polyvinyl alcohol aqueous gel containing the drug, a membrane consisting of ethylene-vinyl acetate copolymer membrane and acrylic adhesive (EV-a). The permeability of ISDN through the EV-a membrane was 2.5 times higher than that through excised hairless rat skin. The ratio of plasma concentration of ISDN after application of MC-TDS on stripped (damaged) skin relative to intact skin was lower than that after application of Frandol tape-S, a marketed ISDN TDS, which suggests that the EV-a membrane might work as a control membrane for overall delivery rate of ISDN to the body. When MC-TDS stored at 30 degrees C for 13.5-48h was applied to the damaged skin, however, the initial plasma concentration of ISDN was very much higher than the expected therapeutic level and was not controlled by the EV-a membrane. The initial high plasma concentration of ISDN after application of the stored MC-TDS on the damaged skin was due to migration of ISDN from the reservoir to the adhesive during storage at 30 degrees C. The migration of drugs into the adhesive might be an important problem in developing efficient MC-TDS.  相似文献   

2.
An acrylate based pressure sensitive adhesive (PSA) was synthesized to design a drug‐in‐adhesive (DIA) type transdermal therapeutic system (TTS) for nitroglycerin used in the treatment of angina pectoris. 2‐Ethylhexyl acrylate (EHA), methyl methacrylate (MMA) and acrylic acid (AA) were used to synthesize the PSA by free radical solution polymerization. The effects of reaction time, reaction temperature, initiator concentration and solvent on polymerization were studied. The synthesized terpolymer was characterized by 1H‐NMR, FT‐IR, differential scanning calorimetry (DSC) and gel permeation chromatography (GPC) and also evaluated for intrinsic viscosity, refractive index, peel strength, moisture uptake and skin irritation potential. The PSA was used to develop DIA type patches of nitroglycerin. The patches were cast using solvent evaporation technique and dried at controlled temperature. The patches were evaluated for thickness uniformity, weight variation, peel strength and moisture pick‐up. The percent drug content and in vitro drug release was determined by high pressure liquid chromatography (HPLC) method. On the basis of in vitro release profile, patches were selected for in vitro skin permeation studies. The developed formulation TP‐1 (K = 24.892 mcg/cm2/hr) followed zero‐order rate kinetics and showed better skin permeation rate in comparison to the marketed TTS (MTTS) (K = 17.413 mcg/cm2/hr). TP‐1 was subjected to stability testing for a period of 1 year according to ICH guidelines. The patches were found to be stable and an expiry date of 2 years was predicted with storage at 25 °C or below. Copyright © 2001 John Wiley & Sons, Ltd.  相似文献   

3.
An acrylate-based pressure sensitive adhesive (PSA) was synthesized to incorporate in a design of a drug-in-adhesive (DIA) type transdermal therapeutic system (TTS) for nitrendipine and nicorandil in treatment of hypertension and angina pectoris, respectively. Solutions of 2-ethylhexyl acrylate (EHA; 85% w/w), methyl methacrylate (MMA; 10% w/w), acrylic acid (AA; 3% w/w) and vinyl acetate (VA; 2% w/w) in either ethyl acetate, acetone or methanol were polymerized under free radical conditions to synthesize the PSA. The effects of solvent, reaction time, initiator concentration and reaction temperature on polymerization were studied. The resultant copolymers were characterized by 1H-NMR, IR, differential scanning calorimetry (DSC) and gel permeation chromatography (GPC) and the intrinsic viscosities, refractive index, peel strength, moisture uptake and skin irritation potential were determined. The PSA was used to develop DIA type patches for delivery of nitrendipine and nicorandil. The TTS were evaluated for thickness, weight, peel strength, moisture uptake, in vitro release and in vitro skin permeation through guinea-pig skin. The copolymer found to effectively control the rate of drug release and the corresponding TTSs could be successfully employed in transdermal delivery of nitrendipine and nicorandil. Copyright © 2003 John Wiley & Sons, Ltd.  相似文献   

