Review ArticleReview

Hot-Melt Extrusion: An Emerging Technique for Solubility Enhancement of Poorly Water-Soluble Drugs

Amit Chivate, Atul Garkal, Namdev Dhas and Tejal Mehta
PDA Journal of Pharmaceutical Science and Technology July 2021, 75 (4) 357-373; DOI: https://doi.org/10.5731/pdajpst.2019.011403

References

  1. 1.↵
    1. Ren Y.,
    2. Mei L.,
    3. Zhou L.,
    4. Guo G.
    Recent Perspectives in Hot Melt Extrusion-Based Polymeric Formulations for Drug Delivery: Applications and Innovations. AAPS PharmSciTech 2019, 20 (3), 92.
    OpenUrl
  2. 2.↵
    1. Deshmukh S.,
    2. Avachat A.,
    3. Garkal A.,
    4. Khurana N.,
    5. Cardot J.-M.
    Optimization of a Dissolution Method in Early Development Based on IVIVC Using Small Animals: Application to a BCS Class II Drug. Dissolution Technol. 2016, 23 (4), 34–41.
    OpenUrl
  3. 3.↵
    1. Vo A. Q.,
    2. Feng X.,
    3. Zhang J.,
    4. Zhang F.,
    5. Repka M. A.
    Dual Mechanism of Microenvironmental pH Modulation and Foam Melt Extrusion to Enhance Performance of HPMCAS Based Amorphous Solid Dispersion. Int. J. Pharm. 2018, 550 (1-2), 216–228.
    OpenUrl
  4. 4.↵
    1. Pawar S. R.,
    2. Barhate S. D.
    Solubility Enhancement (Solid Dispersions) Novel Boon to Increase Bioavailability. J. Drug Delivery Ther. 2019, 9 (2), 583–590.
    OpenUrl
  5. 5.↵
    1. Bookwala M.,
    2. Thipsay P.,
    3. Ross S.,
    4. Zhang F.,
    5. Bandari S.,
    6. Repka M. A.
    Preparation of a Crystalline Salt of Indomethacin and Tromethamine by Hot Melt Extrusion Technology. Eur. J. Pharm. Biopharm. 2018, 131, 109–119.
    OpenUrl
  6. 6.↵
    1. Fernandes G. J.,
    2. Rathnanand M.,
    3. Kulkarni V.
    Mechanochemical Synthesis of Carvedilol Cocrystals Utilizing Hot Melt Extrusion Technology. J. Pharm. Innovation. 2019, 14 (4), 373–381.
    OpenUrl
  7. 7.↵
    1. Simões M. F.,
    2. Pinto R. M. A.,
    3. Simões S.
    Hot-Melt Extrusion in the Pharmaceutical Industry: Toward Filing a New Drug Application. Drug Discovery Today 2019, 24 (9), 1749–1768.
    OpenUrl
  8. 8.↵
    1. Shah S.,
    2. Maddineni S.,
    3. Lu J.,
    4. Repka M. A.
    Melt Extrusion with Poorly Soluble Drugs. Int. J. Pharm. 2013, 453 (1), 233–252.
    OpenUrl
  9. 9.↵
    1. Shuwisitkul D.
    Hot Melt Extrusion: An Application for Enhancing Drug Solubility. Asian J. Pharm. Sci 2016, 11 (1), 45–46.
    OpenUrl
  10. 10.↵
    1. Keen J. M.,
    2. McGinity J. W.,
    3. Williams R. O.
    Enhancing Bioavailability through Thermal Processing. Int. J. Pharm. 2013, 450 (1–2), 185–196.
    OpenUrl
  11. 11.↵
    1. Martin C.
    Continuous Mixing of Solid Dosage Forms via Hot-Melt Extrusion. Pharm. Technol. 2008, 32 (10), 76–86.
    OpenUrl
  12. 12.↵
    1. Hengsawas Surasarang S.,
    2. Keen J. M.,
    3. Huang S.,
    4. Zhang F.,
    5. McGinity J. W.,
    6. Williams R. O.
    Hot Melt Extrusion versus Spray Drying: hot Melt Extrusion Degrades Albendazole. Drug Dev. Ind. Pharm. 2017, 43 (5), 797–811.
    OpenUrl
  13. 13.↵
    1. Ghebremeskel A. N.,
    2. Vemavarapu C.,
    3. Lodaya M.
    Use of Surfactants as Plasticizers in Preparing Solid Dispersions of Poorly Soluble API: Selection of Polymer–Surfactant Combinations Using Solubility Parameters and Testing the Processability. Int. J. Pharm. 2007, 328 (2), 119–129.
