Recent Perspectives in Hot Melt Extrusion-Based Polymeric Formulations for Drug Delivery: Applications and Innovations

Abstract

Hot melt extrusion (HME), a technology which mixing the advantages of solid dispersion technology and mechanical preparation, is accepted in varied applications in pharmaceutical formulations. When combined with other techniques, such as nanotechnique, three-dimensional printing, and co-extrusion, HME becomes much more multifunctional in the application of drug delivery. While in most cases, polymers employed in HME are responsible for the final property of products. The process of HME together with the selection of materials employed in HME were described briefly. In addition, the applications of HME in drug delivery and its currently status in the pharmaceutical field were also included. Some commercial products produced by HME have met the approval of FDA, indicating the commercial viability of this technique. Although showing great potential in pharmaceutical manufacturing, HME is still challenged by high temperature, shear force, and high input energy. Development of equipment, modifying the parameters, and optimization of polymeric formulations are needed for a safe, effective, and multifunctional hot melt extrusion drug delivery system. Also, wider range of combinations between HME and other techniques may provide guideline for developing multiple applications in drug delivery.

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References

  1. 1.

    Loftsson T, Brewster ME. Pharmaceutical applications of cyclodextrins: basic science and product development. J Pharm Pharmacol. 2010;62(11):1607–21.

    CAS  PubMed  Google Scholar 

  2. 2.

    Savjani KT, Gajjar AK, Savjani JK. Drug solubility: importance and enhancement techniques. ISRN Pharm. 2012;2012:1–10.

    Google Scholar 

  3. 3.

    Tiwari RV, Patil H, Repka MA. Contribution of hot-melt extrusion technology to advance drug delivery in the 21st century. Expert Opin Drug Deliv. 2016;13(3):451–64.

    CAS  PubMed  Google Scholar 

  4. 4.

    Speiser P. Galenic aspects of drug effects. Pharm Acta Helv. 1966;41(6):321–42.

    CAS  PubMed  Google Scholar 

  5. 5.

    El-Egakey MA, Soliva M, Speiser P. Hot extruded dosage forms. I. Technology and dissolution kinetics of polymeric matrices. Pharm Acta Helv. 1971;46(1):31–52.

    CAS  PubMed  Google Scholar 

  6. 6.

    Pimparade MB, Vo A, Maurya AS, Bae J, Morott JT, Feng X, et al. Development and evaluation of an oral fast disintegrating anti-allergic film using hot-melt extrusion technology. Eur J Pharm Biopharm. 2017;119:81–90.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Khor CM, Ng WK, Kanaujia P, Chan KP, Dong Y. Hot-melt extrusion microencapsulation of quercetin for taste-masking. J Microencapsul. 2017;34(1):29–37.

    CAS  PubMed  Google Scholar 

  8. 8.

    Yang Y, Shen L, Li J, Shan WG. Preparation and evaluation of metoprolol tartrate sustained-release pellets using hot melt extrusion combined with hot melt coating. Drug Dev Ind Pharm. 2017;43(6):939–46.

    CAS  PubMed  Google Scholar 

  9. 9.

    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.

    CAS  PubMed  Google Scholar 

  10. 10.

    Chen R, Li G, Han A, Wu H, Guo S. Controlled release of diclofenac sodium from polylactide acid-based solid dispersions prepared by hot-melt extrusion. J Biomater Sci Polym Ed. 2016;27(6):529–43.

    CAS  PubMed  Google Scholar 

  11. 11.

    Breitenbach J. Melt extrusion: from process to drug delivery technology. Eur J Pharm Biopharm. 2002;54(2):107–17.

    CAS  Google Scholar 

  12. 12.

    Van Laarhoven J, Kruft M, Vromans H. In vitro release properties of etonogestrel and ethinyl estradiol from a contraceptive vaginal ring. Int J Pharm. 2002;232(1):163–73.

    PubMed  Google Scholar 

  13. 13.

    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.

    CAS  PubMed  Google Scholar 

  14. 14.

    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.

