Melt extrusion: Process to product

Expert Opinion on Drug Delivery

Volumn 9, Issue 1, 2012, Pages 105-125

  Repka, Michael A ^a,b   Shah, Sejal ^b   Lu, Jiannan ^b   Maddineni, Sindhuri ^b   Morott, Joe ^b   Patwardhan, Ketaki ^b   Mohammed, Noorullah Naqvi ^b  

^a UNIVERSITY OF MISSISSIPPI   (United States)

^b UNIVERSITY OF MISSISSIPPI   (United States)

Author keywords

Bioadhesion; Bioavailability; Controlled release; Drug delivery systems; Hot melt extrusion; Melt extruded films; Melt extruded tablets; Solid dispersion; Sustained release

Indexed keywords

3,3 DIPHENYLPROPYLAMIN MONOESTER DERIVATIVE; ALPHA TOCOPHEROL; CARBOMER; DRUG CARRIER; ETHINYLESTRADIOL PLUS ETONOGESTREL; ETHYLENE VINYL ACETATE COPOLYMER; EUDRAGIT; GLYCEROL PALMITOSTEARATE; GUAIFENESIN; IBUPROFEN; ITRACONAZOLE; NIMODIPINE; NONSTEROID ANTIINFLAMMATORY AGENT; PARACETAMOL; PLASTICIZER; POLYMER; POVIDONE; PROPYLAMINE; SALICYLIC ACID; TETRAHYDROCANNABINOL; TRIMYRISTIN; UNCLASSIFIED DRUG;

DRUG BIOAVAILABILITY; DRUG DELIVERY SYSTEM; DRUG FORMULATION; DRUG MANUFACTURE; DRUG RELEASE; HOT MELT EXTRUSION; HUMAN; MAXIMUM PLASMA CONCENTRATION; NONHUMAN; PHARMACEUTICS; REVIEW; URINE INCONTINENCE;

ADMINISTRATION, CUTANEOUS; ADMINISTRATION, ORAL; ANIMALS; DRUG CARRIERS; DRUG DELIVERY SYSTEMS; EQUIPMENT DESIGN; HUMANS; PHARMACEUTICAL PREPARATIONS; PLASTICIZERS; SOLUBILITY; SURFACE PROPERTIES; TECHNOLOGY, PHARMACEUTICAL;

EID: 84255167308     PISSN: 17425247     EISSN: 17447593     Source Type: Journal    
DOI: 10.1517/17425247.2012.642365     Document Type: Review

References (108)

