Antifungal efficacy of liquid poloxamer 407-based emulsions loaded with sertaconazole nitrate.

Drug delivery into the human nail plate for the treatment of onychomycosis is difficult due to limited permeability of the nail plate. Semisolid poloxamer 407-based formulations have recently shown promising results for drug delivery into and through the nail plate. In this study, liquid poloxamer 407-based emulsions loaded with sertaconazole nitrate have been developed and the permeation behavior was determined in vitro using modified Franz diffusion cells. The antifungal efficacy was evaluated in an infected nail plate model, where the growth inhibition of Trichophyton rubrum was observed. Bovine hoof plates and keratin films made from human hair were used as models for the human nail plate. In both cases, formulations with low viscosity and high water content showed best results despite a lower solubility of sertaconazole nitrate, suggesting that the composition of the vehicle plays a major role in permeation through the membrane. In addition, an API content close to saturation solubility had a positive effect on permeation.

An update on formulation strategies of benzoyl peroxide in efficient acne therapy with special focus on minimizing undesired effects.

Benzoyl peroxide (BPO) in the form of over the counter monotherapeutics or prescription-only combinations is a key component of topical acne therapy, but its unfavourable side effect profile reduces the therapeutic value of this compound. Various galenic approaches have been pursued to resolve this ambivalence, but only a few have managed to enter the market. This article aims to give a comprehensive overview of the published experimental vehicle systems and to identify the fundamental rationales. With regard to the formulation, an increase in the tolerability of BPO can essentially be achieved by combining BPO with re-fattening and moisturizing substances, by incorporating it and controlling its release, as well as by targeted deposition of the active ingredient at the site of action, i.e. drug targeting. Recently, novel particulate formulations have been proposed that combine several of these design principles and are expected to bring new developments in this dynamic field of research.

Plasma Permeabilization of Human Excised Full-Thickness Skin by µs- and ns-pulsed DBD.

INTRODUCTION: Cold atmospheric plasma (CAP) is gaining increasing importance as a medical or cosmetic treatment for various indications. The technology is best suited to the treatment of surfaces such as the skin and is already used in wound care and, in exemplary case studies, the reduction of superficial tumors. Several plasma sources have been reported to affect the skin barrier function and potentially enable drug delivery across or into plasma-treated skin. OBJECTIVE: In this study, this effect was quantified for different plasma sources in order to elucidate the influence of voltage rise time, pulse duration, and power density in treatments of full-thickness skin. METHODS: We compared three different dielectric barrier discharges (DBDs) as to their permeabilization efficiency using Franz diffusion cell permeation experiments and measurements of the transepithelial electrical resistance (TEER) with full-thickness human excised skin. RESULTS: We found a significant reduction of the TEER for all three plasma sources. Permeation of the hydrophilic sodium fluorescein molecule was enhanced by a factor of 11.7 (low power) to 41.6 (high power) through µs-pulsed DBD-treated skin. A smaller effect was observed after treatment with the ns-pulsed DBD. CONCLUSIONS: The direct treatment of excised human full-thickness skin with CAP, specifically a DBD, can lead to pore formation and enhances transdermal transport of sodium fluorescein.

Incorporation of benzoyl peroxide nanocrystals into adapalene-loaded solid lipid microparticles: Part II - Solid-in-Oil dispersion of nanoparticulate benzoyl peroxide.

Benzoyl peroxide as a monotherapeutic and in combination with adapalene is a cornerstone of current acne therapy, but its unfavourable side effect profile reduces the therapeutic value of this compound. The incorporation into an adapalene-loaded microparticulate lipid matrix, which - via the principle of targeted erosion - allows the targeted release of active substances in the hair follicles, is a promising approach to reduce side effects such as skin redness, increased scaling and allergic reactions. However, there are challenges to the production of such a vehicle which require a galenic solution. That is in particular the redispersion of nanoparticulate benzoyl peroxide in lipids while maintaining its nanodisperse character. In the present work, the lamellar liquid crystalline phase of a binary water/phospholipid system is used to stabilize a nanosuspension during freeze-drying. Both after redispersing in water and after dispersing in nonpolar fat phases, the initial size of the nanosuspension was recovered with only minor deviations. The found cryoprotective effect of purified phospholipid allows the generation of highly concentrated solid-in-oil systems both in fat phases liquid at room temperature and in lipid melts, which after solidification can serve as starting material for the preparation of lipid microparticles loaded with benzoyl peroxide nanocrystals.