    CAS  PubMed  Google Scholar 

  15. 15.

    Zhang J, Feng X, Patil H, Tiwari RV, Repka MA. Coupling 3D printing with hot-melt extrusion to produce controlled-release tablets. Int J Pharm. 2017;519(1–2):186–97.

    CAS  PubMed  Google Scholar 

  16. 16.

    Dierickx L, Van Snick B, Monteyne T, et al. Co-extruded solid solutions as immediate release fixed-dose combinations. Eur J Pharm Biopharm. 2014;88(2):502–9.

    CAS  PubMed  Google Scholar 

  17. 17.

    Lakshman JP, Cao Y, Kowalski J, Serajuddin ATM. 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.

    CAS  PubMed  Google Scholar 

  18. 18.

    Patil H, Tiwari RV, Repka MA. Hot-melt extrusion: from theory to application in pharmaceutical formulation. AAPS PharmSciTech. 2016;17(1):20–42.

    CAS  PubMed  Google Scholar 

  19. 19.

    Ye X, Patil H, Feng X, Tiwari RV, Lu J, Gryczke A, et al. Conjugation of hot-melt extrusion with high-pressure homogenization: a novel method of continuously preparing nanocrystal solid dispersions. AAPS PharmSciTech. 2016;17(1):78–88.

    CAS  PubMed  Google Scholar 

  20. 20.

    Nelson KD. 6—Absorbable, drug-loaded, extruded fiber for implantation. A2—Blair, Todd. Biomedical textiles for orthopaedic and surgical applications: Woodhead Publishing; 2015. p. 119–43.

  21. 21.

    Schrank S, Kann B, Saurugger E, Hainschitz M, Windbergs M, Glasser BJ, et al. The effect of the drying temperature on the properties of wet-extruded calcium stearate pellets: pellet microstructure, drug distribution, solid state and drug dissolution. Int J Pharm. 2015;478(2):779–87.

    CAS  PubMed  Google Scholar 

  22. 22.

    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.

    CAS  PubMed  Google Scholar 

  23. 23.

    Vo AQ, Feng X, Pimparade M, Ye X, Kim DW, Martin ST, et al. Dual-mechanism gastroretentive drug delivery system loaded with an amorphous solid dispersion prepared by hot-melt extrusion. Eur J Pharm Sci. 2017;102(Supplement C):71–84.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Van Laarhoven J, Kruft M, 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):309–17.

    PubMed  Google Scholar 

  25. 25.

    Katz IM. Shaped ophthalmic inserts for treating dry eye syndrome. Merck&Co. US 4343787.

  26. 26.

    Thiry J, Kok MG, Collard L, et al. Bioavailability enhancement of itraconazole-based solid dispersions produced by hot melt extrusion in the framework of the Three Rs rule. Eur J Pharm Sci. 2017;99:1–8.

    CAS  PubMed  Google Scholar 

  27. 27.

    Mofidfar M, Wang J, Long L, Hager CL, Vareechon C, Pearlman E, et al. Polymeric nanofiber/antifungal formulations using a novel co-extrusion approach. AAPS PharmSciTech. 2016;18(6):1917–24.

    PubMed  Google Scholar 

  28. 28.

    Pawar J, Narkhede R, Amin P, Tawde V. Design and evaluation of topical diclofenac sodium gel using hot melt extrusion technology as a continuous manufacturing process with Kolliphor® P407. AAPS PharmSciTech. 2017;18(6):2303–15.

    CAS  PubMed  Google Scholar 

  29. 29.

    Leelakanok N, Geary SM, Salem AK. Antitumor efficacy and toxicity of 5-fluorouracil-loaded poly (lactide co-glycolide) pellets. J Pharm Sci. 2018;107(2):690–7.

    CAS  PubMed  Google Scholar 

  30. 30.

    Navitha A, Jogala S, Krishnamohan C, Aukunuru J. Development of novel risperidone implants using blends of polycaprolactones and in vitro in vivo correlation studies. J Adv Pharm Technol Res. 2014;5(2):84–9.