1. Crowley MM, Zhang F, Repka MA, et al. Pharmaceutical applications of hot-melt extrusion: part I. Drug Dev Ind Pharm 2007;33(9):909-26 (Pubitemid 47463803)
2. Repka MA, Battu SK, Upadhye SB, et al. Pharmaceutical applications of hot-melt extrusion: Part II. Drug Dev Ind Pharm 2007;33(10):1043-57 (Pubitemid 350034836)
3. Repka MA, Majumdar S, Battu SK, et al. Applications of hot-melt extrusion for drug delivery. Expert Opin Drug Deliv 2008;5(12):1357-76
4. Breitenbach J. Melt extrusion: from process to drug delivery technology. Eur J Pharm Biopharm 2002;54(2):107-17 (Pubitemid 34919382)
5. Kerns EH. High throughput physicochemical profiling for drug discovery. J Pharm Sci 2001;90(11):1838-58 (Pubitemid 33062605)
6. Serajuddin AT. Solid dispersion of poorly water-soluble drugs: early promises, subsequent problems, and recent breakthroughs. J Pharm Sci 1999;88(10):1058-66
7. Forster A, Hempenstall J, Rades T. Characterization of glass solutions of poorly water-soluble drugs produced by melt extrusion with hydrophilic amorphous polymers. J Pharm Pharmacol 2001;53(3):303-15 (Pubitemid 32229189)
8. Ndindayino F, Vervaet C, Van den Mooter G, et al. Bioavailability of hydrochlorothiazide from isomalt-based moulded tablets. Int J Pharm 2002;246(1-2):199-202 (Pubitemid 35247992)
9. Breitenbach J, Magerlein M. editors. Melt extruded molecular dispersions. Informa Healthcare; 2003
10. Miller DA, McConville JT, Yang W, et al. Hot-melt extrusion for enhanced delivery of drug particles. J Pharm Sci 2007;96(2):361-76 (Pubitemid 46363567)
11. Sauer D, Zheng W, Coots LB, et al. Influence of processing parameters and formulation factors on the drug release from tablets powder-coated with Eudragit L 100-55. Eur J Pharm Biopharm 2007;67(2):464-75 (Pubitemid 47211905)
12. Fukuda M, Miller DA, Peppas NA, et al. Influence of sulfobutyl ether beta-cyclodextrin (Captisol) on the dissolution properties of a poorly soluble drug from extrudates prepared by hot-melt extrusion. Int J Pharm 2008;350(1-2):188-96
13. Upadhye SB, Kulkarni SJ, Majumdar S, et al. Preparation and characterization of inclusion complexes of a hemisuccinate ester prodrug of delta9-tetrahydrocannabinol with modified beta-cyclodextrins. AAPS PharmSciTech 2010;11(2):509-17
14. Prodduturi S, Urman KL, Otaigbe JU, et al. Stabilization of hot-melt extrusion formulations containing solid solutions using polymer blends. AAPS PharmSciTech 2007;8(2):Article 50
15. Schilling SU, Shah NH, Waseem Malick A, et al. Properties of melt extruded enteric matrix pellets. Eur J Pharm Biopharm 2010;74(2):352-61
16. 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
17. 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
18. Liu J, Zhang F, McGinity JW. Properties of lipophilic matrix tablets containing phenylpropanolamine hydrochloride prepared by hot-melt extrusion. Eur J Pharm Biopharm 2001;52(2):181-90 (Pubitemid 32755897)
19. Ndindayino F, Vervaet C, Van den Mooter G, et al. Direct compression and moulding properties of co-extruded isomalt/drug mixtures. Int J Pharm 2002;235(1-2):159-68 (Pubitemid 34185447)
20. Bialleck S, Rein H. Preparation of starch-based pellets by hot-melt extrusion. Eur J Pharm Biopharm 2011;79(2):440-8
21. Verreck G, Decorte A, Li H, 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 Fluid 2006;38(3):383-91 (Pubitemid 44515184)
22. Thumma S, ElSohly MA, Zhang SQ, et al. Influence of plasticizers on the stability and release of a prodrug of Delta(9)-tetrahydrocannabinol incorporated in poly (ethylene oxide) matrices. Eur J Pharm Biopharm 2008;70(2):605-14
23. Schilling SU, Shah NH, Malick AW, et al. Citric acid as a solid-state plasticizer for Eudragit RS PO. J Pharm Pharmacol 2007;59(11):1493-500 (Pubitemid 350057451)
24. Repka MA, Gerding TG, Repka SL, et al. 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 (Pubitemid 29186295)
25. Crowley MM, Fredersdorf A, Schroeder B, et al. The influence of guaifenesin and ketoprofen on the properties of hot-melt extruded polyethylene oxide films. Eur J Pharm Sci 2004;22(5):409-18 (Pubitemid 38953899)
26. Crowley MM, Zhang F, Koleng JJ, et al. Stability of polyethylene oxide in matrix tablets prepared by hot-melt extrusion. Biomaterials 2002;23(21):4241-8 (Pubitemid 34814993)
27. Wu C, McGinity JW. Influence of methylparaben as a solid-state plasticizer on the physicochemical properties of Eudragit RS PO hot-melt extrudates. Eur J Pharm Biopharm 2003;56(1):95-100 (Pubitemid 36802052)
