Insights into drug precipitation kinetics during in vitro digestion of a lipid-based drug delivery system using in-line raman spectroscopy and mathematical modeling

Pharmaceutical Research

Volumn 30, Issue 12, 2013, Pages 3114-3130

  Stillhart, Cordula ^a,b   Imanidis, Georgios ^a,b   Kuentz, Martin ^a  

^a UNIVERSITY OF APPLIED SCIENCES AND ARTS NORTHWESTERN SWITZERLAND   (Switzerland)

^b UNIVERSITY OF BASEL   (Switzerland)

Author keywords

in vitro lipolysis; kinetics of precipitation; lipid based drug delivery systems; Raman spectroscopy; supersaturation

Indexed keywords

FATTY ACID; FENOFIBRATE; PHOSPHATIDYLCHOLINE; TAURODEOXYCHOLIC ACID;

ARTICLE; CRYSTALLIZATION; DRUG DELIVERY SYSTEM; DRUG MONITORING; DRUG PRECIPITATION; DRUG SOLUBILITY; IN VITRO STUDY; LIGHT SCATTERING; LIPOLYSIS; MATHEMATICAL MODEL; NANOFILTRATION; PRECIPITATION; PRIORITY JOURNAL; QUANTITATIVE ANALYSIS; RAMAN SPECTROMETRY; ULTRACENTRIFUGATION;

CHEMICAL PRECIPITATION; CRYSTALLIZATION; DRUG CARRIERS; FENOFIBRATE; HYPOLIPIDEMIC AGENTS; KINETICS; LIPIDS; LIPOLYSIS; MODELS, CHEMICAL; SOLUBILITY; SPECTRUM ANALYSIS, RAMAN;

EID: 84890570134     PISSN: 07248741     EISSN: 1573904X     Source Type: Journal    
DOI: 10.1007/s11095-013-0999-2     Document Type: Article

References (62)

