Gordana Vuleta

Polyhydroxy surfactants for the formulation of lipid nanoparticles (SLN and NLC): effects on size, physical stability and particle matrix structure

The two polyhydroxy surfactants polyglycerol 6-distearate (Plurol(®)Stearique WL1009 - (PS)) and caprylyl/capryl glucoside (Plantacare(®) 810 - (PL)) are a class of PEG-free stabilizers, made from renewable resources. They were investigated for stabilization of aqueous solid lipid nanoparticle (SLN) and nanostructured lipid carrier (NLC) dispersions. Production was performed by high pressure homogenization, analysis by photon correlation spectroscopy (PCS), laser diffraction (LD), zeta potential measurements and differential scanning calorimetry (DSC). Particles were made from Cutina CP as solid lipid only (SLN) and its blends with Miglyol 812 (NLC, the blends containing increasing amounts of oil from 20% to 60%). The obtained particle sizes were identical for both surfactants, about 200 nm with polydispersity indices below 0.20 (PCS), and unimodal size distribution (LD). All dispersions with both surfactants were physically stable for 3 months at room temperature, but Plantacare (PL) showing a superior stability. The melting behaviour and crystallinity of bulk lipids/lipid blends were compared to the nanoparticles. Both were lower for the nanoparticles. The crystallinity of dispersions stabilized with PS was higher, the zeta potential decreased with storage time associated with this higher crystallinity, and leading to a few, but negligible larger particles. The lower crystallinity particles stabilized with PL remained unchanged in zeta potential (about -50 mV) and in size. These data show that surfactants have a distinct influence on the particle matrix structure (and related stability and drug loading), to which too little attention was given by now. Despite being from the same surfactant class, the differences on the structure are pronounced. They are attributed to the hydrophobic-lipophilic tail structure with one-point anchoring in the interface (PL), and the loop conformation of PS with two hydrophobic anchor points, i.e. their molecular structure and its interaction with the matrix surface and matrix bulk. Analysis of the effects of the surfactants on the particle matrix structure could potentially be used to further optimization of stability, drug loading and may be drug release.

A comparison of electrical and rheological techniques for the characterisation of creams

Abstract Two complex semi-solid emulsion systems, one ionic and one non-ionic, have been evaluated using both conventional (conductivity measurements and continuous flow theology) and oscillatory (dielectric spectroscopy and oscillatory rheology) methods. The results of specific conductivity measurements indicated differences in charge mobility, with the ionic cream showing a considerable higher conductivity (171.0 μS/cm compared to 9.3 μS/cm for the non-ionic system). Dielectric spectroscopy allowed a more sophisticated electrical analysis to be obtained, and a discussion is given of how the data relates to the current model for interpreting the low frequency response. Flow and oscillatory results indicated that greater internal structuring, leading to higher elasticity, was achieved for the ionic system. It is demonstrated that both techniques yield different yet complimentary information on the cream structure. The study has indicated that the use of dielectric spectroscopy and oscillatory rheometry, in addition to conventional methods, may lead to a better understanding of the emulsion microstructure.

Lactobionic acid in a natural alkylpolyglucoside-based vehicle: assessing safety and efficacy aspects in comparison to glycolic acid

Background/aims  Lactobionic acid (LA) is a newer cosmeceutical active belonging to the class of alpha‐hydroxyacids (AHAs), showing advantages over them. The aim of part I of this study was to compare efficacy and irritation potential of LA vs. glycolic acid (GA) from two types of vehicles – gel and emulsion. In part II, effects of LA‐containing emulsions based on a new, natural emulsifier of alkylpolyglucoside (APG) type were evaluated.

Preparation of novel apigenin-enriched, liposomal and non-liposomal, antiinflammatory topical formulations as substitutes for corticosteroid therapy.

Two oil‐in‐water formulations, containing equal amounts of apigenin‐enriched chamomile flower extracts, for potential use as topical antiinflammatory agents, were prepared and their physicochemical properties evaluated. A pilot clinical study was then carried out to assess patient acceptability and efficacy. The creams were either non‐liposomal or liposomal. The liposomal formulations were more viscous, thus producing superior release characteristics in vitro. The clinical study also showed that the liposomal creams were, as antiinflammatory agents, slightly more effective in vivo than the non‐liposomal formulations. These results suggest that there is scope for the further development of even more effective and safer alternatives to corticosteroids. Copyright

Improved percutaneous delivery of ketoprofen using combined application of nanocarriers and silicon microneedles.

The aim of our study was to evaluate the effect of designing ketoprofen‐loaded nanosized spheres and combining them with solid silicon microneedles for enhanced and sustained percutaneous drug delivery.

The Physicochemical Characterization and In Vitro/In Vivo Evaluation of Natural Surfactants-based Emulsions as Vehicles for Diclofenac Diethylamine

ABSTRACT Two sugar-based emulsifiers, cetearyl alcohol & cetearyl glycoside and sorbitan stearate & sucrose cocoate, known as potential promoters of lamellar liquid crystals/gel phases, were investigated in order to formulate an optimal vehicle for amphiphilic drug—diclofenac diethylamine (DDA). Physico-chemical characterization and study of vehicles physical stability were performed. Then, the in vitro DDA liberation profile, dependent on the mode of drug incorporation to the system, and the in vivo, short-term effects of chosen samples on skin parameters were examined. Droplets size distribution and rheological behavior indicated satisfying physical stability of both types of vehicles. Unexpectedly, the manner of DDA incorporation to the system had no significant influence on DDA release. In vivo study pointed to emulsions favorable potential for skin hydration and barrier improvement, particularly in cetearyl glycoside-based vehicle.

