Hot-Melt Extrusion: from Theory to Application in Pharmaceutical Formulation

AAPS PharmSciTech

Volumn 17, Issue 1, 2016, Pages 20-42

  Patil, Hemlata ^a   Tiwari, Roshan V ^a   Repka, Michael A ^a  

^a UNIVERSITY OF MISSISSIPPI   (United States)

Author keywords

hot melt extrusion; process analytical technology; quality by design; screw design; solid dispersion

Indexed keywords

ANTIOXIDANT; EUDRAGIT; EXCIPIENT; FILLER; IBUPROFEN; LUBRICATING AGENT; PLASTICIZER; POVIDONE; STABILIZING AGENT; DRUG;

ARTICLE; CHEMICAL REACTION; CONTINUOUS PROCESS; DOWNSTREAM PROCESSING; DRUG BIOAVAILABILITY; DRUG DELIVERY SYSTEM; DRUG DEVELOPMENT; DRUG DOSAGE FORM; DRUG INDUSTRY; DRUG MANUFACTURE; DRUG RELEASE; DRUG SOLUBILITY; ENERGY CONSUMPTION; ENTROPY; EQUIPMENT DESIGN; FLOW RATE; HOT MELT EXTRUSION; IMPLANT; MICROENCAPSULATION; MISCIBILITY; MOLECULAR WEIGHT; NANOTECHNOLOGY; PARTICLE SIZE; PHYSICAL CHEMISTRY; PRESCRIPTION; PRIORITY JOURNAL; PROCESS OPTIMIZATION; SCALE UP; SHEAR RATE; SUSTAINED RELEASE PREPARATION; TORQUE; BIOAVAILABILITY; CHEMISTRY; HEAT; MEDICINAL CHEMISTRY; PHARMACEUTICS; PROCEDURES; SOLUBILITY;

BIOLOGICAL AVAILABILITY; CHEMISTRY, PHARMACEUTICAL; DRUG DELIVERY SYSTEMS; DRUG INDUSTRY; EQUIPMENT DESIGN; HOT TEMPERATURE; PHARMACEUTICAL PREPARATIONS; SOLUBILITY; TECHNOLOGY, PHARMACEUTICAL;

EID: 84959240559     PISSN: None     EISSN: 15309932     Source Type: Journal    
DOI: 10.1208/s12249-015-0360-7     Document Type: Article

References (136)

1. El-Egakey MA, Soliva M, Speiser P. Hot extruded dosage forms. Technology and dissolution kinetics of polymeric matrices. Pharm Acta Helv. 1971;46(1):31–52.
2. Dreiblatt A. Process design. In: Ghebre-Sellassie I, Martin C, editors. Pharmaceutical extrusion technology, vol. 133. New York: Marcel Dekker, Inc; 2003. p. 153–69.
3. McGinity JW, Zhang F, Koleng J, Repka M. Hot-melt extrusion as a pharmaceutical process. Am Pharm Rev. 2001;4:25–37.
4. Breitenbach J. Melt extrusion: from process to drug delivery technology. Eur J Pharm Biopharm. 2002;54(2):107–17.
5. Shah S, Repka MA. Melt extrusion in drug delivery: three decades of progress. In: Repka MA, Langley N, DiNunzio J, editors. Melt extrusion. New York: Springer; 2013. p. 3–46.
6. Crowley MM, Zhang F, Repka MA, Thumma S, Upadhye SB, Battu SK, et al. Pharmaceutical applications of hot-melt extrusion: part I. Drug Dev Ind Pharm. 2007;33(9):909–26.
7. Repka MA, Battu SK, Upadhye SB, Thumma S, Crowley MM, Zhang F, et al. Pharmaceutical applications of hot-melt extrusion: part II. Drug Dev Ind Pharm. 2007;33(10):1043–57.
8. Patil H, Kulkarni V, Majumdar S, Repka MA. Continuous manufacturing of solid lipid nanoparticles by hot melt extrusion. Int J Pharm. 2014;471(1–2):153–6.
9. Repka MA, Majumdar S, Kumar Battu S, Srirangam R, Upadhye SB. Applications of hot-melt extrusion for drug delivery. Expert Opin Drug Deliv. 2008;5(12):1357–76.
