Hot Melt Extrusion: A Viable Option for Implementing Continuous Manufacturing in the Pharmaceutical Industry
Abstract
In recent years, hot melt extrusion (HME) has been most widely investigated for developing pharmaceutical medications. HME is a single-step manufacturing process and is suitable for the extrusion of drug-loaded filaments, films, or patches, and granules. The filaments can be processed as pellets or can be processed into tablets or capsules. The HME can be coupled with various downstream processing equipments and process analytical technology (PAT) tools for transforming into a continuous manufacturing line. Establishing a continuous manufacturing line will ensure product quality and will benefit both the industries and the patient population. In fact, the HME can also be paired with additive manufacturing platforms such as fused deposition modeling (FDM) for the fabrication of on-demand and patient-centric medications. Even complex medications can be easily manufactured using an additive manufacturing approach. Despite various advantages of HME, a few limitations, such as the availability of suitable materials and a more in-depth understanding of the process, is still warranted. However, compared with other manufacturing approaches, the HME-based continuous manufacturing is a viable option for the pharmaceutical industry.
Keywords: hot melt extrusion, solubility enhancement, continuous manufacturing, additive manufacturing, 3D printing
Keywords:
Hot melt Extrusion, Solubility Enhancement, continuous manufacturing, additive manufacturing, 3D printingDOI
https://doi.org/10.22270/jddt.v15i10.7381References
1. Mamidi H. Establishment of Design Space for Direct Compression of PEG (400) Loaded Neusilin® US2 by Modified SeDeM Expert System. St. John's University; 2017. https://scholar.google.com/scholar?hl=en&as_sdt=0%2C22&q=Establishment+of+Design+Space+for+Direct+Compression+of+PEG+%28400%29+Loaded+Neusilin%C2%AE+US2+by+Modified+SeDeM+Expert+System&btnG=
2. Siddharatha Dhoppalapudi, Prashanth Parupathi. Hot melt extrusion: A single-step continuous manufacturing process for developing amorphous solid dispersions of poorly soluble drug substances. GSC Advanced Research and Reviews. 2022;13(2):126-135. https://doi.org/10.30574/gscarr.2022.13.2.0311
3. Konda K, Dhoppalapudi S. A Review of Various Manufacturing Approaches for Developing Amorphous Solid Dispersions. Journal of Drug Delivery and Therapeutics. 2022;12(6):189-200. https://doi.org/10.22270/jddt.v12i6.5787
4. Indulkar AS, Lou X, Zhang GGZ, Taylor LS. Role of Surfactants on Release Performance of Amorphous Solid Dispersions of Ritonavir and Copovidone. Pharm Res. 2022;39(2):381-397. https://doi.org/10.1007/s11095-022-03183-4 PMid:35169959
5. Schittny A, Philipp-Bauer S, Detampel P, Huwyler J, Punchkov M. Mechanistic insights into effect of surfactants on oral bioavailability of amorphous solid dispersions. Journal of Controlled Release. 2020;320:214-225. https://doi.org/10.1016/j.jconrel.2020.01.031 PMid:31978445
6. Deshpande TM, Shi H, Pietryka J, Hoag SW, Medek A. Investigation of Polymer/Surfactant Interactions and Their Impact on Itraconazole Solubility and Precipitation Kinetics for Developing Spray-Dried Amorphous Solid Dispersions. Mol Pharm. 2018;15(3):962-974. https://doi.org/10.1021/acs.molpharmaceut.7b00902 PMid:29345955
7. Correa Soto CE, Gao Y, Indulkar AS, Ueda K, Zhang GGZ, Taylor LS. Impact of Surfactants on the Performance of Clopidogrel-Copovidone Amorphous Solid Dispersions: Increased Drug Loading and Stabilization of Nanodroplets. Pharm Res. 2022;39(1):167-188. https://doi.org/10.1007/s11095-021-03159-w PMid:35013849
