Inline Determination of Residence Time Distribution in Hot-Melt-Extrusion
Abstract
:1. Introduction
2. Materials and Methods
2.1. Hot-Melt-Extrusion on a Co-Rotating Twin-Screw-Extruder
2.2. Offline Determination: HPLC-UV
2.3. Inline Determination: UV/Vis Spectroscopy
3. Results & Discussion
3.1. Data
3.2. Comparison of Offline and Inline RTD Determination
3.3. Suitability for RTD Monitoring
3.4. Determination of the Limit of Quantification
4. Conclusions
Symbols
A | absorbance of light as function of wavelength | [-] |
Bo | Bodenstein-number | [-] |
c0 | initial concentration | [mol·m−3] |
cmarker | marker concentration | [mol·m−3] |
cv | coefficient of variation | * |
dpath | path length of light beam through sample | [m] |
E | residence time density function | [s−1] |
EAD | residence time density function of Axial-Dispersion-Model | [s−1] |
F | cumulative residence time density function | [-] |
I | transmitted light intensity as function of wavelength | [-] |
I0 | basic light intensity as function of wavelength | [-] |
LoQ | limit of quantification | [-] |
total mass flow of powder inlet | [kg·s−1] | |
mmarker | total marker mass | [kg] |
s | standard deviation | * |
sbasic | standard deviation of basic signal | * |
t | time | [s] |
mean residence time | [s] | |
ti | quantile of the cumulative residence time density function corresponding to the value i | [-] |
Tr | transmission of light as function of wavelength | [-] |
mean value of signal x | * | |
mean value of basic signal of the residence time density function | [s−1] | |
absorbance coefficient as function of wavelength | [m2·mol−1] | |
λ | wavelength | [nm] |
θ | dimensionless time | [-] |
* unit depends on measured signal |
Acknowledgments
Author Contributions
Conflicts of Interest
References
- ICH. Q8(R2)-Pharmaceutical Development. Available online: https://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q8_R1/Step4/Q8_R2_Guideline.pdf (accessed on 2 January 2018).
- Gurunath, S.; Pradeep Kumar, S.; Basavaraj, N.K.; Patil, P.A. Amorphous solid dispersion method for improving oral bioavailability of poorly water-soluble drugs. J. Pharm. Res. 2013, 6, 476–480. [Google Scholar] [CrossRef]
- Breitenbach, J. Melt extrusion: From process to drug delivery technology. Eur. J. Pharm. Biopharm. 2002, 54, 107–117. [Google Scholar] [CrossRef]
- Muehlenfeld, C.; Thommes, M. Small-scale twin-screw extrusion—Evaluation of continuous split feeding. J. Pharm. Pharmacol. 2014, 66, 1667–1676. [Google Scholar] [CrossRef] [PubMed]
- Alshahrani, S.M.; Morott, J.T.; Alshetaili, A.S.; Tiwari, R.V.; Majumdar, S.; Repka, M.A. Influence of degassing on hot-melt extrusion process. Eur. J. Pharm. Sci. 2015, 80, 43–52. [Google Scholar] [CrossRef] [PubMed]
- Wening, K.; Breitkreutz, J. Novel delivery device for monolithical solid oral dosage forms for personalized medicine. Int. J. Pharm. 2010, 395, 174–181. [Google Scholar] [CrossRef] [PubMed]
- Hasa, D.; Perissutti, B.; Grassi, M.; Zacchigna, M.; Pagotto, M.; Lenaz, D.; Kleinebudde, P.; Voinovich, D. Melt extruded helical waxy matrices as a new sustained drug delivery system. Eur. J. Pharm. Biopharm. 2011, 79, 592–600. [Google Scholar] [CrossRef] [PubMed]
- Eitzlmayr, A.; Matić, J.; Khinast, J. Analysis of flow and mixing in screw elements of corotating twin-screw extruders via SPH. AIChE J. 2017, 63, 2451–2463. [Google Scholar] [CrossRef]
- Koch, L.; Emin, M.A.; Schuchmann, H.P. Influence of processing conditions on the formation of whey protein-citrus pectin conjugates in extrusion. J. Food Eng. 2017, 193, 1–9. [Google Scholar] [CrossRef]
- Sridhar, R.; Narasimha Murthy, H.N.; Pattar, N.; Vishnu Mahesh, K.R.; Krishna, M. Parametric study of twin screw extrusion for dispersing MMT in vinylester using orthogonal array technique and grey relational analysis. Compos. Part B Eng. 2012, 43, 599–608. [Google Scholar] [CrossRef]
- Yang, Y.P.; Zhang, Y.; Dawelbeit, A.; Yu, M.H. Dissolving cellulose with twin-screw extruder in a NaOH complex aqueous solution. In Proceedings of the 2016 Global Conference on Polymer and Composite Materials, PCM 2016, Hangzhou, China, 20–23 May 2016; Institute of Physics Publishing: Bristol, UK, 2016. [Google Scholar]