10. Repka MA, Shah S, Lu J, Maddineni S, Morott J, Patwardhan K, et al. Melt extrusion: process to product. Expert Opin Drug Deliv. 2012;9(1):105–25.
11. Shah S, Maddineni S, Lu J, Repka MA. Melt extrusion with poorly soluble drugs. Int J Pharm. 2013;453(1):233–52.
12. Patil H, Tiwari RV, Upadhye SB, Vladyka RS, Repka MA. Formulation and development of pH-independent/dependent sustained release matrix tablets of ondansetron HCl by a continuous twin-screw melt granulation process. Int J Pharm. 2015. doi:10.1016/j.ijpharm.2015.04.009.
13. Kleinebudde P, Lindner H. Experiments with an instrumented twin-screw extruder using a single-step granulation/extrusion process. Int J Pharm. 1993;94(1):49–58.
14. Cheremisinoff NP. Guidebook to extrusion technology. Englewood Cliffs, NJ: Prentice-Hall; 1993. p. 23–38.
15. Maniruzzaman M, Boateng JS, Snowden MJ, Douroumis D. A review of hot-melt extrusion: process technology to pharmaceutical products. ISRN Pharm. 2012. doi:10.5402/2012/436763.
16. Steiner R. Extruder design. In: Ghebre-Sellassie I, Martin C, editors. Pharmaceutical extrusion technology, vol. 133. New York: Marcel Dekker, Inc; 2003. p. 19–38.
17. Luker K. Single-screw extrusion: principle. In: Douroumis D, editor. Hot-melt extrusion: pharmaceutical application. 1st ed. UK: John Wiley & Sons, Ltd; 2012. p. 1–21.
18. Stevens M, Covas J. Extrusion, principles and operation. 2nd ed. London: Chapman & Hall; 1995. p. 270–95.
19. Mollan M. Historical overview. In: Ghebre-Sellassie I, Martin C, editors. Pharmaceutical extrusion technology, vol. 133. New York: Marcel Dekker, Inc; 2003. p. 1–18.
20. Thiele W. Twin-screw extrusion and screw design. In: Ghebre-Sellassie I, Martin C, editors. Pharmaceutical extrusion technology, vol. 133. New York: Marcel Dekker, Inc; 2003. p. 69–98.
21. Repka MA, McGinity JW, Zhang F, Koleng JJ. Hot-melt extrusion technology. In: Swarbrick J, Boylan J, editors. Encyclopedia of pharmaceutical technology. 2nd ed. New York: Marcel Dekker; 2002. p. 203–66.
22. Wang Y. Compounding in co-rotating twin-screw extruders. Shrewsbury UK: Smithers RAPRA; Report 116, 2000. p. 3.
23. Loukus JE, Halonen A, Gupta M. Elongational flow in multiple screw extruders. ANTEC-Conference Proceeding. 2004;1:133–137.
24. Luker K. Single-screw extrusion and screw design. In: Ghebre-Sellassie I, Martin C, editors. Pharmaceutical extrusion technology, vol. 133. New York: Marcel Dekker, Inc; 2003. p. 39–68.
25. Chokshi R, Zia H. Hot-melt extrusion technique: a review. Iran J Pharm Res. 2010;3:3–16.
26. Nakamichi K, Yasuura H, Kukui H, Oka M, Izumi S, Andou T, et al. New preparation method of solid dispersion by twin screw extruder. Pharm Technol Jpn. 1996;12:715–29.
27. Douroumis D. Taste masking using hot-melt extrusion. In: Douroumis D, editor. Hot-melt extrusion: pharmaceutical application. 1st ed. UK: John Wiley & Sons, Ltd; 2012. p. 201–21.
28. Gogos CG, Liu H, Wang P. Laminar dispersive and distributive mixing with dissolution and applications to hot-melt extrusion. In: Douroumis D, editor. Hot-melt extrusion: pharmaceutical applications. 1st ed. UK: John Wiley & Sons, Ltd; 2012. p. 261–84.
