Skip to content
2000
Volume 31, Issue 27
  • ISSN: 1381-6128
  • E-ISSN: 1873-4286

Abstract

For the pharmaceutical industry, hot-melt extrusion (HME) has become a cutting-edge production process. Compared to conventional procedures, HME is a solvent-free approach that offers numerous applications, cost-effectiveness, and continuous manufacturing. Studying the formulation and process characteristics should be prioritized in order to satisfy requirements. Many distinct dosage forms for different purposes can be formulated by altering the equipment design and a few processing parameters. For the intended outcome, the HME process must run smoothly and continuously. In this regard, pre-formulation study plays a main role in selecting the carrier, drug, and other required excipients. This review provides a comprehensive understanding of various equipment parts, HME materials and processes, formulation development, and HME in the delivery of drugs. It also highlights the applications and patents of HME.

Loading

Article metrics loading...

/content/journals/cpd/10.2174/0113816128357733250324054151
2025-04-21
2025-10-26
Loading full text...

Full text loading...

References

  1. CrowleyM.M. ZhangF. RepkaM.A. Pharmaceutical applications of hot-melt extrusion: Part I.Drug Dev. Ind. Pharm.200733990992610.1080/03639040701498759 17891577
    [Google Scholar]
  2. NukalaP.K. PalekarS. PatkiM. FuY. PatelK. Multi-dose oral abuse deterrent formulation of loperamide using hot melt extrusion.Int. J. Pharm.201956911862910.1016/j.ijpharm.2019.118629 31425818
    [Google Scholar]
  3. YangY. ShenL. LiJ. ShanW. Preparation and evaluation of metoprolol tartrate sustained-release pellets using hot melt extrusion combined with hot melt coating.Drug Dev. Ind. Pharm.201743693994610.1080/03639045.2017.1287715 28128647
    [Google Scholar]
  4. MillerD.A. DiNunzioJ.C. YangW. McGinityJ.W. WilliamsR.O.III Targeted intestinal delivery of supersaturated itraconazole for improved oral absorption.Pharm. Res.20082561450145910.1007/s11095‑008‑9543‑1 18288449
    [Google Scholar]
  5. KhorC.M. NgW.K. KanaujiaP. ChanK.P. DongY. Hot-melt extrusion microencapsulation of quercetin for taste-masking.J. Microencapsul.2017341293710.1080/02652048.2017.1280095 28067579
    [Google Scholar]
  6. RepkaM.A. MajumdarS. BattuK.S. SrirangamR. UpadhyeS.B. Applications of hot-melt extrusion for drug delivery.Expert Opin. Drug Deliv.20085121357137610.1517/17425240802583421 19040397
    [Google Scholar]
  7. HuangS. O’DonnellK.P. Delpon de VauxS.M. O’BrienJ. StutzmanJ. WilliamsR.O.III Processing thermally labile drugs by hot-melt extrusion: The lesson with gliclazide.Eur. J. Pharm. Biopharm.2017119566710.1016/j.ejpb.2017.05.014 28583588
    [Google Scholar]
  8. LenzE. LöbmannK. RadesT. KnopK. KleinebuddeP. Hot melt extrusion and spray drying of co-amorphous indomethacin-arginine with polymers.J. Pharm. Sci.2017106130231210.1016/j.xphs.2016.09.027 27817830
    [Google Scholar]
  9. GhalanborZ. KörberM. BodmeierR. Improved lysozyme stability and release properties of poly(lactide-co-glycolide) implants prepared by hot-melt extrusion.Pharm. Res.201027237137910.1007/s11095‑009‑0033‑x 20033474
    [Google Scholar]
  10. CruzC.N. MaduraweR. PavuralaN. ChatterjeeS. Control strategy considerations for continuous manufacturing using hot melt extrusion.In: Pharmaceutical Extrusion Technology.2nd edCRC Press20185370
    [Google Scholar]
  11. McGinityJ.W. ZhangF. KolengJ.J. RepkaM.A. Hot-melt extrusion as a pharmaceutical process.Am. Pharm. Rev.2001422536
    [Google Scholar]
  12. SarabuS. BandariS. KallakuntaV.R. TiwariR. PatilH. RepkaM.A. An update on the contribution of hot-melt extrusion technology to novel drug delivery in the twenty-first century: Part II.Expert Opin. Drug Deliv.201916656758210.1080/17425247.2019.1614912 31046479
    [Google Scholar]
  13. ZhangJ. FengX. PatilH. TiwariR.V. RepkaM.A. Coupling 3D printing with hot-melt extrusion to produce controlled-release tablets.Int. J. Pharm.20175191-218619710.1016/j.ijpharm.2016.12.049 28017768
    [Google Scholar]
  14. YeX. PatilH. FengX. Conjugation of hot-melt extrusion with high-pressure homogenization: A novel method of continuously preparing nanocrystal solid dispersions.AAPS PharmSciTech2016171788810.1208/s12249‑015‑0389‑7 26283197
    [Google Scholar]
  15. DanielT.S.S. Pellet production by hot melt extrusion and die] face pelletisin.2013Available from: https://graz.elsevierpure.com/en/publications/pellet-production-by-hot-melt-extrusion-and-die-face-pelletising
    [Google Scholar]
  16. ManiruzzamanM. NokhodchiA. Continuous manufacturing via hot-melt extrusion and scale up: Regulatory matters.Drug Discov. Today201722234035110.1016/j.drudis.2016.11.007 27866007
    [Google Scholar]
  17. United States Department of Health and Human ServicesGuidance for Industry: PAT-A framework for innovative pharmaceutical development, manufacturing, and quality assurance: Pharmaceutical CGMP.Food and Drug Administration2004
    [Google Scholar]
