Enhanced oral bioavailability and sustained delivery of glimepiride via niosomal encapsulation: in-vitro characterization and in-vivo evaluation

This study was designed to investigate the potency of niosomes, for glimepiride (GLM) encapsulation, aiming at enhancing its oral bioavailability and hypoglycemic efficacy. Niosomes containing nonionic surfactants (NIS) were prepared by thin film hydration technique and characterized. In-vitro release study was performed using a dialysis technique. In-vivo pharmacodynamic studies, as well as pharmacokinetic evaluation were performed on alloxan-induced diabetic rats. GLM niosomes exhibited high-entrapment efficiency percentages (E.E. %) up to 98.70% and a particle size diameter ranging from 186.8?±?18.69 to 797.7?±?12.45?nm, with negatively charged zeta potential (ZP). Different GLM niosomal formulation showed retarded in vitro release, compared to free drug. In-vivo studies revealed the superiority of GLM niosomes in lowering blood glucose level (BGL) and in maintaining a therapeutic level of GLM for a longer period of time, as compared to free drug and market product. There was no significant difference between mean plasma AUC_0-48?hr of GLM-loaded niosomes and that of market product. GLM-loaded niosomes exhibited seven-fold enhancement in relative bioavailability in comparison with free drug. These findings reinforce the potential use of niosomes for enhancing the oral bioavailability and prolonged delivery of GLM via oral administration.     

Preparation and evaluation of zolmitriptan submicron emulsion for rapid and effective nasal absorption in beagle dogs

Submicron emulsion was prepared for rapid and effective nasal absorption of zolmitriptan (ZT). The different charge inducers and pH values of the formulations were evaluated to optimize the formulations. Submicron emulsion prepared by using stearylamine as positive charge inducer with pH of 5.0 was stable and most of ZT was freely dispersed in the aqueous phase of the preparation. In vitro release study demonstrated that ZT from the submicron emulsion preparation could be released as fast as that from the solution preparation. The pharmacokinetics was studied after intranasal administration of the submicron emulsion and solution preparation of ZT to beagle dogs. ZT from the submicron emulsion was absorbed much more rapidly and the absolute availability of the submicron emulsion preparation was significantly higher compared with the solution preparation. The nasal ciliotoxicity of the preparations was evaluated by using in situ toad palate model, which indicated that the submicron emulsion of ZT did not exhibit any obvious nasal ciliotoxicity. These results demonstrated that the submicron emulsion preparation of ZT was a relatively safe dosage form for rapid and effective intranasal delivery of ZT.     

Development and evaluation of nanosized niosomal dispersion for oral delivery of Ganciclovir

Encapsulation of Ganciclovir in lipophilic vesicular structure may be expected to enhance the oral absorption and prolong the existence of the drug in the systemic circulation. So the purpose of the present study was to improve the oral bioavailability of Ganciclovir by preparing nanosized niosomal dispersion. Niosomes were prepared from Span40, Span60, and Cholesterol in the molar ratio of 1:1, 2:1, 3:1, and 3:2 using reverse evaporation method. The developed niosomal dispersions were characterized for entrapment efficiency, size, shape, in vitro drug release, release kinetic study, and in vivo performance. Optimized formulation (NG8; Span60:Cholesterol 3:2 molar ratio) has shown a significantly high encapsulation of Ganciclovir (89?±?2.13%) with vesicle size of 144?±?3.47?nm (polydispersity index [PDI]?=?0.08). The in vitro release study signifies sustained release profile of niosomal dispersions. Release profile of prepared formulations have shown that more than 85.2?±?0.015% drug was released in 24?h with zero-order release kinetics. The results obtained also revealed that the types of surfactant and Cholesterol content ratio altered the entrapment efficiency, size, and drug release rate from niosomes. In vivo study on rats reveals five-time increment in bioavailability of Ganciclovir after oral administration of optimized formulation (NG8) as compared with tablet. The effective drug concentration (>0.69 µg/mL in plasma) was also maintained for at least 8?h on administration of the niosomal formulation. In conclusion, niosomes can be proposed as a potential oral delivery system for the effective delivery of Ganciclovir.     