    PubMed  PubMed Central  Google Scholar 

  31. 31.

    Jedinger N, Schrank S, Fischer JM, Breinhälter K, Khinast J, Roblegg E. Development of an abuse- and alcohol-resistant formulation based on hot-melt extrusion and film coating. AAPS PharmSciTech. 2016;17(1):68–77.

    CAS  PubMed  Google Scholar 

  32. 32.

    Ashour EA, Majumdar S, Alsheteli A, Alshehri S, Alsulays B, Feng X, et al. Hot melt extrusion as an approach to improve solubility, permeability and oral absorption of a psychoactive natural product, piperine. J Pharm Pharmacol. 2016;68(8):989–98.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Kulkarni C, Kelly AL, Gough T, Jadhav V, Singh KK, Paradkar A. Application of hot melt extrusion for improving bioavailability of artemisinin a thermolabile drug. Drug Dev Ind Pharm. 2018;44(2):206–14.

    CAS  PubMed  Google Scholar 

  34. 34.

    Oh KS, Song JY, Cho SH, Lee BS, Kim SY, Kim K, et al. Paclitaxel-loaded pluronic nanoparticles formed by a temperature-induced phase transition for cancer therapy. J Control Release. 2010;148(3):344–50.

    CAS  PubMed  Google Scholar 

  35. 35.

    Bansal SS, Vadhanam MV, Gupta RC. Development and in vitro-in vivo evaluation of polymeric implants for continuous systemic delivery of curcumin. Pharm Res. 2011;28(5):1121–30.

    CAS  PubMed  Google Scholar 

  36. 36.

    Cosse A, Konig C, Lamprecht A, et al. Hot melt extrusion for sustained protein release: matrix erosion and in vitro release of PLGA-based implants. AAPS PharmSciTech. 2017;18(1):15–26.

    CAS  PubMed  Google Scholar 

  37. 37.

    Lee PW, Maia J, Pokorski JK. Milling solid proteins to enhance activity after melt-encapsulation. Int J Pharm. 2017;533(1):254–65.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. 38.

    Lee PW, Shukla S, Wallat JD, Danda C, Steinmetz NF, Maia J, et al. Biodegradable viral nanoparticle/polymer implants prepared via melt-processing. ACS Nano. 2017;11(9):8777–89.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. 39.

    Ma Q, Wang C, Li X, Guo H, Meng J, Liu J, et al. Fabrication of water-soluble polymer-encapsulated As4S4 to increase oral bioavailability and chemotherapeutic efficacy in AML mice. Sci Rep. 2016;6:29348.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. 40.

    Lee S, Nam S, Choi Y, Kim M, Koo J, Chae BJ, et al. Fabrication and characterizations of hot-melt extruded nanocomposites based on zinc sulfate monohydrate and Soluplus. Appl Sci. 2017;7(9):902.

    Google Scholar 

  41. 41.

    Liu X, Zhou L, Zhang F. Reactive melt extrusion to improve the dissolution performance and physical stability of naproxen amorphous solid dispersions. Mol Pharm. 2017;14(3):658–73.

    PubMed  Google Scholar 

  42. 42.

    Albarahmieh E, Qi S, Craig DQ. Hot melt extruded transdermal films based on amorphous solid dispersions in Eudragit RS PO: the inclusion of hydrophilic additives to develop moisture-activated release systems. Int J Pharm. 2016;514(1):270–81.

    CAS  PubMed  Google Scholar 

  43. 43.

    Fang L, Xin W, Ding H, Zhang Y, Zhong L, Luo H, et al. Pharmacokinetically guided algorithm of 5-fluorouracil dosing, a reliable strategy of precision chemotherapy for solid tumors: a meta-analysis. Sci Rep. 2016;6:25913.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. 44.

    Maddineni S, Battu SK, Morott J, Majumdar S, Murthy SN, Repka MA. Influence of process and formulation parameters on dissolution and stability characteristics of Kollidon(R) VA 64 hot-melt extrudates. AAPS PharmSciTech. 2015;16(2):444–54.