29. Dreiblatt A. Technological considerations related to scale-up of hot-melt extrusion processes. In: Douroumis D, editor. Hot-melt extrusion: pharmaceutical application. 1st ed. UK: John Wiley & Sons, Ltd; 2012. p. 285–300.
30. Perdikoulias J, Dobbie T. Die design. In: Ghebre-Sellassie I, Martin C, editors. Pharmaceutical extrusion technology. New York: Marcel Dekker, Inc; 2003. p. 99–109.
31. Verreck G. The influence of plasticizers in hot-melt extrusion. In: Douroumis D, editor. Hot-melt extrusion: pharmaceutical application. 1st ed. UK: John Wiley & Sons, Ltd; 2012. p. 93–112.
32. Repka MA, Shah S, Lu J, Maddineni S, Morott J, Patwardhan K, et al. Melt extrusion: process to product. Expert Opin Drug Deliv. 2012;9(1):105–25.
33. Miyagawa Y, Okabe T, Yamaguchi Y, Miyajima M, Sato H, Sunada H. Controlled-release of diclofenac sodium from wax matrix granule. Int J Pharm. 1996;138(2):215–24.
34. Tantishaiyakul V, Kaewnopparat N, Ingkatawornwong S. Properties of solid dispersions of piroxicam in polyvinylpyrrolidone. Int J Pharm. 1999;181(2):143–51.
35. Zingone G, Moneghini M, Rupena P, Vojnovic D. Characterization and dissolution study of solid dispersions of theophylline and indomethacin with PVP/VA copolymers. STP Pharm Sci. 1992;2(2):186–92.
36. Follonier N, Doelker E, Cole ET. Various ways of modulating the release of diltiazem hydrochloride from hot-melt extruded sustained release pellets prepared using polymeric materials. J Control Release. 1995;36(72):243–50.
37. Perissutti B, Newton JM, Podczeck F, Rubessa F. Preparation of extruded carbamazepine and PEG 4000 as a potential rapid release dosage form. Eur J Pharm Biopharm. 2002;53(1):125–32.
38. Yano K, Kajiyama A, Hamada M, Yamamoto K. Constitution of colloidal particles formed from a solid dispersion system. Chem Pharm Bull. 1997;45(8):1339–44.
39. Abd A, El-Bary A, Geneidi AS, Amin SY, Elainan AA. Preparation and pharmacokinetic evaluation of carbamazepine controlled release solid dispersion granules. J Drug Res Egypt. 1998;22:15–31.
40. Li L, AbuBaker O, Shao ZJ. Characterization of poly(ethylene oxide) as a drug carrier in hot-melt extrusion. Drug Dev Ind Pharm. 2006;32(8):991–1002.
41. Repka MA, Gerding TG, Repka SL, McGinity JW. Influence of plasticizers and drugs on the physical-mechanical properties of hydroxypropylcellulose films prepared by hot melt extrusion. Drug Dev Ind Pharm. 1999;25(5):625–33.
42. Ahmed HA, Alfredson TV, Birudaraj K, Brandl MT, Phuapradit W, Shah NH, et al. Pharmaceutical composition and process. U.S. Patent 7,795,237, September 14, 2010.
43. Repka MA, McGinity JW. Influence of chlorpheniramine maleate on topical hydroxypropylcellulose films produced by hot-melt extrusion. Pharm Dev Technol. 2001;6(72):297–304.
44. Quinten T, Andrews GP, De Beer T, Saerens L, Bouquet W, Jones DS, et al. Preparation and evaluation of sustained-release matrix tablets based on metoprolol and an acrylic carrier using injection moulding. AAPS PharmSciTech. 2012;13(4):1197–211.
45. Hancock BC, Zografi G. Characteristics and significance of the amorphous state in pharmaceutical systems. J Pharm Sci. 1997;86(1):1–12.
46. Follonier N, Doelker E, Cole ET. Evaluation of hot-melt extrusion as a new technique for the production of polymer-based pellets for sustained release capsules containing high loadings of freely soluble drugs. Drug Dev Ind Pharm. 1994;20(8):1323–39.
47. Cuff G, Raouf F. A preliminary evaluation of injection molding as a technology to produce tablets. Pharm Technol. 1998;22(6):96–106.