4.
In this paper the batch suspension copolymerization of ethyl acrylate/2 ethyl hexylacrylate (EA/2-EHA) for production of suspension-based microsphere acrylic pressure sensitive adhesives (PSA) is presented. The effects on the adhesion properties of PSA different process (reaction temperature and stirrer speed) as well as chemical parameters (amount of EA, initiator concentration) are discussed. The conversion was monitored in-line using Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) spectroscopy and the results were compared with the standard gravimetrical method. The glass transition temperatures (Tg) of the PSAs were measured using differential scanning calorimetry (DSC) technique, while molecular weight distribution (MWD) was determined by gel permeation chromatography (GPC). The adhesion properties of PSAs were characterized via the measurements of tack, peel adhesion and peel strength. The results of the experiments have shown that the kinetics of the suspension polymerization for production of PSAs is significantly affected by temperature of polymerization and the initiator concentration, but are shown to be relatively independent of the EA amount and the stirrer speed. The tack, peel and shear strength depend on the mean particle size and particle size (PS) distribution (PSD) and Tg. The mean particle size and PSD depend primarily on the stirrer speed during the PSA synthesis process, while the Tg is most affected by amount of EA used for the synthesis. The results have also shown a rather unexpected relationship between MWD of the PSAs and the applicative properties: tack, peel and shear are seen to be increasing to the decreasing values of weight average MWD, which is the exact opposite of the previously published research. The most likely explanation for this relationship is the formation of a gel during the synthesis of PSA.  相似文献   

5.
UV-crosslinkable polyacrylates were synthesized for use as pressure sensitive adhesives (PSAs). These polyacrylates acted as polymeric photoinitiators due to the benzophenone incorporated into their backbones. Hydrogenated rosin epoxy methacrylate (HREM; based on hydrogenated rosin and glycidyl methacrylate) was also synthesized as a tackifier, and blended at different levels with the synthesized, UV-crosslinkable polyacrylates for use as PSAs. The effect of the new tackifier, HREM, on the properties of the UV-crosslinkable PSAs was examined in comparison with the properties exhibited by PSA/hydrogenated rosin blends. The characteristics of these PSA/tackifier blends were examined by Fourier-transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC) and an advanced rheometric expansion system (ARES). In addition, the adhesion performance of the PSA blends was investigated using probe tack tests. DSC and ARES revealed all the PSA blends with HREM or hydrogenated rosin to be miscible at the molecular level. The glass transition temperature (Tg) of HREM was −25.6 °C, which is lower than that of other commercially available rosin tackifiers. FTIR revealed changes in the relative concentration of benzophenone groups in the PSAs at 1580 cm−1, which demonstrated that the crosslinking efficiency is proportional to the benzophenone content and UV dose, but decreases with increasing hydrogenated rosin content. However, the reduced crosslinking reaction efficiency was improved in the PSA/HREM blends due to the low Tg of HREM which only slightly increased the Tg of the PSA blends. Moreover, the relative initial decrease in the probe tack of the PSA/HREM blends was lower than that of the PSA/hydrogenated rosin blends after UV irradiation.  相似文献   

6.
Electron beam irradiation was used to synthesize a matrix type transdermal system of isosorbide dinitrate, an effective anti-anginal agent. The drug was dissolved in two monomeric systems, 2-ethylhexyl acrylate (EHA) and 2-ethylhexyl acrylate : methyl methacrylate (9 : 1). The solutions were then directly irradiated on a backing membrane (Scotchpak®1006) at different doses to get transdermal patches. The developed systems were evaluated for residual monomer content, equilibrium weight swelling ratio, weight uniformity, thickness uniformity, drug content, peel strength, in vitro release and skin permeation kinetics. They possessed excellent tack and adhesive properties. In the case of isosorbide dinitrate–EHA systems, an increase in the peel strength values with respect to the skin was observed with increasing radiation doses. The systems exhibited promising skin permeation kinetics favorable for transdermal drug delivery. The radiation stability of the drug in the pure solid state form was also assessed.  相似文献   