Oral bioavailability enhancement of raloxifene by developing microemulsion using D-optimal mixture design: optimization and in-vivo pharmacokinetic study

The objective of this work was to utilize a potential of microemulsion for the improvement in oral bioavailability of raloxifene hydrochloride, a BCS class-II drug with 2% bioavailability. Drug-loaded microemulsion was prepared by water titration method using Capmul MCM C8, Tween 20, and Polyethylene glycol 400 as oil, surfactant, and co-surfactant respectively. The pseudo-ternary phase diagram was constructed between oil and surfactants mixture to obtain appropriate components and their concentration ranges that result in large existence area of microemulsion. D-optimal mixture design was utilized as a statistical tool for optimization of microemulsion considering oil, S_mix, and water as independent variables with percentage transmittance and globule size as dependent variables. The optimized formulation showed 100?±?0.1% transmittance and 17.85?±?2.78?nm globule size which was identically equal with the predicted values of dependent variables given by the design expert software. The optimized microemulsion showed pronounced enhancement in release rate compared to plain drug suspension following diffusion controlled release mechanism by the Higuchi model. The formulation showed zeta potential of value ?5.88?±?1.14?mV that imparts good stability to drug loaded microemulsion dispersion. Surface morphology study with transmission electron microscope showed discrete spherical nano sized globules with smooth surface. In-vivo pharmacokinetic study of optimized microemulsion formulation in Wistar rats showed 4.29-fold enhancements in bioavailability. Stability study showed adequate results for various parameters checked up to six months. These results reveal the potential of microemulsion for significant improvement in oral bioavailability of poorly soluble raloxifene hydrochloride.     

Proniosomal gel-mediated transdermal delivery of bromocriptine: in vitro and ex vivo evaluation

Vesicular systems endow large opportunities for the transdermal delivery of therapeutics. The present study was designed to investigate the potential of a novel class of vesicular system ‘proniosome’ as a carrier for transdermal delivery of bromocriptine (BCT). Proniosome formulations were prepared by the coacervation-phase separation method and the influence of factors like surfactant type and its amount, lipid concentration, cholesterol amount and drug content were studied. Span 60 was the most appropriate surfactant, and yielded vesicle size and percentage encapsulation efficiency of 1.3 µm and 98.9%, respectively. The developed system was characterised w.r.t. morphology, transition temperature, drug release, skin permeation and skin irritancy. Proniosomes exhibited a sustained release pattern of BCT in vitro. Skin permeation study revealed high penetration of proniosomes with sustained release of BCT through rat skin. The optimised proniosomal formulation showed enhanced transdermal flux of 16.15 μg/cm²/h as compared to 3.67 μg/cm²/h for drug dispersion. The developed formulations were observed as non-irritant to the rat skin and were found as quite stable at 4 and 25 °C for 90 days w.r.t. vesicle size and drug content. The dried proniosomal formulation could act as a promising alternative to niosomes and preferably for transdermal delivery of BCT.     

Preparation, in vitro and in vivo evaluation of liposomal/niosomal gel delivery systems for clotrimazole

Clotrimazole, which is an imidazole derivative antifungal agent, was widely used for the treatment of mycotic infections of the genitourinary tract. To develop alternative formulation for the vaginal administration of clotrimazole to provide sustained and controlled release of appropriate drug for local vaginal therapy, liposomes/niosomes were evaluated as delivery vehicles. To optimize the preparation of liposomes/niosomes with regard to size and entrapment efficiency, multilamellar liposomes/niosomes containing drug were prepared by lipid hydration method. The prepared liposomes/niosomes were incorporated into 2% carbopol gel, and the systems were evaluated for drug stability in phosphate-buffered saline (pH 7.4) and simulated vaginal fluid at 37 +/- 1 degrees C. Further, the vesicle gel system was evaluated by antifungal activity and tolerability on tissue level in rat.     

