The Effect of Counterions in Hydrophobic Ion Pairs on Oral Bioavailability of Exenatide.

The aim of this study was to evaluate the potential of -octadecyl sulfate (SOS) as a counterion for hydrophobic ion pairing (HIP) with exenatide-a potent glucagon-like peptide-1 (GLP-1) analogue in the treatment of diabetes mellitus-to improve its oral bioavailability. Exenatide was ion-paired with SOS and docusate (DOC) serving as the gold standard followed by the incorporation in a self-emulsifying drug delivery system (SEDDS) comprising Capmul MCM EP, Captex 355, Kolliphor RH40, and propylene glycol at a mass ratio of 41:15:40:4. The hydrophobicity of exenatide-SOS and exenatide-DOC was characterized by determining the butanol-water partition coefficient (log ).

Cellular uptake of self-emulsifying drug-delivery systems: polyethylene glycol versus polyglycerol surface.

Comparison of the impact of polyethylene glycol (PEG) and polyglycerol (PG) surface decoration on self-emulsifying drug delivery system (SEDDS)-membrane interaction and cellular uptake.   PEG-, PEG/PG- and PG-SEDDS were assessed regarding their self-emulsifying properties, surface charge, bile salt fusibility, cellular uptake and interaction with endosome-mimicking membranes. SEDDS exhibited droplet sizes between 150 and 175 nm, a narrow size distribution and self-emulsified within 7 min.

A gellan gum derivative as in-situ gelling cationic polymer for nasal drug delivery.

The aim of the present study was the development of a novel gellan gum derivative exhibiting mucoadhesive properties for nasal application. Accomplishing this, amino groups have been introduced to the polymeric backbone. The resulting synthesis products were characterized in terms of the amount of attached amino groups, regarding hydration, zeta potential and gel characteristics.

Synthesis and in vitro characterization of a preactivated thiolated acrylic acid/acrylamide-methylpropane sulfonic acid copolymer as a mucoadhesive sprayable polymer.

Aim: Development of a preactivated thiomer as sprayable excipient for mucoadhesive formulations.

Methods: CG4500 (acrylic acid/acrylamide-methyl propane sulfonic acid copolymer) was thiolated by conjugation with L-cysteine and preactivated by further modification with 2-mercaptonicotinic acid (MNA) in a two-step synthesis and characterized regarding degree of modification and cytotoxicity on Caco-2 cells. The mucoadhesive properties of this novel thiomer were evaluated via rheological synergism, tensile and mucosal residence time studies.

Hydrophobic ion pairing (HIP) of (poly)peptide drugs: Benefits and drawbacks of different preparation methods.

In order to incorporate hydrophilic macromolecular drugs into lipid-based formulations (LBF), HIP has shown great potential. In this study, different HIP methods were compared with each other. Hydrophobic complexes were formed between bovine serum albumin (BSA) and either dodecyl sulfate, cetyl trimethylammonium or 1,2-dipalmitoyl-sn-glycero-3-phosphate applying the organic solvent-free method, Bligh-Dyer method and biphasic metathesis reaction either with ethyl acetate or chloroform as organic phase.

Development and In Vitro Evaluation of Stearic Acid Phosphotyrosine Amide as New Excipient for Zeta Potential Changing Self-Emulsifying Drug Delivery Systems.

Purpose: Development of zeta potential changing SEDDS containing newly synthesized derivative stearic acid phosphotyrosine amide.

Methods: Stearoyl chloride was conjugated with phosphotyrosine, which is substrate for the brush border enzyme intestinal alkaline phosphate. The synthesized derivative was implemented in different SEDDS formulations and the zeta potential changing properties and the concluding mucus diffusion abilities were evaluated.

Zeta potential changing nanoemulsions: Impact of PEG-corona on phosphate cleavage.

The aim of this study was to evaluate the impact of a PEG-corona on oily droplets of a nanoemulsion on phosphate cleavage on their surface. A PEG-free nanoemulsion composed of 60% oleic acid, 30% Capmul MCM EP and 10% Span 85 being additionally stabilized by 1% cetyltrimethylammonium bromide (CTAB) and 3% phosphatidic acid (PA) was evaluated regarding phosphate release, zeta potential change and mucus permeation properties. In order to evaluate the impact of PEG-corona on phosphate release 10%, 20% and 30% of polyethoxylated-35 castor oil were incorporated in the nanoemulsion.

Phosphorylated PEG-emulsifier: Powerful tool for development of zeta potential changing self-emulsifying drug delivery systems (SEDDS).

Aim: It was the aim of this study to synthesize a phosphorylated emulsifier possessing a PEG-linker for establishment of a potent zeta potential changing system in self-emulsifying drug delivery systems (SEDDS).

Methods: N,N'-Bis(polyoxyethylene)oleylamine (POA) was phosphorylated utilizing pyrophosphoric acid. Successful synthesis of POA bisphosphate (POAP) was confirmed by NMR and HR CS MAS.

Development and in vitro characterization of an oral self-emulsifying delivery system (SEDDS) for rutin fatty ester with high mucus permeating properties.

The aim of this study was to develop and evaluate a self-emulsifying delivery system (SEDDS) for oral rutin fatty ester administration and to improve its mucus permeating properties by the incorporation of the silicon polymer poly [dimethylsiloxane-co-(3-(2-(2-hydroxyethoxy)ethoxy)propyl]methylsiloxane] (PDMSHEPMS) in the formulation. In order to increase the lipophilicity of the flavonoid and to dissolve it in SEDDS, enzymatic acylation of rutin with lauric acid was catalyzed by lipase from Candida antarctica in acetone. Different formulations were evaluated regarding their emulsifying properties and ability to dissolve the rutin ester.

Development and in vitro evaluation of a self-emulsifying drug delivery system (SEDDS) for oral vancomycin administration.

The aim of this study was to develop a self-emulsifying drug delivery system (SEDDS) containing the glycopeptide antibiotic vancomycin (VAN) with improved intestinal mucosa permeating properties in order to increase oral drug absorption. VAN was effectively incorporated into SEDDS increasing the lipophilicity of the drug via hydrophobic ion pairing (HIP) with cetyltrimethylammonium bromid (CTAB). Newly developed SEDDS formulations containing VAN/CTAB complex were characterized with respect to droplet size, polydispersity index and zeta potential.

Development of self-emulsifying drug delivery systems (SEDDS) for ciprofloxacin with improved mucus permeating properties.

The aim of this study was to develop a self-emulsifying drug delivery system (SEDDS) containing the fluoroquinolone antibiotic ciprofloxacin (CIP) exhibiting highly mucus permeating properties and antimicrobial activity in in vitro models. Various SEDDS formulations were developed and evaluated regarding droplet size, polydispersity index, zeta potential and formulation stability. Furthermore, SEDDS permeating properties were investigated in porcine intestinal mucus, as well as in cystic fibrosis (CF) sputum freshly collected from CF patients using Transwell® setup and single particle tracking (SPT), respectively.

In vivo evaluation of an oral self-emulsifying drug delivery system (SEDDS) for exenatide.

Background: The aim of the study was to develop an oral self-emulsifying drug delivery system (SEDDS) for exenatide and to evaluate its in vivo efficacy.

Methods: Exenatide was lipidised via hydrophobic ion pairing with sodium docusate (DOC) and incorporated in SEDDS consisting of 35% Cremophor EL, 25% Labrafil 1944, 30% Capmul-PG 8 and 10% propylene glycol. Exenatide/DOC was characterized in terms of lipophilicity evaluating the octanol/water phase distribution (logP).