48. Aitken-Nichol C, Zhang F, McGinity JW. Hot melt extrusion of acrylic films. Pharm Res. 1996;13(5):804–8.
49. Mehuys E, Remon JP, Vervaet C. Production of enteric capsules by means of hot-melt extrusion. Eur J Pharm Sci. 2005;24(2–3):207–12.
50. Repka MA, McGinity JW. Physical-mechanical, moisture absorption and bioadhesive properties of hydroxypropylcellulose hot-melt extruded films. Biomaterials. 2000;21(14):1509–17.
51. Ghebremeskel AN, Vemavarapu C, Lodaya M. Use of surfactants as plasticizers in preparing solid dispersions of poorly soluble API: stability testing of selected solid dispersions. Pharm Res. 2006;23(8):1928–36.
52. De Brabander C, Van Den Mooter G, Vervaet C, Remon JP. Characterization of ibuprofen as a nontraditional plasticizer of ethyl cellulose. J Pharm Sci. 2002;91(7):1678–85.
53. Verreck G, Six K, Van den Mooter G, Baert L, Peeters J, Brewster ME. Characterization of solid dispersions of itraconazole and hydroxypropylmethylcellulose prepared by melt extrusion–part I. Int J Pharm. 2003;251(1–2):165–74.
54. Six K, Berghmans H, Leuner C, Dressman J, Van Werde K, Mullens J, et al. Characterization of solid dispersions of itraconazole and hydroxypropylmethylcellulose prepared by melt extrusion. Part II. Pharm Res. 2003;20(7):1047–54.
55. Lakshman JP, Cao Y, Kowalski J, Serajuddin AT. Application of melt extrusion in the development of a physically and chemically stable high-energy amorphous solid dispersion of a poorly water-soluble drug. Mol Pharm. 2008;5(6):994–1002.
56. Kazarian S. Polymer processing with supercritical fluids. Polym Sci Ser C. 2000;42(1):78–101.
57. Kiran E. Polymer formation, modifications and processing in or with supercritical fluids, Supercritical fluids. New York: Springer; 1994. p. 541–88.
58. Chiou J, Barlow JW, Paul DR. Plasticization of glassy polymers by CO2. J Appl Polym Sci. 1985;30(6):2633–42.
59. Verreck G, Decorte A, Li H, Tomasko D, Arien A, Peeters J, et al. The effect of pressurized carbon dioxide as a plasticizer and foaming agent on the hot melt extrusion process and extrudate properties of pharmaceutical polymers. J Supercrit Fluids. 2006;38:383–91.
60. DiNunzio JC, Zhang F, Martin C, McGinity JW. Melt extrusion. In: Robet III OW, Watts AB, Miller DA, editors. Formulating poorly water soluble drugs. New York: Springer; 2012. p. 311–62.
61. Leuner C, Dressman J. Improving drug solubility for oral delivery using solid dispersions. Eur J Pharm Biopharm. 2000;50(1):47–60.
62. Breitenbach J, Magerlein M. Melt extruded molecular dispersions. In: Ghebre-Sellassie I, Martin C, editors. Pharmaceutical extrusion technology, vol. 133. New York: Marcel Dekker Inc; 2003. p. 245–60.
63. Serajuddin AT. Solid dispersion of poorly water-soluble drugs: early promises, subsequent problems, and recent breakthroughs. J Pharm Sci. 1999;88(10):1058–66.
64. Hulsmann S, Backensfeld T, Keitel S, Bodmeier R. Melt extrusion—an alternative method for enhancing the dissolution rate of 17beta-estradiol hemihydrate. Eur J Pharm Biopharm. 2000;49(3):237–42.
65. Nakamichi K, Nakano T, Yasuura H, Izumi S, Kawashima Y. The role of the kneading paddle and the effects of screw revolution speed and water content on the preparation of solid dispersions using a twin-screw extruder. Int J Pharm. 2002;241(2):203–11.
66. He H, Yang R, Tang X. In vitro and in vivo evaluation of fenofibrate solid dispersion prepared by hot-melt extrusion. Drug Dev Ind Pharm. 2010;36(6):681–7.