7.
The aim of this study was to design new soy protein-based bi-layered co-injection moulded matrix systems aimed to achieve controlled drug delivery. The devices consisted of a drug-free outer layer (skin) and a drug-containing core. The systems overcame the inherent disadvantage of non-linear release associated with diffusion-controlled single-layer matrix devices by providing additional releasing area with time to compensate for the decreasing release rate. As expected, the bi-layer devices presented a significant decrease in drug release rate when compared with a correspondent single layer matrix system. The skin thickness and the degree of crosslinking of the core appeared to be very important tools to tailor the release patterns. Furthermore, due to the amphoteric nature of the soy protein, the developed devices evidenced a pH-dependent behaviour. The mechanisms of drug release were also elucidated at two different pH values: i) pH 5.0, near the isoelectric point of soy (low matrix solubility); and ii) pH 7.4, physiological pH (high matrix solubility). Consequently, changing the release medium from pH 5.0 to pH 7.4 after two hours, led to an abrupt increase in drug release and the devices presented a typical controlled drug delivery profile: slow release/fast release. These evidences may provide for the development of individual systems with different release onsets that in combination may exhibit drug releases at predetermined times in a pre-programmed way. Another possibility is the production of three-layer devices presenting bimodal release profiles (fast release/slow release/fast release) by similar technologies. Scanning electron micrograph of a developed bi-layer device.  相似文献   

8.
Ketoprofen is a non-steroidal anti-inflammatory drug (NSAID) widely used to treat rheumatoid arthritis and other inflammatory diseases. Normally used by oral route, this drug presents numerous side effects related to this administration route, such as nausea, dyspepsia, diarrhea, constipation and even renal complications. To avoid that, topical administration of ketoprofen represents a good alternative, since this drug has both partition coefficient and aqueous solubility suitable for skin application, compared to other NSAIDs. In this study, we describe the production of a nanoemulsion containing ketoprofen, its skin permeation and in vitro release study and a novel validation method to analyze this drug in the permeation samples and a forced degradation study using skin and nanoemulsion samples. The new HPLC method was validated, with all specifications in accordance with validation parameters and with an easy chromatographic condition. Forced degradation study revealed that ketoprofen is sensitive to acid and basic hydrolysis, developing degradation peaks after exposure to these factors. Concerning in vitro release from the nanoemulsion, release curves presented first order profile and were not similar to each other. After 8 h, 85% of ketoprofen was release from the nanoemulsion matrix while 49% was release from control group. In skin permeation study, nanoemulsion enabled ketoprofen to pass through the skin and enhanced retention in the epidermis and stratum corneum, layer on which the formulation presented statistically different values compared to the control group.  相似文献   

9.
The contribution of ionized and unionized species to the overall permeation of weak electrolytes through the skin was investigated to determine the effect of pH in the vehicle on the permeability of indomethacin (IDM), as a model drug, through hairless rat skin. The permeability of IDM through polydimethylsiloxane (silicone) and poly(2-hydroxyethyl methacrylate) (pHEMA) membranes which may reflect lipid and aqueous pathway, respectively, was also measured for comparison. As the pH in the vehicle increased, there was an exponential increase in the skin permeation rate of IDM. The permeation rate of IDM through the silicone membrane was constant independent of pH, whereas that through the pHEMA membrane increased with increasing pH, similar to the skin permeation. The permeability coefficients of ionized and unionized species through the skin estimated using the skin permeation rates and solubilities of IDM at various pHs were 1.50 x 10(-7) and 2.79 x 10(-5) cm/s, respectively. These results indicated that the permeation of ionized species greatly contributed to the total permeation of IDM at higher pH, and that the total permeation rate of IDM was determined by the permeation of unionized species at lower pH. These contributions depend on the pH and pKa values and the ratio of permeability coefficient of each species. It was also confirmed that the skin has at least two kinds of permeation pathways and these two species permeate through a different pathway.  相似文献   

10.
An investigation has been made of successive differential absorption and differential permeation of water vapor in polyacrylamide a t 30°C. The successive differential ab sorptions showed two types of non-Fickian anomalies: sigmoid type and two-stage type curves. The experimental data have been analyzed in terms of the Fick diffusion equation assuming a time-dependent approach of the surface concentration. The calculated family of absorption curves agreed with the experimental results. The permeation curves in the region of high and low pressure increments were apparently normal, but at medium pressures they showed anomalous behavior. It was found that in the differential type of permeation experiment the stress effect induced by a concentration gradient between the surfaces of the film was eliminated. By assuming the time-dependent approach of the equilibrium surface concentration, we calculated the time lag as a function of film thickness and applied the theory to the data for permeation through polyacrylamide film with different film thicknesses a t relatively small pressure intervals. The rate parameter calculated from permeation data was found to be in good agreement with that from successive differential absorption data.  相似文献   

