Glyceryl dibehenate, a glyceride with a high melting point used as a modified release agent or lubricant in tablets. It can also be used in lipid coating technologies and as a lipid carrier for nanoparticles. Additionally, it can act as a lipid carrier former for solid lipid nanoparticle (SLN) and nanostructured lipid carrier (NLC), and a coating agent for taste masking and protection of sensitive APIs.
Fig.1 Chemical structure of glyceryl dibehenate.
SLN containing rifabutin (RFB), with pulmonary administration purposes, was developed through a technique that avoids the use of organic solvents or sonication. RFB-loaded glyceryl dibehenate and glyceryl tristearate SLN were successfully incorporated in mannitol and trehalose microspheres using a spray drying process, resulting in dry powders with suitable properties for pulmonary administration. This method allows to overcome stability issues of liquid nanoparticle formulations, as well as to reach deep lung deposition upon inhalation. In vitro results confirmed that the micro-nanoformulations kept the antimycobacterial activity of RFB. In vivo studies demonstrated that the dry powder was an effective formulation to deliver RFB to the lung, although relevant quantities were also detected in the liver and spleen. The RFB in microencapsulated-glyceryl dibehenate SLN reduced the growth index of the M. tuberculosis infection in all studied organs compared to non-treated animals. Thereby, it was confirmed that these microencapsulated SLN are a promising platform for pulmonary delivery of therapeutic antibiotics for the treatment of mycobacterial infections in the lung, contributing to improved chemotherapy of TB.
Fig.2 Confocal imaging of dry powders: mannitol microspheres containing (A) glyceryl dibehenate SLN and (B) glyceryl tristearate SLN and trehalose microspheres containing (C) glyceryl dibehenate SLN and (D) glyceryl tristearate SLN. SLN were labeled with coumarin-6 (green channel) and excipients were stained with Bodipy (red channel). (Gaspar, 2017)
Solid lipid excipients composed of long-chain fatty acids are classically used for sustained-release and SLN formulations. These lipids are considered non-erodible and non-digestible. Drug sustained-release or drug vectorization can only be effective if the lipid matrix/nanoparticle retains its shape during its transit through the gastrointestinal tract. SLN comprising only glyceryl dibehenate (Compritol 888 ATO) produced by Spray-Flash Evaporation (SFE) has a mean particle size between 235 and 411 nm depending on process parameters. These nanoparticles were not digested by lipases. The presence of surfactant at the lipid/water interface of the SLN seems to be mandatory to allow the adsorption of the lipase and the degradation of glyceryl behenate. Glyceryl dibehenate as a solid particle-even as a SLN-is not digested by pancreatin during in vitro lipolysis test.
Fig.3 SEM-FEG images of SLN of Compritol 888 ATO obtained by SFE with various concentrations of the lipid excipient in dichloromethane. (Jannin, 2018)
Creative Biolabs is a world-leading biotechnology company that has been at the forefront of mRNA research for years. Our team of highly qualified and experienced technical staff will work with you to develop and deliver testing and analytical solutions to add value to your product or project. Please contact us for more information and a detailed quote.
References