8. Baghel S, Cathcart H, O'Reilly NJ. Investigation into the Solid-State Properties and Dissolution Profile of Spray-Dried Ternary Amorphous Solid Dispersions: A Rational Step toward the Design and Development of a Multicomponent Amorphous System. Mol Pharm. 2018;15(9):3796-3812. https://doi.org/10.1021/acs.molpharmaceut.8b00306 PMid:30020788
9. Vidiyala N, Parupathi P, Sunkishala P, et al. Artificial intelligence: a new era in prostate cancer diagnosis and treatment. Int J Pharm. 2025;683:126024. https://doi.org/10.1016/j.ijpharm.2025.126024 PMid:40769449
10. Szabo E, Za P, Brecska niel, et al. Comparison of amorphous solid dispersions of spironolactone prepared by spray drying and electrospinning: The influence of the preparation method on the. Mol Pharm. 2021;18(1):317-327. https://doi.org/10.1021/acs.molpharmaceut.0c00965 PMid:33301326 PMCid:PMC7788570
11. Dã B, Farkas A, Szabó B, et al. Development and tableting of directly compressible powder from electrospun nanofibrous amorphous solid dispersion. Elsevier. Published online 2017. https://doi.org/10.1016/j.apt.2017.03.026
12. Li J, Li C, Zhang H, et al. Preparation of Azithromycin Amorphous Solid Dispersion by Hot-Melt Extrusion: An Advantageous Technology with Taste Masking and Solubilization Effects. Polymers 2022, Vol 14, Page 495. 2022;14(3):495. https://doi.org/10.3390/polym14030495 PMid:35160485 PMCid:PMC8840525
13. Janssens S, Van den Mooter G. Review: Physical chemistry of solid dispersions. Journal of Pharmacy and Pharmacology. 2009;61(12):1571-1586. https://doi.org/10.1211/jpp/61.12.0001 PMid:19958579
14. Kennedy M, Hu J, Gao P, et al. Enhanced bioavailability of a poorly soluble VR1 antagonist using an amorphous solid dispersion approach: A case study. Mol Pharm. 2008;5(6):981-993. https://doi.org/10.1021/mp800061r PMid:19434920
15. Nyavanandi D, Mandati P, Narala S, et al. Twin Screw Melt Granulation: A Single Step Approach for Developing Self-Emulsifying Drug Delivery System for Lipophilic Drugs. Pharmaceutics. 2023;15(9):2267. https://doi.org/10.3390/pharmaceutics15092267 PMid:37765237 PMCid:PMC10534719
16. Nyavanandi D, Mandati P, Vidiyala N, Parupathi P, Kolimi P, Mamidi HK. Enhancing Patient-Centric Drug Development: Coupling Hot Melt Extrusion with Fused Deposition Modeling and Pressure-Assisted Microsyringe Additive Manufacturing Platforms with Quality by Design. Pharmaceutics. 2024;17(1):14. https://doi.org/10.3390/pharmaceutics17010014 PMid:39861666 PMCid:PMC11769097
17. Andrews G, AbuDiak O, Jones D. Physicochemical characterization of hot melt extruded bicalutamide-polyvinylpyrrolidone solid dispersions. J Pharm Sci. 2010;99(3):1322-1335. https://doi.org/10.1002/jps.21914 PMid:19798757
18. Cid A, Simonazzi A, Palma S, Bermudez J. Solid dispersion technology as a strategy to improve the bioavailability of poorly soluble drugs. Ther Deliv. 2019;10(6). https://doi.org/10.4155/tde-2019-0007 PMid:31094298
19. Alonzo DE, Gao YI, Zhou D, Mo H, Zhang GGZ, Taylor LS. Dissolution and precipitation behavior of amorphous solid dispersions. J Pharm Sci. 2011;100(8):3316-3331. https://doi.org/10.1002/jps.22579 PMid:21607951
20. Konno H, Handa T, Alonzo D, Taylor L. Effect of polymer type on the dissolution profile of amorphous solid dispersions containing felodipine. European Journal of Pharmaceutics and Biopharmaceutics. 2008;70(2):493-499. https://doi.org/10.1016/j.ejpb.2008.05.023 PMid:18577451