67. Sathigari SK, Radhakrishnan VK, Davis VA, Parsons DL, Babu RJ. Amorphous-state characterization of efavirenz-polymer hot-melt extrusion systems for dissolution enhancement. J Pharm Sci. 2012;101(9):3456–64.
68. Wang W, Kang Q, Liu N, Zhang Q, Zhang Y, Li H, et al. Enhanced dissolution rate and oral bioavailability of Ginkgo biloba extract by preparing solid dispersion via hot-melt extrusion. Fitoterapia. 2014. doi:10.1016/j.fitote.2014.10.004.
69. Alshahrani SM, Lu W, Park JB, Morott JT, Alsulays BB, Majumdar S, et al. Stability-enhanced hot-melt extruded amorphous solid dispersions via combinations of Soluplus® and HPMCAS-HF. AAPS PharmSciTech. 2015. doi:10.1208/s12249-014-0269-6.
70. Mehuys E, Vervaet C, Remon JP. Hot-melt extruded ethylcellulose cylinders containing a HPMC-Gelucire core for sustained drug delivery. J Control Release. 2004;94(2–3):273–80.
71. Yamashita F, Hashida M. Pharmacokinetic considerations for targeted drug delivery. Adv Drug Deliv Rev. 2013;65(1):139–47.
72. Bruce LD, Shah NH, Malick AW, Infeld MH, McGinity JW. Properties of hot-melt extruded tablet formulations for the colonic delivery of 5-aminosalicylic acid. Eur J Pharm Biopharm. 2005;59(1):85–97.
73. Miller DA, DiNunzio JC, Yang W, McGinity JW, Williams 3rd RO. Targeted intestinal delivery of supersaturated itraconazole for improved oral absorption. Pharm Res. 2008;25(6):1450–9.
74. Cassidy CM, Tunney MM, Caldwell DL, Andrews GP, Donnelly RF. Development of novel oral formulations prepared via hot melt extrusion for targeted delivery of photosensitizer to the colon. Photochem Photobiol. 2011;87(4):867–76.
75. Remington JP, Troy DB, Beringer P. Remington: the science and practice of pharmacy. 20th ed. Easton: Mack Publishing Company; 2002. p. 1018–20.
76. Gryczke A, Schminke S, Maniruzzaman M, Beck J, Douroumis D. Development and evaluation of orally disintegrating tablets (ODTs) containing Ibuprofen granules prepared by hot melt extrusion. Colloids Surf B: Biointerfaces. 2011;86(2):275–84.
77. Michalk A, Kanikanti VR, Hamann HJ, Kleinebudde P. Controlled release of active as a consequence of the die diameter in solid lipid extrusion. J Control Release. 2008;132(1):35–41.
78. Witzleb R, Kanikanti VR, Hamann HJ, Kleinebudde P. Solid lipid extrusion with small die diameters—electrostatic charging, taste masking and continuous production. Eur J Pharm Biopharm. 2011;77(1):170–7.
79. Breitkreutz J, El-Saleh F, Kiera C, Kleinebudde P, Wiedey W. Pediatric drug formulations of sodium benzoate: II. Coated granules with a lipophilic binder. Eur J Pharm Biopharm. 2003;56(2):255–60.
80. Maniruzzaman M, Boateng JS, Bonnefille M, Aranyos A, Mitchell JC, Douroumis D. Taste masking of paracetamol by hot-melt extrusion: an in vitro and in vivo evaluation. Eur J Pharm Biopharm. 2012;80(2):433–42.
81. Douroumis D. Practical approaches of taste masking technologies in oral solid forms. Expert Opin Drug Deliv. 2007;4(4):417–26.
82. Douroumis D. Orally disintegrating dosage forms and taste-masking technologies; 2010. Expert Opin Drug Deliv. 2011;8(5):665–75.
83. Morott JT, Pimparade M, Park JB, Worley CP, Majumdar S, Lian Z, et al. The effects of screw configuration and polymeric carriers on hot-melt extruded taste-masked formulations incorporated into orally disintegrating tablets. J Pharm Sci. 2015;104(1):124–34.