  18. DadouS.M. Senta-LoysZ. AlmajaanA. The development and validation of a quality by design based process analytical tool for the inline quantification of Ramipril during hot-melt extrusion.Int. J. Pharm.202058411938210.1016/j.ijpharm.2020.119382 32360547
    [Google Scholar]
  19. ICH Harmonised Tripartite GuidelinePharmaceutical Development. Q8(R2).2009Available from: https://database.ich.org/sites/default/files/Q8_R2_Guideline.pdf
    [Google Scholar]
  20. NagyB. FarkasA. GyürkésM. In-line Raman spectroscopic monitoring and feedback control of a continuous twin-screw pharmaceutical powder blending and tableting process.Int. J. Pharm.20175301-2212910.1016/j.ijpharm.2017.07.041 28723408
    [Google Scholar]
  21. IbrahimM. ZhangJ. RepkaM. ChenR. Characterization of the solid physical state of API and its distribution in pharmaceutical hot melt extrudates using terahertz raman imaging.AAPS PharmSciTech20192026210.1208/s12249‑018‑1282‑y 30627934
    [Google Scholar]
  22. IslamM.T. ScoutarisN. ManiruzzamanM. Implementation of transmission NIR as a PAT tool for monitoring drug transformation during HME processing.Eur. J. Pharm. Biopharm.20159610611610.1016/j.ejpb.2015.06.021 26209124
    [Google Scholar]
  23. KrierF. MantanusJ. SacréP.Y. PAT tools for the control of co-extrusion implants manufacturing process.Int. J. Pharm.20134581152410.1016/j.ijpharm.2013.09.040 24148661
    [Google Scholar]
  24. WesholowskiJ. PrillS. BerghausA. ThommesM. Inline UV/Vis spectroscopy as PAT tool for hot-melt extrusion.Drug Deliv. Transl. Res.2018861595160310.1007/s13346‑017‑0465‑5 29327264
    [Google Scholar]
  25. KellyA.L. GoughT. IsrebM. In-process rheometry as a] PAT tool for hot melt extrusion.Drug Dev. Ind. Pharm.201844467067610.1080/03639045.2017.1408641 29161918
    [Google Scholar]
  26. HitzerP. BäuerleT. DrieschnerT. Process analytical techniques for hot-melt extrusion and their application to amorphous solid dispersions.Anal. Bioanal. Chem.2017409184321433310.1007/s00216‑017‑0292‑z 28343348
    [Google Scholar]
  27. DarwichM. MohylyukV. KolterK. BodmeierR. DashevskiyA. An approach for pH-independent release of poorly soluble ionizable drugs using hot-melt extrusion.J. Drug Deliv. Sci. Technol.202410010602710.1016/j.jddst.2024.106027
    [Google Scholar]
  28. YangF. StahnkeR. LawalK. Development of poly (lactic-co-glycolic acid) (PLGA) based implants using hot melt extrusion (HME) for sustained release of drugs: The impacts of PLGA’s material characteristics.Int. J. Pharm.202466312455610.1016/j.ijpharm.2024.124556
    [Google Scholar]
  29. MüllerV. CaldasB.S. RadovanovicE. MunizE.C. Development of hot melt extruded polycaprolactone (PCL) matrices for an oral ultra-long-lasting delivery of galantamine for Alzheimer’s disease therapy.J. Drug Deliv. Sci. Technol.202510410646410.1016/j.jddst.2024.106464
    [Google Scholar]
  30. KawakamiK. IshitsukaT. FukiageM. Long-term physical stability of amorphous solid dispersions: Comparison of detection powers of common evaluation methods for spray-dried and hot-melt extruded formulations.J. Pharm. Sci.2024114114515610.1016/j.xphs.2024.06.020 38950881
    [Google Scholar]
  31. WangH. ChenX. YangH. A novel gelatin composite film with melt extrusion for walnut oil packaging.Food Chem.202546214102110.1016/j.foodchem.2024.141021 39226644
    [Google Scholar]
  32. ElkanayatiR.M. DarweshA.Y. TahaI. Quality by design approach for fabrication of extended-release buccal films for xerostomia employing hot-melt extrusion technology.Eur. J. Pharm. Biopharm.202420011433510.1016/j.ejpb.2024.114335 38768765
    [Google Scholar]
  33. AlmutairiM. HefnawyA. AlmotairyA. Formulation and evaluation of inhaled Sildenafil-loaded PLGA microparticles for treatment of pulmonary arterial hypertension (PAH): A novel high drug loaded formulation and scalable process via hot melt extrusion technology (Part I).Int. J. Pharm.202465512404410.1016/j.ijpharm.2024.124044 38527563
    [Google Scholar]
  34. ElkanayatiR.M. OmariS. YoussefA.A.A. Multilevel categoric factorial design for optimization of raloxifene hydrochloride solid dispersion in PVP K30 by hot-melt extrusion technology.J. Drug Deliv. Sci. Technol.20249210536210.1016/j.jddst.2024.105362
    [Google Scholar]
  35. GhatoleS. DilipJ. AshokbhaiM.K. VishwakarmaH. BanerjeeS.K.S. Hot melt extrusion assisted additive manufacturing of mixed polymeric 3D printed metoprolol succinate extended-release tablets for controlled oral drug delivery.Chem Phy Imp202510100811
    [Google Scholar]
  36. ZhangP. WangH. ChungS. LiJ. VemulaS.K. RepkaM.A. Fabrication of suppository shells via hot-melt extrusion paired with fused deposition modeling 3D printing techniques.J. Drug Deliv. Sci. Technol.20249410549110.1016/j.jddst.2024.105491
    [Google Scholar]
  37. PartheniadisI. NikolakakisI. Development and characterization of co-amorphous griseofulvin/L-leucin by modified solvent processing hot-melt extrusion.Int. J. Pharm.202465212382410.1016/j.ijpharm.2024.123824 38246478
    [Google Scholar]