21. Marsac PJ, Li T, Taylor LS. Estimation of drug-polymer miscibility and solubility in amorphous solid dispersions using experimentally determined interaction parameters. Pharm Res. 2009;26(1):139-151. https://doi.org/10.1007/s11095-008-9721-1 PMid:18779927
22. Rumondor ACF, Stanford LA, Taylor LS. Effects of polymer type and storage relative humidity on the kinetics of felodipine crystallization from amorphous solid dispersions. Pharm Res. 2009;26(12):2599-2606. https://doi.org/10.1007/s11095-009-9974-3 PMid:19806435
23. Mooter G Van den, Wuyts M, Blaton N, et al. Physical stabilisation of amorphous ketoconazole in solid dispersions with polyvinylpyrrolidone K25. European Journal of Pharmaceutical Sciences. 2001;12(3):261-269. https://doi.org/10.1016/S0928-0987(00)00173-1 PMid:11113645
24. Ambike A, Mahadik K, Paradkar A. Spray-dried amorphous solid dispersions of simvastatin, a low Tg drug: in vitro and in vivo evaluations. Pharm Res. 2005;22(6):990-998. https://doi.org/10.1007/s11095-005-4594-z PMid:15948043
25. Qian F, Huang J, Hussain M. Drug-polymer solubility and miscibility: stability consideration and practical challenges in amorphous solid dispersion development. J Pharm Sci. 2010;99(7):2941-2947. https://doi.org/10.1002/jps.22074 PMid:20127825
26. Teja SB, Patil SP, Shete G, Patel S, Kumar Bansal A. Drug-excipient behavior in polymeric amorphous solid dispersions. Journal of Excipients and Food Chemicals4. 2013;4(3):70-94. Accessed October 18, 2022. https://jefc.scholasticahq.com/article/1048.pdf
27. Baghel S, Cathcart H, O'Reilly N. Polymeric amorphous solid dispersions: a review of amorphization, crystallization, stabilization, solid-state characterization, and aqueous solubilization of. J Pharm Sci. 2016;105(9):2527-2544. https://doi.org/10.1016/j.xphs.2015.10.008 PMid:26886314
28. Azs D Emuth B, Farkas A, Balogh A, et al. Lubricant-induced crystallization of itraconazole from tablets made of electrospun amorphous solid dispersion. J Pharm Sci. 2016;105(9):2982-2988. https://doi.org/10.1016/j.xphs.2016.04.032 PMid:27290626
29. Balogh A, Farkas B, Farkas A, et al. Homogenization of amorphous solid dispersions prepared by electrospinning in low-dose tablet formulation. Pharmaceutics. 2018;10(3):114. https://doi.org/10.3390/pharmaceutics10030114 PMid:30072667 PMCid:PMC6161125
30. Casian T, Borbás E, Ilyés K, et al. Electrospun amorphous solid dispersions of meloxicam: Influence of polymer type and downstream processing to orodispersible dosage forms. Int J Pharm. 2019;569:118593. https://doi.org/10.1016/j.ijpharm.2019.118593 PMid:31398371
31. Becelaere J, Van E, Broeck D, et al. Stable amorphous solid dispersion of flubendazole with high loading via electrospinning. Journal of Controlled Release. 2022;351:123-136. https://doi.org/10.1016/j.jconrel.2022.09.028 PMid:36122898
32. Démuth B, Farkas A, Pataki H, et al. Detailed stability investigation of amorphous solid dispersions prepared by single-needle and high speed electrospinning. Int J Pharm. 2017;498(1-2):234-244. https://doi.org/10.1016/j.ijpharm.2015.12.029 PMid:26705153
33. Dã B, Farkas A, Szabó B, et al. Development and tableting of directly compressible powder from electrospun nanofibrous amorphous solid dispersion. Advanced Powder Technology. 2017;28(6):1554-1563. https://doi.org/10.1016/j.apt.2017.03.026
34. Nagy Z, Balogh A, Démuth B, et al. High speed electrospinning for scaled-up production of amorphous solid dispersion of itraconazole. Int J Pharm. 2015;480(1-2):137-142. https://doi.org/10.1016/j.ijpharm.2015.01.025 PMid:25596415