Preparation and evaluation of zolmitriptan submicron emulsion for rapid and effective nasal absorption in beagle dogs

Submicron emulsion was prepared for rapid and effective nasal absorption of zolmitriptan (ZT). The different charge inducers and pH values of the formulations were evaluated to optimize the formulations. Submicron emulsion prepared by using stearylamine as positive charge inducer with pH of 5.0 was stable and most of ZT was freely dispersed in the aqueous phase of the preparation. In vitro release study demonstrated that ZT from the submicron emulsion preparation could be released as fast as that from the solution preparation. The pharmacokinetics was studied after intranasal administration of the submicron emulsion and solution preparation of ZT to beagle dogs. ZT from the submicron emulsion was absorbed much more rapidly and the absolute availability of the submicron emulsion preparation was significantly higher compared with the solution preparation. The nasal ciliotoxicity of the preparations was evaluated by using in situ toad palate model, which indicated that the submicron emulsion of ZT did not exhibit any obvious nasal ciliotoxicity. These results demonstrated that the submicron emulsion preparation of ZT was a relatively safe dosage form for rapid and effective intranasal delivery of ZT.     

Preparation,characterization, and in vivo evaluation of injectable long-acting curcumin microcrystal

In this research, curcumin microcrystal was produced using the wet milling method, and its pharmacokinetic behavior was compared after intramuscular (i.m.) and oral administration. The effects of milling time on the prepared curcumin microcrystal were investigated. Curcumin microcrystal was characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder x-ray diffraction (PXRD), FTIR, and in vitro dissolution. The results showed that there were no obvious changes in the crystal structure between bulk curcumin and curcumin microcrystal. Significantly higher dissolution rate from curcumin microcrystal (83.5%) at 90?min was observed, compared with that of bulk curcumin (74.1%). Furthermore, the in vivo pharmacokinetic behavior and muscular irritation after i.m. administration were also evaluated. The results showed that the release of curcumin lasted for 1 week by processing into microcrystal. The histological examination implied that curcumin microcrystal was safe for i.m. injection and was appropriate for the i.m. delivery of curcumin.     

Preparation and evaluation of curcumin-loaded self-assembled micelles

Objective: Curcumin being used to treat various chronic diseases while its poor bioavailability issue limited its wide clinical application as a therapeutic agent. The aim of this work was to prepare curcumin-loaded self-assembled micelles using soluplus and solutol^®HS15 (SSCMs) to enhance curcumin’s solubility and thus oral bioavailability.

Methods: Optimum formulation was investigated and the optimized ratio of drugs and excipients was obtained and the SSCMs were prepared via ethanol solvent evaporation method. The optimal SSCMs were characterized by transmission electron microscopy, drug content analysis including loading efficiency (LE%) and entrapment efficiency (EE%), and the cumulative amount of curcumin released from the micelles were all calculated using HPLC method. The in vitro cytotoxicity and the permeability of SSCMs were measured by Caco-2 cell monolayers and the oral bioavailability was evaluated by SD rats.

Key findings: The solubility of curcumin in self-assembled micelles was dramatically increased by 4200 times as compared to free curcumin. Caco-2 cells transport experiment exhibited that while soluplus and solutol^®HS15 were self-assembled into micelles, it could not only promote the permeability of curcumin across membrane for better absorption, but also could restrain the curcumin pumped outside due to the role of P-gp efflux mechanism of soluplus and solutol^®HS15. Furthermore, the prepared SSCMs formulation was almost nontoxic and had safety performance on Caco-2 cells model. Moreover, curcumin’s oral bioavailability of SSCMs formulation in SD rats had doubled than that of free curcumin.

Conclusions: The prepared SSCMs were characterized by PS, PDI, LE%, EE% data analysis. After the soluplus and solutol^®HS15 were self assembled into micelles, both the solubility and membrane permeability of curcumin were evaluated to have been enhanced, as well as the effect of efflux pump of curcumin was inhibited, hence to promote oral absorption and generate an increased bioavailability.     