1. O'Driscoll CM, Griffin BT. Biopharmaceutical challenges associated with drugs with low aqueous solubility - the potential impact of lipid-based formulations. Adv Drug Del Rev. 2008;60(6):617-24.
2. Porter CJH, Trevaskis NL, Charman WN. Lipids and lipid-based formulations: optimizing the oral delivery of lipophilic drugs. Nat Rev Drug Discov. 2007;6(3):231-48.
3. Gao P, Akrami A, Alvarez F, Hu J, Li L, Ma C, et al. Characterization and optimization of AMG 517 supersaturatable self-emulsifying drug delivery system (S-SEDDS) for improved oral absorption. J Pharm Sci. 2009;98(2):516-28.
4. Anby MU, Williams HD, McIntosh M, Benameur H, Edwards GA, Pouton CW, et al. Lipid digestion as a trigger for supersaturation: evaluation of the impact of supersaturation stabilization on the in vitro and in vivo performance of self-emulsifying drug delivery systems. Mol Pharm. 2012;9(7):2063-79.
5. Cuine JF, McEvoy CL, Charman WN, Pouton CW, Edwards GA, Benameur H, et al. Evaluation of the impact of surfactant digestion on the bioavailability of danazol after oral administration of lipidic self-emulsifying formulations to dogs. J Pharm Sci. 2008;97(2):995-1012.
6. Arnold YE, Imanidis G, Kuentz M. Study of drug concentration effects on in vitro lipolysis kinetics in medium-chain triglycerides by considering oil viscosity and surface tension. Eur J Pharm Sci. 2011;44(3):351-8.
7. Sek L, Porter CJH, Charman WN. Characterisation and quantification of medium chain and long chain triglycerides and their in vitro digestion products, by HPTLC coupled with in situ densitometric analysis. J Pharmaceut Biomed. 2001;25(3-4):651-61.
8. Dressman J, Schamp K, Beltz K, Alsenz J. Characterizing release from lipid-based formulations. In: Hauss DJ, editor. Oral lipid-based formulations: enhancing the bioavailability of poorly water-soluble drugs. New York: Informa Healthcare; 2007.
9. Zangenberg NH, Mullertz A, Kristensen HG, Hovgaard L. A dynamic in vitro lipolysis model I. Controlling the rate of lipolysis by continuous addition of calcium. Eur J Pharm Sci. 2001;14(2):115-22.
10. Zangenberg NH, Mullertz A, Kristensen HG, Hovgaard L. A dynamic in vitro lipolysis model II: evaluation of the model. Eur J Pharm Sci. 2001;14(3):237-44.
11. Williams HD, Sassene P, Kleberg K, Bakala-N'Goma JC, Calderone M, Jannin V, et al. Toward the establishment of standardized in vitro tests for lipid-based formulations, part 1: method parameterization and comparison of in vitro digestion profiles across a range of representative formulations. J Pharm Sci. 2012;10(9):3360-80.
12. Williams HD, Anby MU, Sassene P, Kleberg K, Bakala N, Goma J-C, et al. Toward the establishment of standardized in vitro tests for lipid-based formulations. 2. The effects of bile salt concentration and drug loading on the performance of type I, II, IIIA, IIIB, and IV formulations during in vitro digestion. Mol Pharm. 2012;9(11):3286-300.
13. Larsen AT, Sassene P, Mullertz A. In vitro lipolysis models as a tool for the characterization of oral lipid and surfactant based drug delivery systems. Int J Pharm. 2011;417(1-2):245-55.
14. Vertzoni M, Markopoulos C, Symillides M, Goumas C, Imanidis G, Reppas C. Luminal lipid phases after administration of a triglyceride solution of danazol in the fed state and their contribution to the flux of Danazol across Caco-2 cell monolayers. Mol Pharm. 2012;9(5):1189-98.
15. Kossena GA, Charman WN, Boyd BJ, Porter CIH. Influence of the intermediate digestion phases of common formulation lipids on the absorption of a poorly water-soluble drug. J Pharm Sci. 2005;94(3):481-92.
16. Fatouros DG, Deen GR, Arleth L, Bergenstahl B, Nielsen FS, Pedersen JS, et al. Structural development of self nano emulsifying drug delivery systems (SNEDDS) during in vitro lipid digestion monitored by small-angle x-ray scattering. Pharm Res. 2007;24(10):1844-53.
17. Fatouros DG, Walrand I, Bergenstahl B, Mullertz A. Colloidal structures in media simulating intestinal fed state conditions with and without lipolysis products. Pharm Res. 2009;26(2):361-74.
18. Kleberg K, Jacobsen F, Fatouros DG, Mullertz A. Biorelevant media simulating fed state intestinal fluids: colloid phase characterization and impact on solubilization capacity. J Pharm Sci. 2010;99(8):3522-32.