    OpenUrlPubMed
  14. 14.↵
    1. Bialleck S.,
    2. Rein H.
    Preparation of Starch-Based Pellets by Hot-Melt Extrusion. Eur. J. Pharm. Biopharm. 2011, 79 (2), 440–448.
    OpenUrlPubMed
  15. 15.↵
    1. Patil H.,
    2. Tiwari R. V.,
    3. Repka M. A.
    Hot-Melt Extrusion: From Theory to Application in Pharmaceutical Formulation. AAPS PharmSciTech 2016, 17 (1), 20–42.
    OpenUrl
  16. 16.↵
    1. Hitzer P.,
    2. Bäuerle T.,
    3. Drieschner T.,
    4. Ostertag E.,
    5. Paulsen K.,
    6. van Lishaut H.,
    7. Lorenz G.,
    8. Rebner K.
    Process Analytical Techniques for Hot-Melt Extrusion and Their Application to Amorphous Solid Dispersions. Anal. Bioanal. Chem. 2017, 409 (18), 4321–4333.
    OpenUrl
  17. 17.↵
    1. Jani R.,
    2. Patel D.
    Hot Melt Extrusion: An Industrially Feasible Approach for Casting Orodispersible Film. Asian J. Pharm. Sci. 2015, 10 (4), 292–305.
    OpenUrl
  18. 18.↵
    1. Alshafiee M.,
    2. Aljammal M. K.,
    3. Markl D.,
    4. Ward A.,
    5. Walton K.,
    6. Blunt L.,
    7. Korde S.,
    8. Pagire S. K.,
    9. Kelly A. L.,
    10. Paradkar A.,
    11. Conway B. R.,
    12. Asare-Addo K.
    Hot-Melt Extrusion Process Impact on Polymer Choice of Glyburide Solid Dispersions: The Effect of Wettability and Dissolution. Int. J. Pharm. 2019, 559, 245–254.
    OpenUrl
  19. 19.↵
    1. Stanković M.,
    2. Frijlink H. W.,
    3. Hinrichs W. L. J.
    Polymeric Formulations for Drug Release Prepared by Hot Melt Extrusion: Application and Characterization. Drug Discovery Today 2015, 20 (7), 812–823.
    OpenUrl
  20. 20.↵
    1. Gao N.,
    2. Guo M.,
    3. Fu Q.,
    4. He Z.
    Application of Hot Melt Extrusion to Enhance the Dissolution and Oral Bioavailability of Oleanolic Acid. Asian J. Pharm. Sci. 2017, 12 (1), 66–72.
    OpenUrl
  21. 21.↵
    1. Hülsmann S.,
    2. Backensfeld T.,
    3. Keitel S.,
    4. Bodmeier R.
    Melt Extrusion—an Alternative Method for Enhancing the Dissolution Rate of 17β-Estradiol Hemihydrate. Eur. J. Pharm. Biopharm. 2000, 49 (3), 237–242.
    OpenUrlCrossRefPubMedWeb of Science
  22. 22.↵
    1. Nakamichi K.,
    2. Nakano T.,
    3. Yasuura H.,
    4. Izumi S.,
    5. 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), 203–211.
    OpenUrlPubMed
  23. 23.↵
    1. He H.,
    2. Yang R.,
    3. Tang X.
    In Vitro and in Vivo Evaluation of Fenofibrate Solid Dispersion Prepared by Hot-Melt Extrusion. Drug Dev. Ind. Pharm. 2010, 36 (6), 681–687.
    OpenUrlPubMed
  24. 24.↵
    1. Sathigari S. K.,
    2. Radhakrishnan V. K.,
    3. Davis V. A.,
    4. Parsons D. L.,
    5. Babu R. J.
    Amorphous-State Characterization of Efavirenz—Polymer Hot-Melt Extrusion Systems for Dissolution Enhancement. J. Pharm. Sci. 2012, 101 (9), 3456–3464.
    OpenUrlPubMed
  25. 25.↵
    1. Wang W.,
    2. Kang Q.,
    3. Liu N.,
    4. Zhang Q.,
    5. Zhang Y.,
    6. Li H.,
    7. Zhao B.,
    8. Chen Y.,
    9. Lan Y.,
    10. Ma Q.,
    11. Wu Q.
    Enhanced Dissolution Rate and Oral Bioavailability of Ginkgo Biloba Extract by Preparing Solid Dispersion via Hot-Melt Extrusion. Fitoterapia 2015, 102, 189–197.