35. Yu D, Yang J, Branford-White C, Lu P, Zhang L, Zhu L. Third generation solid dispersions of ferulic acid in electrospun composite nanofibers. Int J Pharm. 2010;400(1-2):158-164. https://doi.org/10.1016/j.ijpharm.2010.08.010 PMid:20713138
36. Karanth H, Shenoy VS, Murthy RR. Industrially feasible alternative approaches in the manufacture of solid dispersions: A technical report. AAPS PharmSciTech. 2006;7(4). https://doi.org/10.1208/pt070487 PMid:17233539 PMCid:PMC2750324
37. Paudel A, Geppi M, Van den Mooter G. Structural and dynamic properties of amorphous solid dispersions: the role of solid-state nuclear magnetic resonance spectroscopy and relaxometry. J Pharm Sci. 2014;103(9):2635-2662. https://doi.org/10.1002/jps.23966 PMid:24715618
38. Pandi P, Bulusu R, Kommineni N, Khan W, Singh M. Amorphous solid dispersions: An update for preparation, characterization, mechanism on bioavailability, stability, regulatory considerations and marketed products. Int J Pharm. 2020;586:119560. https://doi.org/10.1016/j.ijpharm.2020.119560 PMid:32565285 PMCid:PMC8691091
39. Marano S, Barker S, Raimi-Abraham B, Missaghi S, Rajabi-Siahboomi A, Craig D. Development of micro-fibrous solid dispersions of poorly water-soluble drugs in sucrose using temperature-controlled centrifugal spinning. European Journal of Pharmaceutics and Biopharmaceutics. 2016;103:84-94. https://doi.org/10.1016/j.ejpb.2016.03.021 PMid:27012901 PMCid:PMC4866555
40. Keen JM, LaFountaine JS, Hughey JR, Miller DA, McGinity JW. Development of Itraconazole Tablets Containing Viscous KinetiSol Solid Dispersions: In Vitro and In Vivo Analysis in Dogs. AAPS PharmSciTech. 2018;19(5):1998-2008. https://doi.org/10.1208/s12249-017-0903-1 PMid:29192405
41. Gala U, Miller D, Su Y, Spangenberg A, Williams III R. The effect of drug loading on the properties of abiraterone-hydroxypropyl beta cyclodextrin solid dispersions processed by solvent free KinetiSol® technology. European Journal of Pharmaceutics and Biopharmaceutics. 2021;165:52-65. https://doi.org/10.1016/j.ejpb.2021.05.001 PMid:33979662
42. Ellenberger DJ, Miller DA, Kucera SU, Williams RO. Improved Vemurafenib Dissolution and Pharmacokinetics as an Amorphous Solid Dispersion Produced by KinetiSol® Processing. AAPS PharmSciTech. 2018;19(5):1957-1970. https://doi.org/10.1208/s12249-018-0988-1 PMid:29541940
43. LaFountaine J, Jermain S, Prasad L, et al. Enabling thermal processing of ritonavir-polyvinyl alcohol amorphous solid dispersions by KinetiSol® dispersing. European Journal of Pharmaceutics and Biopharmaceutics. 2016;101:72-81. https://doi.org/10.1016/j.ejpb.2016.01.018 PMid:26861929
44. Jermain S V., Miller D, Spangenberg A, et al. Homogeneity of amorphous solid dispersions-an example with KinetiSol®. Drug Dev Ind Pharm. 2019;45(5):724-735. https://doi.org/10.1080/03639045.2019.1569037 PMid:30653376
45. Hughey J, Keen J, Brough C, Saeger S, McGinity J. Thermal processing of a poorly water-soluble drug substance exhibiting a high melting point: the utility of KinetiSol® dispersing. Int J Pharm. 2011;419(1-2):222-230. https://doi.org/10.1016/j.ijpharm.2011.08.007 PMid:21864663
46. DiNunzio J, Brough C, Miller D, Williams R, McGinity J. Applications of KinetiSol® Dispersing for the production of plasticizer free amorphous solid dispersions. European Journal of Pharmaceutical Sciences. 2010;40(3):179-187. https://doi.org/10.1016/j.ejps.2010.03.002 PMid:20230894