Novel colloidal associations of soyasaponins and lipid components (DPPC, cholesterol) as potential adjuvants for vaccines.

Soyasaponins from soybean (Glycine max) represent promising new potent adjuvants for vaccine research because of their immunostimulating properties and weak hemolytic activity. In the present study, saponin microstructures of soyasaponins (soyasaponin Bb, soyasaponin Ab) with lipid components (cholesterol, DPPC (dipalmitoylphosphatidylcholine)) were designed by the lipid film method. In interaction studies between soyasaponins (soyasaponin Ab/Bb) and Langmuir monolayers (model membranes), composed of cholesterol and DPPC, marked interactions between soyasaponins and a pure cholesterol monolayer were observed. No interaction was detected for soyasaponins with a pure DPPC monolayer. The intercalation of soyasaponins in a mixed DPPC/cholesterol (3:1, w/w) monolayer was only observed for the monodesmosidic soyasaponin Bb whereas the second sugar chain of the bidesmosidic soyasaponin Ab impaired the access to the monolayer. Transmission electron microscopy was used for visualizing particle formation of soyasaponins and lipid components. Pseudo-binary systems (soyasaponin Ab/Bb, cholesterol) formed colloidal associations built up from ring-like subunits in the nanometer size range. In pseudo-ternary systems (soyasaponin, cholesterol, DPPC) soyasaponin Bb attacked the liposomal membrane by forming colloidal associations. Colloidal associations in pseudo-ternary systems with soyasaponin Ab, cholesterol and a phospholipid were only observed in the presence of PE (phosphatidylethanolamine) instead of DPPC. In an MTT assay with a HaCaT cell line (keratinocyte cell line) the cell viability was neither affected by the soyasaponins nor by the corresponding formulations. Both the pure soyasaponin solution and the saponin formulations may be promising adjuvant systems for the intradermal vaccine application. Furthermore, interaction studies between the model antigen ovalbumin and colloidal associations of saponins and cholesterol using MST (Microscale Thermophoresis) gave first indications of an antigen binding to colloidal associations. Ex vivo T-cell proliferation in the presence of soyasaponin Ab was confirmed.

Influence of pulse characteristics and power density on stratum corneum permeabilization by dielectric barrier discharge.

BACKGROUND: In recent years, the medical use of cold atmospheric plasma has received much attention. Plasma sources can be suited for widely different indications depending on their physical and chemical characteristics. Being interested in the enhancement of drug transport across the skin by plasma treatment, we evaluated three dielectric barrier discharges (DBDs) as to their potential use in permeabilizing human isolated stratum corneum (SC). METHODS: Imaging techniques (electrochemical and redox-chemical imaging, fluorescence microscopy), transepithelial electrical resistance measurements and permeation studies were employed to study the permeabilizing effect of different DBD-treatments on SC. RESULTS: Filamentous µs-pulsed DBDs induced robust pore formation in SC. Increasing the power of the µs-pulsed DBD lead to more pronounced pore formation but might increase the risk of undesired side-effects. Plasma permeabilization was much smaller for the ns-pulsed DBD, which left SC samples largely intact. CONCLUSIONS: The comparison of different DBDs provided insight into the mechanism of DBD-induced SC permeabilization. It also illustrated the need to tailor electrical characteristics of a DBD to optimize it for a particular treatment modality. For future applications in drug delivery it would be beneficial to monitor the permeabilization during a plasma treatment. GENERAL SIGNIFICANCE: Our results provide mechanistic insight into the potential of an emerging interdisciplinary technology - plasma medicine - as a prospective tool or treatment option. While it might become a safe and pain-free method to enhance skin permeation of drug substances, this is also a mechanism to keep in mind when tailoring plasma sources for other uses.

Development of a design of experiments optimized method for quantification of polysorbate 80 based on oleic acid using UHPLC-MS.