    OpenUrl
  26. 26.↵
    1. Alshahrani S. M.,
    2. Lu W.,
    3. Park J.-B.,
    4. Morott J. T.,
    5. Alsulays B. B.,
    6. Majumdar S.,
    7. Langley N.,
    8. Kolter K.,
    9. Gryczke A.,
    10. Repka M. A.
    Stability-Enhanced Hot-Melt Extruded Amorphous Solid Dispersions via Combinations of Soluplus® and HPMCAS-HF. AAPS PharmSciTech 2015, 16 (4), 824–834.
    OpenUrl
  27. 27.↵
    1. Tang B.,
    2. Liu Z.,
    3. Tian Z.,
    4. Zhang J.,
    5. Chen X.,
    6. Fang G.,
    7. Song H.
    Development and Evaluation of Synchronized and Sustained Release Tripergium Wilfordii Tablets Based Hot-Melt Extrusion and Direct Powder Compression. J. Drug Delivery Sci. Technol. 2019, 53, 101208.
    OpenUrl
  28. 28.↵
    1. Hwang I.,
    2. Kang C. Y.,
    3. Park J. B.
    Advances in Hot-Melt Extrusion Technology toward Pharmaceutical Objectives. J. Pharm. Invest. 2017, 47 (2), 123–132.
    OpenUrl
  29. 29.↵
    1. Gajda M.,
    2. Nartowski K. P.,
    3. Pluta J.,
    4. Karolewicz B.
    The Role of the Polymer Matrix in Solvent-Free Hot Melt Extrusion Continuous Process for Mechanochemical Synthesis of Pharmaceutical Cocrystal. Eur. J. Pharm. Biopharm. 2018, 131, 48–59.
    OpenUrl
  30. 30.↵
    1. Hu X.-Y.,
    2. Lou H.,
    3. Hageman M. J.
    Preparation of Lapatinib Ditosylate Solid Dispersions Using Solvent Rotary Evaporation and Hot Melt Extrusion for Solubility and Dissolution Enhancement. Int. J. Pharm. 2018, 552 (1–2), 154–163.
    OpenUrl
  31. 31.↵
    Woalder, HHS Public Access, Physiol. Orexin activation counteracts decreases in nonexercise activity thermogenesis (NEAT) caused by high-fat diet. Behav 176 (2017), 139–148.
    OpenUrl
  32. 32.↵
    1. Bode C.,
    2. Kranz H.,
    3. Fivez A.,
    4. Siepmann F.,
    5. Siepmann J.
    Often Neglected: PLGA/PLA Swelling Orchestrates Drug Release: HME Implants. J. Controlled Release 2019, 306, 97–107.
    OpenUrl
  33. 33.↵
    1. Pathak Y.
    1. Mehta T. A.,
    2. Shah N.,
    3. Parekh K.,
    4. Dhas N.,
    5. Patel J. K.
    Surface-Modified PLGA Nanoparticles for Targeted Drug Delivery to Neurons. In: Surface Modification of Nanoparticles for Targeted Drug Delivery; Pathak Y., Ed.; Springer International Publishing: Cham, 2019., pp 33–71.
  34. 34.↵
    1. Dhas N. L.,
    2. Ige P. P.,
    3. Kudarha R. R.
    Design, Optimization and in-Vitro Study of Folic Acid Conjugated-Chitosan Functionalized PLGA Nanoparticle for Delivery of Bicalutamide in Prostate Cancer. Powder Technol. 2015, 283, 234–245.
    OpenUrl
  35. 35.↵
    1. Boschmann E.
    Physical and Chemical Properties. J. Chem. Educ. 1987, 64 (10), 891.
    OpenUrl
  36. 36.↵
    1. Kallakunta V. R.,
    2. Sarabu S.,
    3. Bandari S.,
    4. Batra A.,
    5. Bi V.,
    6. Durig T.,
    7. Repka M. A.
    Stable Amorphous Solid Dispersions of Fenofibrate Using Hot Melt Extrusion Technology: Effect of Formulation and Process Parameters for a Low Glass Transition Temperature Drug. J. Drug Delivery Sci. Technol. 2020, 58, 101395.
    OpenUrl
  37. 37.↵
    1. Mitra A.,
    2. Li L.,
    3. Marsac P.,
    4. Marks B.,
    5. Liu Z.,
    6. Brown C.
    Impact of Polymer Type on Bioperformance and Physical Stability of Hot Melt Extruded Formulations of a Poorly Water Soluble Drug. Int. J. Pharm. 2016, 505 (1–2), 107–114.