    CAS  PubMed  Google Scholar 

  45. 45.

    Breitenbach A, Meese C, Wolff H-M, et al. Transdermal delivery of (R)-3, 3-diphenylpropylamin-monoestern. UCB Pharma GmbH. US 7919117 B2.

  46. 46.

    Trey SM, Wicks DA, Mididoddi PK, et al. Delivery of itraconazole from extruded HPC films. Drug Dev Ind Pharm. 2008;33(7):727–35.

    Google Scholar 

  47. 47.

    Balogh A, Farkas B, Domokos A, Farkas A, Démuth B, Borbás E, et al. Controlled-release solid dispersions of Eudragit® FS 100 and poorly soluble spironolactone prepared by electrospinning and melt extrusion. Eur Polym J. 2017;95:406–17.

    CAS  Google Scholar 

  48. 48.

    Zhang F. Melt-extruded Eudragit® FS-based granules for colonic drug delivery. AAPS PharmSciTech. 2015;17(1):56–67.

    PubMed  PubMed Central  Google Scholar 

  49. 49.

    Li JWH, Vederas JC. Drug discovery and natural products: end of an era or an endless frontier? Science. 2009;325(5937):161–5.

    PubMed  Google Scholar 

  50. 50.

    Pimparade MB, Morott JT, Park JB, Kulkarni VI, Majumdar S, Murthy SN, et al. Development of taste masked caffeine citrate formulations utilizing hot melt extrusion technology and in vitro-in vivo evaluations. Int J Pharm. 2015;487(1–2):167–76.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. 51.

    Chen J, Gu J, Zhao R, Dai R, Wang J. Simultaneous nonchiral determination of artemisinin and arteannuin B in Artemisia annua using circular dichroism detection. Chromatographia. 2009;69(3):361–3.

    CAS  Google Scholar 

  52. 52.

    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. 2015;102:189–97.

    PubMed  Google Scholar 

  53. 53.

    Boksa K, Otte A, Pinal R. Matrix-assisted cocrystallization (MAC) simultaneous production and formulation of pharmaceutical cocrystals by hot-melt extrusion. J Pharm Sci. 2014;103(9):2904–10.

    CAS  PubMed  Google Scholar 

  54. 54.

    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):1–11.

    CAS  PubMed  Google Scholar 

  55. 55.

    Even M-P, Young K, Winter G, Hook S, Engert J. In vivo investigation of twin-screw extruded lipid implants for vaccine delivery. Eur J Pharm Biopharm. 2014;87(2):338–46.

    CAS  PubMed  Google Scholar 

  56. 56.

    Lang B, McGinity JW, Williams RO 3rd. Hot-melt extrusion—basic principles and pharmaceutical applications. Drug Dev Ind Pharm. 2014;40(9):1133–55.

    CAS  PubMed  Google Scholar 

  57. 57.

    Crowley MM, Schroeder B, Fredersdorf A, Obara S, Talarico M, Kucera S, et al. Physicochemical properties and mechanism of drug release from ethyl cellulose matrix tablets prepared by direct compression and hot-melt extrusion. Int J Pharm. 2004;269(2):509–22.

    CAS  PubMed  Google Scholar 

  58. 58.

    Repka MA, McGinity JW. Bioadhesive properties of hydroxypropylcellulose topical films produced by hot-melt extrusion. J Control Release. 2001;70(3):341–51.

    CAS  PubMed  Google Scholar 

  59. 59.

    Mendonsa NS, Thipsay P, Kim DW, Martin ST, Repka MA. Bioadhesive drug delivery system for enhancing the permeability of a BCS class III drug via hot-melt extrusion technology. AAPS PharmSciTech. 2017;18(7):2639–47.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. 60.

    Tanno F, Nishiyama Y, Kokubo H, Obara S. Evaluation of hypromellose acetate succinate (HPMCAS) as a carrier in solid dispersions. Drug Dev Ind Pharm. 2004;30(1):9–17.

