Characterising Lipid Lipolysis and Its Implication in Lipid-Based Formulation Development

Abstract

Abstract. Facing the increasing number of poorly water-soluble drugs, pharmaceutical scientists are required to break new grounds for the delivery of these pharmaceutically problematic drugs. Lipid-based drug delivery systems (LBDDS) have received increased interest as a novel drug delivery platform during the last decades and several successfully marketed products have shown the potential for LBDDS. However, there exists a discrepancy between the clear need for innovative delivery forms and their rational design. In the case of LBDDS, this can be attributed to the complexity of LBDDS after administration. Unlike conventional formulations, LBDDS are susceptible to digestion in the gastrointestinal tract, the interplay of delivery system, drug and physiology ultimately effecting drug disposition. In vitro lipolysis has become an important technique to mimic the enzymatic degradation. For the better understanding of how LBDDS promote drug delivery, in vitro lipolysis requires advanced characterisation methods. In this review, the physiological background of lipid digestion is followed by a thorough summary of the techniques that are currently used to characterise in vitro lipolysis. It would be desirable that the increasing knowledge about LBDDS will foster their rationale development thereby increasing their broader application.KEY WORDS: in vitro digestion; in vitro lipolysis models; lipid-based drug delivery systems; poorly soluble drugs; self-nanoemulsifying drug delivery systems (SNEDDS).

In Vitro Lipolysis Data Does Not Adequately Predict the In Vivo Performance of Lipid-Based Drug Delivery Systems Containing Fenofibrate

“…Throughout the subsequent 60-min intestinal lipolysis, the pH was maintained at 6.5 by the titration of liberated fatty acids with 1 M NaOH, and the lipolysis rate was controlled by the constant addition of 0.5 M calcium chloride (0.09 mL/ min) (23). Background titration experiments were carried out to determine the sodium hydroxide consumption during the unspecific digestion of phospholipids and impurities present in the formulation-free lipolysis media (24). The initial compositions of the gastric and intestinal lipolysis media are compiled in Table II.…”

A method based on 1H NMR spectral data useful to evaluate the hydrolysis level in complex lipid mixtures

“…The technique most commonly employed to estimate hydrolysis level during digestion is the titration of fatty acids released by means of a pH-stat apparatus, in which titration with NaOH is carried out (Brogård, Troedsson, Thuresson, & Ljusberg-Wahren, 2007;Fatouros, Bergenstahl, & Mullertz, 2007;Helbig, Silletti, Timmerman, Hamer, & Gruppen, 2012;Li & McClements, 2010;Zhu, Ye, Verrier, & Singh, 2013). However, it has been pointed out that the accuracy of the pH-stat titration technique in quantifying the fatty acids released during lipid digestion is highly dependent on the ionization of each fatty acid and its availability to be titrated, which is in turn dependent on several factors, including chain length, the pH of the medium and the bile salt and electrolyte concentrations (Sek, Porter, Kaukonen, & Charman, 2002;Thomas, Holm, Rades, & Müllertz, 2012;Zhu et al, 2013). In fact, this methodology is usually performed to monitor lipolysis only during the intestinal step and by using simple solutions (buffers) that do not mimic the composition of in vivo digestion juices, in order to avoid any interference from the complex media (Di Maio & Carrier, 2011).…”

“…Nevertheless, these methodologies are timeconsuming, usually implying many preparation steps, including calibration with standard compounds, and also involving large amounts of polluting organic solvents. Moreover, some authors have reported unspecificity or discrepancies among data obtained when some of the above mentioned techniques are compared (Helbig et al, 2012;Sek et al, 2002;Thomas et al, 2012). Therefore, the need for further research on methodological developments to study lipid hydrolysis is evident.…”

Current Status of Supersaturable Self-Emulsifying Drug Delivery Systems

“…There are several paper including the solid-state characterization techniques used to evaluate drug precipitates during in vitro digestion. Differential scanning calorimetry, powder X-ray diffraction, polarized light microscopy, scanning electron microscopy, and Fourier-transform infrared spectroscopy can be used for solid-state characterization in conjunction with in vitro digestion tests [18,74,75]. From a different perspective, potential polymorphic transitions during precipitation may further complicate supersaturation behavior and warrant solid-state analysis [76,77].…”