  38. RyuS.J. YouH.S. LeeH.Y. BaekJ.S. Manufacture of mesoporous silica coated multi-walled carbon nanotubes containing silver nanoparticles synthesized by Angelica gigas Nakai using hot-melt extrusion for enhanced antimicrobial activities.Colloids Surf. A Physicochem. Eng. Asp.202469313402310.1016/j.colsurfa.2024.134023
    [Google Scholar]
  39. LukerK. Single-screw extrusion: Principles.Hot-Melt Extrusion: Pharmaceutical Applications.Douroumis D, Ed.; John Wiley & Sons, Ltd.2012[https://dx.doi.org/10.1002/9780470711415.ch1
    [Google Scholar]
  40. StevensM.J. CovasJ.A. Operation of single-screw extruders.Extruder Principles and Operation.Springer, Dordrecht199527031510.1007/978‑94‑011‑0557‑6_9
    [Google Scholar]
  41. MollanM. Historical overview.Pharmaceutical Extrusion Technology2003133118Available from: https://www.researchgate.net/publication/329320238_Historical_overview
    [Google Scholar]
  42. ThieleW. Twin-screw extrusion and screw design.Pharmaceutical Extrusion2nd ed.CRC Press2018Available from: https://www.taylorfrancis.com/chapters/edit/10.1201/9781351129015-4/twin-screw-extrusion-screw-design-william-thiele
    [Google Scholar]
  43. RepkaM.A. McGinityJ.W. ZhangF. KolengJ.J. Hot-melt extrusion technology.Encyclopedia of Pharmaceutical Technology4th ed.CRC Press2013Vol. 6Available from: https://www.taylorfrancis.com/chapters/edit/10.1081/E-EPT4-120050288/hot-melt-extrusion-technology-michael-repka-johnkoleng-feng-zhang-james-mcginity
    [Google Scholar]
  44. LoukusJ.E. HalonenA.C. GuptaM. Elongational flow in multiple screw extruders.Conf Proceed20041133137
    [Google Scholar]
  45. BialleckS. ReinH. Preparation of starch-based pellets by hot-melt extrusion.Eur. J. Pharm. Biopharm.201179244044810.1016/j.ejpb.2011.04.007 21570466
    [Google Scholar]
  46. VerreckG. The influence of plasticizers in hot-melt extrusion. DouroumisD. Hot-Melt Extrusion: Pharmaceutical Applications.John Wiley & Sons201210.1002/9780470711415.ch5
    [Google Scholar]
  47. RepkaM.A. ShahS. LuJ. Melt extrusion: Process to product.Expert Opin. Drug Deliv.20129110512510.1517/17425247.2012.642365 22145932
    [Google Scholar]
  48. MiyagawaY. OkabeT. YamaguchiY. MiyajimaM. SatoH. SunadaH. Controlled-release of diclofenac sodium from wax matrix granule.Int. J. Pharm.1996138221522410.1016/0378‑5173(96)04547‑4
    [Google Scholar]
  49. TantishaiyakulV. KaewnopparatN. IngkatawornwongS. Properties of solid dispersions of piroxicam in polyvinylpyrrolidone.Int. J. Pharm.1999181214315110.1016/S0378‑5173(99)00070‑8 10370210
    [Google Scholar]
  50. ZingoneG. MoneghiniM. RupenaP. VojnovicD. Characterization and dissolution study of solid dispersions of theophylline and indomethacin with PVP/VA copolymers.STP Pharma Sciences199222186192
    [Google Scholar]
  51. FollonierN. DoelkerE. ColeE.T. Various ways of modulating the release of diltiazem hydrochloride from hot-melt extruded sustained release pellets prepared using polymeric materials.J. Control. Release199536324325010.1016/0168‑3659(95)00041‑6
    [Google Scholar]
  52. PerissuttiB. NewtonJ.M. PodczeckF. RubessaF. Preparation of extruded carbamazepine and PEG 4000 as a potential rapid release dosage form.Eur. J. Pharm. Biopharm.200253112513210.1016/S0939‑6411(01)00209‑0 11777760
    [Google Scholar]
  53. YanoK. KajiyamaA. HamadaM. YamamotoK. Constitution of colloidal particles formed from a solid dispersion system.Chem. Pharm. Bull.19974581339134410.1248/cpb.45.1339
    [Google Scholar]
  54. BaryA.A. GeneidiA.S. AminS.T. Abu El AinanA. Preparation and pharmacokinetic evaluation of carbamazepine controlled release solid dispersion granules.J Drug Res Egypt1998221-21531
    [Google Scholar]
  55. LiL. AbuBakerO. ShaoZ.J. Characterization of poly(ethylene oxide) as a drug carrier in hot-melt extrusion.Drug Dev. Ind. Pharm.2006328991100210.1080/03639040600559057 16954112
    [Google Scholar]
  56. RepkaM.A. GerdingT.G. RepkaS.L. McGinityJ.W. Influence of plasticizers and drugs on the physical-mechanical properties of hydroxypropylcellulose films prepared by hot melt extrusion.Drug Dev. Ind. Pharm.199925562563310.1081/DDC‑100102218 10219532
    [Google Scholar]
  57. AhmedHA AlfredsonTV BirudarajK Pharmaceutical composition and process.Patent U.S. 7,795,2372010
    [Google Scholar]
  58. RepkaM.A. McGinityJ.W. Influence of chlorpheniramine maleate on topical hydroxypropylcellulose films produced by hot-melt extrusion.Pharm. Dev. Technol.20016329730410.1081/PDT‑100002610 11485171
    [Google Scholar]
  59. QuintenT. AndrewsG.P. BeerD.T. Preparation and evaluation of sustained-release matrix tablets based on metoprolol and an acrylic carrier using injection moulding.AAPS PharmSciTech20121341197121110.1208/s12249‑012‑9848‑6 22965662
    [Google Scholar]
  60. HancockB.C. ZografiG. Characteristics and significance of the amorphous state in pharmaceutical systems.J. Pharm. Sci.199786111210.1021/js9601896 9002452
    [Google Scholar]
  61. FollonierN. DoelkerE. ColeE.T. 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.19942081323133910.3109/03639049409038373