84. Steuernagel CR. Latex emulsions for controlled drug delivery. In: McGinity JW, editor. Aqueous polymeric coatings for pharmaceutical dosage forms, vol. 79. New York, USA: Marcel Dekker; 1997.
85. Barnhart S. Thin film oral dosage forms. In: Rathbone MJ, Hadgraft J, Roberts MS, Lane ME, editors. Modified-release drug delivery technology. New York: Informa Healthcare; 2008. p. 209–16.
86. Repka MA, Gutta K, Prodduturi S, Munjal M, Stodghill SP. Characterization of cellulosic hot-melt extruded films containing lidocaine. Eur J Pharm Biopharm. 2005;59(1):189–96.
87. Mididoddi PK, Repka MA. Characterization of hot-melt extruded drug delivery systems for onychomycosis. Eur J Pharm Biopharm. 2007;66(1):95–105.
88. Low AQ, Parmentier J, Khong YM, Chai CC, Tun TY, Berania JE, et al. Effect of type and ratio of solubilising polymer on characteristics of hot-melt extruded orodispersible films. Int J Pharm. 2013;455(1–2):138–47.
89. Palem CR, Kumar Battu S, Maddineni S, Gannu R, Repka MA, Yamsani MR. Oral transmucosal delivery of domperidone from immediate release films produced via hot-melt extrusion technology. Pharm Dev Technol. 2013;18(1):186–95.
90. Chen M, Lu J, Deng W, Singh A, Mohammed NN, Repka MA, et al. Influence of processing parameters and formulation factors on the bioadhesive, temperature stability and drug release properties of hot-melt extruded films containing miconazole. AAPS PharmSciTech. 2014;15(3):522–9.
91. Rothen-Weinhold A, Oudry N, Schwach-Abdellaoui K, Frutiger-Hughes S, Hughes GJ, Jeannerat D, et al. Formation of peptide impurities in polyester matrices during implant manufacturing. Eur J Pharm Biopharm. 2000;49(3):253–7.
92. Ghalanbor Z, Korber M, Bodmeier R. Improved lysozyme stability and release properties of poly(lactide-co-glycolide) implants prepared by hot-melt extrusion. Pharm Res. 2010;27(2):371–9.
93. Ghalanbor Z, Korber M, Bodmeier R. Protein release from poly(lactide-co-glycolide) implants prepared by hot-melt extrusion: thioester formation as a reason for incomplete release. Int J Pharm. 2012;438(1–2):302–6.
94. Li D, Guo G, Fan R, Liang J, Deng X, Luo F, et al. PLA/F68/dexamethasone implants prepared by hot-melt extrusion for controlled release of anti-inflammatory drug to implantable medical devices: I. Preparation, characterization and hydrolytic degradation study. Int J Pharm. 2013;441(1–2):365–72.
95. Stankovic M, Tomar J, Hiemstra C, Steendam R, Frijlink HW, Hinrichs WL. Tailored protein release from biodegradable poly(epsilon-caprolactone-PEG)-b-poly(epsilon-caprolactone) multiblock-copolymer implants. Eur J Pharm Biopharm. 2014;87(2):329–37.
96. Verhoeven E, De Beer TR, Van den Mooter G, Remon JP, Vervaet C. Influence of formulation and process parameters on the release characteristics of ethylcellulose sustained-release mini-matrices produced by hot-melt extrusion. Eur J Pharm Biopharm. 2008;69(1):312–9.
97. Ozguney I, Shuwisitkul D, Bodmeier R. Development and characterization of extended release Kollidon SR mini-matrices prepared by hot-melt extrusion. Eur J Pharm Biopharm. 2009;73(1):140–5.
98. Almeida A, Saerens L, De Beer T, Remon JP, Vervaet C. Upscaling and in-line process monitoring via spectroscopic techniques of ethylene vinyl acetate hot-melt extruded formulations. Int J Pharm. 2012;439(1–2):223–9.
99. Patil H, Feng X, Ye X, Majumdar S, Repka MA. Continuous production of fenofibrate solid lipid nanoparticles by hot-melt extrusion technology: a systematic study based on a quality by design approach. AAPS J. 2015;17(1):194–205.