    OpenUrl
  38. 38.↵
    1. Alshehri S. M.,
    2. Park J. B.,
    3. Alsulays B. B.,
    4. Tiwari R. V.,
    5. Almutairy B.,
    6. Alshetaili A. S.,
    7. Morott J.,
    8. Shah S.,
    9. Kulkarni V.,
    10. Majumdar S.,
    11. Martin S. T.,
    12. Mishra S.,
    13. Wang L.,
    14. Repka M. A.
    Mefenamic Acid Taste-Masked Oral Disintegrating Tablets with Enhanced Solubility via Molecular Interaction Produced by Hot Melt Extrusion Technology. J. Drug Delivery Sci. Technol. 2015, 27, 18–27.
    OpenUrl
  39. 39.↵
    1. Yang Z.,
    2. Hu Y.,
    3. Tang G.,
    4. Dong M.,
    5. Liu Q.,
    6. Lin X.
    Development of Ibuprofen Dry Suspensions by Hot Melt Extrusion: Characterization, Physical Stability and Pharmacokinetic Studies. J. Drug Delivery Sci. Technol. 2019, 54, 101313.
    OpenUrl
  40. 40.↵
    1. Sarode A. L.,
    2. Sandhu H.,
    3. Shah N.,
    4. Malick W.,
    5. Zia H.
    Hot Melt Extrusion (HME) for Amorphous Solid Dispersions: Predictive Tools for Processing and Impact of Drug–Polymer Interactions on Supersaturation. Eur. J. Pharm. Sci. 2013, 48 (3), 371–384.
    OpenUrl
  41. 41.↵
    1. Balogh A.,
    2. Farkas B.,
    3. Domokos A.,
    4. Farkas A.,
    5. Démuth B.,
    6. Borbás E.,
    7. Nagy B.,
    8. Marosi G.,
    9. Nagy Z. K.
    Controlled-Release Solid Dispersions of Eudragit® FS 100 and Poorly Soluble Spironolactone Prepared by Electrospinning and Melt Extrusion. Eur. Polym. J. 2017, 95, 406–417.
    OpenUrl
  42. 42.↵
    1. Chivate A.,
    2. Garkal A.,
    3. Dhas N.,
    4. Mehta T.
    Three Dimensional Printing by Hot-Melt Extrusion; New Era for Development of Personalized Medicines and Continuous Manufacturing of Pharmaceuticals. Int. J. Pharm. Invest. 2020, 10 (3), 233–236.
    OpenUrl
  43. 43.↵
    1. Amit C.,
    2. Viral P.,
    3. Prakash S. O.,
    4. Atul G.,
    5. Mehta T.
    Application and Functional Characterization of Kollicoat Smartseal 30D as a Solid Dispersion Carrier for Improving Solubility. Asian J. Pharm. 2020, 14 (2), 220–228.
    OpenUrl
  44. 44.↵
    1. Tahir F.,
    2. Islam M. T.,
    3. Mack J.,
    4. Robertson J.,
    5. Lovett D.
    Process Monitoring and Fault Detection on a Hot-Melt Extrusion Process Using in-Line Raman Spectroscopy and a Hybrid Soft Sensor. Comput. Chem. Eng. 2019, 125, 400–414.
    OpenUrl
  45. 45.↵
    1. Walsh D.,
    2. Serrano D. R.,
    3. Worku Z. A.,
    4. Madi A. M.,
    5. O'Connell P.,
    6. Twamley B.,
    7. Healy A. M.
    Engineering of Pharmaceutical Cocrystals in an Excipient Matrix: Spray Drying versus Hot Melt Extrusion. Int. J. Pharm. 2018, 551 (1–2), 241–256.
    OpenUrl
  46. 46.↵
    1. Karimi-Jafari M.,
    2. Ziaee A.,
    3. Iqbal J.,
    4. O'Reilly E.,
    5. Croker D.,
    6. Walker G.
    Impact of Polymeric Excipient on Cocrystal Formation via Hot-Melt Extrusion and Subsequent Downstream Processing. Int. J. Pharm. 2019, 566, 745–755.
    OpenUrl
  47. 47.↵
    1. Verhoeven E.,
    2. De Beer T. R. M.,
    3. Van den Mooter G.,
    4. Remon J. P.,
    5. 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), 312–319.
    OpenUrlPubMed
  48. 48.↵
    1. Kamel R.,
    2. Abbas H.
    PLGA-Based Monolithic Filaments Prepared by Hot-Melt Extrusion: In-Vitro Comparative Study. Ann. Pharm. Fr. 2018, 76 (2), 97–106.