    [Google Scholar]
  62. CuffG. RaoufF. A preliminary evaluation of injection moulding as a tabletting technology.Pharma Tech Europe19991141826
    [Google Scholar]
  63. Aitken-NicholC. ZhangF. McGinityJ.W. Hot melt extrusion of acrylic films.Pharm. Res.199613580480810.1023/A:1016076306279 8860442
    [Google Scholar]
  64. MehuysE. RemonJ.P. VervaetC. Production of enteric capsules by means of hot-melt extrusion.Eur. J. Pharm. Sci.2005242-320721210.1016/j.ejps.2004.10.011 15661492
    [Google Scholar]
  65. RepkaM.A. McGinityJ.W. Physical-mechanical, moisture absorption and bioadhesive properties of hydroxypropylcellulose hot-melt extruded films.Biomaterials200021141509151710.1016/S0142‑9612(00)00046‑6 10872780
    [Google Scholar]
  66. GhebremeskelA.N. VemavarapuC. LodayaM. Use of surfactants as plasticizers in preparing solid dispersions of poorly soluble API: Stability testing of selected solid dispersions.Pharm. Res.20062381928193610.1007/s11095‑006‑9034‑1 16871443
    [Google Scholar]
  67. Brabander dC, van den Mooter G, Vervaet C, Remon JP. Characterization of ibuprofen as a nontraditional plasticizer of ethyl cellulose.J. Pharm. Sci.20029171678168510.1002/jps.10159 12115829
    [Google Scholar]
  68. VerreckG. SixK. Van den MooterG. BaertL. PeetersJ. BrewsterM.E. Characterization of solid dispersions of itraconazole and hydroxypropylmethylcellulose prepared by melt extrusion—part I.Int. J. Pharm.20032511-216517410.1016/S0378‑5173(02)00591‑4 12527186
    [Google Scholar]
  69. SixK. BerghmansH. LeunerC. Characterization of solid dispersions of itraconazole and hydroxypropylmethylcellulose prepared by melt extrusion, Part II.Pharm. Res.20032071047105410.1023/A:1024414423779 12880291
    [Google Scholar]
  70. LakshmanJ.P. CaoY. KowalskiJ. SerajuddinA.T.M. 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.200856994100210.1021/mp8001073 19434852
    [Google Scholar]
  71. FlemingO.S. KazarianS.G. Polymer Processing with Supercritical Fluids.Pol Sci Ser200642178101
    [Google Scholar]
  72. KiranE. Polymer formation, modifications and processing in or with supercritical fluids. KiranE. SengersJ.M.H.L. Supercritical Fluids, NATO ASI Series.ChamSpringer, Dordrecht1994Vol. 27354158810.1007/978‑94‑015‑8295‑7_22
    [Google Scholar]
  73. ChiouJ.S. BarlowJ.W. PaulD.R. Plasticization of glassy polymers by CO 2.J. Appl. Polym. Sci.19853062633264210.1002/app.1985.070300626
    [Google Scholar]
  74. VerreckG. DecorteA. LiH. 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. Fluids200638338339110.1016/j.supflu.2005.11.022
    [Google Scholar]
  75. DoetschW. Material handling and feeder technology.Pharmaceutical Extrusion Technology2003111134Available from: https://www.researchgate.net/publication/329320454_Material_handling_and_feeder_technology
    [Google Scholar]
  76. LukerK. Single-screw extrusion and screw design.Pharmaceutical Extrusion Technology20033968Available from: https://www.researchgate.net/publication/329320559_Single-screw_extrusion_and_screw_design
    [Google Scholar]
  77. GriffA.L. Plastics extrusion technology.2nd edReinhold Pub. Corp, New York1962Available from: https://archive.org/details/plasticsextrusio02edunse
    [Google Scholar]
  78. MccrumN.G. BuckleyC.P. BucknallC.B. Principles of Polymer Engineering.2nd edOxford University Press1997
    [Google Scholar]
  79. RauwendaalC. Polymer Extrusion.5th edHanser; Munich, Germany1994
    [Google Scholar]
  80. GoffJ. WhelanT. The Dynisco Extrusion Processors.LondonSchool of Polymer Technology19881259
    [Google Scholar]
  81. McGinityJWZF Melt-extruded controlled-release dosage forms.CRC Press: Pharmaceutical Extrusion Technology200318320810.1201/9780203911532.ch10
    [Google Scholar]
  82. Process design Ghebre-SellassieI. Marcel Dekker CRC Press: Pharmaceutical Extrusion Technology2003
    [Google Scholar]
  83. BeylerC.L. HirschlerM.M. Thermal decomposition of polymers.Chemistry of Materials20112534953508
    [Google Scholar]
  84. JanssensS. Van den MooterG. Review: Physical chemistry of solid dispersions.J. Pharm. Pharmacol.200961121571158610.1211/jpp.61.12.0001 19958579
    [Google Scholar]
  85. HancockB.C. ShamblinS.L. ZografiG. Molecular mobility of amorphous pharmaceutical solids below their glass transition temperatures.Pharm. Res.199512679980610.1023/A:1016292416526 7667182
    [Google Scholar]
  86. YuL. Amorphous pharmaceutical solids: Preparation, characterization and stabilization.Adv. Drug Deliv. Rev.2001481274210.1016/S0169‑409X(01)00098‑9 11325475
    [Google Scholar]
  87. BhattacharyaS. SuryanarayananR. Local mobility in amorphous pharmaceuticals-characterization and implications on stability.J. Pharm. Sci.20099892935295310.1002/jps.21728 19499564
    [Google Scholar]
  88. VyazovkinS. DrancaI. Physical stability and relaxation of amorphous indomethacin.J. Phys. Chem. B200510939186371864410.1021/jp052985i 16853398
    [Google Scholar]
  89. QianF. HuangJ. HussainM.A. Drug-polymer solubility and miscibility: Stability consideration and practical challenges in amorphous solid dispersion development.J. Pharm. Sci.20109972941294710.1002/jps.22074 20127825