28. Schilling SU, Lirola HL, Shah NH, et al. Influence of plasticizer type and level on the properties of Eudragit S100 matrix pellets prepared by hot-melt extrusion. J Microencapsul 2010;27(6):521-32
29. De Brabander C, Vervaet C, Fiermans L, et al. Matrix mini-tablets based on starch/microcrystalline wax mixtures. Int J Pharm 2000;199(2):195-203 (Pubitemid 30236191)
30. Verhoeven E, Vervaet C, Remon JP. Xanthan gum to tailor drug release of sustained-release ethylcellulose mini-matrices prepared via hot-melt extrusion: in vitro and in vivo evaluation. Eur J Pharm Biopharm 2006;63(3):320-30 (Pubitemid 43776225)
31. Schilling SU, Bruce CD, Shah NH, et al. Citric acid monohydrate as a release-modifying agent in melt extruded matrix tablets. Int J Pharm 2008;361(1-2):158-68
32. Thumma S, Majumdar S, ElSohly MA, et al. Chemical stability and bioadhesive properties of an ester prodrug of Delta 9-tetrahydrocannabinol in poly(ethylene oxide) matrices: effect of formulation additives. Int J Pharm 2008;362(1-2):126-32
33. 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 (Pubitemid 44200557)
34. Zhou F, Vervaet C, Remon JP. Matrix pellets based on the combination of waxes, starches and maltodextrins. Int J Pharm 1996;133(1-2):155-60 (Pubitemid 26163331)
35. Gryczke A, Schminke S, Maniruzzaman M, et al. 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
36. Repka MA, McGinity JW. Influence of chlorpheniramine maleate on topical hydroxypropylcellulose films produced by hot-melt extrusion. Pharm Dev Technol 2001;6(3):297-304 (Pubitemid 32678235)
37. Mididoddi PK, Prodduturi S, Repka MA. Influence of tartaric acid on the bioadhesion and mechanical properties of hot-melt extruded hydroxypropyl cellulose films for the human nail. Drug Dev Ind Pharm 2006;32(9):1059-66 (Pubitemid 44521823)
38. Mididoddi PK, Repka MA. Characterization of hot-melt extruded drug delivery systems for onychomycosis. Eur J Pharm Biopharm 2007;66(1):95-105 (Pubitemid 46412960)
39. Prodduturi S, Manek RV, Kolling WM, et al. Water vapor sorption of hot-melt extruded hydroxypropyl cellulose films: effect on physico-mechanical properties, release characteristics, and stability. J Pharm Sci 2004;93(12):3047-56 (Pubitemid 39657808)
40. Bruce C, Fegely KA, Rajabi-Siahboomi AR, et al. Crystal growth formation in melt extrudates. Int J Pharm 2007;341(1-2):162-72 (Pubitemid 47088120)
41. Sri Venkata S, Tumuluri SP, Michael M, 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
42. Ingo Alig DF, Lellinger D, Steinhoff B. Combination of NIR, raman, ultrasonic and dielectric spectroscopy for in-line monitoring of the extrusion process. Macromol Symp 2005;230(1):51-8 (Pubitemid 43120137)
43. Mollan M. Historical Overview. Marcel Dekker, Inc; New York, Ny: 2003
44. Ferns A. Twin-screw machines for polymer compounding operations. Plast Polym 1974;42(8):149-57
45. Breitenbach J, Grabowski S, Rosenbberg J. Extrusion von polymer-wirkstoff-gemischen zur herstellung von Arzneiformen. Spektrum der Wissenschaft 1995;11:18-19
46. Trey SM, Wicks DA, Mididoddi PK, et al. Delivery of itraconazole from extruded HPC films. Drug Dev Ind Pharm 2007;33(7):727-35 (Pubitemid 47123800)
47. Young CR, Koleng JJ, McGinity JW. Production of spherical pellets by a hot-melt extrusion and spheronization process. Int J Pharm 2002;242(1-2):87-92
48. 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 (Pubitemid 44537498)
49. Quinten T, Gonnissen Y, Adriaens E, et al. Development of injection moulded matrix tablets based on mixtures of ethylcellulose and low-substituted hydroxypropylcellulose. Eur J Pharm Sci 2009;37(3-4):207-16
50. Robinson JR, Mcginity JW, Ethypharm SA. inventors Effervescent granules and methods for their preparation. US6071539. 2000
51. Dreiblatt A. editor. Process design. Marcel Dekker, Inc; New York: 2003
52. Doetsch W. editor. Material handling and feeder technology. Marcel Dekker, Inc.; New York: 2003
53. Liu L, Wang P, Xanthos M, et al. Review Paper: Processing aspects of Hot Melt Extrusion in Pharmaceutical Applications. ANTEC; Chicago: 2009. p. 2370-5
54. Arnum Atfmb PV. Exploring excipient functionality. Pharm Technol 2011;35:6-11
55. Thompson MR, Sun J. Wet granulation in a twin-screw extruder: implications of screw design. J Pharm Sci 2010;99(4):2090-103
56. Nakamichi K, Nakano T, Yasuura H, et al. 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 (Pubitemid 34718022)