Preparation and evaluation of isoliquiritigenin-loaded F127/P123 polymeric micelles

Isoliquiritigenin (ISL) possesses a variety of pharmacological activities amid poor solubility in water which has restricted its clinical application. In this study, isoliquiritigenin-loaded F127/P123 polymeric micelles (ISL-FPM) were successfully prepared and evaluated in vitro and in vivo. The particle size, polydispersity index, and zeta potential of the selected formulation were 20.12?±?0.72?nm, 0.183?±?0.046, and ?38.31?±?0.33?mV, respectively, coupled with high encapsulation efficiency of 93.76?±?0.31%. Drug-loading test showed the solubility of ISL after formulating into micelles was 232 times higher than its intrinsic solubility. Moreover, critical micelle concentration (CMC) was tested with fluorescence probe method and turned out to be quite low, which implied high stability of ISL-FPM. Release profile in HCl (pH 1.2), double distilled water, and PBS (pH 7.4) of ISL-FPM reached over 80%, while free ISL was around 40%. Pharmacokinetic research revealed that formulated ISL-FPM significantly increased bioavailability by nearly 2.23-fold compared to free ISL. According to the results of in vitro antioxidant activity, scavenging DPPH activity of ISL was significantly strengthened when it was loaded into polymeric micelles. Altogether, ISL-FPM can act as a promising approach to improve solubility as well as enhance bioavailability and antioxidant activity of ISL.     

Histopathological evaluation of caffeine-loaded solid lipid nanoparticles in efficient treatment of cellulite

Context: Cellulite refers to dimpled appearance of the skin, usually located in the thighs and buttocks regions of most adult women.

Objective: The aim of this study was to formulate topically used caffeine-loaded solid lipid nanoparticle (SLN) for the treatment of cellulite.

Methods: SLNs were prepared by hot homogenization technique using Precirol® as lipid phase. The physical characterization and stability studies of SLNs as well as in vitro skin permeation and histological studies in rat skin were conducted.

Results: The mean particle size, encapsulation efficiency and loading efficiency percentages for optimized SLN formulation were 94?nm, 86 and 28%, respectively. In vitro drug release demonstrated that caffeine-loaded SLN incorporated into carbopol made hydrogel (caffeine-SLN-hydrogel) exhibited a sustained drug release compared to the caffeine hydrogel over 24?h. Caffeine-loaded SLNs showed a good stability during 12 months of storage at room temperature. The DSC and XRD results showed that caffeine was dispersed in SLN in an amorphous state. In vitro permeation studies illustrated higher drug accumulation in the skin with caffeine-SLN-hydrogel compared to caffeine hydrogel. The flux value of caffeine through rat skin in caffeine-SLN-hydrogel was 3.3 times less than caffeine hydrogel, representing lower systemic absorption. In contrast with caffeine hydrogel, the histological studies showed the complete lysis of adipocytes by administration of caffeine-SLN-hydrogel in the deeper skin layers.

Conclusion: Results of this study indicated that SLNs are promising carrier for improvement of caffeine efficiency in the treatment of cellulite following topical application on the skin.     

Preparation,characterization and pharmacokinetic evaluation of rosuvastatin calcium incorporated cyclodextrin-polyanhydride nanoparticles

Abstract

Objective: The aim of the study was to formulate, cyclodextrin (CD)-polyanhydride (PA) nanoparticles (CPNs) with rosuvastatin calcium (RCa) in order to enhance the poor oral bioavailability.

Methods: CPNs containing RCa/CD complexes were prepared by a modified solvent displacement method and morphological analyses, particle size (PS), polydispersity index (PDI), zeta potential (ZP), encapsulation efficiency (EE), DSC, FT-IR, XRD, ¹H-NMR analyses were performed. In vitro release properties, release kinetics, cytotoxicity, in vitro permeability and pharmacokinetic studies were also studied. The stability of the formulations were evaluated during the storage period of 3?months.