100. Baumgartner R, Eitzlmayr A, Matsko N, Tetyczka C, Khinast J, Roblegg E. Nano-extrusion: a promising tool for continuous manufacturing of solid nano-formulations. Int J Pharm. 2014;477(1–2):1–11.
101. Singh BN, Kim KH. Floating drug delivery systems: an approach to oral controlled drug delivery via gastric retention. J Control Release. 2000;63(3):235–59.
102. Fukuda M, Peppas NA, McGinity JW. Floating hot-melt extruded tablets for gastroretentive controlled drug release system. J Control Release. 2006;115(2):121–9.
103. Van Melkebeke B, Vervaet C, Remon JP. Validation of a continuous granulation process using a twin-screw extruder. Int J Pharm. 2008;356(1–2):224–30.
104. Gamlen M, Eardley C. Continuous extrusion using a raker perkins MP50 (multipurpose) extruder. Drug Dev Ind Pharm. 1986;12(11–13):1701–13.
105. Lindberg N-O, Tufvesson C, Holm P, Olbjer L. Extrusion of an effervescent granulation with a twin screw extruder, Baker Perkins MPF 50 D. Influence on intragranular porosity and liquid saturation. Drug Dev Ind Pharm. 1988;14(13):1791–8.
106. Ghebre-Sellassie I, Mollan MJ, Pathak N, Lodaya M, Fessehaie M. Continuous production of pharmaceutical granulation. US Patent 6,499,984 B1, December 31, 2002
107. Keleb EI, Vermeire A, Vervaet C, Remon JP. Continuous twin screw extrusion for the wet granulation of lactose. Int J Pharm. 2002;239(1–2):69–80.
108. Mu B, Thompson MR. Examining the mechanics of granulation with a hot melt binder in a twin-screw extruder. Chem Eng Sci. 2012;81:46–56.
109. Potente H. Existing scale-up rules for single-screw plasticating extruders. Int Polym Process. 1991;6(4):267–78.
110. Rauwendaal CH. Polymer extrusion. München, Germany: Hanser publishers; 1986. p. 20–5.
111. Guns S, Mathot V, Martens JA, Van den Mooter G. Upscaling of the hot-melt extrusion process: comparison between laboratory scale and pilot scale production of solid dispersions with miconazole and Kollicoat IR. Eur J Pharm Biopharm. 2012;81(3):674–82.
112. Dreiblatt A. Technological considerations related to scale-up of hot-melt extrusion processes. In: Douroumis D, editor. Hot-melt extrusion: pharmaceutical application. 1st ed. Ltd, UK: John Wiley & Sons; 2012. p. 285–300.
113. Gupta A, Khan MA. Hot-melt extrusion: an FDA perspective on product and process understanding. In: Douroumis D, editor. Hot-melt extrusion: pharmaceutical application. 1st ed. UK: John Wiley & Sons, Ltd; 2012. p. 323–31.
114. Woodcock J. The concept of pharmaceutical quality. Am Pharm Rev. 2004;7(6):10–5.
115. ICH Q8(R2). Pharmaceutical development. ICH Harmonised Tripartite Guideline. (2009). http://www.ich.org/products/guidelines/quality/quality-single/article/pharmaceutical-development.html. Accessed 10 April 2015.
116. ICH topic Q3C (R5) impurities: residual solvents. International Conference on Harmonization. 2009. http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q3C/Step4/Q3C_R5_Step4.pdf. Accessed 10 April 2015.
117. Kayrak-Talay D, Dale S, Wassgren C, Litster J. Quality by design for wet granulation in pharmaceutical processing: assessing models for a priori design and scaling. Powder Technol. 2013;240:7–18.
118. Aksu B, De Beer T, Folestad S, Ketolainen J, Lindén H, Lopes JA, et al. Strategic funding priorities in the pharmaceutical sciences allied to quality by design (QbD) and process analytical technology (PAT). Eur J Pharm Sci. 2012;47(2):402–5.
119. Kasper JC, Winter G, Friess W. Recent advances and further challenges in lyophilization. Eur J Pharm Biopharm. 2013;85(2):162–9.