47. DiNunzio J, Brough C, Hughey J, Miller D, Williams R, McGinity J. Fusion production of solid dispersions containing a heat-sensitive active ingredient by hot melt extrusion and Kinetisol® dispersing. European Journal of Pharmaceutics and Biopharmaceutics. 2010;74(2):340-351. https://doi.org/10.1016/j.ejpb.2009.09.007 PMid:19818402
48. Brough C, RO Williams R. Amorphous solid dispersions and nano-crystal technologies for poorly water-soluble drug delivery. Int J Pharm. 2013;453(1):157-166. https://doi.org/10.1016/j.ijpharm.2013.05.061 PMid:23751341
49. He Y, Ho C. Amorphous solid dispersions: utilization and challenges in drug discovery and development. J Pharm Sci. 2015;104(10):3237-3258. https://doi.org/10.1002/jps.24541 PMid:26175316
50. Vidiyala N, Sunkishala P, Parupathi P, et al. High Drug Loading of Amorphous Solid Dispersion by Hot Melt Extrusion: The Role of Magnesium Aluminometasilicate (Neusilin® US2). Sci Pharm. 2025;93(3):30. https://doi.org/10.3390/scipharm93030030
51. Tan DK, Davis DA, Miller DA, Williams RO, Nokhodchi A. Innovations in Thermal Processing: Hot-Melt Extrusion and KinetiSol® Dispersing. AAPS PharmSciTech. 2020;21(8). https://doi.org/10.1208/s12249-020-01854-2 PMid:33161479 PMCid:PMC7649167
52. Ellenberger DJ, Miller DA, Kucera SU, Williams RO. Generation of a Weakly Acidic Amorphous Solid Dispersion of the Weak Base Ritonavir with Equivalent In Vitro and In Vivo Performance to Norvir Tablet. AAPS PharmSciTech. 2018;19(5):1985-1997. https://doi.org/10.1208/s12249-018-1060-x PMid:29869311
53. Jr DD, Miller D, Santitewagun S, Zeitler J, Su Y, Williams R. Formulating a heat-and shear-labile drug in an amorphous solid dispersion: Balancing drug degradation and crystallinity. Int J Pharm X. 2021;3:100092. https://doi.org/10.1016/j.ijpx.2021.100092 PMid:34977559 PMCid:PMC8683684
54. Dinunzio JC, Hughey JR, Brough C, Miller DA, Williams RO, McGinity JW. Production of advanced solid dispersions for enhanced bioavailability of itraconazole using KinetiSol® Dispersing. Drug Dev Ind Pharm. 2010;36(9):1064-1078. https://doi.org/10.3109/03639041003652973 PMid:20334539
55. Ekdahl A, Mudie D, Malewski D, Amidon G, Goodwin A. Effect of spray-dried particle morphology on mechanical and flow properties of felodipine in PVP VA amorphous solid dispersions. J Pharm Sci. 2019;108(11):3657-3666. https://doi.org/10.1016/j.xphs.2019.08.008 PMid:31446144
56. Poudel S, Kim D. Developing pH-modulated spray dried amorphous solid dispersion of candesartan cilexetil with enhanced in vitro and in vivo performance. Pharmaceutics. 2021;13(4):497. https://doi.org/10.3390/pharmaceutics13040497 PMid:33917403 PMCid:PMC8067465
57. Sawicki E, Beijnen J, Schellens J, Nuijen B. Pharmaceutical development of an oral tablet formulation containing a spray dried amorphous solid dispersion of docetaxel or paclitaxel. Int J Pharm. 2016;511(2):765-773. https://doi.org/10.1016/j.ijpharm.2016.07.068 PMid:27480397
58. Zaitone A, Al-Zahrani B;, Ahmed O, Saeed U, Taimoor AA. Spray Drying of PEG6000 Suspension: Reaction Engineering Approach (REA) Modeling of Single Droplet Drying Kinetics. Process. 2022;10(7):1365. https://doi.org/10.3390/pr10071365
59. Li J, Zordan C, Ponce S, Lu X. Impact of Swelling of Spray Dried Dispersions in Dissolution Media on their Dissolution: An Investigation Based on UV Imaging. J Pharm Sci. 2022;111(6):1761-1769. https://doi.org/10.1016/j.xphs.2021.12.007 PMid:34896344
60. Patel K, Shah S, Patel J. Solid dispersion technology as a formulation strategy for the fabrication of modified release dosage forms: A comprehensive review. DARU, Journal of Pharmaceutical Sciences. 2022;30(1):165-189. https://doi.org/10.1007/s40199-022-00440-0 PMid:35437630 PMCid:PMC9114203