57. Mccrum NG, Buckley CP. editors. Principles of polymer engineering. Oxford University Press; Oxford: 1997
58. Rauwendaal C. editor. Polymer extrusion. 3rd edition. Hanser Publisher; Munich: 1994
59. Repka MA, McGinity JW, Zhang F, et al. editors. Hot-melt extrusion technology. 2nd edition. Marcel Dekker, Inc.; New York: 2002
60. Saerens L, Dierickx L, Lenain B, et al. 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
61. Dhumal RS, Kelly AL, York P, et al. Cocrystalization and simultaneous agglomeration using hot melt extrusion. Pharm Res 2010;27(12):2725-33
62. van Laarhoven JA, Kruft MA, Vromans H. Effect of supersaturation and crystallization phenomena on the release properties of a controlled release device based on EVA copolymer. J Control Release 2002;82(2-3):309-17 (Pubitemid 34880186)
63. van Laarhoven JA, Kruft MA, Vromans H. In vitro release properties of etonogestrel and ethinyl estradiol from a contraceptive vaginal ring. Int J Pharm 2002;232(1-2):163-73 (Pubitemid 34076762)
64. Dierickx L, Saerens L, Almeida A, et al. Co-extrusion as manufacturing technique for fixed-dose combination mini-tablets [abstract ID: W5073]. American Association of Pharmaceutical Scientists Annual Meeting; Washington Convention Center, Washington, DC; 2011
65. Reitz C, Kleinebudde P. Solid lipid extrusion of sustained release dosage forms. Eur J Pharm Biopharm 2007;67(2):440-8 (Pubitemid 47211916)
66. Windbergs M, Gueres S, Strachan CJ, et al. Two-step solid lipid extrusion as a process to modify dissolution behavior. AAPS PharmSciTech 2010;11(1):2-8
67. Aharoni SM. Increased glass transition temperature in motionally constrained semicrystalline polymers. Polym Adv Technol 1998;9(3):169-201 (Pubitemid 128606534)
68. 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 (Pubitemid 24201240)
69. Aitken-Nichol C, Zhang F, McGinity JW. Hot melt extrusion of acrylic films. Pharm Res 1996;13(5):804-8 (Pubitemid 26160100)
70. Repka MA, McGinity JW. Influence of vitamin E TPGS on the properties of hydrophilic films produced by hot-melt extrusion. Int J Pharm 2000;202(1-2):63-70 (Pubitemid 30466230)
71. 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(3):243-50
72. Verreck G, Decorte A, Heymansa K, et al. The effect of pressurized carbon dioxide as a temporary plasticize and foaming agnet on the hot stage extruion process and extrudate properties of solid dispersion of itraconzaole with PVP-VA 64. Eur J Pharm Sci 2005;26(3-4):349-58 (Pubitemid 41278641)
73. Physical and Chemical Properties, Klucel-Hydroxypropylcellulose. Hercules Inc. Aqualon Division; Wilmington DE: 1997. p. 2-6
74. Physical and Chemical Properties, Aqualon-Ethylcellulose. Technical Bulletin. Hercules, Inc; Wilmington: 1996. p. 250-2
75. Bailey FE, Koleske JV. Poly(ethylene oxide). Academic Press; New York: 1976
76. Perissutti B, Newton JM, Fea P. Preparation of extruded carbamazepine and PEG 4000 as a potential rapid release dosage form. Eur J Pharm Biopharm 2002;53(1):125-32 (Pubitemid 34037004)
77. Mank R, Kala H, Richter M. Preparation of extrusion pellets containing drugs on the base of thermoplastics. 2. Investigations on the improvement of the drug release on the base of thermoplastics. Pharmazie 1990;45(8):592-3 (Pubitemid 20356307)
78. McGinity JW, Koleng JJ. Preparation and Evaluation of Rapid-Release Granules using a Novel Hot-Melt Extrusion Technique. Pharmaceutical Technology Conference: Pharmaceutical technology; 1997. p. 153-4
79. Fu J, Xu L, Wang X, et al. Nimodipine (NM) tablets with high dissolution containing NM solid dispersions prepared by hot-melt extrusion. Drug Dev Ind Pharm 2011;37(8):934-44
80. Sun Y, Rui Y, Wenliang Z, et al. Nimodipine semi-solid capsules containing solid dispersion for improving dissolution. Int J Pharm 2008;359(1-2):144-9
81. Sherry R. inventor. Reckitt Benckiser Healthcare (UK) Limited assignee. Granules comprising paracetamol, a NSAID and a sugar alcohol made by melt extrusion patent. EP1799195; 2007
82. Mohammed N, Majumdar S, Repka MA, et al. Tablets manufactured via HME as a processing technique for solubility enhancement: Stability assessment and in vitro release comparison to a marketed fromulation [abstract ID: #T3277]. American Association of Pharmaceutical Scientists Annual Meeting and Exposition; Washington Convention Center, Washington, DC, USA; 2011