11.
The aim of the present study was to formulate and evaluate the nonionic surfactant vesicles of frusemide in order to enhance its skin permeation. The process variables which could affect the preparation and properties of the niosome formulation studied included type of spans, ratio of span and cholesterol, ratio of cholesterol and dicetylphosphate (DCP), concentration of drug, type of solvent, hydration media and time of hydration. The formulated niosomes thus were characterized for various parameters such as surface morphology, size, entrapment efficiency, skin permeation, etc. Stability of the niosomes in terms of drug holding capacity was assessed for a period of 30 days on storage under defined conditions. The maximum entrapment efficiency of 77.73±2.36% was obtained with niosomes formulated from Span 60∶Cholesterol∶DCP (47.5∶47.5∶5) using chloroform:methanol (4∶1) as the solvent system at the hydration time of 1 hr. A direct relationship was observed between the percentage leaching of the drug out of the vesicles and temperature. Higher transdermal flux was obtained with niosomal gel (9.2±0.5 μg/cm2/hour) in comparison to conventional gel (6.4±0.3 μg/cm2/hour).  相似文献   

12.
A transdermal eyelid delivery system for treating ocular diseases (eye-stick) has been developed. Ketotifen fumarate (KT) was used as a model drug. An in vivo study using rabbits showed that the eye-stick device maintained a constant conjunctival concentration of the drug for an extended period of time, which was equivalent or higher than the therapeutic level following eye drop administration. Moreover, the conjunctival concentration after eye-stick application was well predicted using the physicochemical parameters, diffusion coefficient and partition coefficient, obtained from in vitro hairless mouse skin permeation experiments.  相似文献   

13.
An application of polyacrylamide-grafted-gum ghatti (PAAm-g-GGH) copolymer for transdermal delivery of an anti-psychotic drug, quetiapine fumerate triggered by electric stimulus was explored. The electro-responsive PAAm-g-GGH was prepared by free radical polymerization underneath nitrogen atmosphere subsequent to alkaline hydrolysis. The PAAm-g-GGH was used as drug reservoir gel and crosslinked films of GGH and PVA as rate controlling membranes (RCM). The reservoir gels were uniform and translucent; pH of gels was 6.56–7.06, which is in the pH range of skin and drug content was from 89.57% to 94.51%. The thickness of RCMs was 163–227?μ; thickness was increased with increased glutaraldehyde concentration and all the RCMs were permeable to water vapors. When electric stimulus was absent, a small amount of drug was permeated from the formulations, while drug conveyance was enhanced in the existence of stimulus. Drug permeation was increased with increase in electric stimulus from 2 to 8?mA. Over two fold increase in flux was observed after application of electric stimulus. Under “on–off” electric stimulus, faster drug permeation was seen under ‘on’ condition and permeation was decreased when stimulus was ‘off.’ Histopathology study confirmed reversible alteration of skin structure under electric stimulus.  相似文献   

14.
Pressure‐sensitive adhesives (PSAs) are finding increasing applications in various areas of industry and medicine. PSAs are a special class of viscoelastic polymers that form strong adhesive joints with substrates of varying chemical nature under application of light external bonding pressures (1–10 Pa) over short periods of time (1–5 s). To be a PSA, a polymer should possess both high fluidity under applied bonding pressure, to form good adhesive contact, and high cohesive strength and elasticity, which are necessary for resistance to debonding stresses and for dissipation of mechanical energy at the stage of adhesive bond failure under detaching force. For rational design of novel PSAs, molecular insight into mechanisms of their adhesive behavior is necessary. As shown in this review, strength of PSA adhesive joints is controlled by a combination of diffusion, viscoelastic, and relaxation mechanisms. At the molecular level, strong adhesion is the result of a narrow balance between two generally conflicting properties: high cohesive strength and large free volume. These conflicting properties are difficult to combine in a single polymer material. Individually, high cohesive interaction energy and large free volume are necessary but insufficient prerequisites for PSA strength. Evident correlations are observed between the adhesive bond strengths of different PSAs, and their relaxation behaviors are described by longer relaxation times. Innovative PSAs with tailored properties can be produced by physical mixing of nonadhesive long‐ and short‐chain linear parent polymers, with groups at the two ends of the short chains complementary to the functional groups in the recurring units of the long chains. Although chemical composition and molecular structure of such innovative adhesives are unrelated to those of conventional PSAs, their mechanical properties and adhesive behaviors obey the same general laws, such as the Dahlquist's criterion of tack. © 2012 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2012  相似文献   