61. Ding Z, Wang X, Wang L, et al. Characterisation of spray dried microencapsules with amorphous lutein nanoparticles: Enhancement of processability, dissolution rate, and storage stability. Food Chem. 2022;383:132200. https://doi.org/10.1016/j.foodchem.2022.132200 PMid:35168049
62. Ikeda C, Zhou G, Lee Y, et al. Application of Online NIR Spectroscopy to Enhance Process Understanding and Enable In-process Control Testing of Secondary Drying Process for a Spray-dried. J Pharm Sci. 2022;111(9):2540-2551. https://doi.org/10.1016/j.xphs.2022.04.009 PMid:35439470
63. Boel E, Reniers F, Dehaen W, Van den Mooter G. The Value of Bead Coating in the Manufacturing of Amorphous Solid Dispersions: A Comparative Evaluation with Spray Drying. Pharmaceutics. 2022;14(3):613. https://doi.org/10.3390/pharmaceutics14030613 PMid:35335989 PMCid:PMC8955898
64. Newman A, Zografi G. Considerations in the Development of Physically Stable High Drug Load API-Polymer Amorphous Solid Dispersions in the Glassy State. J Pharm Sci. 2022;In Press. https://doi.org/10.1016/j.xphs.2022.08.007 PMid:35948156
65. Duarte Í, Santos JL, Pinto JF, Temtem M. Screening methodologies for the development of spray-dried amorphous solid dispersions. Pharm Res. 2015;32(1):222-237. https://doi.org/10.1007/s11095-014-1457-5 PMid:25135702
66. Lang B, Liu S, McGinity JW, Williams RO. Effect of hydrophilic additives on the dissolution and pharmacokinetic properties of itraconazole-enteric polymer hot-melt extruded amorphous solid dispersions. Drug Dev Ind Pharm. 2016;42(3):429-445. https://doi.org/10.3109/03639045.2015.1075031 PMid:26355819
67. Kowalczuk M, Li J, Li C, et al. Preparation of Azithromycin Amorphous Solid Dispersion by Hot-Melt Extrusion: An Advantageous Technology with Taste Masking and Solubilization Effects. Polymers (Basel). 2022;14(3):495. https://doi.org/10.3390/polym14030495 PMid:35160485 PMCid:PMC8840525
68. Liu X, Lu M, Guo Z, Huang L, Feng X, Wu C. Improving the chemical stability of amorphous solid dispersion with cocrystal technique by hot melt extrusion. Pharm Res. 2012;29(3):806-817. https://doi.org/10.1007/s11095-011-0605-4 PMid:22009589
69. Sarode A, Sandhu H, Shah N, Malick W, Zia H. Hot melt extrusion (HME) for amorphous solid dispersions: predictive tools for processing and impact of drug-polymer interactions on supersaturation. European Journal of Pharmaceutical Sciences. 2013;48(3):371-384. https://doi.org/10.1016/j.ejps.2012.12.012 PMid:23267847
70. Tian Y, Jacobs E, Jones D, McCoy C, Wu H, Andrews G. The design and development of high drug loading amorphous solid dispersion for hot-melt extrusion platform. Int J Pharm. 2020;586:119545. https://doi.org/10.1016/j.ijpharm.2020.119545 PMid:32553496
71. Giri BR, Kwon J, Vo AQ, Bhagurkar AM, Bandari S, Kim DW. Hot-melt extruded amorphous solid dispersion for solubility, stability, and bioavailability enhancement of telmisartan. Pharmaceutics. 2021;14(1):73. https://doi.org/10.3390/ph14010073 PMid:33477557 PMCid:PMC7831136
72. Fan W, Zhu W, Zhang X, Xu Y, Di L. Application of the combination of ball-milling and hot-melt extrusion in the development of an amorphous solid dispersion of a poorly water-soluble drug with. RSC Adv. 2019;9:22263-22273. https://doi.org/10.1039/C9RA00810A PMid:35519487 PMCid:PMC9066646
73. Mishra S, Richter M, Mejia L, Sauer A. Downstream Processing of Itraconazole: HPMCAS Amorphous Solid Dispersion: From Hot-Melt Extrudate to Tablet Using a Quality by Design Approach. Pharmaceutics. 2022;14(7):1429. https://doi.org/10.3390/pharmaceutics14071429 PMid:35890324 PMCid:PMC9323274