    [Google Scholar]
  90. PajulaK. TaskinenM. LehtoV.P. KetolainenJ. KorhonenO. Predicting the formation and stability of amorphous small molecule binary mixtures from computationally determined Flory-Huggins interaction parameter and phase diagram.Mol. Pharm.20107379580410.1021/mp900304p 20361760
    [Google Scholar]
  91. CraigD.Q.M. The mechanisms of drug release from solid dispersions in water-soluble polymers.Int. J. Pharm.2002231213114410.1016/S0378‑5173(01)00891‑2 11755266
    [Google Scholar]
  92. IvanisevicI. BatesS. ChenP. Novel methods for the assessment of miscibility of amorphous drug-polymer dispersions.J. Pharm. Sci.20099893373338610.1002/jps.21717 19283767
    [Google Scholar]
  93. QiS. BeltonP. NollenbergerK. ClaydenN. ReadingM. CraigD.Q.M. Characterisation and prediction of phase separation in hot-melt extruded solid dispersions: A thermal, microscopic and NMR relaxometry study.Pharm. Res.20102791869188310.1007/s11095‑010‑0185‑8 20585845
    [Google Scholar]
  94. SixK. MurphyJ. WeutsI. Identification of phase separation in solid dispersions of itraconazole and Eudragit E100 using microthermal analysis.Pharm. Res.200320113513810.1023/A:1022219429708 12608548
    [Google Scholar]
  95. ClarkM.R. JohnsonT.J. MccabeR.T. A hot-melt extruded intravaginal ring for the sustained delivery of the antiretroviral microbicide UC781.J. Pharm. Sci.2012101257658710.1002/jps.22781 21976110
    [Google Scholar]
  96. FriesenD.T. ShankerR. CrewM. SmitheyD.T. CuratoloW.J. NightingaleJ.A.S. Hydroxypropyl methylcellulose acetate succinate-based spray-dried dispersions: An overview.Mol. Pharm.2008561003101910.1021/mp8000793 19040386
    [Google Scholar]
  97. AlbersJ. AllesR. MatthéeK. KnopK. NahrupJ.S. KleinebuddeP. Mechanism of drug release from polymethacrylate-based extrudates and milled strands prepared by hot-melt extrusion.Eur. J. Pharm. Biopharm.200971238739410.1016/j.ejpb.2008.10.002 18951978
    [Google Scholar]
  98. AlonzoD.E. GaoY. ZhouD. MoH. ZhangG.G.Z. TaylorL.S. Dissolution and precipitation behavior of amorphous solid dispersions.J. Pharm. Sci.201110083316333110.1002/jps.22579 21607951
    [Google Scholar]
  99. MaruS.M. Matas dM, Kelly A, Paradkar A. Characterization of thermal and rheological properties of zidovidine, lamivudine and plasticizer blends with ethyl cellulose to assess their suitability for hot melt extrusion.Eur. J. Pharm. Sci.201144447147810.1016/j.ejps.2011.09.003 21925600
    [Google Scholar]
  100. KohlgrüberK. Co-rotating twin-screw extruders, fundamentals, technology, and applications, Hanser Publications2008Available from: https://www.amazon.com/Co-Rotating-Twin-Screw-Extruders-Fundamentals-Applications/dp/1569904227
  101. Ghebre-SellassieI Ghebre-SelassieI MartinCE ZhangF DiNunzioJ MartinC Pharmaceutical extrusion technology.CRC Press2003May 14.
    [Google Scholar]
  102. SherryR. Granules Comprising Paracetamol, a Nsaid and a Sugar Alchohol Made by Melt Extrusion.(UK) Limited: Reckitt Benckiser Healthcare2008
    [Google Scholar]
  103. MankR. KalaH. RichterM. Preparation of extrusion pellets containing drugs on the base of thermoplastics. 1. Investigation of drug release.Pharmazie19894411773776 2616625
    [Google Scholar]
  104. McginityJ.W. KolengJ.J. Preparation and evaluation of rapid-release granules using a novel hot-melt extrusion technique.Pharm. Technol.19972153154
    [Google Scholar]
  105. HülsmannS. BackensfeldT. KeitelS. BodmeierR. Melt extrusion - an alternative method for enhancing the dissolution rate of 17β-estradiol hemihydrate.Eur. J. Pharm. Biopharm.200049323724210.1016/S0939‑6411(00)00077‑1 10799815
    [Google Scholar]
  106. HülsmannS. BackensfeldT. BodmeierR. Stability of extruded 17 β-estradiol solid dispersions.Pharm. Dev. Technol.20016222322910.1081/PDT‑100002198 11416996
    [Google Scholar]
  107. CrowleyM.M. SchroederB. FredersdorfA. Physicochemical properties and mechanism of drug release from ethyl cellulose matrix tablets prepared by direct compression and hot-melt extrusion.Int. J. Pharm.2004269250952210.1016/j.ijpharm.2003.09.037 14706261
    [Google Scholar]
  108. YangR. WangY. ZhengX. MengJ. TangX. ZhangX. Preparation and evaluation of ketoprofen hot-melt extruded enteric and sustained-release tablets.Drug Dev. Ind. Pharm.2008341838910.1080/03639040701580572 18214759
    [Google Scholar]
  109. RippieE.G. JohnsonJ.R. Regulation of dissolution rate by pellet geometry.J. Pharm. Sci.196958442843110.1002/jps.2600580408 5787440
    [Google Scholar]
  110. YoungC.R. KolengJ.J. McGinityJ.W. Properties of drug-containing spherical pellets produced by a hot-melt extrusion and spheronization process.J. Microencapsul.200320561362510.3109/02652040309178350 12909545
    [Google Scholar]
  111. YoungC.R. DietzschC. McGinityJ.W. Compression of controlled-release pellets produced by a hot-melt extrusion and spheronization process.Pharm. Dev. Technol.200510113313910.1081/PDT‑49695 15776821