    CAS  PubMed  Google Scholar 

  61. 61.

    Charoenthai N, Kleinebudde P, Puttipipatkhachorn S. Influence of chitosan type on the properties of extruded pellets with low amount of microcrystalline cellulose. AAPS PharmSciTech. 2007;8(3):E64.

    PubMed  Google Scholar 

  62. 62.

    Liu W-C, Halley PJ, Gilbert RG. Mechanism of degradation of starch, a highly branched polymer, during extrusion. Macromolecules. 2010;43(6):2855–64.

    CAS  Google Scholar 

  63. 63.

    Wolf B. Polysaccharide functionality through extrusion processing. Curr Opin Colloid Interface Sci. 2010;15(1–2):50–4.

    CAS  Google Scholar 

  64. 64.

    Refaat A, Sokar M, Ismail F, Boraei N. A dual strategy to improve psychotic patients' compliance using sustained release quetiapine oral disintegrating tablets. Acta Pharma. 2016;66(4):515–32.

    CAS  Google Scholar 

  65. 65.

    Middleton JC, Tipton AJ. Synthetic biodegradable polymers as orthopedic devices. Biomaterials. 2000;21(23):2335–46.

    CAS  PubMed  Google Scholar 

  66. 66.

    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.

    CAS  PubMed  Google Scholar 

  67. 67.

    Sabir MI, Xu X, Li L. A review on biodegradable polymeric materials for bone tissue engineering applications. J Mater Sci. 2009;44(21):5713–24.

    CAS  Google Scholar 

  68. 68.

    Verstraete G, Van Renterghem J, Van Bockstal PJ, et al. Hydrophilic thermoplastic polyurethanes for the manufacturing of highly dosed oral sustained release matrices via hot melt extrusion and injection molding. Int J Pharm. 2016;506(1–2):214–21.

    CAS  PubMed  Google Scholar 

  69. 69.

    Göpferich A, Tessmar J. Polyanhydride degradation and erosion. Adv Drug Deliv Rev. 2002;54(7):911–31.

    PubMed  Google Scholar 

  70. 70.

    Li D, Guo G, Deng X, Fan RR, Guo QF, Fan M, et al. PLA/PEG-PPG-PEG/dexamethasone implant prepared by hot-melt extrusion for controlled release of immunosuppressive drug to implantable medical devices, part 2: in vivo evaluation. Drug Deliv. 2013;20(3–4):134–42.

    CAS  PubMed  Google Scholar 

  71. 71.

    AstraZeneca. ZOLADEX (goserelin acetate implant) 3.6mg-prescribing information 2010. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019726s054lbl.pdf.

  72. 72.

    Zhang X, Wang M, Li P, Wang A, Liang R, Gai Y, et al. Application of hot-melt extrusion technology for designing an elementary osmotic pump system combined with solid dispersion for a novel poorly water-soluble antidepressant. Pharm Dev Technol. 2016;21(8):1006–14.

    CAS  PubMed  Google Scholar 

  73. 73.

    Kindermann C, Matthee K, Strohmeyer J, et al. Tailor-made release triggering from hot-melt extruded complexes of basic polyelectrolyte and poorly water-soluble drugs. Eur J Pharm Biopharm. 2011;79(2):372–81.

    CAS  PubMed  Google Scholar 

  74. 74.

    Maniruzzaman M, Ross SA, Islam MT, Scoutaris N, Nair A, Douroumis D. Increased dissolution rates of tranilast solid dispersions extruded with inorganic excipients. Drug Dev Ind Pharm. 2017;43(6):947–57.

    CAS  PubMed  Google Scholar 

  75. 75.

    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.

    CAS  PubMed  Google Scholar 

  76. 76.

    Hurley D, Potter CB, Walker GM, Higginbotham CL. Investigation of ethylene oxide-co-propylene oxide for dissolution enhancement of hot-melt extruded solid dispersions. J Pharm Sci. 2018;107(5):1372–82.

    CAS  PubMed  Google Scholar 

  77. 77.