15.
Penetration enhancing potential of tulsi and turpentine oil on transdermal delivery of flurbiprofen, a potent non-steroidal anti-inflammatory agent, was investigated. The transdermal permeation rate of flurbiprofen across the rat abdominal skin from binary solvent mixture composition of propylene glycol (PG):isopropyl alcohol (IPA) (30:70%, v/v) was 98.88 microg/cm(2)/h, significantly higher than other binary solvent mixtures. The corresponding steady state plasma concentration, 0.71 microg/ml, was much lower than required steady state plasma concentration of 3-5 microg/ml. Hence influence of tulsi and turpentine oil in the optimized binary solvent mixture along with the increased drug load on the flurbiprofen permeation was evaluated. The magnitude of the flux enhancement factor with turpentine oil and tulsi oil was 2.4 and 2.0 respectively at 5% (v/v) concentration beyond which there was no significant increase in the flux. Addition of 2% (w/v) hydroxypropyl methylcellulose (HPMC), as a thickening agent, resulted in desired consistency for the fabrication of patch with insignificant effect on permeation rate of flurbiprofen. The reservoir type of transdermal patch formulation, fabricated by encapsulating the flurbiprofen reservoir solution within a shallow compartment moulded from polyester backing film and microporous ethyl vinyl acetate membrane, did not modulate the skin permeation of flurbiprofen through rat skin in case of turpentine formulations whereas flux of formulations with tulsi oil was significantly altered. The influence of penetration enhancer and solvents on the anatomical structure of the rat skin was studied. Enhancement properties exhibited by turpentine oil and tulsi oil in optimized binary solvent mixture were superior as compared to solvent treated and normal control groups with negligible skin irritation. The fabricated transdermal patches were found to be stable. The bioavailability of flurbiprofen with reference to orally administered flurbiprofen in albino rats was found to increase by 2.97, 3.80 and 5.56 times with transdermal patch formulation without enhancer, tulsi and turpentine oil formulations, respectively. The results were confirmed by pharmacodynamic studies in rat edema inflammation model.  相似文献   

16.
Pressure-sensitive adhesives (PSAs) demand the ability to simultaneously improve toughness and adhesion. However, these requirements of PSAs have remained a great challenge because robust and recoverable characteristics are usually contradictory properties of PSAs. Dual cross-linking networks developed by incorporating dynamic noncovalent bonds into chemical cross-linking networks have the potential to mitigate these requirements in a wide variety of applications including adhesives, hydrogels, and elastomers. Herein, a facile approach to achieve dual cross-linking networks of acrylic PSAs with excellent mechanical properties and high-adhesive performance that integrate physically cross-linked networks into chemically cross-linked networks is proposed. Diurethane acrylic monomer-pentaerythritol ethoxylate (DAM-PEEL) groups were introduced into the acrylic PSA system through photopolymerization. The PSA/DAM-PEEL dual cross-linking networks led to the development of the chemically cross-linked networks for both PSA and DAM via covalent bonds and the physically cross-linked networks between the amide groups of DAM and the hydroxyl groups of PEEL via hydrogen bonds. Consequently, the PSA/DAM-PEEL dual cross-linking networks were able to simultaneously improve the modulus and stretchability. This design strategy for developing dual cross-linking networks of materials could offer potential applications for various adhesive-related applications.  相似文献   

