Examining the gastrointestinal transit of lipid-based liquid crystalline systems using whole-animal imaging.
Lipid-based liquid crystalline (LC) systems have the potential to sustain the oral absorption of poorly water-soluble drugs in vivo, facilitating slow drug release from their complex internal structure. To further evaluate the dynamic relationship between gastric retention and sustained drug absorption for these systems, this study aimed to explore non-invasive X-ray micro-CT imaging as an approach to assess gastric retention. Pharmacokinetic studies were also conducted with cinnarizine-loaded LC formulations to correlate gastric retention of the formulation to drug absorption. The in vivo studies demonstrated the interplay between gastric retention and drug absorption based on the digestibility of the LC structures. An increase in non-digestible phytantriol (PHY) composition in the formulation relative to digestible glyceryl monooleate (GMO) increased the gastric retention, with 68 ± 4 % of formulation intensity remaining at 8 h for 85 % w/w PHY, and 26 ± 9 % for 60 % w/w PHY. Interestingly, it was found that PHY 30 % w/w in GMO provided the highest bioavailability for cinnarizine (CZ) amongst the other combinations, including GMO alone. The studies demonstrated that combining digestible and non-digestible lipids into LC systems allowed for an optimal balance between sustaining drug absorption whilst increasing plasma concentration (C max) over time, leading to enhanced oral bioavailability. The results demonstrate the potential for utilising non-invasive X-ray micro-CT imaging to dynamically assess the GI transit of orally administered liquid crystal-forming formulations.
Drug Delivery Disposition and Dynamics - Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, Victoria, 3052, Australia.
Anna C
AC
Pham
Drug Delivery Disposition and Dynamics - Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, Victoria, 3052, Australia. tri-hung.nguyen@monash.edu.
Tri-Hung
TH
Nguyen
Drug Discovery Biology - Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, Victoria, 3052, Australia.
Cameron J
CJ
Nowell
Medicinal Chemistry - Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, Victoria, 3052, Australia.
Bim
B
Graham
Drug Delivery Disposition and Dynamics - Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, Victoria, 3052, Australia. ben.boyd@monash.edu.|ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, Victoria, 3052, Australia. ben.boyd@monash.edu.
Ben J
BJ
Boyd
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002936:Cinnarizine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D016503:Drug Delivery Systems / Q000379:methods; D005233:Fatty Alcohols / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005772:Gastrointestinal Transit; D005989:Glycerides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D050866:Liquid Crystals; D051381:Rats; D017207:Rats, Sprague-Dawley; D051598:Whole Body Imaging; D055114:X-Ray Microtomography
D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005233:Fatty Alcohols; D005989:Glycerides; D002936:Cinnarizine; C508873:3,7,11,15-tetramethyl-1,2,3-hexadecanetriol; C005953:monoolein
Gastrointestinal transit; Glyceryl monooleate; Liquid crystalline; Oral drug delivery; Phytantriol; Sustained release; X-ray computed tomography