Elastic Liposomal Formulation for Sustained Delivery of Antimigraine Drug: In Vitro Characterization and Biological Evaluation

The aim of this study was to prepare and characterize a topical formulation for sustained delivery of rizatriptan. Elastic liposomal formulation of rizatriptan was prepared and characterized for different characteristics by evaluating in vitro and in vivo parameters. The in vivo performance of optimized formulation was evaluated for antimigraine activity in mice using morphine withdrawal-induced hyperalgesia. The in vitro skin permeation study across rat skin suggested carrier-mediated transdermal permeation for different elastic liposomal formulation to range between 18.1 ± 0.6 and 42.7 ± 2.3 μg/h/cm², which was approximately 8–19 times higher than that obtained using drug solution. The amount of drug deposited was 10-fold higher for elastic liposome (39.9 ± 3.2%) than using drug solution (3.8 ± 1%); similarly the biological activity of optimized elastic liposome formulation was found to be threefold higher than the drug solution. On the basis of the results, it can be concluded that the elastic liposomal formulation provided sustained action of rizatriptan due to depot formation in the deeper layer of skin.     

Microemulsion loaded hydrogel as a promising vehicle for dermal delivery of the antifungal sertaconazole: design,optimization and ex vivo evaluation

The purpose of the present study was to develop and optimize sertaconazole microemulsion-loaded hydrogel (STZ ME G) to enhance the dermal delivery and skin retention of the drug. Following screening of various oils for maximum drug solubility, 12 pseudoternary phase diagrams were constructed using oils (Peceol^®, Capryol^® 90), surfactants (Tween^® 80, Cremophor^® EL), a cosurfactant (Transcutol^® P) and water. A 2¹ × 3¹ × 2¹ × 3¹ full factorial design was employed to optimize a ME of desirable characteristics. The MEs were formulated by varying the oil type, oil concentration, surfactant type and surfactant: cosurfactant ratio. Optimized ME formulae F22 [5% Peceol^®, 55% Tween^® 80: Transcutol^® (1:2), 40% water] and F31 [5% Peceol^®, 55% Cremophor^® EL: Transcutol^® (1:2), 40% water] acquired mean droplet size of 75.21 and 8.68?nm, and zeta potential of 34.65 and 24.05?mV, respectively. Since F22 showed higher STZ skin retention during ex vivo studies (686.47?μg/cm²) than F31 (338.11?μg/cm²); hence it was incorporated in 0.5% Carbopol 934 gel to augment STZ skin retention capability. STZ ME G exhibited higher STZ skin retention (1086.1?μg/cm²) than the marketed product “Dermofix^® cream” (270.3?μg/cm²). The antimycotic activity against C.albicans revealed increased zones of inhibition for F22 and STZ ME G (35.75 and 30.5?mm, respectively) compared to Dermofix^® cream (26?mm). No histopathological changes were observed following topical application of STZ ME G on rats’ skin (n?=?9). Overall, the obtained results confirmed that the fabricated formulation could be a promising vehicle for the dermal delivery of STZ.     

Development and in vitro characterization of chitosan-coated polymeric nanoparticles for oral delivery and sustained release of the immunosuppressant drug mycophenolate mofetil

Objective: To develop an oral sustained release formulation of mycophenolate mofetil (MMF) for once-daily dosing, using chitosan-coated polylactic acid (PLA) or poly(lactic-co-glycolic) acid (PLGA) nanoparticles. The role of polymer molecular weight (MW) and drug to polymer ratio in encapsulation efficiency (EE) and release from the nanoparticles was explored in vitro.

Methods: Nanoparticles were prepared by a single emulsion solvent evaporation method where MMF was encapsulated with PLGA or PLA at various polymer MW and drug: polymer ratios. Subsequently, chitosan was added to create coated cationic particles, also at several chitosan MW grades and drug: polymer ratios. All the formulations were evaluated for mean diameter and polydispersity, EE as well as in vitro drug release. Differential scanning calorimetry (DSC), surface morphology, and in vitro mucin binding of the nanoparticles were performed for further characterization.

Results: Two lead formulations comprise MMF: high MW, PLA: medium MW chitosan 1:7:7 (w/w/w), and MMF: high MW, PLGA: high MW chitosan 1:7:7 (w/w/w), which had high EE (94.34% and 75.44%, respectively) and sustained drug release over 12?h with a minimal burst phase. DSC experiments revealed an amorphous form of MMF in the nanoparticle formulations. The surface morphology of the MMF NP showed spherical nanoparticles with minimal visible porosity. The potential for mucoadhesiveness was assessed by changes in zeta potential after incubation of the nanoparticles in mucin.