    OpenUrl
  49. 49.↵
    1. Tan D. C. T.,
    2. Ong J. J.,
    3. Gokhale R.,
    4. Heng P. W. S.
    Hot Melt Extrusion of Ion-Exchange Resin for Taste Masking. Int. J. Pharm. 2018, 547 (1–2), 385–394.
    OpenUrl
  50. 50.↵
    1. Pradip Sonwane M.,
    2. O.G. B.,
    3. V G.,
    4. Ali S.,
    5. Atul G.,
    6. Santosh K.
    A Review—Formulation & Development of Orodispersible Tablet. Indo Am. J. Pharm. Res. 2015, 5 (12), 3868–3881.
    OpenUrl
  51. 51.↵
    1. Pietrzak K.,
    2. Isreb A.,
    3. Alhnan M. A.
    A Flexible-Dose Dispenser for Immediate and Extended Release 3D Printed Tablets. Eur. J. Pharm. Biopharm. 2015, 96, 380–387.
    OpenUrl
  52. 52.↵
    1. Musazzi U. M.,
    2. Selmin F.,
    3. Ortenzi M. A.,
    4. Mohammed G. K.,
    5. Franzé S.,
    6. Minghetti P.,
    7. Cilurzo F.
    Personalized Orodispersible Films by Hot Melt Ram Extrusion 3D Printing. Int. J. Pharm. 2018, 551 (1-2), 52–59.
    OpenUrl
  53. 53.↵
    1. Samiei N.
    Recent Trends on Applications of 3D Printing Technology on the Design and Manufacture of Pharmaceutical Oral Formulation: A Mini Review. Beni-Suef Univ. J. Basic Appl. Sci. 2020, 9 (1), 12.
    OpenUrl
  54. 54.↵
    1. Di Prima M.,
    2. Coburn J.,
    3. Hwang D.,
    4. Kelly J.,
    5. Khairuzzaman A.,
    6. Ricles L.
    Additively Manufactured Medical Products—the FDA Perspective. 3D Print. Med. 2016, 2, 4–9.
    OpenUrl
  55. 55.↵
    1. Vyavahare S.,
    2. Teraiya S.,
    3. Panghal D.,
    4. Kumar S.
    Fused Deposition Modelling: A Review. Rapid Prototyp. J. 2020, 26 (1), 176–201.
    OpenUrl
  56. 56.
    1. McFall H.,
    2. Sarabu S.,
    3. Shankar V.,
    4. Bandari S.,
    5. Murthy S. N.,
    6. Kolter K.,
    7. Langley N.,
    8. Kim D. W.,
    9. Repka M. A.
    Formulation of Aripiprazole-Loaded pH-Modulated Solid Dispersions via Hot-Melt Extrusion Technology: In Vitro and in Vivo Studies. Int. J. Pharm. 2019, 554, 302–311.
    OpenUrl
  57. 57.↵
    1. Iwashita M.,
    2. Hashizume K.,
    3. Umehara M.,
    4. Ishigami T.,
    5. Onishi S.,
    6. Yamamoto M.,
    7. Higashi K.,
    8. Moribe K.
    Development of Nobiletin–Methyl Hesperidin Amorphous Solid Dispersion: Novel Application of Methyl Hesperidin as an Excipient for Hot-Melt Extrusion. Int. J. Pharm. 2019, 558, 215–224.
    OpenUrl
  58. 58.↵
    1. Maniruzzaman M.,
    2. Boateng J. S.,
    3. Bonnefille M.,
    4. Aranyos A.,
    5. Mitchell J. C.,
    6. Douroumis D.
    Taste Masking of Paracetamol by Hot-Melt Extrusion: An In Vitro and In Vivo Evaluation. Eur. J. Pharm. Biopharm. 2012, 80 (2), 433–442.
    OpenUrlPubMed
  59. 59.↵
    1. Robet O. W.
    1. Watts A. B.
    1. Miller D. A.
    1. Dinunzio J. C.,
    2. Zhang F.,
    3. Martin C.,
    4. Mcginity J. W.
    Melt Extrusion. In Formulating Poorly Water Soluble Drugs; Robet O. W. III; Watts A. B.; Miller D. A., Eds.; AAPS Advances in the Pharmaceutical Sciences Series; Springer: New York, 2012.
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Hot-Melt Extrusion: An Emerging Technique for Solubility Enhancement of Poorly Water-Soluble Drugs
Amit Chivate, Atul Garkal, Namdev Dhas, Tejal Mehta
PDA Journal of Pharmaceutical Science and Technology Jul 2021, 75 (4) 357-373; DOI: 10.5731/pdajpst.2019.011403
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