74. 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):2303-2315. https://doi.org/10.1208/s12249-017-0713-5 PMid:28108974
75. Genina N, Hadi B, Löbmann K. Hot melt extrusion as solvent-free technique for a continuous manufacturing of drug-loaded mesoporous silica. J Pharm Sci. 2018;107(1):149-155. https://doi.org/10.1016/j.xphs.2017.05.039 PMid:28603020
76. Patil H, Kulkarni V, Majumdar S, Repka M. Continuous manufacturing of solid lipid nanoparticles by hot melt extrusion. Int J Pharm. 2014;471(1-2):153-156. https://doi.org/10.1016/j.ijpharm.2014.05.024 PMid:24853459
77. Maniruzzaman M, Nokhodchi A. Continuous manufacturing via hot-melt extrusion and scale up: regulatory matters. Drug Discov Today. 2016;22(2):340-351. https://doi.org/10.1016/j.drudis.2016.11.007 PMid:27866007
78. Seem T, Rowson N, Ingram A, et al. Twin screw granulation-A literature review. Elsevier Powder Technology. 2015;276:89-102. https://doi.org/10.1016/j.powtec.2015.01.075
79. Mamidi H, Mishra S, Rohera B. Application of modified SeDeM expert diagram system for selection of direct compression excipient for liquisolid formulation of Neusilin® US2. J Drug Deliv Sci Technol. 2021;64:102506. https://doi.org/10.1016/j.jddst.2021.102506
80. 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):255-263. https://doi.org/10.1016/j.ijpharm.2016.05.036 PMid:27215535
81. Santos J Dos, Silveira Da Silva G, Velho MC, Carlos R, Beck R. Eudragit®: A Versatile Family of Polymers for Hot Melt Extrusion and 3D Printing Processes in Pharmaceutics. Pharmaceutics. 2021;13(9):1424. https://doi.org/10.3390/pharmaceutics13091424 PMid:34575500 PMCid:PMC8471576
82. Cunha-Filho M, Araújo MR, Gelfuso GM, Gratieri T. FDM 3D printing of modified drug-delivery systems using hot melt extrusion: A new approach for individualized therapy. Ther Deliv. 2017;8(11):957-966. https://doi.org/10.4155/tde-2017-0067 PMid:29061104
83. Madan S, Madan S. Hot melt extrusion and its pharmaceutical applications. Asian J Pharm Sci. 2012;7(1):123-133. Accessed October 18, 2022. https://search.ebscohost.com/login.aspx?direct=true&profile=ehost&scope=site&authtype=crawler&jrnl=18180876&AN=76385092&h=E%2BnVOb8JShE%2Fb6%2Bg80lQW%2BBTmz%2BnljjuMYmY%2FvaKoGIsN47xWWlcY76lISjNTYsgoAT8kIdiEdvkiONgQRBsuw%3D%3D&crl=c
84. Simões M, Pinto R, Simões S. Hot-melt extrusion in the pharmaceutical industry: toward filing a new drug application. Drug Discov Today. 2019;24(9):1749-1768. https://doi.org/10.1016/j.drudis.2019.05.013 PMid:31132415
85. Lang B, McGinity JW, Williams RO. Hot-melt extrusion-basic principles and pharmaceutical applications. Drug Dev Ind Pharm. 2014;40(9):1133-1155. https://doi.org/10.3109/03639045.2013.838577 PMid:24520867
86. Maniruzzaman M, Boateng JS, Snowden MJ, et al. A review of hot-melt extrusion: process technology to pharmaceutical products. ISRN Pharm. 2012;2012. https://doi.org/10.5402/2012/436763 PMid:23326686 PMCid:PMC3543799
87. Newman A, Knipp G, Zografi G. Assessing the performance of amorphous solid dispersions. J Pharm Sci. 2012;101(4):1355-1377. https://doi.org/10.1002/jps.23031 PMid:22213468
88. Thompson S, Williams III R. Specific mechanical energy-An essential parameter in the processing of amorphous solid dispersions. Adv Drug Deliv Rev. 2021;173:374-393. https://doi.org/10.1016/j.addr.2021.03.006 PMid:33781785
89. Vasconcelos T, Marques S, Neves J, Sarmento B. Amorphous solid dispersions: Rational selection of a manufacturing process. Adv Drug Deliv Rev. 2016;100:85-101. https://doi.org/10.1016/j.addr.2016.01.012 PMid:26826438
