Display omitted
The purpose of this study was to compare different solidification techniques (i.e., adsorption technique, spray-drying process, high-shear granulation, fluid-bed granulation) for ...preparing solid SMEDDS powders by using solid carriers identified as appropriate and to produce a single (tablets) or multiunit (minitablets) solid dosage form based on prepared solid SMEDDS loaded with naproxen in a dissolved (6% w/w) or supersaturated (18% w/w) state. Among the solidification techniques and carriers tested, the powders produced using the spray-drying process and maltodextrin (MD) as a carrier exhibited the best self-microemulsifying properties, comparable with liquid SMEDDS. Furthermore, DoE (Design of Experiments) showed that pressure at the nozzle and pump speed (regulating feed flow rate) applied during spray drying had a major and significant influence on self-microemulsifying properties (mean droplet size and PDI) of the solid SMEDDS prepared. Furthermore, it was shown that compression of solid SMEDDS into (mini) tablets influences its self-microemulsifying properties in a negative direction. This resulted in lowering the dissolution profile of naproxen from tablets and minitablets in comparison with liquid and solid SMEDDS. However, all compressed SMEDDS formulations still had considerable influence on the dissolution profile and solubility enhancement of naproxen.
This study explores the use of a statistical model to build a design space for freeze-drying two formulations with ibuprofen. A 2 × 3 factorial experimental design was used to evaluate independent ...variables (filling volume and annealing time) and responses as residual moisture content, specific surface area and reconstitution time. A statistical model and response surface plots were generated to define the interactions among the selected variables. The models constructed for both formulations suggest that 1 mL of filled volume and no annealing should be used to achieve optimal residual moisture content, specific surface area and reconstitution time. The proposed models were validated with additional experiments, in which the responses observed were mainly in close agreement with the predicted ones. Additionally, the established models demonstrate the reliability of the evaluation procedure in predicting the selected responses.
Abstract
Context: Despite its promising therapeutic activities, clinical use of resveratrol (RSV) is compromised with unfavorable biopharmaceutical properties, namely low water solubility.
Objective: ...This work deals with improving RSV solubility and release rate through its incorporation in innovative mixed lipid phase self-microemulsifying drug delivery systems (SMEDDS).
Methods: (Pseudo)ternary diagrams were constructed for different oils and surfactant mixtures. Selected systems were further evaluated for RSV solubility, self-emulsification ability, accelerated stability, dynamic viscosity, compatibility with hard gelatin capsules and in vitro dissolution of RSV.
Results: Lipid phase composed of diverse lipid species, castor oil (long-chained triglyceride) and Capmul MCM (mixture of medium chain mono and diglycerides) allowed formulation of mixed lipid SMEDDS with lower surfactants content (60% Cremophor EL RH 40 RH 60). Mixed lipid phase SMEDDS showed best self-emulsifying ability with regard to self-emulsifying time as well as droplet size and monodispersity of microemulsions obtained upon SMEDDS dilution with aqueous phase. Overall, incorporation of RSV in SMEDDS resulted in improved solubility (over 23-fold) and dissolution rate compared to crystalline RSV. All SMEDDS formulations were adequately viscous for filling into hard gelatin capsules (>150 mPa s for empty SMEDDS; >400 mPa s for RSV-loaded SMEDDS) and no leaking was observed during three months of storage.
Conclusion: The presented work indicates the promising potential of mixed lipid SMEDDS formulations for future development of SMEDDS with lower surfactant content and no added cosolvents for incorporation of RSV and other poorly soluble drugs.
Liquid crystalline systems with a lamellar structure have been extensively studied as dermal delivery systems. Ascorbyl palmitate (AP) is one of the most studied and used ascorbic acid derivatives ...and is employed as an antioxidant to prevent skin aging. The aim of this study was to develop and characterize skin-compliant dermal delivery systems with a liquid crystalline structure for AP. First, a pseudoternary phase diagram was constructed using Tween 80/lecithin/isopropyl myristate/water at a Tween 80/lecithin mass ratio of 1/1, and the region of lamellar liquid crystals was identified. Second, selected unloaded and AP-loaded lamellar liquid crystal systems were physicochemically characterized with polarizing optical microscopy, small-angle X-ray scattering, differential scanning calorimetry, and rheology techniques. The interlayer spacing and rheological parameters differ regarding quantitative composition, whereas the microstructure of the lamellar phase was affected by the AP incorporation, resulting either in additional micellar structures (at 25 and 32°C) or being completely destroyed at higher temperature (37°C). After this, the study was oriented towards in vitro cytotoxicity evaluation of lamellar liquid crystal systems on a keratinocyte cell line. The results suggest that the lamellar liquid crystals that were developed could be used as a physiologically acceptable dermal delivery system.
The freeze-drying process is an expensive, time-consuming and rather complex process. Therefore, process analytical technology (PAT) tools have been introduced to develop an optimized process and ...control critical process parameters, which affect the final product quality. The aim of the present work was to study the applicability of at-line near-infrared (NIR) and Raman spectroscopy approach in the monitoring of the freeze-drying process. Freeze-dried powders, which were developed previously, were manufactured as a multi-component system, containing ibuprofen (IBP). The NIR proved to be a useful tool for the monitoring of the freeze-drying process, since it was able to determine residual moisture content (RMC) and hence predict its values by using the partial least square (PLS) model. In addition, the evaluation of the correlation between the NIR and off-line HPLC IBP content results showed that NIR spectra were consistent with the HPLC measurements, even though overlapping absorption bands in multi-component system were observed. This research also studied the ability of using the at-line Raman measurements for the evaluation of the crystallinity and polymorphic transformations during the process, such as IBP ionization and mannitol polymorphism. The results were in correlation with XRPD results, but parameters of PLS models were not optimal. Nevertheless, this approach still assured better process understanding. To conclude, high applicability of the at-line NIR in the monitoring of the freeze-dried powder production was successfully demonstrated, suggesting that it can be used as a single tool to monitor RMC and IBP content as well as process deviations during the freeze-drying process.