    Friesen DT, Shanker R, Crew M, Smithey DT, Curatolo WJ, Nightingale JAS. Hydroxypropyl methylcellulose acetate succinate-based spray-dried dispersions: an overview. Mol Pharm. 2008;5(6):1003–19.

    CAS  PubMed  Google Scholar 

  78. 78.

    Hohl R, Scheibelhofer O, Stocker E, et al. Monitoring of a hot melt coating process via a novel multipoint near-infrared spectrometer. AAPS PharmSciTech. 2016;18(1):182–93.

    PubMed  Google Scholar 

  79. 79.

    Hinz DC. Process analytical technologies in the pharmaceutical industry: the FDA’s PAT initiative. Anal Bioanal Chem. 2006;384(5):1036–42.

    CAS  PubMed  Google Scholar 

  80. 80.

    Agrawal G, Samal SK. Raman spectroscopy for advanced polymeric biomaterials. ACS Biomater Sci Eng. 2018;4(4):1285–99.

    CAS  Google Scholar 

  81. 81.

    Wesholowski J, Prill S, Berghaus A, Thommes M. Inline UV/Vis spectroscopy as PAT tool for hot-melt extrusion. Drug Deliv Transl Res. 2018;8:1595–603.

    CAS  PubMed  Google Scholar 

  82. 82.

    Krier F, Mantanus J, Sacre PY, et al. PAT tools for the control of co-extrusion implants manufacturing process. Int J Pharm. 2013;458(1):15–24.

    CAS  PubMed  Google Scholar 

  83. 83.

    Chavan RB, Thipparaboina R, Yadav B, Shastri NR. Continuous manufacturing of co-crystals: challenges and prospects. Drug Deliv Transl Res. 2018;8:1726–39.

    CAS  PubMed  Google Scholar 

  84. 84.

    Crawford DE, Miskimmin CK, Cahir J, James SL. Continuous multi-step synthesis by extrusion—telescoping solvent-free reactions for greater efficiency. Chem Commun (Camb). 2017;53(97):13067–70.

    CAS  Google Scholar 

  85. 85.

    Kuminek G, Cao F, Bahia de Oliveira da Rocha A, et al. Cocrystals to facilitate delivery of poorly soluble compounds beyond-rule-of-5. Adv Drug Deliv Rev. 2016;101:143–66.

    CAS  PubMed  PubMed Central  Google Scholar 

  86. 86.

    Medina C, Daurio D, Nagapudi K, Alvarez-Nunez F. Manufacture of pharmaceutical co-crystals using twin screw extrusion: a solvent-less and scalable process. J Pharm Sci. 2010;99(4):1693–6.

    CAS  PubMed  Google Scholar 

  87. 87.

    Gross BC, Erkal JL, Lockwood SY, Chen C, Spence DM. Evaluation of 3D printing and its potential impact on biotechnology and the chemical sciences. Anal Chem. 2014;86(7):3240–53.

    CAS  PubMed  Google Scholar 

  88. 88.

    Nadgorny M, Xiao Z, Chen C, Connal LA. Three-dimensional printing of pH-responsive and functional polymers on an affordable desktop printer. ACS Appl Mater Interfaces. 2016;8(42):28946–54.

    CAS  PubMed  Google Scholar 

  89. 89.

    Li Q, Guan X, Cui M, Zhu Z, Chen K, Wen H, et al. Preparation and investigation of novel gastro-floating tablets with 3D extrusion-based printing. Int J Pharm. 2018;535(1):325–32.

    CAS  Google Scholar 

  90. 90.

    Zhang J, Yang W, Vo AQ, Feng X, Ye X, Kim DW, et al. Hydroxypropyl methylcellulose-based controlled release dosage by melt extrusion and 3D printing: structure and drug release correlation. Carbohydr Polym. 2017;177:49–57.

    CAS  PubMed  PubMed Central  Google Scholar 

  91. 91.

