A novel cubic phase of medium chain lipid origin for the delivery of poorly water soluble drugs.
The existence of a novel cubic liquid crystalline phase is described within the pseudo-ternary system comprising lauric acid, monolaurin, and simulated endogenous intestinal fluid (SEIF). This phase behaviour has been characterized using cross-polarizing light microscopy (CPLM), and the structure of the cubic phase identified by small angle X-ray scattering (SAXS). The presence of the cubic phase was found to be temperature sensitive within the 20-37 degrees C range making it putative material for in situ gelation purposes. The cubic phase was shown to have a high capacity to solubilise a model poorly water-soluble drug, cinnarizine, and initial in vitro release data highlight the potential of this phase to provide sustained release. Absorption of cinnarizine from the cubic phase was studied in an unconscious rat model via duodenal administration and blood sampling via the carotid artery. The rate of absorption was significantly reduced when compared to a simple suspension formulation, a likely combination of retarded erosion of the cubic phase together with hindered drug release from the cubic matrix. The results of this study suggest that this cubic phase may potentially be of benefit in the delivery of poorly water-soluble compounds due to its high loading capacity and potential for sustained release. The ability to manipulate this system using temperature may warrant further interest in delivery applications via other routes of administration.
Kossena
Greg A
GA
Department of Pharmaceutics, Victorian College of Pharmacy, Monash University (Parkville Campus), 381 Royal Pde, Parkville, 3052, Australia.
Charman
William N
WN
Boyd
Ben J
BJ
Porter
Christopher J H
CJ
D000818:Animals; D001315:Australia; D002404:Catheterization / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods / Q000639:trends*; D002936:Cinnarizine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D003460:Crystallization; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004386:Duodenum / Q000187:drug effects; D005989:Glycerides / Q000737:chemistry / Q000493:pharmacokinetics*; D057927:Hydrophobic and Hydrophilic Interactions; D007419:Intestinal Secretions / Q000737:chemistry; D007848:Laurates / Q000737:chemistry / Q000493:pharmacokinetics*; D007850:Lauric Acids / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D008859:Microscopy, Polarization / Q000379:methods; D050178:Monoglycerides; D051381:Rats; D017207:Rats, Sprague-Dawley; D013535:Suspensions / Q000008:administration & dosage / Q000493:pharmacokinetics
D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005989:Glycerides; D007848:Laurates; D007850:Lauric Acids; D050178:Monoglycerides; D013535:Suspensions; C030358:lauric acid; C020777:monolaurin; D002936:Cinnarizine