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      Chain length affects pancreatic lipase activity and the extent and pH–time profile of triglyceride lipolysis

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      Experimental data: droplet size and total surface area of the equimolar triglyceride emulsions following the dispersion in the lipolysis buffer (14.74Kb)
      Experimental data: In vitro lipolysis of equimolar amounts of different triglycerides + Back-titration studies (1.970Mb)
      Experimental data: Solubility effect of glyceryl triacetate on the extent of lipolysis (1.141Mb)
      Experimental data: Optimisation of the lipolysis model - 0.5 M NaOH, 1 mL/min maximum rate, 10 μL/min minimum rate (1.018Mb)
      Experimental data: Optimisation of the lipolysis model - 1 M NaOH, 1 mL/min maximum rate, 3 μL/min minimum rate (846.9Kb)
      Experimental data: Optimisation of the lipolysis model - 1 M NaOH, 1 mL/min maximum rate, 10 μL/min minimum rate (573Kb)
      Experimental data: Optimisation of the lipolysis model - 1 M NaOH, 3.5 mL/min maximum rate, 3 μL/min minimum rate (1.028Mb)
      Publication date
      2016-07-01
      Creators
      Gershkovich, Pavel
      Benito, Paloma
      Metadata
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      Description
      Triglycerides (TG) are one of the most common excipients used in oral lipid-based formulations. The chain length of the TG plays an important role in the oral bioavailability of the co-administered drug. Fatty acid (FA) chain-length specificity of porcine pancreatic lipase was studied by means of an in vitro lipolysis model under bio-relevant conditions at pH 6.80. In order to determine the total extent of lipolysis, back-titration experiments at pH 11.50 were performed. Results suggest that there is a specific chain length range (C2–C8) for which pancreatic lipase shows higher activity. This specificity could result from a combination of physicochemical properties of TGs, 2-monoglycerides (2-MGs) and FAs, namely the droplet size of the TGs, the solubility of 2-MGs within mixed micelles, and the relative stability of the FAs as leaving groups in the hydrolysis reaction. During experimentation, it was evident that an optimisation of lipolysis conditions was needed for tighter control over pH levels so as to better mimic in vivo conditions. 1 M NaOH, 3.5 mL/min maximum dosing rate, and 3 μL/min minimum dosing rate were the optimised set of conditions that allowed better pH control, as well as the differentiation of the lipolysis of different lipid loads.
      External URI
      • https://rdmc.nottingham.ac.uk/handle/internal/51
      DOI
      • http://doi.org/10.17639/nott.48
      Related publication DOI
      • 10.1016/j.ejpb.2015.04.027
      Links
      • http://www.sciencedirect.com/science/article/pii/S0939641115002076
      • http://doi.org/10.17639/nott.48
      Subjects
      • Oral medication
      • Lipids
      • Triglycerides -- Pharmacokinetics
      • Drug delivery systems
      • Drug carriers (Pharmacy)
      • Solubility
      • Bioavailability
      • Volumetric analysis
      • Fatty acids
      • Pharmacokinetics
      • Monoglyceride
      • Lipid based drug delivery systems; Poorly water-soluble drugs; Oral bioavailability; Back-titration; Fatty acid; Monoglyceride
      • Subjects Allied to Medicine::Pharmacology, toxicology & pharmacy::Pharmacology, toxicology & pharmacy not elsewhere classified
      • R Medicine::RM Therapeutics. Pharmacology
      • R Medicine::RS Pharmacy and materia medica
      • QS-QZ Preclinical sciences (NLM Classification)::QV Pharmacology
      Divisions
      • University of Nottingham, UK Campus::Faculty of Science::School of Pharmacy
      Deposit date
      2016-07-01
      Data type
      Excel files with raw and processed data corresponding to the publication Benito-Gallo P., et al. Eur J Pharm Biopharm. (2015) 353-62
      Funders
      • Engineering & Physical Sciences Research Council
      Grant number
      • EP/I01375X/1
      Collection dates
      • 2014
      Data collection method
      In vitro lipolysis, DLS
      Resource languages
      • en
      Copyright
      • University of Nottingham
      Publisher
      The University of Nottingham

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