83. Maddineni S, Langley N, Repka MA, et al. Formulation, evalutation and comparison of nifedipine hot-melt extruded tablets [abstract ID: #R6052]. American Association of Pharmaceutical Scientists Annual Meeting; New Orleans, LA; 2010
84. Ali S, Langley N, Djuric D, et al. Eye on excipients: Soluplus, a novel graft copolymer. Tablets & Capsules; 2010
85. De Brabander C, Vervaet C, Van Bortel L. Bioavailability of ibuprofen from hot-melt extruded mini-matrices. Int J Pharm 2004;271(1-2):77-84 (Pubitemid 38210086)
86. 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
87. Almeida A, Possemiers S, Boone MN, et al. Ethylene vinyl acetate as matrix for oral sustained release dosage forms produced via hot-melt extrusion. Eur J Pharm Biopharm 2011;77(2):297-305
88. Verhoeven E, De Beer T, Schacht E, et al. Influence of polyethylene glycol/polyethylene oxide on the release characteristics of sustained-release ethylcellulose mini-matrices produced by hot-melt extrusion: in vitro and in vivo evaluations. Eur J Pharm Biopharm 2009;72(2):463-70
89. Quintavalle U, Voinovich D, Bea P. Preparation of sustained release co-extrudates by hot-melt extrusion and mathematical modelling of in vitro/in vivo drug release profiles. Eur J Pharm Sci 2008;33(3):282-93
90. Andrews GP, Jones DS, Diak OA, et al. The manufacture and characterisation of hot-melt extruded enteric tablets. Eur J Pharm Biopharm 2008;69(1):264-73
91. Schilling SU, McGinity JW. Novel application of hot-melt extrusion for the preparation of monolithic matrices containing enteric-coated particles. Int J Pharm 2010;400(1-2):24-31
92. Miller DA, DiNunzio JC, Yang W, et al. Targeted Intestinal Delivery of Supersaturated Itraconazole for Improved Oral Absorption. Pharm Res 2008;25(6):1450-9
93. Cassidy CM, Tunney MM, Caldwell DL, et al. 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
94. Bruce LD, Shah NH, Malick AW, et al. Properties of hot-melt extruded tablet formulations for the colonic delivery of 5-aminosalicylic acid. Eur J Pharm Biopharm 2005;59(1):85-97 (Pubitemid 39573440)
95. Breitenbach A, Meese C, Wolff H-M, et al. inventors. Transdermal delivery of (R)-3,3-diphenylpropylamin-monoestern patent. US20090274761; 2009
96. Crowley M. inventor. Process for the preparation of a hot-melt extruded laminate patent. US0136555; 2009
97. Prodduturi S, Manek RV, Kolling WM, et al. Solid-state stability and characterization of hot-melt extruded poly(ethylene oxide) films. J Pharm Sci 2005;94(10):2232-45 (Pubitemid 41665283)
98. Munjal M, Stodghill SP, Elsohly MA, et al. Polymeric systems for amorphous Delta 9-tetrahydrocannabinol produced by a hot-melt method. Part I: chemical and thermal stability during processing. J Pharm Sci 2006;95(8):1841-53 (Pubitemid 44229590)
99. Munjal M, Elsohly MA, Repka MA. Polymeric systems for amorphous Delta9-tetrahydrocannabinol produced by a hot-melt method. Part II: Effect of oxidation mechanisms and chemical interactions on stability. J Pharm Sci 2006;95(11):2473-85 (Pubitemid 44726387)
100. Palem C, Battu S, Maddineni S, et al. Oral transmucosal delivery of domperidone from immediate release films produced via hot-melt extrusion technology. Pharm Dev Technol 2011; In press
101. Fuisz RC. inventor. Smokeless Tobacco Product patent. US0242978; 2010
102. Fuisz RC. inventor. Extrudable and Extruded Compositions for Delivery of Bioactive Agents, Method of Making Same and Method of Using Same patent. US0098192; 2009
103. Repka MA, Mididoddi PK, Stodghill SP. Influence of human nail etching for the assessment of topical onychomycosis therapies. Int J Pharm 2004;282(1-2):95-106 (Pubitemid 39178487)
104. Repka MA, inventor University of Mississippi (University, MS), assignee. Delivery of medicaments to the nail United States patent 7,959,904. 2011
105. Rothen-Weinhold A, Oudry N, Schwach-Abdellaoui K, et al. Formation of peptide impurities in polyester matrices during implant manufacturing. Eur J Pharm Biopharm 2000;49(3):253-7 (Pubitemid 30229874)
106. Bhardwaj R, Blanchard J. In vitro evaluation of Poly(d,l-lactide- coglycolide) polymer-based implants containing the alpha-melanocyte stimulating hormone analog, Melanotan-I. J Control Release 1997;45:49-55 (Pubitemid 27055792)
107. Grewell D, Benatar A. Welding of Plastics: Fundamentals and New Developments. Intern Polymer Process 2007;1:43-60
108. Johnson TJ, Gupta KM, Fabian J, et al. Segmented polyurethane intravaginal rings for the sustained combined delivery of antiretroviral agents dapivirine and tenofovir. Eur J Pharm Sci 2010;39(4):203-12