Application of Lipids in Hot Melt Extrusion Technology

  • Anil Kumar Dindigala Thermofisher Scientific, Greenville, NC - 27858, USA
  • Mounika Rajya Lakshmi Kodam Doctor of Pharmacy, Palamuru University, Telangana State, India


Lipids are commonly used excipients in drug delivery for improving solubility of low soluble drugs, enhancing bioavailability through avoiding first pass metabolism through nanoparticulate approach, modifying the drug release, binders, permeation enhancers, transfection agents etc. Lipids alone or in combination of polymers are increasingly being used in hot melt extrusion (HME) technology for preparation of controlled release formulations, solid dispersions, self-emulsifying drug delivery systems, semi-solid formulations, solid lipid nanoparticles and others. Properties like low melting temperature, viscosity, ability to extrude at low temperature and ability to load high doses of drug favor use of lipids in HME technology. This review emphasizes the use of lipids for variety of applications in HME technology.

Keywords: Lipids, Hot melt extrusion, solubility, bioavailability, parameters.

Keywords: Lipids, Hot melt extrusion, solubility, bioavailability, parameters


Download data is not yet available.

Author Biographies

Anil Kumar Dindigala, Thermofisher Scientific, Greenville, NC - 27858, USA

Thermofisher Scientific, Greenville, NC - 27858, USA

Mounika Rajya Lakshmi Kodam, Doctor of Pharmacy, Palamuru University, Telangana State, India