19. Kossena GA, Boyd BJ, Porter CJH, Charman WN. Separation and characterization of the colloidal phases produced on digestion of common formulation lipids and assessment of their impact on the apparent solubility of selected poorly water-soluble drugs. J Pharm Sci. 2003;92(3):634-48.
20. Mohsin K, Long MA, Pouton CW. Design of lipid-based formulations for oral administration of poorly water-soluble drugs: precipitation of drug after dispersion of formulations in aqueous solution. J Pharm Sci. 2009;98(10):3582-95.
21. Patton JS, Carey MC. Watching fat digestion. Science. 1979;204(4389):145-8.
22. Bevernage J, Forier T, Brouwers J, Tack J, Annaert P, Augustijns P. Excipient-mediated supersaturation stabilization in human intestinal fluids. Mol Pharm. 2011;8(2):564-70.
23. Bevernage J, Brouwers J, Annaert P, Augustijns P. Drug precipitation-permeation interplay: Supersaturation in an absorptive environment. Eur J Pharm Biopharm. 2012;82(2):424-8.
24. Sassene PJ, Knopp MM, Hesselkilde JZ, Koradia V, Larsen A, Rades T, et al. Precipitation of a poorly soluble model drug during in vitro lipolysis: characterization and dissolution of the precipitate. J Pharm Sci. 2010;99(12):4982-91.
25. Warren DB, Anby MU, Hawley A, Boyd BJ. Real time evolution of liquid crystalline nanostructure during the digestion of formulation lipids using synchrotron small-angle x-ray scattering. Langmuir. 2011;27(15):9528-34.
26. Cornel J, Lindenberg C, Mazzotti M. Quantitative application of in situ ATR-FTIR and Raman spectroscopy in crystallization processes. Ind Eng Chem Res. 2008;47(14):4870-82.
27. Hu YR, Liang JK, Myerson AS, Taylor LS. Crystallization monitoring by Raman spectroscopy: simultaneous measurement of desupersaturation profile and polymorphic form in flufenamic acid systems. Ind Eng Chem Res. 2005;44(5):1233-40.
28. Caillet A, Puel F, Fevotte G. In-line monitoring of partial and overall solid concentration during solvent-mediated phase transition using Raman spectroscopy. Int J Pharm. 2006;307(2):201-8.
29. Ono T, ter Horst JH, Jansens PJ. Quantitative measurement of the polymorphic transformation of L-glutamic acid using in-situ Raman spectroscopy. Cryst Growth Des. 2004;4(3):465-9.
30. Scholl J, Bonalumi D, Vicum L, Mazzotti M, Muller M. In situ monitoring and modeling of the solvent-mediated polymorphic transformation of L-glutamic acid. Cryst Growth Des. 2006;6(4):881-91.
31. Pienack N, Bensch W. In-situ monitoring of the formation of crystalline solids. Angew Chem Int Ed. 2011;50(9):2014-34.
32. Arnold YE, Imanidis G, Kuentz MT. Advancing in-vitro drug precipitation testing: new process monitoring tools and a kinetic nucleation and growth model. J Pharm Pharmacol. 2011;63(3):333-41.
33. Reis MM, Araujo PHH, Sayer C, Giudici R. Spectroscopic on-line monitoring of reactions in dispersed medium: chemometric challenges. Anal Chim Acta. 2007;595(1-2):257-65.
34. Fernandez S, Jannin V, Rodier JD, Ritter N, Mahler B, Carriere F. Comparative study on digestive lipase activities on the self emulsifying excipient Labrasol®, medium chain glycerides and PEG esters. BBA - Mol Cell Biol L. 2007;1771(5):633-40.
35. Fernandez S, Rodier JD, Ritter N, Mahler B, Demarne F, Carriere F, et al. Lipolysis of the semi-solid self-emulsifying excipient Gelucire® 44/14 by digestive lipases. BBA - Mol Cell Biol L. 2008;1781(8):367-75.
36. Garner CW. Boronic acid inhibitors of porcine pancreatic lipase. J Biol Chem. 1980;255(11):5064-8.
37. Juenemann D, Jantratid E, Wagner C, Reppas C, Vertzoni M, Dressman JB. Biorelevant in vitro dissolution testing of products containing micronized or nanosized fenofibrate with a view to predicting plasma profiles. Eur J Pharm Biopharm. 2011;77(2):257-64.
38. Geladi P, Macdougall D, Martens H. Linearization and scatter-correction for near-infrared reflectance spectra of meat. Appl Spectrosc. 1985;39(3):491-500.
39. Barnes RJ, Dhanoa MS, Lister SJ. Standard normal variate transformation and de-trending of near-infrared diffuse reflectance spectra. Appl Spectrosc. 1989;43(5):772-7.