    [Google Scholar]
  112. YoungC.R. CrowleyM. DietzschC. McGinityJ.W. Physicochemical properties of film-coated melt-extruded pellets.J. Microencapsul.2007241577110.1080/02652040601058483 17438942
    [Google Scholar]
  113. MiyagawaY. SatoH. OkabeT. NishiyamaT. MiyajimaM. SunadaH. In vivo performance of wax matrix granules prepared by a twin-screw compounding extruder.Drug Dev. Ind. Pharm.199925442943510.1081/DDC‑100102192 10194597
    [Google Scholar]
  114. SatoH. MiyagawaY. OkabeT. MiyajimaM. SunadaH. Dissolution mechanism of diclofenac sodium from wax matrix granules.J. Pharm. Sci.199786892993410.1021/js960221w 9269871
    [Google Scholar]
  115. Gutierrez-roccaJ.C. McginityJ.W. Influence of aging on the physical-mechanical properties of acrylic resin films cast from aqueous dispersions and organic solutions.Drug Dev. Ind. Pharm.199319331533210.3109/03639049309038770
    [Google Scholar]
  116. ThummaS. MajumdarS. ElSohlyM.A. GulW. RepkaM.A. Chemical stability and bioadhesive properties of an ester prodrug of Δ9-tetrahydrocannabinol in poly(ethylene oxide) matrices: Effect of formulation additives.Int. J. Pharm.20083621-212613210.1016/j.ijpharm.2008.06.025 18652884
    [Google Scholar]
  117. ProdduturiS. ManekR.V. KollingW.M. StodghillS.P. RepkaM.A. Water vapor sorption of hot‐melt extruded hydroxypropyl cellulose films: Effect on physico‐mechanical properties, release characteristics, and stability.J. Pharm. Sci.200493123047305610.1002/jps.20222 15515008
    [Google Scholar]
  118. RepkaM.A. GuttaK. ProdduturiS. MunjalM. StodghillS.P. Characterization of cellulosic hot-melt extruded films containing lidocaine.Eur. J. Pharm. Biopharm.200559118919610.1016/j.ejpb.2004.06.008 15567317
    [Google Scholar]
  119. ProdduturiS. ManekR.V. KollingW.M. StodghillS.P. RepkaM.A. Solid-state stability and characterization of hot-melt extruded poly(ethylene oxide) films.J. Pharm. Sci.200594102232224510.1002/jps.20437 16136579
    [Google Scholar]
  120. MunjalM. StodghillS.P. ElSohlyM.A. RepkaM.A. Polymeric systems for amorphous Δ9-tetrahydrocannabinol produced by a hot-melt method. Part I: Chemical and thermal stability during processing.J. Pharm. Sci.20069581841185310.1002/jps.20667 16795020
    [Google Scholar]
  121. RepkaM.A. MunjalM. ElSohlyM.A. RossS.A. Temperature stability and bioadhesive properties of delta9-tetrahydrocannabinol incorporated hydroxypropylcellulose polymer matrix systems.Drug Dev. Ind. Pharm.2006321213210.1080/03639040500387914 16455601
    [Google Scholar]
  122. RepkaM.A. ProdduturiS. StodghillS.P. Production and characterization of hot-melt extruded films containing clotrimazole.Drug Dev. Ind. Pharm.200329775776510.1081/DDC‑120021775 12906333
    [Google Scholar]
  123. MididoddiP.K. ProdduturiS. RepkaM.A. 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.20063291059106610.1080/03639040600683410 17012118
    [Google Scholar]
  124. MididoddiP.K. RepkaM.A. Characterization of hot-melt extruded drug delivery systems for onychomycosis.Eur. J. Pharm. Biopharm.20076619510510.1016/j.ejpb.2006.08.013 17045468
    [Google Scholar]
  125. Rothen-WeinholdA. OudryN. Schwach-AbdellaouiK. Formation of peptide impurities in polyester matrices during implant manufacturing.Eur. J. Pharm. Biopharm.200049325325710.1016/S0939‑6411(00)00066‑7 10799817
    [Google Scholar]
  126. BhardwajR. BlanchardJ. In vitro evaluation of Poly(d,l-lactide-co-glycolide) polymer-based implants containing the α-melanocyte stimulating hormone analog, Melanotan-I.J. Control. Release1997451495510.1016/S0168‑3659(96)01544‑1
    [Google Scholar]
  127. BhardwajR. BlanchardJ. In vitro characterization and in vivo release profile of a poly (d,l-lactide-co-glycolide)-based implant delivery system for the α-MSH analog, melanotan-I.Int. J. Pharm.1998170110911710.1016/S0378‑5173(98)00149‑5
    [Google Scholar]
  128. WittC. MäderK. KisselT. The degradation, swelling and erosion properties of biodegradable implants prepared by extrusion or compression moulding of poly(lactide-co-glycolide) and ABA triblock copolymers.Biomaterials200021993193810.1016/S0142‑9612(99)00262‑8 10735470
    [Google Scholar]
  129. PotenteH. Existing scale-up rules for single-screw plasticating extruders.Int. Polym. Process.19916426727810.3139/217.910267
    [Google Scholar]
  130. RaduschHJ DingJ AkovaliG Compatibilization of heterogeneous polymer mixtures from the plastics waste streams.Frontiers in the science and technology of polymer recycling.199815389
    [Google Scholar]
  131. GunsS. MathotV. MartensJ.A. Van den MooterG. 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.201281367468210.1016/j.ejpb.2012.03.020 22521332
    [Google Scholar]
  132. DreiblattA. Technological considerations related to scale-ip of hot-melt extrusion processes. DouroumisD. Hot-Melt Extrusion: Pharmaceutical Applications.John Wiley & Sons Ltd.201228530010.1002/9780470711415.ch13
    [Google Scholar]
  133. GuptaA. KhanM.A. Hot-Melt Extrusion: An FDA perspective on product and process understanding.Hot-Melt Extrusion: Pharmaceutical Applications. DouroumisD. John Wiley & Sons, Ltd.201232333110.1002/9780470711415.ch15
