Lipolysis of the semi-solid self-emulsifying excipient Gelucire ® 44/14 by digestive lipases

• Published in: Biochimica et biophysica acta Vol. 1781; no. 8; pp. 367 - 375
• Main Authors: Fernandez, Sylvie, Rodier, Jean-David, Ritter, Nicolas, Mahler, Bruno, Demarne, Frédéric, Carrière, Frédéric, Jannin, Vincent
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-08-2008
• Subjects: Animals; Caprylates - metabolism; Digestive System - enzymology; Emulsifying Agents - metabolism; Esters - metabolism; Excipients - metabolism; Fatty Acids - metabolism; Glycerides - metabolism; Humans; Hydrogen-Ion Concentration; Lipase; Lipase - metabolism; Lipolysis; Macrogolglycerides; Oral drug delivery; Pancreatic Juice - enzymology; Polyethylene Glycols - metabolism; Semi-solid excipient, PEG esters; Substrate Specificity; Tissue Extracts; Macrogolglycerides; Oral drug delivery; Lipase; Lipolysis; Semi-solid excipient, PEG esters
• ISSN: 1388-1981; 0006-3002; 1879-2618
• DOI: 10.1016/j.bbalip.2008.05.006

Gelucire
® 44/14 is a semi-solid self-emulsifying excipient used for the oral delivery of poorly water-soluble drugs. It is composed of C8-C18 acylglycerols and PEG-32 esters, all of which are potential substrates for digestive lipases. Here we studied the lipolysis of Gelucire
® 44/14 by porcine pancreatic extracts, human pancreatic juice and several purified digestive lipases. Human pancreatic lipase (HPL), the main lipase involved in the digestion of triacylglycerols, did not show any significant activity on Gelucire
® 44/14 or on either of its individual compounds, C8-C18 acylglycerols and PEG-32 esters. Other pancreatic lipases such as human pancreatic lipase-related protein 2 (HPLRP2) showed low activity on Gelucire
® 44/14 although the highest activity of HPLRP2 was that observed on the C8-C18 acylglycerol fraction, which accounts for 20% (w/w) of Gelucire
® 44/14. In addition, HPLRP2 showed low activities on the PEG-32 esters, whether these were tested individually or mixed together. Carboxyl ester hydrolase (CEH) showed high activity on Gelucire
® 44/14, and the highest activities of CEH were those recorded on the total PEG-32 ester fraction and on each individual PEG-32 ester, except for PEG-32 monostearate. The highest activity of all the enzymes tested was that of dog gastric lipase (DGL) on Gelucire
® 44/14, although DGL showed low activity on the PEG-32 ester fraction and on each individual PEG-32 ester. We compared the lipolysis of Gelucire
® 44/14 with that of Labrasol
®, another self-emulsifying excipient, which is liquid at room temperature. Human pancreatic juice showed similar rates of activity on both Gelucire
® 44/14 and Labrasol
®. This finding means that these excipients are hydrolyzed in vivo during pancreatic digestion, mainly by CEH in the case of Gelucire
® 44/14 and by both HPLRP2 and CEH in that of Labrasol
®, whereas HPL showed very low activities on each of these two excipients. This is the first time the effects of PEG and acyl chain length on the lipolytic activity of digestive lipases on PEG esters have been investigated.