The aim was to develop a straightforward UHPLC-MS quantification method for polysorbate 80 using oleic acid as surrogate marker, which was the commonest substance within the emulsifier. However, hydrolysis of polysorbate 80 and subsequent analysis of fatty acids revealed a co-elution of oleic acid and an isomer while all the other fatty acids were successfully separated by varying retention times and mass-to-charge ratios. For identification and separation of the isomer a derivatization method was evaluated. Oxidation to the corresponding dihydroxystearic acids with potassium permanganate resulted in peak separation of cis/trans and structural isomers of the 18:1 fatty acids. Hydrolyzed and derivatized polysorbate 80 was quantified indirectly in the range of 0.046-5.83 µg/mL (R2 > 0.997) with a limit of detection of 11.4 ng/mL. Quantification of polysorbate 80 using oleic acid as a surrogate marker showed good reproducibility and linearity. As all isomers of the 18:1 fatty acids were successfully separated, the previously co-eluting peak was identified as elaidic acid and was found as a component in the mixture of the emulsifier polysorbate 80. Additionally, cis-vaccenic acid was separated as a second co-eluting isomer. Therefore, derivatization led to successful chromatographical separation of cis/trans and structural 18:1 fatty acid isomers.

Influence of emulsifier concentration on partition behavior and chemical stability of betamethasone dipropionate in emulsion gels.

The partitioning of active pharmaceutical ingredients (API) in emulsions is influenced by various factors, such as composition of the phases, emulsifier type and concentration, and temperature. Therefore, the chemical stability of the API can be influenced by its partitioning into the aqueous phase as degradation is typically facilitated in water. With increasing emulsifier concentration from 0.15% to 5.0%, more betamethasone dipropionate (BDP) was solubilized in polysorbate 80 micelles leading to a small, but increased fraction of BDP exposed to the aqueous phase along with preferential partitioning of BDP to the aqueous phase and thus increased degradation. Similarly, by enhancing solubility and partitioning to the aqueous phase, the addition of polyethylene glycol 400 also led to increased BDP degradation. Due to pH dependent degradation of BDP, increasing emulsifier concentrations resulted in a more pronounced degradation of BDP at pH 8, which is beyond the stability optimum, whereas at pH 5 the API was sufficiently stable and no differences in concentration were detected within 12 weeks even under accelerated conditions. No significant differences were seen with the varying emulsifier concentrations regarding ex vivo skin penetration.

Correlation of antimicrobial effects of phenoxyethanol with its free concentration in the water phase of o/w-emulsion gels.

Antimicrobial testing is a time consuming and cost-intensive but essential method for evaluation of newly developed pharmaceutical formulations for topical use. In this study the correlation between free preservative concentration in emulsion gels measured by equilibrium dialysis and the successful preservative effectiveness testing for Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans and Aspergillus brasiliensis (analyzed according to Ph. Eur. and USP) was investigated. The higher the lipophilicity of the oil phase and the lower the content of the aqueous phase with regard to dissolved ingredients the more preferably distributed is phenoxyethanol to the water phase and, consequently, the higher was the efficacy against the microbes. Increased emulsifier concentrations reduced the free amount of the preservative due to micellar interactions. Aspergillus brasiliensis was the most resistant and Staphylococcus aureus the most sensitive germ towards phenoxyethanol in o/w-emulsion gels.

Novel Colloidal Microstructures of ß-Escin and the Liposomal Components Cholesterol and DPPC.

The discovery of immunostimulating complex formation by the saponin Quil A from the plant Quillaja saponaria with cholesterol and a phospholipid opened up new avenues for the development of drug delivery systems for vaccine application with additional adjuvant properties. In this study, ß-escin, a monodesmosidic triterpene saponin from horse chestnut, was investigated in terms of its interaction with liposomal components (cholesterol, dipalmitoylphosphatidylcholine) by Langmuir film balance studies and with regard to particle formation visualized by transmission electron microscopy. A strong interaction of ß-escin with cholesterol was observed by Langmuir isotherms due to the intercalation of the saponin into the monolayer, whereas no interaction occurred with dipalmitoylphosphatidylcholine. Transmission electron microscopy studies also confirmed the strong interaction of ß-escin with cholesterol. In aqueous pseudo-ternary systems (ß-escin, dipalmitoylphosphatidylcholine, cholesterol) and in pseudo-binary systems (ß-escin, cholesterol), new colloidal structures built up from ring-like and worm-like subunits were observed with a size of about 100 - 200 nm. These colloidal structures are formed in pseudo-binary systems by aggregation of the subunits, whereas in pseudo-ternary systems, they are formed among others by attacking the liposomal membrane. The rehydration of the liposomal dispersions in NANOpure water or Tris buffer pH 7.4 (140 mM) resulted in the same particle formation. In contrast, the sequence of the dispersions' production process affected the particle formation. Unless adding the saponin to the other components from the beginning, just a liposomal dispersion was formed without any colloidal aggregates of the subunits mentioned above.