    [Google Scholar]
  134. WoodcockJ. The concept of pharmaceutical quality.Am. Pharm. Rev.2004761015
    [Google Scholar]
  135. ICH Q8(R2) Pharmaceutical development2009Available from: http://www.ich.org/products/guidelines/quality/quality single/article/pharmaceutical-development.html
  136. ICH topic Q3C (R5) impurities: Residual solvents.Inter Conf Harmonizat200916
    [Google Scholar]
  137. Kayrak-TalayD DaleS WassgrenC LitsterJ Quality by design for wet granulation in pharmaceutical processing: Assessing models for a priori design and scaling.Powder Technol201324071810.1016/j.powtec.2012.07.013
    [Google Scholar]
  138. AksuB. BeerT.D. FolestadS. Strategic funding priorities in the pharmaceutical sciences allied to Quality by Design (QbD) and Process Analytical Technology (PAT).Eur. J. Pharm. Sci.201247240240510.1016/j.ejps.2012.06.009 22749874
    [Google Scholar]
  139. TombaE. FaccoP. BezzoF. BaroloM. Latent variable modeling to assist the implementation of Quality-by-Design paradigms in pharmaceutical development and manufacturing: A review.Int. J. Pharm.2013457128329710.1016/j.ijpharm.2013.08.074 24016743
    [Google Scholar]
  140. SchaeferC. ClicqD. LecomteC. MerschaertA. NorrantE. FotiaduF. A process analytical technology (PAT) approach to control a new api manufacturing process: Development, validation and implementation.Talanta201412011412510.1016/j.talanta.2013.11.072 24468350
    [Google Scholar]
  141. ChenZ. LovettD. MorrisJ. Process analytical technologies and real time process control a review of some spectroscopic issues and challenges.J. Process Contr.201121101467148210.1016/j.jprocont.2011.06.024
    [Google Scholar]
  142. ICH Expert Working GroupICH Harmonised Tripartite Guideline. Quality Risk Management Q9. ICH Harmonised Tripartite Guideline.2005Available from: http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q9/Step4/Q9_Guideline.pdf%5Cn http://scholar.google.com/scholar?hl=en&btnG=Search&q=intitle:Quality+Risk+Management+Q9#0%5Cn http://www.cls.co.at/downloads/ich-q9---qualityrisk-ma
  143. US Department of Health and Human Services Guidance for industryPAT—a framework for innovative pharmaceutical development, manufacturing and quality assurance.Silver Spring, MarylandFood and Drug Administration2018
    [Google Scholar]
  144. WahlP.R. TrefferD. MohrS. RobleggE. KoscherG. KhinastJ.G. Inline monitoring and a PAT strategy for pharmaceutical hot melt extrusion.Int. J. Pharm.20134551-215916810.1016/j.ijpharm.2013.07.044 23911343
    [Google Scholar]
  145. BeerD.T. BurggraeveA. FonteyneM. SaerensL. RemonJ.P. VervaetC. Near infrared and Raman spectroscopy for the in-process monitoring of pharmaceutical production processes.Int. J. Pharm.20114171-2324710.1016/j.ijpharm.2010.12.012 21167266
    [Google Scholar]
  146. GendrinC. RoggoY. ColletC. Pharmaceutical applications of vibrational chemical imaging and chemometrics: A review.J. Pharm. Biomed. Anal.200848353355310.1016/j.jpba.2008.08.014 18819769
    [Google Scholar]
  147. RoggoY ChalusP MaurerL Lema-MartinezC EdmondA JentN. A review of near infrared spectroscopy and chemometrics in pharmaceutical technologies.J Pharm Biomed Anal2007443 SPEC. ISS.68370010.1016/j.jpba.2007.03.023
    [Google Scholar]
  148. VankeirsbilckT. VercauterenA. BaeyensW. Applications of Raman spectroscopy in pharmaceutical analysis.Trends Analyt. Chem.2002211286987710.1016/S0165‑9936(02)01208‑6
    [Google Scholar]
  149. CoatesP.D. BarnesS.E. SibleyM.G. BrownE.C. EdwardsH.G.M. ScowenI.J. In-process vibrational spectroscopy and ultrasound measurements in polymer melt extrusion.Polymer200344195937594910.1016/S0032‑3861(03)00544‑5
    [Google Scholar]
  150. TumuluriS.V.S. ProdduturiS. CrowleyM.M. The use of near-infrared spectroscopy for the quantitation of a drug in hot-melt extruded films.Drug Dev. Ind. Pharm.200430550551110.1081/DDC‑120037481 15244086
    [Google Scholar]
  151. BarnesS.E. BrownE.C. SibleyM.G. EdwardsH.G.M. CoatesP.D. Vibrational spectroscopic and ultrasound analysis for the in-process monitoring of poly(ethylene vinyl acetate) copolymer composition during melt extrusion.Analyst2005130328629210.1039/b416244g
    [Google Scholar]
  152. CarraherC.E. SeymourR.B. Introduction to polymer science and technology.Applied Polymer Science, ACS Symposium Series1985Vol. 285134710.1021/bk‑1985‑0285.ch002
    [Google Scholar]
  153. McGinityJ.W. SchillingS.U. Hot-Melt Extrusion of Modified Release Multi-Particles.Patent WO/2010/0221932010
    [Google Scholar]
  154. TelekiA AdlerC Formulation of sparingly soluble compounds by hot-melt extrusion Patent US10022337B22018
    [Google Scholar]
  155. MillarD. McConvilleJ. McGinityJ.W. WilliamsR.O.III Stabilized HME composition with small drug particles.Patent WO/2007/0014512007
    [Google Scholar]
  156. MaruyamaN. WarashinaS. KusakiF. ObaraS. KikuchiK. Hypromellose acetate succinate for use as hot-melt extrusion carrier, hot-melt extrusion composition, and method for producing hot-melt extrudate.US Patent 14/453,9352015