Results: The physicochemical studies showed that the RCa/CD complexes were well incorporated into CPNs resulted in nanosized particles (215.22 and 189.13?nm) with homogenous size distribution (PDI: 0.203 and 0.182) with relatively high incorporation capacity (76.11 and 68.18%) for the CPN1 and CPN2 formulations respectively. Sustained release of RCa from CPNs were achieved. The cytotoxicity values showed that the safety of the formulations. According to permeability studies, pure RCa had lowest permeability data (3.08?×?10^?7?cm?s^?1 P_app value) while CPNs gained higher permeability data (1.36?×?10^?5 and 1.12?×?10^?5?cm?s^?1 P_app values) for the CPN1 and CPN2 formulations respectively. CPN2 formulation was selected for pharmacokinetic studies and analyses results demonstrated that approximately 8-fold relative oral bioavailability enhancement compared to the pure RCa was achieved.

Conclusion: Considering the analyses results of the study, CPNs can be regarded as suitable, safe, functional oral delivery systems for RCa with enhanced oral bioavailability.     

FePt单层连续膜和颗粒膜的制备与磁性能研究

利用磁控溅射在不同Ar气压下制备了不同膜厚的FePt薄膜。利用透射电镜（TEM）研究了溅射气压和膜厚对薄膜形貌的影响,利用振动样品磁强计（VSM）研究了溅射气压和膜厚对薄膜磁性能的影响。结果表明溅射气压和膜厚对溅射态单层FePt薄膜的表面形貌、颗粒尺寸有很大影响。随着溅射气压的增大,颗粒尺寸减小,从连续膜转变成颗粒膜;随着膜厚的增加,颗粒尺寸变大,从颗粒膜变成连续膜。通过调节溅射气压可以控制FePt的岛状结构,从而获得较理想的FePt颗粒薄膜。溅射气压和膜厚对经过热处理的L10-FePt薄膜的磁性能有很大影响。随着溅射气压增加,形核场由正值转变成负值,矩形比有增大趋势;随着厚度的增加,无序-有序相转变更充分。     

Topical delivery of tetrahydrocurcumin lipid nanoparticles effectively inhibits skin inflammation: in vitro and in vivo study

Tetrahydrocurcumin (THC) also referred to as ‘white curcumin’, is a stable colorless hydrogenated product of curcumin with superior antioxidant and anti-inflammatory properties. The present study is an attempt to elevate the topical bioavailability of THC, post-incorporation into a nano-carrier system with its final dosage as a hydrogel. Lipid nanoparticles of THC (THC-SLNs) prepared by microemulsification technique were ellipsoidal in shape (revealed in transmission electron microscopy) with a mean particle size of 96.6?nm and zeta potential of ?22?mV. Total drug content and entrapment efficiency of THC-SLNs was 94.51%?±?2.15% and 69.56%?±?1.35%, respectively. Differential scanning calorimetry and X-ray diffraction studies confirmed the formation of THC-SLNs. In vitro drug release studies showed the drug release from THC-SLNs gel to follow Higuchi’s equation revealing a Fickian diffusion. Ex vivo permeation studies indicated a 17 times (approximately) higher skin permeation of THC-SLNs gel as compared with the free THC gel. Skin irritation, occlusion, and stability studies indicated the formulation to be nonirritating, and stable with a desired occlusivity. Pharmacodynamic evaluation in an excision wound mice model clearly revealed the enhanced anti-inflammatory activity of THC-SLNs gel and was further confirmed using biochemical and histopathological studies. It is noteworthy to report here that THC-SLNs gel showed significantly better (p?≤?0.001) activity than free THC in gel. As inflammation is innate to all the skin disorders, the developed product opens up new therapeutic avenues for several skin diseases. To the best of our knowledge, this is the first paper elaborating the therapeutic usefulness of white curcumin-loaded lipidic nanoparticles for skin inflammation.     

Formulation and rheological evaluation of ethosome-loaded carbopol hydrogel for transdermal application

Objective: To select a suitable ethosome-loaded Carbopol hydrogel formulation, specifically tailored for transdermal application that exhibits (i) plastic flow with yield stress of approximately 50–80?Pa at low polymer concentration, (ii) relatively frequency independent elastic (G′) and viscous (G″) properties and (iii) thermal stability.