Improved in vitro models for preclinical drug and formulation screening focusing on 2D and 3D skin and cornea constructs.

The present overview deals with current approaches for the improvement of in vitro models for preclinical drug and formulation screening which were elaborated in a joint project at the Center of Pharmaceutical Engineering of the TU Braunschweig. Within this project a special focus was laid on the enhancement of skin and cornea models. For this reason, first, a computation-based approach for in silico modeling of dermal cell proliferation and differentiation was developed. The simulation should for example enhance the understanding of the performed 2D in vitro tests on the antiproliferative effect of hyperforin. A second approach aimed at establishing in vivo-like dynamic conditions in in vitro drug absorption studies in contrast to the commonly used static conditions. The reported Dynamic Micro Tissue Engineering System (DynaMiTES) combines the advantages of in vitro cell culture models and microfluidic systems for the emulation of dynamic drug absorption at different physiological barriers and, later, for the investigation of dynamic culture conditions. Finally, cryopreserved shipping was investigated for a human hemicornea construct. As the implementation of a tissue-engineering laboratory is time-consuming and cost-intensive, commercial availability of advanced 3D human tissue is preferred from a variety of companies. However, for shipping purposes cryopreservation is a challenge to maintain the same quality and performance of the tissue in the laboratory of both, the provider and the customer.

Development of Acyclovir-Loaded Albumin Nanoparticles and Improvement of Acyclovir Permeation Across Human Corneal Epithelial T Cells.

PURPOSE: The aim of the present study was to develop acyclovir (ACV) ocular drug delivery systems of bovine serum albumin (BSA) nanoparticles as well as to assess their in vitro transcorneal permeation across human corneal epithelial (HCE-T) cell multilayers. METHODS: The ACV-loaded BSA nanoparticles were prepared by desolvation method along with physicochemical characterization, cytotoxicity, as well as in vitro transcorneal permeation studies across HCE-T cell multilayers. RESULTS: The nanoparticles appeared to be spherical in shape and nearly uniform in size of about 200 nm. The size of nanoparticles became smaller with decreasing BSA concentration, while the ratios of water to ethanol seemed not to affect the size. Increasing the amount of ethanol in desolvation process led to significant reduction of drug entrapment of nanoparticles with smaller size and more uniformity. The ACV-loaded BSA nanoparticles prepared were shown to have no cytotoxic effect on HCE-T cells used in permeation studies. The in vitro transcorneal permeation results revealed that ACV could permeate through the HCE-T cell multilayers significantly higher from BSA nanoparticles than from aqueous ACV solutions. CONCLUSION: The ACV-loaded BSA nanoparticles could be prepared by desolvation method without glutaraldehyde in the formulation. ACV could increasingly permeate through the multilayers of HCE-T cells from the ACV-loaded BSA nanoparticles. Therefore, the ACV-loaded BSA nanoparticles could be a highly potential ocular drug delivery system.

Saponin Interactions with Model Membrane Systems - Langmuir Monolayer Studies, Hemolysis and Formation of ISCOMs.

Saponins are used in medicine due to their pharmacological and immunological effects. To better understand interactions of saponins with model membranes and natural membranes of, for example, erythrocytes, Langmuir film balance experiments are well established. For most saponins, a strong interaction with cholesterol was demonstrated in dependence of both the aglycone part and the sugar moieties and is suggested to be correlated with a strong hemolytic activity, high toxicity, and high surface activity, as was demonstrated for the steroid saponin digitonin. In general, changes in the sugar chain or in substituents of the aglycone result in a modification of the saponin properties. A promising saponin with regard to fairly low hemolytic activity and high adjuvant effect is α-tomatine, which still shows a high affinity for cholesterol. An interaction with cholesterol and lipids has also been proven for the Quillaja saponin from the bark of Quillaja saponaria Molina. This triterpene saponin was approved in marketed vaccines as an adjuvant due to the formation of immunostimulating complexes. Immunostimulating complexes consist of a Quillaja saponin, cholesterol, phospholipids, and a corresponding antigen. Recently, another saponin from Quillaja brasiliensis was successfully tested in immunostimulating complexes, too. Based on the results of interaction studies, the formation of drug delivery systems such as immunostimulating complexes or similar self-assembled colloids is postulated for a variety of saponins.

