Jannin V

References (6)

Title : In vitro evaluation of the gastrointestinal delivery of acid-sensitive pancrelipase in a next generation enteric capsule using an exocrine pancreatic insufficiency disease model - Jannin_2023_Int.J.Pharm_630_122441
Author(s) : Jannin V , Duysburgh C , Gonzalez V , Govaert M , Agisson M , Marzorati M , Madit N
Ref : Int J Pharm , 630 :122441 , 2023
Abstract : The dissolution characteristics of five capsules (Next Generation Enteric [NGE], Vcaps(a) Enteric [VCE], VCE DUOCAP(a) [VCE/VCE] system, Hard Gelatin Capsule [HGC] as negative control, and Creon(a) 10,000 U as market reference) were evaluated using an in vitro simulation of the stomach and upper intestinal tract with an acidic duodenal incubation (pH 4.5 for the first 10 min, pH 6 for the remaining 17 min) to simulate exocrine pancreatic insufficiency. Caffeine was a marker of capsule dissolution, and tributyrin to butyrate conversion measured pancrelipase activity. All capsules were filled with pancrelipase; the NGE, VCE, VCE/VCE, and HGC capsules also contained 50 mg caffeine. Caffeine was released first from the HGC capsule, followed by the VCE, NGE, and VCE/VCE capsules. Pancrelipase activity followed this trend and demonstrated a similar activity level over time for the NGE, VCE/VCE, and Creon(a) capsules. The HGC formulation confirmed gastric degradation of unprotected pancrelipase. NGE capsules provided similar protection to the simple fill formulation as observed for the complex formulation of the Creon(a) capsule in a setting with increased pepsin activity and may hasten the time needed to go from formula development to first-in-human studies for pH sensitive drugs or those requiring small intestine targeting.
ESTHER : Jannin_2023_Int.J.Pharm_630_122441
PubMedSearch : Jannin_2023_Int.J.Pharm_630_122441
PubMedID: 36442722

Title : In vitro lipolysis tests on lipid nanoparticles: comparison between lipase\/co-lipase and pancreatic extract - Jannin_2015_Drug.Dev.Ind.Pharm_41_1582
Author(s) : Jannin V , Dellera E , Chevrier S , Chavant Y , Voutsinas C , Bonferoni C , Demarne F
Ref : Drug Dev Ind Pharm , 41 :1582 , 2015
Abstract : Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLC) are lipid nanocarriers aimed to the delivery of drugs characterized by a low bioavailability, such as poorly water-soluble drugs and peptides or proteins. The oral administration of these lipid nanocarriers implies the study of their lipolysis in presence of enzymes that are commonly involved in dietary lipid digestion in the gastrointestinal tract. In this study, a comparison between two methods was performed: on one hand, the lipase/co-lipase assay, commonly described in the literature to study the digestion of lipid nanocarriers, and on the other hand, the lipolysis test using porcine pancreatic extract and the pH-stat apparatus. This pancreatic extract contains both the pancreatic lipase and carboxyl ester hydrolase (CEH) that permit to mimic in a biorelevant manner the duodenal digestive lipolysis. The test was performed by means of a pH-stat apparatus to work at constant pH, 5.5 or 6.25, representing respectively the fasted or fed state pH conditions. The evolution of all acylglycerol entities was monitored during the digestion by sampling the reaction vessel at different time points, until 60 min, and the lipid composition of the digest was analyzed by gas chromatography. SLN and NLC systems obtained with long-chain saturated acylglycerols were rapidly and completely digested by pancreatic enzymes. The pH-stat titration method appears to be a powerful technique to follow the digestibility of these solid lipid-based nanoparticles.
ESTHER : Jannin_2015_Drug.Dev.Ind.Pharm_41_1582
PubMedSearch : Jannin_2015_Drug.Dev.Ind.Pharm_41_1582
PubMedID: 25342478

Title : Polyoxylglycerides and glycerides: effects of manufacturing parameters on API stability, excipient functionality and processing - Jannin_2014_Int.J.Pharm_466_109
Author(s) : Jannin V , Rodier JD , Musakhanian J
Ref : Int J Pharm , 466 :109 , 2014
Abstract : Lipid-based formulations are a viable option to address modern drug delivery challenges such as increasing the oral bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs), or sustaining the drug release of molecules intended for chronic diseases. Esters of fatty acids and glycerol (glycerides) and polyethylene-glycols (polyoxylglycerides) are two main classes of lipid-based excipients used by oral, dermal, rectal, vaginal or parenteral routes. These lipid-based materials are more and more commonly used in pharmaceutical drug products but there is still a lack of understanding of how the manufacturing processes, processing aids, or additives can impact the chemical stability of APIs within the drug product. In that regard, this review summarizes the key parameters to look at when formulating with lipid-based excipients in order to anticipate a possible impact on drug stability or variation of excipient functionality. The introduction presents the chemistry of natural lipids, fatty acids and their properties in relation to the extraction and refinement processes. Then, the key parameters during the manufacturing process influencing the quality of lipid-based excipients are provided. Finally, their critical characteristics are discussed in relation with their intended functionality and ability to interact with APIs and others excipients within the formulation.
ESTHER : Jannin_2014_Int.J.Pharm_466_109
PubMedSearch : Jannin_2014_Int.J.Pharm_466_109
PubMedID: 24607211