One of the major contributions to skin photoageing and diseases is oxidative stress, caused by UV radiation inducing reactive oxygen and nitrogen species. Successful prophylaxis and therapy would ...necessitate control of the oxidant/antioxidant balance at the affected site, which can be achieved through the external supply of endogenous antioxidants.
This review discusses possible strategies for dermal delivery of the antioxidant vitamins E and C, as oral supplementation has proved insufficient. These antioxidants have low skin bioavailability, owing to their poor solubility, inefficient skin permeability, or instability during storage. These drawbacks can be overcome by various approaches, such as chemical modification of the vitamins and the use of new colloidal drug delivery systems. New knowledge is included about the importance of: enhancing the endogenous skin antioxidant defense through external supply; the balance between various skin antioxidants; factors that can improve the skin bioavailability of antioxidants; and new delivery systems, such as microemulsions, used to deliver vitamins C and E into the skin simultaneously.
A promising strategy for enhancing skin protection from oxidative stress is to support the endogenous antioxidant system, with antioxidants containing products that are normally present in the skin.
Biofilm-associated diseases such as periodontitis are widespread and challenging to treat which calls for new strategies for their effective management. Probiotics represent a promising approach for ...targeted treatment of dysbiosis in biofilm and modulation of host immune response. In this interdisciplinary study, nanofibers with two autochthonous Bacillus strains 27.3.Z and 25.2.M were developed. The strains were isolated from the oral microbiota of healthy individuals, and their genomes were sequenced and screened for genes associated with antimicrobial and immunomodulatory activities, virulence factors, and transferability of resistance to antibiotics. Spores of two Bacillus strains were incorporated individually or in combination into hydrophilic poly(ethylene oxide) (PEO) and composite PEO/alginate nanofibers. The nanofiber mats were characterised by a high loading of viable spores (> 7 log CFU/mg) and they maintained viability during electrospinning and 6 months of storage at room temperature. Spores were rapidly released from PEO nanofibers, while presence of alginate in the nanofibers prolonged their release. All formulations exhibited swelling, followed by transformation of the nanofiber mat into a hydrogel and polymer erosion mediating spore release kinetics. The investigated Bacillus strains released metabolites, which were not cytotoxic to peripheral blood mononuclear cells (PBMCs) in vitro. Moreover, their metabolites exhibited antibacterial activity against two periodontopathogens, an antiproliferative effect on PBMCs, and inhibition of PBMC expression of proinflammatory cytokines. In summary, the developed nanofiber-based delivery system represents a promising therapeutic approach to combat biofilm-associated disease on two fronts, namely via modulation of the local microbiota with probiotic bacteria and host immune response with their metabolites.
Display omitted
•Bacillus strains investigated exhibit probiotic potential based on genotyping.•Their metabolites exhibit antibacterial and immunomodulatory activity in vitro.•PEO and composite PEO/alginate nanofibers preserve the strain viability.•Nanofiber mats swell and release spores by polymer erosion up to several hours.•Increased alginate content in nanofibers results in slower spore release.
Display omitted
Despite extensive investigations of lamellar liquid crystals for dermal application, the effects of these systems at the cellular level are still not well elucidated. The key aim of ...this study was to determine the elasticity and morphological features of keratinocytes after exposure to a lamellar liquid crystal system (LLCS) using atomic force microscopy (AFM) as the method of choice. Prior to AFM assessment, a cell proliferation test and light plus fluorescence imaging were applied to determine the sub-toxic concentration of LLCS. According to the AFM results, slightly altered morphology was observed in the case of fixed keratinocytes, while an intact morphology was visualized on live cells. From the quantitative study, decreased Young’s moduli were determined for fixed cells (i.e., 8.6 vs. 15.2 MPa and 1.3 vs. 2.9 MPa for ethanol or PFA-fixed LLCS-treated vs. control cells, respectively) and live cells (i.e., ranging from 0.6 to 2.8 for LLCS-treated vs. 1.1–4.5 MPa for untreated cells), clearly demonstrating increased cell elasticity. This is related to improved membrane fluidity as a consequence of interactions between the acyl chains of cell membrane phosphatidylcholine and those of LLCS. What seems to be of major importance is that the study confirms the potential clinical relevance of such systems in treatment of aged skin with characteristically more rigid epithelial cells.
Display omitted
The purpose of this study was to prepare solid SMEDDS (sSMEDDS) particles produced by spray-drying using maltodextrin (MD), hypromellose (HPMC), and a combination of the two as a ...solid carrier. Naproxen (NPX) as the model drug was dissolved (at 6% concentration) or partially suspended (at 18% concentration) in a liquid SMEDDS composed of Miglyol® 812, Peceol™, Gelucire® 44/14, and Solutol® HS 15. Among the sSMEDDSs tested, the MD-based sSMEDDSs (with a granular, smooth-surfaced, microspherical appearance) preserved the self-microemulsifying properties of liquid SMEDDSs and exhibited dissolution profiles similar to those of liquid SMEDDSs, irrespective of the concentration of NPX. In contrast, HPMC-based sSMEDDSs (irregular-shaped microparticles) exhibited slightly prolonged release times due to the polymeric nature of the carrier. Differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), and Raman mapping analysis confirmed molecularly dissolved NPX (at 6% of drug loading), whereas at 18% NPX loading drug is partially molecularly dissolved and partially in the crystalline state.
PDF