In vitro evaluation of the antifungal efficacy of poloxamer 407-based formulations in an infected nail plate model.

The in vitro efficacy of poloxamer 407-based formulations with antifungal ciclopirox olamine has been analysed in an infected nail plate model. As artificial nail plates, keratin films made of human hair keratin and slices from bovine hooves have been utilised. Several poloxamer 407-based formulations with 1 % active ingredient indicated complete growth inhibition of the dermatophyte fungus Trichophyton rubrum after 6days of incubation.

In vitro model of infected stratum corneum for the efficacy evaluation of poloxamer 407-based formulations of ciclopirox olamine against Trichophyton rubrum as well as differential scanning calorimetry and stability studies.

Superficial fungal skin infections are a common disease and concern 20-25% of the world's population with the dermatophyte Trichophyton rubrum being the main trigger. Due to autoinoculation, fungal skin infections of the feet (tinea pedis) often occur simultaneously with fungal nail infections (onychomycosis). Therefore, the overall objective was the development and characterisation of poloxamer 407-based formulations with the antimycotic active ingredient ciclopirox olamine (CPX) for simultaneous antifungal therapy. The formulations consisted of poloxamer 407, water, isopropyl alcohol, propylene glycol and medium chain triglycerides in given ratios. The in vitro antifungal efficacy against T. rubrum was tested in a novel in vitro model of infected stratum corneum in comparison to a marketed semi-solid formulation containing 1% (w/w) ciclopirox olamine and a marketed nail lacquer containing 8% ciclopirox. Several liquid poloxamer 407-based formulations with only 1% CPX completely inhibited fungal growth after 6 days of incubation, whereas the marketed semi-solid formulation did not inhibit fungal growth. Differential scanning calorimetry studies revealing the interaction between the formulations and the SC showed that increasing isopropyl alcohol/propylene glycol concentrations as well as increasing CPX concentrations caused increasing endothermic transition shifts. Moreover, stability studies at 30 °C exhibited only a slight decrease of the CPX amount after 12 months of storage. Each formulation contained >90% of the initial CPX concentration after termination of the stability studies.

Design of lipid microparticle dispersions based on the physicochemical properties of the lipid and aqueous phase.

Lipid microparticle (LMP) dispersions may be utilized as novel pharmaceutical dosage forms for different administration routes. The particle size and particle size distribution of the LMPs can be classified to the most crucial specifications for therapeutical and research applications. The size parameters can be adjusted via the physicochemical properties of the inner lipid and the outer aqueous phase. In the present study, ten different solid lipids with incorporated lecithin and four concentrations of the surfactant poloxamer 407 (P407) were utilized for LMP dispersion preparation. Physicochemical properties of the bulk and dispersed lipid matrices as well as features of the P407 solutions were determined. Correlations between the mean particle size (mean) of the LMPs and the span as parameter for the particle size distribution as responses were identified by plotting against the measured physicochemical parameters. Most significant linear correlations were found between the mean and the micellization onset temperature (Tmicell) in the parent solution and the dynamic viscosity of the emulsifier solution at 25 °C and between the span and the Tmicell in the LMP dispersion. Consequently, P407 micelles as a reservoir for surfactant monomers and the overall viscosity as a separator between newly-formed lipid droplets are fundamental stabilizing parameters.

Applications and limitations of lipid nanoparticles in dermal and transdermal drug delivery via the follicular route.

Lipid nanoparticles (LN) such as solid lipid nanoparticles (SLN) and nanolipid carriers (NLC) feature several claimed benefits for topical drug therapy including biocompatible ingredients, drug release modification, adhesion to the skin, and film formation with subsequent hydration of the superficial skin layers. However, penetration and permeation into and across deeper skin layers are restricted due to the barrier function of the stratum corneum (SC). As different kinds of nanoparticles provide the potential for penetration into hair follicles (HF) LN are applicable drug delivery systems (DDS) for this route in order to enhance the dermal and transdermal bioavailability of active pharmaceutical ingredients (API). Therefore, this review addresses the HF as application site, published formulations of LN which showed follicular penetration (FP), and characterization methods in order to identify and quantify the accumulation of API delivered by the LN in the HF. Since LN are based on lipids that appear in human sebum which is the predominant medium in HF an increased localization of the colloidal carriers as well as a promoted drug release may be assumed. Therefore, sebum-like lipid material and a size of less or equal 640 nm are appropriate specifications for FP of particulate formulations.