Conclusion: Two chitosan-coated nanoparticles formulations of MMF had high EE and a desirable sustained drug release profile in the effort to design a once-daily dosage form for MMF.     

In situ forming implants for the delivery of metronidazole to periodontal pockets: formulation and drug release studies

This study was performed to obtain prolonged drug release with biodegradable in situ forming implants for the local delivery of metronidazole to periodontal pockets. The effect of polymer type (capped and uncapped PLGA), solvent type (water-miscible and water-immiscible) and the polymer/drug ratio on in vitro drug release studies were investigated. In situ implants with sustained metronidazole release and low initial burst consisted of capped PLGA and N-methyl-2-pyrolidone as solvent. Mucoadhesive polymers were incorporated into the in situ implants in order to modify the properties of the delivery systems towards longer residence times in vivo. Addition of the polymers changed the adhesiveness and increased the viscosity and drug release of the formulations. However, sustained drug release over 10 days was achievable. Biodegradable in situ forming implants are therefore an attractive delivery system to achieve prolonged release of metronidazole at periodontal therapy.     

Precursor system of liquid crystalline phase containing propolis microparticles for the treatment of periodontal disease: development and characterization

Precursor systems of liquid crystalline phase were prepared using the surfactant PPG-5-Ceteth-20, isopropyl myristate, and water; gelatin microparticles containing propolis were then added into these systems. Homogeneity of dispersion, the in-system microparticle morphology, and sedimentation behavior of each formulation were evaluated. The rheological and mechanical properties (hardness, compressibility, and adhesiveness), the work of syringing, and the propolis release profile were also evaluated. All the formulations exhibited pseudoplastic flow and thixotropy, and they displayed storage modulus, loss modulus, dynamic viscosity, and loss tangent that depended on temperature, frequency, and composition. Mechanical properties varied significantly among the formulations being affected by changes in the composition and temperature. Raising the concentration of surfactant and adding propolis microparticles significantly decreased the work of syringing. The drug release was non-Fickian (anomalous) and there was no significant difference between the tested systems in the times required for 10%, 30%, and 50% release of the initial drug loading.     

Strain energy release rate calculation for a moving delamination front of arbitrary shape based on the virtual crack closure technique. Part I: Formulation and validation

This paper proposes a simple, efficient algorithm to trace a moving delamination front with an arbitrary and changing shape so that delamination growth can be analyzed by using stationary meshes. Based on the algorithm, a delamination front can be defined by two vectors that pass through any point on the front. The normal vector and the tangent vector for the local coordinate system can then be obtained based on the two delamination front vectors. An important feature of this approach is that it does not require the use of meshes that are orthogonal to the delaminations front. Therefore, the approach avoids adaptive re-meshing techniques that may create a large computational burden in delamination growth analysis. An interface element that can trace the instantaneous delamination front, determine the local coordinate system, approximate strain energy release rate components and apply fracture mechanics criteria has been developed and implemented into ABAQUS^® with its user-defined element (UEL) feature. In this Part I of a two-part paper, the approach and its implementation are described and validated by comparison to results from existing cases having analytical solutions or other established FEA predictions.     

Reprint of “Safe places for pedestrians: Using cognitive work analysis to consider the relationships between the engineering and urban design of footpaths”

Footpaths provide an integral component of our urban environments and have the potential to act as safe places for people and the focus for community life. Despite this, the approach to designing footpaths that are safe while providing this sense of place often occurs in silos. There is often very little consideration given to how designing for sense of place impacts safety and vice versa. The aim of this study was to use a systems analysis and design framework to develop a design template for an ‘ideal’ footpath system that embodies both safety and sense of place. This was achieved through using the first phase of the Cognitive Work Analysis framework, Work Domain Analysis, to specify a model of footpaths as safe places for pedestrians. This model was subsequently used to assess two existing footpath environments to determine the extent to which they meet the design requirements specified. The findings show instances where the existing footpaths both meet and fail to meet the design requirements specified. Through utilising a systems approach for footpaths, this paper has provided a novel design template that can inform new footpath design efforts or be used to evaluate the extent to which existing footpaths achieve their safety and sense of place requirements.