Development and in vitro characterisation of an oral self-emulsifying delivery system for daptomycin.
It was the aim of this study to develop an oral self-emulsifying drug delivery system (SEDDS) for the peptide drug daptomycin exhibiting an anionic net charge. Drug lipophilicity was increased by hydrophobic ion pairing with cationic surfactant dodecylamine hydrochloride in molar ratio of surfactant to peptide 5:1. Log P (octanol/water) of -5.0 was even raised to +4.8 due to complexation with dodecylamine hydrochloride. Various SEDDS formulations were developed and characterised regarding emulsification properties, droplet size, polydispersity index and zeta potential. When the daptomycin dodecylamine complex (DAP/DOA) was dissolved in a formulation containing 35% Dermofeel MCT, 30% Capmul MCM and 35% Cremophor RH40, a maximum payload of even 8.0% (w/w) corresponding to 5.5% pure daptomycin was achieved. The formulation was degraded by lipase within 90min. Release studies of daptomycin from this formulation emulsified in 50mM phosphate buffer pH6.8 demonstrated a sustained drug release for at least six hours. Moreover, SEDDS exhibited also mucus permeating properties as well as a protective effect towards drug degradation by α-chymotrypsin. According to these results, SEDDS containing 8% DAP/DOA complex may be considered as a new potential oral delivery system for daptomycin.
Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
Ožbej
O
Zupančič
Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
Alexandra
A
Partenhauser
Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
Hung Thanh
HT
Lam
Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
Julia
J
Rohrer
Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria. Electronic address: andreas.bernkop@uibk.ac.at.
Andreas
A
Bernkop-Schnürch
D020003:1-Octanol / Q000737:chemistry; D000284:Administration, Oral; D000588:Amines / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000378:metabolism; D002918:Chymotrypsin / Q000737:chemistry; D017576:Daptomycin / Q000737:chemistry* / Q000378:metabolism; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004655:Emulsions; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D008049:Lipase / Q000737:chemistry; D010539:Permeability; D013552:Swine; D014867:Water / Q000737:chemistry
D000588:Amines; D000900:Anti-Bacterial Agents; D004655:Emulsions; D014867:Water; D008049:Lipase; D002918:Chymotrypsin; C117608:alpha-chymotrypsin; D020003:1-Octanol; D017576:Daptomycin; C003935:dodecylamine
Mucus permeation; Oral peptide delivery; Pancreatic lipase; Payload; Self-emulsifying drug delivery systems; α-Chymotrypsin