90. Ma X, Williams III R. Characterization of amorphous solid dispersions: An update. J Drug Deliv Sci Technol. 2019;50:113-124. https://doi.org/10.1016/j.jddst.2019.01.017
91. Van der Mooter G. The use of amorphous solid dispersions: A formulation strategy to overcome poor solubility and dissolution rate. Drug Discov Today Technol. 2012;9(2):79-85. https://doi.org/10.1016/j.ddtec.2011.10.002 PMid:24064267
92. LaFountaine JS, McGinity JW, Williams RO. Challenges and Strategies in Thermal Processing of Amorphous Solid Dispersions: A Review. AAPS PharmSciTech. 2016;17(1):43-55. https://doi.org/10.1208/s12249-015-0393-y PMid:26307759 PMCid:PMC4766121
93. Park S, Rajesh P, Sim Y, et al. Addressing scale-up challenges and enhancement in performance of hydrogen-producing microbial electrolysis cell through electrode modifications. Energy Reports. 2022;8:2726-2746. https://doi.org/10.1016/j.egyr.2022.01.198
94. Ghadge R, Nagwani N, Saxena N, Dasgupta S, Sapre A. Design and scale-up challenges in hydrothermal liquefaction process for biocrude production and its upgradation. Energy Conversion and Management: X. 2022;14:100223. https://doi.org/10.1016/j.ecmx.2022.100223
95. Tonkovich A, Kuhlmann D, Rogers A, et al. Microchannel technology scale-up to commercial capacity. Chemical Engineering Research and Design. 2005;83(6):634-639. https://doi.org/10.1205/cherd.04354
96. Khairnar S V, Pagare P, Thakre A, et al. Review on the Scale-Up Methods for the Preparation of Solid Lipid Nanoparticles. Pharmaceutics. 2022;14(9):1886. https://doi.org/10.3390/pharmaceutics14091886 PMid:36145632 PMCid:PMC9503303
97. Tran P, Pyo Y, Kim D, Lee S, Kim J, Park J. Overview of the manufacturing methods of solid dispersion technology for improving the solubility of poorly water-soluble drugs and application to anticancer drugs. Pharmaceutics. 2019;11(3):132. https://doi.org/10.3390/pharmaceutics11030132 PMid:30893899 PMCid:PMC6470797
98. Sharma A, Jain C. Solid dispersion: A promising technique to enhance solubility of poorly water soluble drug. International Journal of Drug Delivery. Published online 2011. https://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.856.1002&rep=rep1&type=pdf
99. Lima ÁAN, Sobrinho JLS, Corrêa RAC, Neto PJR. Alternative technologies to improve solubility of poorly water soluble drugs. Latin American Journal of Pharmacy. 2008;27(5):789-797. http://www.latamjpharm.org/trabajos/27/5/LAJOP_27_5_4_2_7QVYB4J43B.pdf
100. Chaudhari S, Dugar R. Application of surfactants in solid dispersion technology for improving solubility of poorly water soluble drugs. J Drug Deliv Sci Technol. 2017;41:68-77. https://doi.org/10.1016/j.jddst.2017.06.010
101. Singh D, Bedi N, Tiwary AK. Enhancing solubility of poorly aqueous soluble drugs: critical appraisal of techniques. Journal of Pharmaceutical Investigation 2017 48:5. 2017;48(5):509-526. https://doi.org/10.1007/s40005-017-0357-1
102. Singh A, Worku ZA, Van Den Mooter G. Oral formulation strategies to improve solubility of poorly water-soluble drugs. Expert Opin Drug Deliv. 2011;8(10):1361-1378. dohttps://doi.org/10.1517/17425247.2011.606808 PMid:21810062
103. Vidiyala N, Sunkishala P, Parupathi P, Nyavanandi D. The Role of Artificial Intelligence in Drug Discovery and Pharmaceutical Development: A Paradigm Shift in the History of Pharmaceutical Industries. AAPS PharmSciTech. 2025;26(5):1-21. https://doi.org/10.1208/s12249-025-03134-3 PMid:40360908
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