Methods: Carbopol (C71, C934, C941, C971 or C974) hydrogels were prepared by dispersing Carbopol in distilled water followed neutralization by sodium hydroxide. The effects of Carbopol grade, Carbopol concentration, ethosome addition and temperature on flow (yield stress and viscosity) and viscoelastic (G′ and G″) properties of Carbopol hydrogel were evaluated. Based on the aforementioned rheological properties evaluated, suitable ethosome-loaded Carbopol hydrogel was selected. In-vitro permeation studies of diclofenac using rat skin were further conducted on ethosome-loaded Carbopol hydrogel along with diclofenac-loaded ethosomal formulation as control.

Results: Based on preliminary screening, C934, C971 and C974 grades were selected and further evaluated for flow and viscoelastic properties. It was observed that ethosome-loaded C974 hydrogel at concentration of 0.50 and 0.75% w/w, respectively, demonstrated acceptable plastic flow with distinct yield stress and a frequency independent G′ and G″. Furthermore, the flow and viscoelastic properties were maintained at the 4, 25 and 32?°C. The results from in vitro skin permeation studies indicate that ethosome-loaded C974 hydrogel at 0.5% w/w polymer concentration exhibited similar skin permeation as that of ethosomal formulation.

Conclusion: The results indicate that suitable rheological properties of C974 could facilitate in achieving desired skin permeation of diclofenac while acting as an efficient carrier system for ethosomal vesicles.     

Preparation,characterization, stability and in vitro-in vivo evaluation of pellet-layered Simvastatin nanosuspensions

The objective of the present study was to develop stable pellets-layered Simvastatin (SIM) nanosuspensions with improved dissolution and bioavailability. The nanosuspensions were prepared with 7% HPMC, antioxidant 0.03% butylated hydroxyanisole and 0.2% citric acid (m/v) by low temperature grinding. After that, SDS with SIM was in a ratio of 1:5 (m/m), was evenly dispersed in the nanosuspensions. Then, they were layered on the surface of sugar pellets. The mean particle size of the SIM nanosuspensions was 0.74 µm, and 80.6% of the particles was below 1 µm in size. The pellets could re-disperse into nanoparticle status in the dissolution medium. In 900?mL pH 7.0 phosphate solutions, the dissolution of the layered pellets was better than that of commercial tablets. Also, nearly 100% of the drug dissolved from the pellets within 5?min under sink conditions. During the stability studies, SIM pellets exhibited good physical and chemical stability. The relative bioavailability of SIM and Simvastatin β-hydroxy acid (SIMA) for nanosuspensions layered pellets compared with commercial tablets was 117% and 173%, respectively. The bioavailability of SIMA was improved significantly (p < 0.05), confirming the improvement of bioavailability. Thus, the present study demonstrates that the pellet-layered SIM nanosuspensions improved both the dissolution and bioavailability of SIM.     

Formulation and evaluation of thymoquinone niosomes: application of developed and validated RP-HPLC method in delivery system

Abstract

A rapid, accurate, and sensitive reverse phase high-performance liquid chromatographic (RP-HPLC) method was developed and validated for the estimation of Thymoquinone (TMQ) in API as well as in noisome. The chromatograms were developed with the mobile phase – water: 2-propanol: methanol (50:45:5 v/v/v) as a solvent system at 254?nm. The method was validated as per ICH guidelines for different parameters and the recovery of TMQ was calculated in developed niosomes. Further, TMQ loaded niosomes (TMQNIOS) were prepared and evaluated for different parameters. The optimized TMQNIOS (F3) was further evaluated for surface morphology, in vitro drug release, permeation study, and confocal laser scanning microscopic (CLSM) study. The method showed linearity range between 6.25 and 100?µg/ml with low detection limit and quantitation limit with a value of 2.08 and 6.25?µg/ml. The developed formulations showed the vesicle size and encapsulation efficiency in the range of 157.32?±?3.15 to 211.44?±?5.23?nm and 59.32?±?4.87 to 83.21?±?3.55%, respectively. The drug release result showed the significant higher release from TMQNIOS in compared to TMQDIS, and the release kinetics data showed Higuchi's equation with highest regression coefficient values. The permeation study and the confocal laser microscopy study further confirmed the enhancement in permeation of TMQ in the intestinal mucosa.     