- Lee, H.L.; Vasoya, J.M.; Cirqueira, M.L.; Yeh, K.L.; Lee, T.; Serajuddin, A.T. Continuous Preparation of 1:1 Haloperidol–Maleic Acid Salt by a Novel Solvent-Free Method Using a Twin Screw Melt Extruder. Mol. Pharm. 2017, 14, 1278–1291. [Google Scholar] [CrossRef] [PubMed]
- Levenspiel, O. Chemical Reaction Engninnering, 3rd ed.; Wiley & Sons: New York, NY, USA, 1999. [Google Scholar]
- Ghosh, I.; Vippagunta, R.; Li, S.; Vippagunta, S. Key considerations for optimization of formulation and melt-extrusion process parameters for developing thermosensitive compound. Pharm. Dev. Technol. 2012, 17, 502–510. [Google Scholar] [CrossRef] [PubMed]
- Crowley, M.M.; Zhang, F.; Koleng, J.J.; McGinity, J.W. Stability of polyethylene oxide in matrix tablets prepared by hot-melt extrusion. Biomaterials 2002, 23, 4241–4248. [Google Scholar] [CrossRef]
- Mu, B.; Thompson, M.R. Examining the mechanics of granulation with a hot melt binder in a twin-screw extruder. Chem. Eng. Sci. 2012, 81, 46–56. [Google Scholar] [CrossRef]
- Janssen, L.P.B.M.; Hollander, R.W.; Spoor, M.W.; Smith, J.M. Residence time distribution in a plasticating Twin Screw Extruder. AIChE J. 1979, 25, 345–351. [Google Scholar] [CrossRef]
- Reitz, E.; Podhaisky, H.; Ely, D.; Thommes, M. Residence time modeling of hot melt extrusion processes. Eur. J. Pharm. Biopharm. 2013, 85, 1200–1205. [Google Scholar] [CrossRef] [PubMed]
- Puaux, J.P.; Bozga, G.; Ainser, A. Residence time distribution in a corotating twin-screw extruder. Chem. Eng. Sci. 2000, 55, 1641–1651. [Google Scholar] [CrossRef]
- Gao, J.; Walsh, G.C.; Bigio, D.; Briber, R.M.; Wetzel, M.D. Residence-time distribution model for twin-screw extruders. AIChE J. 1999, 45, 2541–2549. [Google Scholar] [CrossRef]
- Wahl, P.R.; Hörl, G.; Kaiser, D.; Sacher, S.; Rupp, C.; Shlieout, G.; Breitenbach, J.; Koscher, G.; Khinast, J.G. In-line measurement of residence time distribution in melt extrusion via video analysis. Polym. Eng. Sci. 2017, 58, 170–179. [Google Scholar] [CrossRef]
- Fel, E.; Massardier, V.; Vergnes, M.B.; Cassagnau, P. Residence time distribution in a high shear twin screw extruder. Int. Polym. Process. 2014, 29, 71–80. [Google Scholar] [CrossRef]
- Kumar, A.; Vercruysse, J.; Toiviainen, M.; Panouillot, P.E.; Juuti, M.; Vanhoorne, V.; Vervaet, C.; Remon, J.P.; Gernaey, K.V.; De Beer, T.; et al. Mixing and transport during pharmaceutical twin-screw wet granulation: Experimental analysis via chemical imaging. Eur. J. Pharm. Biopharm. 2014, 87, 279–289. [Google Scholar] [CrossRef] [PubMed]
- ICH. Q2(R1)-Validation of Analytical Procedures. Available online: https://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q2_R1/Step4/Q2_R1_Guideline.pdf (accessed on 2 January 2018).
- Ward, N.J.; Edwards, H.G.M.; Johnson, A.F.; Fleming, D.J.; Coates, P.D. Application of Raman Spectroscopy for Determining Residence Time Distributions in Extruder Reactors. Appl. Spectrosc. 1996, 50, 812–815. [Google Scholar] [CrossRef]
Method & Measuring Site | t10 [s] | t50 [s] | t90 [s] | |
---|---|---|---|---|
HPLC | 145.4 ± 3.6 | 221.2 ± 24.1 | 390.4 ± 44.3 | |
POS 1 | 148.5 ± 7.9 | 247.4 ± 23.9 | 483.4 ± 67.6 | |
POS 2 | 152.8 ± 2.2 | 252.8 ± 23.1 | 483.5 ± 48.7 |
Method & Measuring Site | c0 [-] | Bo1 [-] | Bo1 [-] | [s] | [s] | |
---|---|---|---|---|---|---|
HPLC | 0.98 ± 0.009 | 57.3 ± 38.1 | 2.75 ± 4.62 | 131.2 ± 40.9 | 110.6 ± 167.8 | |
POS 1 | 1.00 ± 0.018 | 400.5 ± 581.2 | 1.71 ± 1.59 | 123.7 ± 17.9 | 80.8 ± 23.5 | |
POS 2 | 1.00 ± 0.005 | 150.9 ± 93.8 | 2.77 ± 1.17 | 122.1 ± 14.2 | 93.8 ± 13.0 |
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Wesholowski, J.; Berghaus, A.; Thommes, M. Inline Determination of Residence Time Distribution in Hot-Melt-Extrusion. Pharmaceutics 2018, 10, 49. https://doi.org/10.3390/pharmaceutics10020049
Wesholowski J, Berghaus A, Thommes M. Inline Determination of Residence Time Distribution in Hot-Melt-Extrusion. Pharmaceutics. 2018; 10(2):49. https://doi.org/10.3390/pharmaceutics10020049
Chicago/Turabian StyleWesholowski, Jens, Andreas Berghaus, and Markus Thommes. 2018. "Inline Determination of Residence Time Distribution in Hot-Melt-Extrusion" Pharmaceutics 10, no. 2: 49. https://doi.org/10.3390/pharmaceutics10020049
APA StyleWesholowski, J., Berghaus, A., & Thommes, M. (2018). Inline Determination of Residence Time Distribution in Hot-Melt-Extrusion. Pharmaceutics, 10(2), 49. https://doi.org/10.3390/pharmaceutics10020049