In vitro permeation and penetration of ciclopirox olamine from poloxamer 407-based formulations--comparison of isolated human stratum corneum, bovine hoof plates and keratin films.

Fungal infections of skin and/or nails are common diseases resulting in major challenges in topical treatment. Therefore, the objective of the present study was to develop a dermal formulation targeting both tinea pedis and onychomycosis. The antifungal agent ciclopirox olamine (CPX) was incorporated into a variety of poloxamer 407-based formulations and analysed regarding its in vitro permeation and penetration behaviour across keratin films (KF) and bovine hoof plates as artificial nail models as well as human stratum corneum (SC). The novel compositions consisted of poloxamer 407 (P407), double distilled water, propylene glycol, isopropyl alcohol and medium chain triglycerides in given ratios. All the formulations exhibited semi-solid to liquid consistencies and were isotropic under a polarising microscope. Upon CPX incorporation, the formulations became softer and the yield stresses decreased. Increasing temperature led to higher complex viscosities. Permeation coefficients (P) from P407-based formulations across KF and bovine hoof plates and normalised retained CPX amounts in KF and bovine hoof plates were higher in comparison to the nail lacquer Ciclopoli(®) as a marketed reference. Data of KF and bovine hoof plates were comparable, therefore KF are suggested as artificial nail model for in vitro permeation studies besides the well-accepted nail model of bovine hoof plates. With regard to SC permeation, several liquid formulations indicated higher P in comparison to the references Ciclopoli(®) and the antimycotic skin formulation Selergo(®) 1% cream, while the normalised retained API amounts in SC were higher in comparison with Selergo(®) 1% cream or in the same range as Ciclopoli(®).

Cytotoxic effect and mechanism inducing cell death of α-mangostin liposomes in various human carcinoma and normal cells.

The aims of this study were to develop α-mangostin liposomes as well as to evaluate their physicochemical properties and cytotoxic activity. α-Mangostin liposomes were prepared using the reverse-phase evaporation method with lipid composition of phosphatidylcholine to cholesterol at 7 : 3 molar ratios; their physicochemical properties and antiproliferative activity were assessed using an MTT assay in four human carcinoma cells [that is, human lung epithelial carcinoma (Calu-3), human colon carcinoma (HT-29), human breast carcinoma (MCF-7), and human colon carcinoma (Caco-2) cells], and two human normal cells [that is, human dermal fibroblasts (HDF) and human adult low-calcium elevated temperature (HaCaT) keratinocytes]. Determinations of morphological changes and oligonucleosomal DNA fragments were also carried out. The liposomal dispersions obtained were unilamellar vesicles as confirmed by cryotransmission and freeze-fracture electron microscopy with a particle size of 114 nm and a ζ potential of -2.56 mV. The P-NMR spectra showed that α-mangostin molecules orientated in the phospholipid bilayer membrane. The α-mangostin could appreciably be entrapped with an efficiency and loading of 81 and 4%, respectively. The antiproliferative activity of α-mangostin liposomes in various cancer and normal cells showed a dose-dependent inhibition in all treated cell lines. The antiproliferative effect of α-mangostin liposomes was found to be associated with apoptosis, with differences in sensitivity among the cell lines treated.

Comparison of rheological properties, follicular penetration, drug release, and permeation behavior of a novel topical drug delivery system and a conventional cream.

A novel adapalene-loaded solid lipid microparticle (SLMA) dispersion as a topical drug delivery system (TDDS) for follicular penetration has been introduced. The objective of the present study was to investigate the rheological properties, the follicular penetration with differential tape stripping on porcine ear skin, the drug release in sebum and stratum corneum (SC) lipid mixtures, and the permeation behavior across human SC in comparison with a commercially available cream as standard. Physicochemical characterization reveals that adapalene is homogeneously distributed within the SLMA dispersion and chemically stable for at least 24 weeks. The SLMA dispersion shows a lower complex viscosity at 20 °C and a higher one at 32 °C than the cream, while the phase angle of the dispersion is always larger at both temperatures. Both formulations feature an equivalent potential for follicular penetration and deposition. However, the superiority of the SLMA dispersion is based on the preferential drug release in sebum while there is no or just a slight release in SC lipids and no permeation for both formulations. Due to the similarity of the glyceride matrix of the SLMA to sebum components, a targeted drug delivery into sebum and thereby an increased follicular penetration may be facilitated.