17.
The in vitro percutaneous transport of sodium diclofenac from various oil vehicles was examined using rat abdominal skin as a model skin membrane. The overall transport of diclofenac through the skin from the oleaginous vehicles was very poor because of a poor solubility of sodium diclofenac in nonpolar oils. To increase the solubility and the permeability of sodium diclofenac, ethanol and n-octanol were added to each oil (designated as the formulated vehicles). The addition of ethanol and n-octanol to the nonpolar vehicles resulted in an extreme increase in drug solubility in each vehicle, with a remarkable increase in the permeation of diclofenac. The effects of oil components in the formulated vehicle on the permeation of diclofenac across the skin were in the following order: squalane greater than or equal to squalene greater than liquid paraffin greater than middle chain triglyceride greater than olive oil greater than castor oil. In order to clarify the reason for the differences in permeation of diclofenac from these formulated vehicles, the release of diclofenac and n-octanol from these vehicles in vitro was studied. The release rates of n-octanol from the formulated vehicles were in the following order: liquid paraffin greater than squalene greater than or equal to squalane greater than middle chain triglyceride greater than or equal to olive oil greater than castor oil. On the other hand, a linear correlation was observed between the initial release rate of diclofenac from the formulated vehicle and the in vitro permeation of diclofenac through the vehicle to the skin.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

18.
Miniemulsion polymerization is a promising approach to produce and tailor pressure sensitive adhesives (PSAs). In this paper, a systematic comparison of the adhesive properties of latexes produced by miniemulsion and conventional emulsion polymerization is presented. Specifically, the influence of the total surfactant concentration, chain transfer agent concentration and chemical composition on the final adhesive properties of the polymer 2-ethyl hexyl acrylate/methyl methacrylate/acrylic acid was discerned using a 23 factorial design for each polymerization method. In addition to the adhesive properties (i.e., loop tack, peel strength and shear strength), molecular weight distribution, particle size distribution (PSD) and glass transition temperature were analyzed. The results show that under the conditions used in this work, it is possible to produce PSAs using miniemulsion polymerization, a process wherein monomer droplet nucleation is the dominant particle nucleation mechanism. The use of a miniemulsion polymerization process, as opposed to the conventional emulsion technique, produced several differences such as larger particles sizes and narrower molecular weight distributions. Focusing on the PSA films that exhibited adhesive rather than cohesive failure, the PSA films generated via miniemulsion polymerization displayed higher values of loop tack and peel strength compared to those produced via conventional emulsion polymerization. Shear strength results were strongly dependent on the amount of gel content and sol molecular weight for both cases.  相似文献   

19.
Two new devices were developed to provide accurate measurements of both the contact area and the tack strength of pressure-sensitive adhesives (PSAs). The first one is the "mechano-optical tack tester" (MOTT), which was designed to apply controlled contact pressure by means of a quartz prism probe, for determined contact times, onto the surfaces of PSA samples. The contact area is measured by the reflection of light at the quartz probe surface, which is in contact with the adhesive. The second device is an "acoustic contact tester" (ACT) that measures the tack strength and the contact area between a silicate glass and an adhesive by the reflection of an acoustic wave. Two ultrasonic sensors of different acoustic wavelengths have been built in order to study the scaling effects of the contact kinetics between an adhesive and the probe. MOTT and ACT experiments on a commercial PSA show that the contact area is the main parameter that governs the tack properties of the PSA. The experiments and the modeling point out that the contact area depends on the compression stress, the roughness, the thickness, and the Young's modulus of the PSA. However, comparison of contact kinetics from MOTT and ACT experiments show that the contact area is a subjective parameter that depends on the wavelength of the reflected beam used for its measurement.  相似文献   

20.
    
Summary Investigations on two commercially available permeation tubes for preparation of test gas mixtures for calibration purposes in trace gas analysis have shown that, depending on the type of permeation membrane, variations of carrier gas pressure may strongly affect the outcoming test gas concentrations. At constant atmospheric pressure both devices work with concentration fluctuations of about 3 to 5%. With carrier gas overpressures up to 2000 mbar the behaviour of permeation tubes with a rigid PTFE-membrane remains almost unchanged whereas test gas generators with soft membranes, e.g. silicon rubber, give a very strong decrease of permeation rate down to 17% of the value at atmospheric pressure. Consequently, the selection of permeation devices demands high carefulness with regard to the ambient pressure at the site of application.  相似文献   

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