Pharmacokinetics,tissue distribution,bioavailability, and excretion of nuciferine,an alkaloid from lotus,in rats by LC/MS/MS

Objective: In order to characterize the pharmacokinetics, tissue distribution, bioavailability, and excretion of nuciferine, a reliable gradient LC/MS/MS-based method was developed and validated.

Methods: Sprague-Dawley rats were intravenously injected with a bolus of nuciferine (0.2?mg/kg) and orally given a single dose of nuciferine (10.0?mg/kg). Blood samples were withdrawn via the ocular vein at specific times. Organs, including the liver, kidney, brain, lung, heart, and spleen, were collected at specific times after oral administration of 10.0?mg/kg nuciferine. The plasma and tissue samples were assayed by LC/MS/MS.

Results: The results indicated that nuciferine had rapid distribution and poor absorption into systemic circulation. The value of absolute bioavailability was only 1.9?±?0.8% after administration of 10.0?mg/kg nuciferine by oral and administration of 0.2?mg/kg nuciferine intravenously (IV) to rats. The AUC_0→4?h values in tissues were in the order of kidney?>?lung?>?spleen?>?liver?>?brain?>?heart. The majority of excretion of nuciferine (50.7%) was excreted through kidneys with parent drug after oral administration without liver metabolism.

Conclusion: This study may provide a meaningful basis for clinical application of such a bioactive compound of herbal medicines.     

A thermoplastic elastomer patch matrix for traditional Chinese medicine: design and evaluation

Objective: To design and evaluate a novel pressure sensitive adhesive (PSA) patch containing traditional Chinese medicine (TCM) using styrene–isoprene–styrene (SIS) copolymer.

Method: A mixture D-optimal design with ternary response surface diagram was employed in the optimization process. The proportions of SIS copolymer, tackifying resin and plasticizer were selected as the independent variables while tack force, peel strength of the patch and skin penetrability of methyl salicylate were selected as the dependent variables. The optimized patch was then evaluated including in vivo absorption, pharmacological activities and skin irritation, by comparing with a commercial patch based on natural rubber.

Results: The optimized patch, which comprised 30.0% SIS copolymer, 26.6% tackifying resin and 43.4% plasticizer, was superior to commercial patch in skin permeation, pharmacological activities and skin biocompatibility.

Conclusion: SIS copolymer was a suitable substitute to natural rubber in producing patches containing TCM formula.     

In vitro and in vivo evaluation of a desonide gel-cream photostabilized with benzophenone-3

Context: Our group previously reported the photoinstability of some desonide topical commercial formulations under direct exposure to UVA radiation.

Objective: This study aimed to prepare and characterize a gel-cream containing desonide, with greater photostability than the commercial gel-cream (C-GC). Benzophenone-3 (BP-3) was used as a photostabilizing agent.

Methods: The gel-cream developed (D-GC) containing BP-3 at 0.1% was prepared and characterized regarding its pH, drug content, spreadability, viscosity, in vitro drug release and in vitro permeation. The in vivo anti-inflammatory effect was assessed by ear edema measurement, croton oil-induced acute skin inflammation and myeloperoxidase assay.

Results and Discussion: D-GC presented characteristics compatible with topical application, appropriate drug content and good spreadability, and non-Newtonian behavior with pseudoplastic flow. D-GC showed a good photostability profile, presenting a desonide content of 95.70% after 48?h of exposure to UVA radiation, and stability under room conditions during 60 days. The amount of desonide released from D-GC and C-GC was 57.8 and 51.7?µg/cm², respectively, measured using the vertical Franz cell. The in vitro skin permeation showed that desonide reached the site of action of the topical corticosteroids, from both formulations; however, the desonide amount retained in the dermis was lower with D-GC. The in vivo evaluation of topical anti-inflammatory activity indicated that D-GC presented the same biological effect as C-GC.

Conclusion: D-GC represents a promising approach to treat dermatological disorders, since it presented satisfactory physicochemical characteristics, the same biological activity as C-GC and superior photostability, conferred by the addition of BP-3 at 0.1%.