Successful development of oral SEDDS: screening of excipients from the industrial point of view.

Oral administration is the most accepted and favored route as various side effects such as fear, pain and risk of infections can be avoided resulting in a comparatively high patient compliance. However, from the industrial point of view the development of oral delivery systems is still challenging as various drugs are poorly soluble as well as slightly permeable leading to low bioavailability. As self-emulsifying drug delivery systems are able to incorporate both hydrophobic and hydrophilic drugs, these carrier systems have received more and more attention within the last years. Based on the broad range of currently available excipients, this review provides a kind of guideline for the selection of excipients useful to improve bioavailability of the drug on the one hand. As the regulatory status of potential excipients are highly important to introduce the formulation on the market, the review is focused on the other hand on excipients listed in the IIG database of the FDA by taking their corresponding maximum concentration into account. Furthermore, the issue of oral sensation and taste masking is discussed useful for the development of intraoral SEDDS.

Zeta potential changing self-emulsifying drug delivery systems containing phosphorylated polysaccharides.

AIM: The aim of the study was to develop novel zeta potential changing self-emulsifying drug delivery systems (SEDDS) containing phosphorylated polysaccharides. METHODS: Starch and hydroxypropyl starch (HPS) were phosphorylated by utilizing phosphorus pentoxide. The modified starches, starch phosphate (SP) and hydroxypropyl starch phosphate (HPSP), were loaded into SEDDS and investigated regarding particle size, zeta potential, stability and cell viability. The release of immobilized phosphate by intestinal alkaline phosphatase (IAP) was analyzed via malachite green assay. In parallel, the resulting shift in zeta potential of SEDDS was determined. Furthermore, Transwell chambers were applied in order to evaluate the mucus diffusion behavior of SEDDS utilizing fluorescein diacetate (FDA) as marker. RESULTS: The amount of attached phosphate for SP and HPSP revealed to be 119µmol/g and 259µmol/g, respectively. SEDDS consisting of 10% glycerol, 30% Capmul MCM, 30% Cremophor EL and 30% Captex 355 showed a droplet size of 39±12nm, stability over 240min and no significant decrease in cell viability within the applied concentrations. SEDDS containing 3mg/ml HPSP with a phosphate release of 204µmol/g, demonstrated a shift in zeta potential from -6.3mV to +1.0mV applying isolated IAP. Zeta potential changing SEDDS achieved a 2.5-fold and 5.4-fold higher amount of diffused FDA compared to the references within mucus permeation studies. CONCLUSION: SEDDS containing HPSP represent comparable high mucus diffusion properties emphasized by a highly significant change in zeta potential.

Combination of SEDDS and Preactivated Thiomer Technology: Incorporation of a Preactivated Thiolated Amphiphilic Polymer into Self-Emulsifying Delivery Systems.

PURPOSE: The aim of the study was to create novel mucoadhesive drug delivery systems by incorporating amphiphilic hydrophobically modified, thiolated and preactivated polymers (preactivated thiomers) into self-emulsifying drug delivery systems (SEDDS). METHODS: L-Cysteine methyl ester was covalently attached to the polymeric backbone of Pemulen TR-2 and preactivated using 2-mercaptonicotinic acid (2-MNA). These thiomers were incorporated in a concentration of 0.3% (w/v) into SEDDS. The size distribution and the zeta potential of the emulsions were evaluated by dynamic light scattering. Mucoadhesive properties of thiomers-SEDDS spiked with FDA (fluorescein diacetate) were examined utilizing rheological measurement, permeation studies and in vitro residence time study on porcine mucosa. Cell viability tests were additionally performed. RESULTS: 734 ± 58 µmol L-Cysteine methyl ester and 562 ± 71 µmol 2-MNA could be attached per gram polymer of Pemulen TR-2. Emulsions exhibited a droplet size range between 180 and 270 nm. Blank SEDDS possessed a zeta potential value between -5.7 and -8.6 mV, whereas thiomers-SEDDS between -14.6 and -17.2 mV. Viscous modulus of thiomer and preactivated thiomer containing SEDDS-mucus mixture was 8-fold and 11-fold increased in comparison to reference. The amount of FDA permeated the mucus layer was 2-fold lower in case of thiomers-SEDDS compared to blank SEDDS. A prolonged residence time was observed for thiomers-SEDDS over 45 min. During cell viability studies no severe toxic effects were detected. CONCLUSION: The novel developed SEDDS with incorporated thiomers might be a promising tool for mucoadhesive oral drug delivery.

Nanoparticular delivery system for a secretoneurin derivative induces angiogenesis in a hind limb ischemia model.

Common therapeutic strategies for peripheral arterial disease often fail to re-establish sufficient blood flow within legs and feet of patients for avoiding critical limb ischemia, what is characterized by a substantial risk for amputation. The neuropeptide secretoneurin induces angiogenesis in models of limb and myocardial ischemia and might be a promising tool in the treatment of patients without the option of revascularization therapy for severe ischemia. Within this manuscript, the biologically active part of secretoneurin was identified, modified by induction of a cysteine residue to gain higher stability against enzymatic degradation and further packed into S-protected thiolated chitosan nanoparticles, which enable intra-muscular application of secretoneurin. Secretoneurin nanoparticles restored blood flow in a mouse hind limb ischemia model within one week, whereas control particles did not. In vitro testing also revealed the angiogenic, antiapoptotic and proliferative effects of the new secretoneurin derivate, as tested in primary human umbilical vein endothelial cells. With the work from this study we provide a new promising tool for treatment of peripheral arterial disease.