    Melocchi A, Parietti F, Maroni A, Foppoli A, Gazzaniga A, Zema L. Hot-melt extruded filaments based on pharmaceutical grade polymers for 3D printing by fused deposition modeling. Int J Pharm. 2016;509(1–2):255–63.

    CAS  PubMed  Google Scholar 

  92. 92.

    Mei L, Fan R, Li X, Wang Y, Han B, Gu Y, et al. Nanofibers for improving the wound repair process: the combination of a grafted chitosan and an antioxidant agent. Polym Chem. 2017;8(10):1664–71.

    CAS  Google Scholar 

  93. 93.

    Feng G, Liu J, Liu R, et al. Ultrasmall conjugated polymer nanoparticles with high specificity for targeted cancer cell imaging. Adv Sci. 2017;4(9):1600407.

    Google Scholar 

  94. 94.

    Abedi-Gaballu F, Dehghan G, Ghaffari M, Yekta R, Abbaspour-Ravasjani S, Baradaran B, et al. PAMAM dendrimers as efficient drug and gene delivery nanosystems for cancer therapy. Appl Mater Today. 2018;12:177–90.

    PubMed  PubMed Central  Google Scholar 

  95. 95.

    Lee Y, Lee S, Jon S. Biotinylated bilirubin nanoparticles as a tumor microenvironment-responsive drug delivery system for targeted cancer therapy. Adv Sci. 2018;5(6):1800017.

    Google Scholar 

  96. 96.

    Barenholz Y. Doxil®—the first FDA-approved nano-drug: lessons learned. J Control Release. 2012;160(2):117–34.

    CAS  Google Scholar 

  97. 97.

    Baumgartner R, Matić J, Schrank S, Laske S, Khinast J, Roblegg E. NANEX: process design and optimization. Int J Pharm. 2016;506(1):35–45.

    CAS  PubMed  Google Scholar 

  98. 98.

    Lenz E, Löbmann K, Rades T, Knop K, Kleinebudde P. Hot melt extrusion and spray drying of co-amorphous indomethacin-arginine with polymers. J Pharm Sci. 2017;106(1):302–12.

    CAS  PubMed  Google Scholar 

  99. 99.

    Butler SF, Fernandez KC, Chang A, Benoit C, Morey LC, Black R, et al. Measuring attractiveness for abuse of prescription opioids. Pain Med. 2010;11(1):67–80.

    PubMed  PubMed Central  Google Scholar 

  100. 100.

    Bartholomaeus JH, Arkenau-Marić E, Galia E. Opioid extended-release tablets with improved tamper-resistant properties. Expert Opin Drug Deliv. 2012;9(8):879–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  101. 101.

    Eder S, Beretta M, Witschnigg A, Koutsamanis I, Eggenreich K, Khinast JG, et al. Establishment of a molding procedure to facilitate formulation development for co-extrudates. AAPS PharmSciTech. 2017;18(8):2971–6.

    CAS  PubMed  Google Scholar 

  102. 102.

    Kollamaram G, Croker DM, Walker GM, Goyanes A, Basit AW, Gaisford S. Low temperature fused deposition modeling (FDM) 3D printing of thermolabile drugs. Int J Pharm. 2018;545(1):144–52.

    CAS  Google Scholar 

Download references

Funding

This work was financially supported by National Natural Sciences Foundation of China (81772693), National S&T Major Project (2011ZX09102-001-10 and 2015ZX09102010), Luzhou Science and Technology Plan (2018CDLZ-10), and Sichuan Provincial Administration of Traditional Chinese Medicine Support Project (2018JC021).

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Correspondence to Gang Guo.

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Ren, Y., Mei, L., Zhou, L. et al. Recent Perspectives in Hot Melt Extrusion-Based Polymeric Formulations for Drug Delivery: Applications and Innovations. AAPS PharmSciTech 20, 92 (2019). https://doi.org/10.1208/s12249-019-1300-8

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KEY WORDS

  • hot melt extrusion
  • three-dimensional printing
  • nanotechnology
  • drug delivery systems
  • amorphous solid dispersion