1262 Introduction An increasing number of new chemical entities obtained from current drug discovery are poorly water soluble. Oral intake of such compounds can lead to incomplete dissolution or precipitation. Diferent formulation prin- ciples were evaluated to enhance compound solubility in the gastro-intestinal tract 1–3 . Among these formulation approaches, lipid-based systems that can range from simple oil mixtures to more complex self-emulsifying drug delivery systems have become particularly impor- tant 4 . he performance of these drug delivery systems depends on the digestion of lipidic formulation compo- nents 5 . Once an excipient is digested, its functionality in the gastro-intestinal tract is diferent with respect to promoting drug solubility and absorption. he knowl- edge of these changes is important for anticipating the dosage form performance in vivo; therefore, in vitro test- ing of lipolysis has become an important research tool in the evaluation of lipid-based formulations. However, further mechanisms can be of relevance: some excipi- ents are known to promote lymphatic uptake whereas others inluence elux transport or presystemic drug clearance 6,7 . Previous research on in vitro digestion provided viable information about the fate of triglyceride formulations and solubilized drugs in the intestinal tract 8–11 . Lipolysis of pharmaceutical systems appears to be complex because the excipients are not only enzymatic substrates, but they can also act as inhibitors 5,12 . Detection of excipient efects requires not only a sensitive in vitro test, but also the in vitro lipolysis should be robust and reliable to become a modern formulation development tool. RESEARCH ARTICLE In vitro digestion kinetics of excipients for lipid-based drug delivery and introduction of a relative lipolysis half life Yvonne E. Arnold 1,2 , Georgios Imanidis 1,2 , and Martin Kuentz 2 1 University of Basel, Division of Pharmaceutical Technology, Basel, Switzerland and 2 University of Applied Sciences Northwestern Switzerland, Institute of Pharma Technology, Muttenz, Switzerland Abstract Background: Lipid-based drug delivery systems are widely used for enhancing the solubility of poorly water soluble drugs in the gastro-intestinal tract. Following oral intake, lipid systems undergo digestion in the stomach as well as the intestine. Lipolysis is here a complex process at the oil/water interface, inluenced by numerous factors. Purpose: To study the digestibility of nine excipients often used in lipid-based drug delivery systems. In addition, we introduced a mathematical model to describe in vitro lipolysis kinetics. A relative lipolysis half life was deined using the reference excipient medium-chain triglycerides. Methods: Using pH-stat equipment, the NaOH consumption was determined in an in vitro lipolysis assay. Results: We identiied two classes of excipients. Some additives were partially hydrolysed, whereas other excipients displayed complete lipolysis. For the latter class, a simpliied mathematical model provided a good irst approximation of initial lipolysis kinetics. Conclusions: Digestion characterization of excipients is important for the development of lipid-based delivery systems. The applied kinetic model and the concept of a relative lipolysis half life seemed to be promising tools for comparing in vitro lipolysis results. Keywords: Pharmaceutical additives, lipid formulations, lipolysis, biorelevant test, lipolysis degree, kinetic model Address for Correspondence: Prof. Dr. Martin Kuentz, University of Applied Sciences Northwestern Switzerland, Institute of Pharma Technology, Gründenstr 40, CH – 4132 Muttenz, Switzerland. Tel: +41 61 467 46 88. Fax: +41 61 467 47 01. E-mail: martin.kuentz@fhnw.ch (Received 13 July 2011; revised 22 November 2011; accepted 28 November 2011) Drug Development and Industrial Pharmacy, 2012; 38(10): 1262–1269 © 2012 Informa Healthcare USA, Inc. ISSN 0363-9045 print/ISSN 1520-5762 online DOI: 10.3109/03639045.2011.645834 Drug Development and Industrial Pharmacy Downloaded from informahealthcare.com by ZHAW Zurich University of Applied Sciences on 09/17/12 For personal use only.