Chitosan-glycolic acid: a possible matrix for progesterone delivery into skin.

BACKGROUND: Chitosan-EDTA is an interesting matrix for dermal delivery; however, the adhesiveness is too small. Therefore, the purpose of this study was to investigate chitosan-glycolic acid as possible dermal matrix for progesterone in comparison to chitosan-EDTA and carrageenan. METHOD: After preparation of the chitosan-glycolic acid salt and characterization by NMR and FTIR, tensile studies using porcine skin and rheology measurements as well as standard diffusion experiments using dermatomed porcine skin were performed. RESULTS: Results showed an improved skin adhesiveness of chitosan-glycolic acid and increased viscosity. Skin diffusion studies indicated the highest cumulative permeation of progesterone after 48 hours from chitosan-glycolic acid followed by carrageenan and chitosan-EDTA. A possible explanation might be a longer residence time on skin caused by the higher adhesiveness and with it higher progesterone skin permeation. CONCLUSION: Chitosan-glycolic acid can be recommended as a suitable polymer for hydrogels and an adhesive matrix for a transdermal application of progesterone exhibiting excellent skin adhesiveness and permeation properties.

The advantage of polymer addition to a non-ionic oil in water microemulsion for the dermal delivery of progesterone.

The influence of progesterone on the physicochemical behaviour of the o/w microemulsion consisting of the non-ionic surfactant polyoxyethylene-10-dodecyl ether, tributyrin and water was investigated. Thereby no significant influence could be detected in terms of droplet size, zeta potential, conductivity and pH by progesterone. However the chemical stability of progesterone was insufficient during the storage of 6 months. Therefore, two different polymeric agents, named silicon dioxide and polymeric emulsifier, were added to the progesterone containing microemulsions. These polymers increased the chemical stability of progesterone significantly. Moreover the polymeric additives improved the skin permeation 1.24- and 1.63-fold and decreased the skin retention in relation to the pure microemulsion. The polymer-stabilized progesterone microemulsions are interesting vehicles for skin application of progesterone.

The influence of selected steroid hormones on the physicochemical behaviour of DPPC liposomes.

The physicochemical properties of DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine) liposomes used for topical application are pharmaceutically important. Therefore the aim of our study was to establish rapid and efficient methods for the exact characterisation of the physicochemical properties of extruded DPPC liposomes containing low concentration (0.5%, w/w) of different, therapeutically interesting steroid hormones, named 17-beta-estradiol, cpa (cyproterone acetate) and finasteride. In a first step it could be shown that all drugs influenced the liposome size and changed the zeta potential compared to the placebo formulations. Our further analytical strategy was to use micro-calorimetry and ATR-FTIR (Fourier transformed infrared spectroscopy), two powerful and non-destructive methods to confirm the drug incorporation into the liposomes by proving interactions between the phospholipids and the steroids. Thereby it was even possible to localize the location of interaction. The characteristic phase transition temperatures of the phospholipid were decreased by the hormones which was detected by micro-DSC (differential scanning calorimetry). The results of the ATR-FTIR measurements indicated shifts of the specific lipid peaks, the C=O stretching bands and PO(2)(-) antisymmetric double stretching band, in the gel and liquid crystalline phase. A polar as well as a non-polar interaction could be proven. It could be shown that the investigated steroid hormones changed the physical properties of the phospholipid bilayers.

Comparative characterization of the physicochemical behavior and skin permeation of extruded DPPC liposomes modified by selected additives.

The purpose of the present study was to analyze the influence of cholesterol (CHOL), stearylamine (SA), dicetyl phosphate (DCP), and xylenesulfonic acid sodium salt (SXS) in extruded DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine) liposomes on their size, shape, and skin permeation of the model drug progesterone. The additives were incorporated in different molar ratios in relation to the phospholipid content. It could be proven that different molar ratios of the additives to lipids were able to modify liposome size, zeta potential, and the characteristic phase transition temperature of the lipids. In standard skin diffusion experiments SA and SXS increased the progesterone permeation two- to fourfold respectively after 48 h compared to the control.

Evaluation of an eucalyptus oil containing topical drug delivery system for selected steroid hormones.

In the present study the permeation and the chemical stability of 17-beta-estradiol, progesterone, cyproterone acetate and finasteride incorporated in an eucalyptus oil containing microemulsion system have been investigated. The formulations contained 1% (w/w) of the steroid hormones. Self diffusion coefficients determined by pulsed-field-gradient spin echo NMR spectroscopy were used to characterise the microemulsion. From these results a bicontinuous structure is proposed for the multicomponent system. However a correlation between the self diffusion of the hormones in the vehicle and the transdermal flux was not indicated. Explanations for this were self assembling, formation of aggregates between the components of the microemulsion and drugs and different effects because of different solubility of the drugs. By addition of certain polymers the skin permeation rates could be improved with exception of cyproterone acetate. Beside standard diffusion experiments, the residual drug content in the skin was investigated. Drug stability was monitored by analysing the steroid hormone content in the different formulations over an observation period of 6 weeks and could be improved by polymers. In addition, viscosity measurements were performed. They indicated an influence of the polymers and drugs on the viscosity in all formulations.

Skin permeation of different steroid hormones from polymeric coated liposomal formulations.

In this study, the effect of various polymers (polycarbophil, chitosan-EDTA, polymeric emulsifier and carrageenan) on the permeation, the chemical and microbial stability of 17-beta-estradiol, progesterone, cyproterone acetate (cpa) and finasteride incorporated in DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine) liposomes has been investigated. The liposomes contained 1% (w/w) of the steroid hormones. Standard diffusion experiments were performed. Drug stability was monitored by analysing the steroid hormone content in the different formulations over a time period of 8 weeks and visually inspecting for microbial contamination. In addition, viscosity measurements were performed. The permeation rate could be improved by addition of polymeric agents depending on their type and drug. In all tested formulations, finasteride exhibited the highest diffusion. Both the chemical and the microbial stability of the hormones were significantly improved by the polymers in comparison to the pure liposomes after an observation period of 8 weeks. After that time microbial stability was still evident for all semisolid formulations. In contrast to this in the pure liposomes already after 2 weeks the steroid drugs showed complete insufficient chemical stability and microbial contamination. Additional rheological measurements indicated an influence of the polymers and drugs on the viscosity in all formulations. The elasticity predominated in nearly all polymeric formulations.