120. Tomba E, Facco P, Bezzo F, Barolo M. Latent variable modeling to assist the implementation of Quality-by-Design paradigms in pharmaceutical development and manufacturing: a review. Int J Pharm. 2013;457(1):283–97.
121. Schaefer C, Clicq D, Lecomte C, Merschaert A, Norrant E, Fotiadu F. A process analytical technology (PAT) approach to control a new API manufacturing process: development, validation and implementation. Talanta. 2014;120:114–25.
122. Chen Z, Lovett D, Morris J. Process analytical technologies and real time process control a review of some spectroscopic issues and challenges. J Process Control. 2011;21(10):1467–82.
123. ICH Q9. Quality risk management. ICH Harmonised Tripartite Guideline. 2006. http://www.ich.org/products/guidelines/quality/quality-single/article/quality-risk-management.html. Accessed 10 April 2015.
124. Guidance for industry PAT-A framework for innovative pharmaceutical manufacturing and quality assurance. 2004. http://www.fda.gov/downloads/Drugs/Guidances/ucm070305.pdf. Accessed 10 April 2015.
125. Wahl PR, Treffer D, Mohr S, Roblegg E, Koscher G, Khinast JG. Inline monitoring and a PAT strategy for pharmaceutical hot melt extrusion. Int J Pharm. 2013;455(1):159–68.
126. De Beer T, Burggraeve A, Fonteyne M, Saerens L, Remon JP, Vervaet C. Near infrared and Raman spectroscopy for the in-process monitoring of pharmaceutical production processes. Int J Pharm. 2011;417(1–2):32–47.
127. Gendrin C, Roggo Y, Collet C. Pharmaceutical applications of vibrational chemical imaging and chemometrics: a review. J Pharm Biomed Anal. 2008;48(3):533–53.
128. Roggo Y, Chalus P, Maurer L, Lema-Martinez C, Edmond A, Jent N. A review of near infrared spectroscopy and chemometrics in pharmaceutical technologies. J Pharm Biomed Anal. 2007;44(3):683–700.
129. Vankeirsbilck T, Vercauteren A, Baeyens W, Van der Weken G, Verpoort F, Vergote G, et al. Applications of Raman spectroscopy in pharmaceutical analysis. TrAC Trends Anal Chem. 2002;21(12):869–77.
130. Coates P, Barnes S, Sibley M, Brown E, Edwards HG, Scowen I. In-process vibrational spectroscopy and ultrasound measurements in polymer melt extrusion. Polymer. 2003;44(19):5937–49.
131. Tumuluri SV, Prodduturi S, Crowley MM, Stodghill SP, McGinity JW, Repka MA, et al. The use of near-infrared spectroscopy for the quantitation of a drug in hot-melt extruded films. Drug Dev Ind Pharm. 2004;30(5):505–11.
132. Barnes S, Brown E, Sibley M, Edwards H, Coates P. Vibrational spectroscopic and ultrasound analysis for the in-process monitoring of poly (ethylene vinyl acetate) copolymer composition during melt extrusion. Analyst. 2005;130(3):286–92.
133. Saerens L, Dierickx L, Lenain B, Vervaet C, Remon JP, De Beer T. Raman spectroscopy for the in-line polymer-drug quantification and solid state characterization during a pharmaceutical hot-melt extrusion process. Eur J Pharm Biopharm. 2011;77(1):158–63.
134. Saerens L, Dierickx L, Quinten T, Adriaensens P, Carleer R, Vervaet C, et al. In-line NIR spectroscopy for the understanding of polymer-drug interaction during pharmaceutical hot-melt extrusion. Eur J Pharm Biopharm. 2012;81(1):230–7.
135. Krier F, Mantanus J, Sacre PY, Chavez PF, Thiry J, Pestieau A, et al. PAT tools for the control of co-extrusion implants manufacturing process. Int J Pharm. 2013;458(1):15–24.
136. Kelly AL, Gough T, Dhumal RS, Halsey SA, Paradkar A. Monitoring ibuprofen-nicotinamide cocrystal formation during solvent free continuous cocrystallization (SFCC) using near infrared spectroscopy as a PAT tool. Int J Pharm. 2012;426(1–2):15–20.