40. Rinnan A, van den Berg F, Engelsen SB. Review of the most common pre-processing techniques for near-infrared spectra. Trac-Trends Anal Chem. 2009;28(10):1201-22.
41. Geladi P, Kowalski BR. Partial least-squares regression - a tutorial. Anal Chim Acta. 1986;185:1-17.
42. Stillhart C, Kuentz M. Comparison of high-resolution ultrasonic resonator technology and Raman spectroscopy as novel process analytical tools for drug quantification in self-emulsifying drug delivery systems. J Pharmaceut Biomed. 2012;59:29-37.
43. Dimo K. Nucleation: Basic theory and applications. Oxford: Butterworth-Heinemann; 2000.
44. Kashchiev D, van Rosmalen GM. Review: Nucleation in solutions revisited. Cryst Res Technol. 2003;38(7-8):555-74.
45. Mullin JW. Crystallization. 4th ed. ed. Oxford: Butterworth-Heinemann; 2001.
46. Sek L, Porter CJH, Kaukonen AM, Charman WN. Evaluation of the in-vitro digestion profiles of long and medium chain glycerides and the phase behaviour of their lipolytic products. J Pharm Pharmacol. 2002;54(1):29-41.
47. Kuentz M. Lipid-based formulations for oral delivery of lipophilic drugs. Drug Discov Today Technol. 2012;9(2):e97-e104.
48. Dahan A, Hoffman A. Use of a dynamic in vitro lipolysis model to rationalize oral formulation development for poor water soluble drugs: Correlation with in vivo data and the relationship to intra-enterocyte processes in rats. Pharm Res. 2006;23(9):2165-74.
49. Hu YR, Wikstrom H, Byrn SR, Taylor LS. Analysis of the effect of particle size on polymorphic quantitation by Raman spectroscopy. Appl Spectrosc. 2006;60(9):977-84.
50. Boetker J, Rades T, Rantanen J, Hawley A, Boyd BJ. Structural elucidation of rapid solution-mediated phase transitions in pharmaceutical solids using in situ synchrotron SAXS/WAXS. Mol Pharm. 2012;9(9):2787-91.
51. Thomas N, Holm R, Mullertz A, Rades T. In vitro and in vivo performance of novel supersaturated self-nanoemulsifying drug delivery systems (super-SNEDDS). J Control Release. 2012;160(1):25-32.
52. Cuine JF, Charman WN, Pouton CW, Edwards GA, Porter CJH. Increasing the proportional content of surfactant (Cremophor EL) relative to lipid in self-emulsifying lipid-based formulations of danazol reduces oral bioavailability in beagle dogs. Pharm Res. 2007;24(4):748-57.
53. Dahan A, Hoffman A. The effect of different lipid based formulations on the oral absorption of lipophilic drugs: The ability of in vitro lipolysis and consecutive ex vivo intestinal permeability data to predict in vivo bioavailability in rats. Eur J Pharm Biopharm. 2007;67(1):96-105.
54. Porter CJH, Kaukonen AM, Boyd BJ, Edwards GA, Charman WN. Susceptibility to lipase-mediated digestion reduces the oral bioavailability of danazol after administration as a medium-chain lipid-based microemulsion formulation. Pharm Res. 2004;21(8):1405-12.
55. Porter CJH, Kaukonen AM, Taillardat-Bertschinger A, Boyd BJ, O'Connor JM, Edwards GA, et al. Use of in vitro lipid digestion data to explain the in vivo performance of triglyceride-based oral lipid formulations of poorly water-soluble drugs: Studies with halofantrine. J Pharm Sci. 2004;93(5):1110-21.
56. Kleberg K, Jacobsen J, Mullertz A. Characterising the behaviour of poorly water soluble drugs in the intestine: application of biorelevant media for solubility, dissolution and transport studies. J Pharm Pharmacol. 2010;62(11):1656-68.
57. Anderson BD, Marra MT. Chemical and related factors controlling lipid solubility. Bulletin Technique Gattéfosse. 1999:11-9.
58. Borgstrom B, Brockman HL. Lipases. 1983.
59. Birner-Grunberger R, Scholze H, Faber K, Hermetter A. Identification of various lipolytic enzymes in crude porcine pancreatic lipase preparations using covalent fluorescent inhibitors. Biotechnol Bioeng. 2004;85(2):147-54.
60. Bakala N'Goma J-C, Amara S, Dridi K, Jannin V, Carrière F. Understanding the lipid-digestion process in the GI tract before designing lipid-based drug-delivery systems. Ther Deliv. 2012;3(1):105-24.
61. Wang CS, Kuksis A, Manganaro F. Studies on the substrate-specificity of purified human-milk lipoprotein-lipase. Lipids. 1982;17(4):278-84.
62. Mattson FH, Volpenhein RA. Digestion and absorption of triglycerides. J Biol Chem. 1964;239(9):2772-77.