Andrea Rübe1, Sandra Klein, Karsten Mäder. 1. Department of Pharmacy, Institute of Pharmaceutics and Biopharmaceutics, Martin Luther University Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120 Halle/Saale, Germany.
Abstract
PURPOSE: The distribution of drugs between water, oil and mixed micelles after the oral application of lipid-based drug delivery systems affects their absorption rate. Since it has not been previously possible to monitor this process online during in vitro lipolysis, it was our aim to develop a suitable real-time method. MATERIALS AND METHODS: To follow the fate of a co-administered drug during fat digestion, the spin probe tempol benzoate was incorporated as a lipophilic model drug into a long-chain triglyceride (olive oil) and an in vitro digestion test was combined with electron paramagnetic resonance (EPR) spectroscopy (X-Band). Additionally the progression of digestion was determined by means of high performance thin layer chromatography (HPTLC). RESULTS: The spectral shape of the EPR spectrum changed significantly during the digestion process. EPR spectra at all times could be simulated with three species indicating a redistribution of the lipophilic model drug between olive oil, phosphate buffer and mixed micelles formed by bile salts and phospholipids. CONCLUSION: This in vitro real-time analysis could be a very helpful tool to monitor the digestibility of novel lipid-based drug nanocarriers which is an important step to optimize and to predict drug delivery processes. In future the EPR monitoring of fat digestion will be transferred to in vivo experiments.
PURPOSE: The distribution of drugs between water, oil and mixed micelles after the oral application of lipid-based drug delivery systems affects their absorption rate. Since it has not been previously possible to monitor this process online during in vitro lipolysis, it was our aim to develop a suitable real-time method. MATERIALS AND METHODS: To follow the fate of a co-administered drug during fat digestion, the spin probe tempol benzoate was incorporated as a lipophilic model drug into a long-chain triglyceride (olive oil) and an in vitro digestion test was combined with electron paramagnetic resonance (EPR) spectroscopy (X-Band). Additionally the progression of digestion was determined by means of high performance thin layer chromatography (HPTLC). RESULTS: The spectral shape of the EPR spectrum changed significantly during the digestion process. EPR spectra at all times could be simulated with three species indicating a redistribution of the lipophilic model drug between olive oil, phosphate buffer and mixed micelles formed by bile salts and phospholipids. CONCLUSION: This in vitro real-time analysis could be a very helpful tool to monitor the digestibility of novel lipid-based drug nanocarriers which is an important step to optimize and to predict drug delivery processes. In future the EPR monitoring of fat digestion will be transferred to in vivo experiments.
Authors: Christopher J H Porter; Ann Marie Kaukonen; Agnes Taillardat-Bertschinger; Ben J Boyd; Jacquelyn M O'Connor; Glenn A Edwards; William N Charman Journal: J Pharm Sci Date: 2004-05 Impact factor: 3.534