  157. RamirezOAE UribeLR EscobarM Dietary supplement derived from natural prodcuts by hot melt extrusion (HME) processing.Patent WO-2018172998-A12020
  158. LeksicE. SamecD.S. SahnicD. KisicekD. HrkovacM. TopicE. Solid state forms of trisodium valsartan: sacubitril.U.S. Patent US10689352B22016
    [Google Scholar]
  159. HemmingsenPH PedersenAV Bar-ShalomD Controlled release pharmaceutical compositions for prolonged effect.Patent US9642809B22017
    [Google Scholar]
  160. LeechR.L. BrzeczkoA.W. Methods and Compositions for Deterring Abuse.Patent WO/2011/0414142017
    [Google Scholar]
  161. WangH. FanY. Solid dispersion of decoquinate, a preparation process and its application.Antimicrob. Agents Chemother.2022665e022182110.1128/aac.02218‑21
    [Google Scholar]
  162. BarnscheidL GaliaE SchwierS BertramU Oxidation-stabilized tamper-resistant dosage form.Patent WO2011009604A12016
    [Google Scholar]
  163. GhebremeskelA.N. RobinsonM.R. Prostamide-containing intraocular implants and methods of use thereof.Patent WO/2015/0665482016
    [Google Scholar]
  164. CrowleyM. KeenJ. KolengJ. Stabilized compositions containing alkaline labile drugs.Patent WO/2007/1122862007
    [Google Scholar]
  165. BreitenbachJ. Melt extrusion: From process to drug delivery technology.Eur. J. Pharm. Biopharm.200254210711710.1016/S0939‑6411(02)00061‑9 12191680
    [Google Scholar]
  166. JanaS. MiloslavaR. Hot-melt extrusion.Ceska Slov. Farm.20126138792 22913823
    [Google Scholar]
  167. CilurzoF. CuponeI.E. MinghettiP. SelminF. MontanariL. Fast dissolving films made of maltodextrins.Eur. J. Pharm. Biopharm.200870389590010.1016/j.ejpb.2008.06.032 18667164
    [Google Scholar]
  168. ZhangF. McGinityJ.W. Properties of sustained-release tablets prepared by hot-melt extrusion.Pharm. Dev. Technol.19994224125010.1081/PDT‑100101358 10231885
    [Google Scholar]
  169. CrowleyM.M. ZhangF. KolengJ.J. McGinityJ.W. Stability of polyethylene oxide in matrix tablets prepared by hot-melt extrusion.Biomaterials200223214241424810.1016/S0142‑9612(02)00187‑4 12194527
    [Google Scholar]
  170. ManiruzzamanM. RanaM.M. BoatengJ.S. MitchellJ.C. DouroumisD. Dissolution enhancement of poorly water-soluble APIs processed by hot-melt extrusion using hydrophilic polymers.Drug Dev. Ind. Pharm.201339221822710.3109/03639045.2012.670642 22452601
    [Google Scholar]
  171. BreitkreutzJ. El-SalehF. KieraC. KleinebuddeP. WiedeyW. Pediatric drug formulations of sodium benzoate.Eur. J. Pharm. Biopharm.200356225526010.1016/S0939‑6411(03)00090‑0 12957640
    [Google Scholar]
  172. BrabanderD.C. VervaetC. FiermansL. Matrix mini-tablets based on starch/microcrystalline wax mixtures.Int. J. Pharm.2000199219520310.1016/s0378‑5173(00)00383‑5
    [Google Scholar]
  173. BrabanderD.C. VervaetC. RemonJ.P. Development and evaluation of sustained release mini-matrices prepared via hot melt extrusion.J. Control. Release200389223524710.1016/S0168‑3659(03)00075‑0 12711447
    [Google Scholar]
  174. RobleggE. JägerE. HodzicA. Development of sustained-release lipophilic calcium stearate pellets via hot melt extrusion.Eur. J. Pharm. Biopharm.201179363564510.1016/j.ejpb.2011.07.004 21801834
    [Google Scholar]
  175. AndrewsG.P. JonesD.S. DiakO.A. McCoyC.P. WattsA.B. McGinityJ.W. The manufacture and characterisation of hot-melt extruded enteric tablets.Eur. J. Pharm. Biopharm.200869126427310.1016/j.ejpb.2007.11.001 18164604
    [Google Scholar]
  176. MillerD.A. McConvilleJ.T. YangW. WilliamsR.O.III McGinityJ.W. Hot-melt extrusion for enhanced delivery of drug particles.J. Pharm. Sci.200796236137610.1002/jps.20806 17075869
    [Google Scholar]
  177. VerreckG. DecorteA. HeymansK. Hot stage extrusion of p-amino salicylic acid with EC using CO2 as a temporary plasticizer.Int. J. Pharm.20063271-2455010.1016/j.ijpharm.2006.07.024 16930886
    [Google Scholar]
  178. GryczkeA. SchminkeS. ManiruzzamanM. BeckJ. DouroumisD. Development and evaluation of orally disintegrating tablets (ODTs) containing Ibuprofen granules prepared by hot melt extrusion.Colloids Surf. B Biointerf.201186227528410.1016/j.colsurfb.2011.04.007 21592751
    [Google Scholar]
  179. ManiruzzamanM. BoatengJ.S. BonnefilleM. AranyosA. MitchellJ.C. DouroumisD. Taste masking of paracetamol by hot-melt extrusion: An in vitro and in vivo evaluation.Eur. J. Pharm. Biopharm.201280243344210.1016/j.ejpb.2011.10.019 22108493
    [Google Scholar]
  180. DouroumisD. Practical approaches of taste masking technologies in oral solid forms.Expert Opin. Drug Deliv.20074441742610.1517/17425247.4.4.417 17683254
    [Google Scholar]
  181. DouroumisD. Orally disintegrating dosage forms and taste-masking technologies; 2010.Expert Opin. Drug Deliv.20118566567510.1517/17425247.2011.566553 21438776
    [Google Scholar]
/content/journals/cpd/10.2174/0113816128357733250324054151
Loading
/content/journals/cpd/10.2174/0113816128357733250324054151
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test