Title : In vitro digestion of the self-emulsifying lipid excipient Labrasol() by gastrointestinal lipases and influence of its colloidal structure on lipolysis rate - Fernandez_2013_Pharm.Res_30_3077
Author(s) : Fernandez S , Jannin V , Chevrier S , Chavant Y , Demarne F , Carriere F
Ref : Pharm Res , 30 :3077 , 2013
Abstract : PURPOSE: Labrasol((a)) is a self-emulsifying excipient used to improve the oral bioavailability of poorly water-soluble drugs. It is a mixture of acylglycerols and PEG esters, these compounds being substrates for digestive lipases. The characterization of Labrasol((a)) gastrointestinal lipolysis is essential for understanding its mode of action. METHODS: Labrasol((a)) lipolysis was investigated using either individual enzymes (gastric lipase, pancreatic lipase-related protein 2, pancreatic carboxyl ester hydrolase) or a combination of enzymes under in vitro conditions mimicking first the gastric phase of lipolysis and second the duodenal one. Specific methods for quantifying lipolysis products were established in order to determine which compounds in Labrasol((a)) were preferentially hydrolyzed. RESULTS: Gastric lipase showed a preference for di- and triacylglycerols and the main acylglycerols remaining after gastric lipolysis were monoacylglycerols. PEG-8 diesters were also hydrolyzed to a large extent by gastric lipase. Most of the compounds initially present in Labrasol((a)) were found to be totally hydrolyzed after the duodenal phase of lipolysis. The rate of Labrasol((a)) hydrolysis by individual lipases was found to vary significantly with the dilution of the excipient in water and the resulting colloidal structures (translucent dispersion; opaque emulsion; transparent microemulsion), each lipase displaying a distinct pattern depending on the particle size. CONCLUSIONS: The lipases with distinct substrate specificities used in this study were found to be sensitive probes of phase transitions occurring upon Labrasol((a)) dilution. In addition to their use for developing in vitro digestion models, these enzymes are interesting tools for the characterization of self-emulsifying lipid-based formulations.
ESTHER : Fernandez_2013_Pharm.Res_30_3077
PubMedSearch : Fernandez_2013_Pharm.Res_30_3077
PubMedID: 23636839
Gene_locus related to this paper: human-PNLIPRP2

Title : Lipolysis of the semi-solid self-emulsifying excipient Gelucire 44\/14 by digestive lipases - Fernandez_2008_Biochim.Biophys.Acta_1781_367
Author(s) : Fernandez S , Rodier JD , Ritter N , Mahler B , Demarne F , Carriere F , Jannin V
Ref : Biochimica & Biophysica Acta , 1781 :367 , 2008
Abstract : 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.
ESTHER : Fernandez_2008_Biochim.Biophys.Acta_1781_367
PubMedSearch : Fernandez_2008_Biochim.Biophys.Acta_1781_367
PubMedID: 18571509

Title : Comparative study on digestive lipase activities on the self emulsifying excipient Labrasol, medium chain glycerides and PEG esters - Fernandez_2007_Biochim.Biophys.Acta_1771_633
Author(s) : Fernandez S , Jannin V , Rodier JD , Ritter N , Mahler B , Carriere F
Ref : Biochimica & Biophysica Acta , 1771 :633 , 2007
Abstract : Labrasol is a lipid-based self-emulsifying excipient used in the preparation of lipophilic drugs intended for oral delivery. It is mainly composed of PEG esters and glycerides with medium acyl chains, which are potential substrates for digestive lipases. The hydrolysis of Labrasol by porcine pancreatic extracts, human pancreatic juice and several purified digestive lipases was investigated in the present study. Classical human pancreatic lipase (HPL) and porcine pancreatic lipase, which are the main lipases involved in the digestion of dietary triglycerides, showed very low levels of activity on the entire Labrasol excipient as well as on separated fractions of glycerides and PEG esters. On the other hand, gastric lipase, pancreatic lipase-related protein 2 (PLRP2) and carboxyl ester hydrolase (CEH) showed high specific activities on Labrasol. These lipases were found to hydrolyze the main components of Labrasol (PEG esters and monoglycerides) used as individual substrates, whereas these esters were found to be poor substrates for HPL. The lipolytic activity of pancreatic extracts and human pancreatic juice on Labrasol(R) is therefore mainly due to the combined action of CEH and PLRP2. These two pancreatic enzymes, together with gastric lipase, are probably the main enzymes involved in the in vivo lipolysis of Labrasol taken orally.
ESTHER : Fernandez_2007_Biochim.Biophys.Acta_1771_633
PubMedSearch : Fernandez_2007_Biochim.Biophys.Acta_1771_633
PubMedID: 17418634