The characterization of the semi-solid W/O/W emulsions with low concentrations of the primary polymeric emulsifier

Semi‐solid multiple W/O/W emulsions with low concentrations (0.8, 1.6 and 2.4% w/w) of lipophilic polymeric primary emulsifier PEG‐30‐dipolyhydroxystearate (PDHS) have been formulated. Both emulsions, primary and multiple, were prepared with high content of inner phase (Φ1 = Φ2 = 0.8). All the formulations differ only in the lipophilic emulsifier concentration. Evaluating several parameters such as macroscopic and microscopic aspect, droplet size, accelerated stability under centrifugation and flow and oscillatory rheological behaviour, assessed the multiple systems. It is possible to formulate the semi‐solid W/O/W multiple emulsions with low concentrations of PDHS as the primary emulsifier. It appeared that the highest long‐term stable multiple emulsion with the lowest droplet size, the highest apparent viscosity and highest elastic characteristic, was the sample with the highest concentration (2.4% w/w) of the primary emulsifier.

Effect of small changes in natural origin-based emulsion systems on hydrocortisone skin absorption and performance: a comparison of two in vivo methods

Abstract Context: Alkyl polyglucoside surfactants (APG) remain prominent natural origin stabilizers offering a prospect of combining satisfactory stability with mild dermatological properties and complete biodegradability. Objective: With the purpose of adjusting the dose to a patient’s needs, dilution of commercial corticosteroid formulations is a practice which may modify efficacy uncontrolledly. The rational of the study was to investigate whether a simple change in ready-to-use bases (co-solvent addition) could address these needs in a more predictive manner. Methods: Hydrocortisone (HC) delivery from such emulsion systems was comparatively assessed employing two in vivo methods: the established human skin blanching assay versus skin stripping technique. Results: HC permeation data obtained after three dose durations showed better overall performance of the APG-stabilized bases relative to reference ones. Although the solubility study showed that all the assessed active samples retained equal thermodynamic activity, diverse HC permeation/penetration implies the importance of the applied base’s colloidal structure and/or changes endured. Isopropyl alcohol (IPA) addition offered faster drug penetration enhancement, while glycerol as a moisturizing agent influenced HC penetration through the increase in skin hydration. Conclusion: Although the performed in vivo methods cannot be considered alternative, skin stripping technique proved to be a cost-efficient mode of percutaneous penetration assessment, providing additional information on vehicle–skin interactions.

Natural Surfactant-Based Emulsion Vehicles: A Correlation Between Colloidal Structure and In Vitro Release of Diclofenac Diethylamine

The need for an official pharmaceutical vehicle or carrier of drug based on natural sugar emulsifiers that protect and regenerate natural barriers of the skin lipid layer is constantly increasing. This article studies the specific structures of emulsions and two manners of water binding that provide prolonged skin moisturization and delayed or prolonged release of drugs insoluble in water. Natural emulsifiers of an alkylpolyglucoside (cetearyl alcohol and cetearyl glycoside) and estar-type (sorbitan stearate and sucrose cocoate) are used for manufacturing vehicle/carriers of drugs (diclofenac diethylamine). Specific hydrofilic groups in emulsifiers, such as glycozide and ester, are capable of binding in different manners and variable quantities of water by hydrogen bonds within the cream, which is responsible for water distribution and prolonged skin moisturization. This lyotropic potential of natural emulsifiers—alkylpolyglucoside and estar type—may affect the physical stability of topical vehicles by determining the colloidal structure, further reflecting the drug delivery from the pharmaceutical excipient to the skin. The aim of this article is to evaluate whether the type of emulsifier influences the structural characteristics of emulsion systems and how the content and availability of water within the cream reflects the delivery of diclofenac diethylamine (1.16%) from the topical vehicles. Freeze-fracture transmission electron microscopy, wide-angle x-ray diffraction, thermogravimetric analysis, and continual and oscilatory rheological measurements are employed for characterization of emulsion system colloidal structure. Diclofenac diethylamine release profiles from investigated emulsion systems were evaluated using the rotation paddle apparatus, modified by addition of diffusion cells (enhancer cell). There is an important difference in water distribution within the creams with emulsifiers of different chemical types. In the sample with ester-type sugar emulsifiers, the quantity of interlamellar-bound water is four times less than bulk and secondary water, while in the sample with alkylpolyglucoside emulsifier, approximately two thirds of total water are bound inside the system and one third is poorly bound, that is, bulk water. It can also be seen that diclofenac diethylamine is gradually released from the vehicle during 6 hours of testing. Formulation of topical vehicle as dermopharmaceutical drug carrier system, with natural emulsifier, like cetearyl alcohol, cetearyl glucoside, sorbitan stearate, and sucrose cocoate, is recommended.

Feasibility of a Natural Surfactant as a Stabilizer for Cosmetics with Liposome-Encapsulated Plant Stem Cells: Pre-Formulation and Formulation Through Stability Studies

Abstract During the formulation of liposome-containing products different problems can occur and the selection of a suitable carrier remains the greatest challenge. To estimate feasibility of a novel alkyl polyglucoside surfactant (hydroxystearyl alcohol and hydroxystearyl glucoside) as an emulsifier for cosmetics with liposome-encapsulated plant stem cells, we performed a two-phase study. In the first, the pre-formulation phase, the emulsifiers critical micelle concentration (CMC) and liposome-encapsulated active-emulsifier interactions were determined. The second phase was carried out to develop and characterize a cosmetic emulsion suitable to serve as a carrier for liposomes. The investigated emulsifier, with the obtained CMC value of 0.0085 wt.%, could be classified as liposome-friendly and can be used to develop stable and aesthetically acceptable cosmetics or even prospective pharmaceutical liposome-containing emulsions.