Doctor of Pharmacy, Palamuru University, Telangana State, India


1. Larsson, K., Quinn, P., Sato, K., & Tiberg, F. (2006). Lipids: structure, physical properties and functionality (Vol. 19). Bridgwater: Oily Press.
2. Dudhipala N. A comprehensive review on solid lipid nanoparticles as delivery vehicle for enhanced pharmacokinetic and pharmacodynamic activity of poorly soluble drugs. International Journal of Pharmaceutical Sciences and Nanotechnology (IJPSN). 2019 Mar 31; 12(2):4421-40.
3. Maurya A, Rangappa S, Bae J, Dhawan T, Ajjarapu SS, Murthy SN. Evaluation of soluble fentanyl microneedles for loco-regional anti-nociceptive activity. International journal of pharmaceutics. 2019; 564:485-91.
4. Fatima T, Ajjarapu S, Shankar VK, Rangappa S, Shivakumar HN, Biswas SK, Hoque M, Murthy SN. Topical pilocarpine formulation for diagnosis of cystic fibrosis. Journal of pharmaceutical sciences. 2020; 109(5):1747-51.
5. Porter CJ, Trevaskis NL, Charman WN. Lipids and lipid-based formulations: optimizing the oral delivery of lipophilic drugs. Nature reviews Drug discovery. 2007; 6(3):231-48.
6. Shrestha H, Bala R, Arora S. Lipid-based drug delivery systems. Journal of pharmaceutics. 2014; 2014.
7. Basim P, Gorityala S, Kurakula M. Advances in functionalized hybrid biopolymer augmented lipid-based systems: A spotlight on their role in design of gastro retentive delivery systems. Archives of Gastroenterology Research. 2021; 2(1):35-47.
8. Dudhipala N, Ettireddy S, Youssef AA, Puchchakayala G. Development and In vivo Pharmacokinetic and Pharmacodynamic Evaluation of an Oral Innovative Cyclodextrin Complexed Lipid Nanoparticles of Irbesartan Formulation for Enhanced Bioavailability. Nanotheranostics. 2023; 7(1):117.
9. Kurakula M, Basim P. Biopolymer-Lipid Hybrid Composites and their Advances in Bio-imaging and Drug Delivery. J Radiol Med Imaging. 2021; 4(1):1041.
10. Kurakula M, Patel DB, Patel B, Gorityala S, Basim P. Functionalized Nanocarriers for Drug delivery: Amalgam of Biopolymers and Lipids. J Nanomed. 2021; 4(1):1037.
11. Ajjarapu S, Banda S, Basim P, Dudhipala N. Melt Fusion Techniques for Solubility Enhancement: A Comparison of Hot Melt Extrusion and KinetiSol® Technologies. Scientia Pharmaceutica. 2022; 90(3):51.
12. White Paper on Solid Lipid Excipients: Born to be extruded! Available online: (Accessed 16 April 2023)
13. Kallakunta VR, Sarabu S, Bandari S, Tiwari R, Patil H, Repka MA. An update on the contribution of hot-melt extrusion technology to novel drug delivery in the twenty-first century: part I. Expert opinion on drug delivery. 2019; 16(5):539-50.
14. Butreddy A, Sarabu S, Almutairi M, Ajjarapu S, Kolimi P, Bandari S, Repka MA. Hot-melt extruded hydroxypropyl methylcellulose acetate succinate based amorphous solid dispersions: Impact of polymeric combinations on supersaturation kinetics and dissolution performance. International Journal of Pharmaceutics. 2022; 615:121471.
15. Zupančič O, Spoerk M, Paudel A. Lipid-based solubilization technology via hot melt extrusion: Promises and challenges. Expert Opinion on Drug Delivery. 2022; 19(9):1013-32.
16. Kallakunta VR, Sarabu S, Dudhipala N, Janga KY, Bandari S, Zhang F, Repka MA. Chrono modulated multiple unit particulate systems (MUPS) via a continuous hot melt double extrusion technique: Investigation of the formulation and process suitability. European Journal of Pharmaceutics and Biopharmaceutics. 2021 Nov 1; 168:184-94.
17. Maniruzzaman M, Boateng JS, Snowden MJ, Douroumis D. A review of hot-melt extrusion: process technology to pharmaceutical products. International Scholarly Research Notices. 2012; 2012.
18. Agrawal AM, Dudhedia MS, Zimny E. Hot melt extrusion: development of an amorphous solid dispersion for an insoluble drug from mini-scale to clinical scale. Aaps Pharmscitech. 2016; 17:133-47.
19. Thakkar R, Komanduri N, Dudhipala N, Tripathi S, Repka MA, Majumdar S. Development and optimization of hot-melt extruded moxifloxacin hydrochloride inserts, for ocular applications, using the design of experiments. International Journal of Pharmaceutics. 2021 Jun 15; 603:120676.
20. Palem CR, Dudhipala N, Battu SK, Goda S, Repka MA, Yamsani MR. Combined dosage form of pioglitazone and felodipine as mucoadhesive pellets via hot melt extrusion for improved buccal delivery with application of quality by design approach. Journal of Drug Delivery Science and Technology. 2015 Dec 1; 30:209-19.
21. Sarode AL, 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):371-84.
22. Adler C, Schönenberger M, Teleki A, Kuentz M. Molecularly designed lipid microdomains for solid dispersions using a polymer/inorganic carrier matrix produced by hot-melt extrusion. International Journal of Pharmaceutics. 2016; 499(1-2):90-100.
23. Dudhipala N. Influence of solid lipid nanoparticles on pharmaco-dynamic activity of poorly oral bioavailable drugs. International Journal of Pharmaceutical Sciences and Nanotechnology (IJPSN). 2020 Jul 11; 13(4):4979-83.
24. Jaipal A, Pandey MM, Charde SY, Sadhu N, Srinivas A, Prasad RG. Controlled release effervescent buccal discs of buspirone hydrochloride: in vitro and in vivo evaluation studies. Drug delivery. 2016; 23(2):452-8.
25. Heng PW. Controlled release drug delivery systems. Pharmaceutical Development and Technology. 2018; 23(9):833.
26. Alshetaili A, Almutairy BK, Alshehri SM, Repka MA. Development and characterization of sustained-released donepezil hydrochloride solid dispersions using hot melt extrusion technology. Pharmaceutics. 2021; 13(2):213.
27. Alqahtani F, Belton P, Ward A, Asare-Addo K, Qi S. An investigation into the use of low quantities of functional additives to control drug release from hot melt extruded solid dispersions for poorly soluble drug delivery. International journal of pharmaceutics. 2020; 579:119172.
28. Vithani K, Maniruzzaman M, Slipper IJ, Mostafa S, Miolane C, Cuppok Y, Marchaud D, Douroumis D. Sustained release solid lipid matrices processed by hot-melt extrusion (HME). Colloids and Surfaces B: Biointerfaces. 2013; 110:403-10.
29. Maniruzzaman M, Islam MT, Halsey S, Amin D, Douroumis D. Novel controlled release polymer-lipid formulations processed by hot melt extrusion. AAPS PharmSciTech. 2016; 17:191-9.
30. Forster SP, Dippold E, Chiang T. Twin-screw melt granulation for oral solid pharmaceutical products. Pharmaceutics. 2021; 13(5):665.
31. Kittikunakorn N, Liu T, Zhang F. Twin-screw melt granulation: Current progress and challenges. International Journal of Pharmaceutics. 2020; 588:119670.
32. Liu J, Zhang F, McGinity JW. Properties of lipophilic matrix tablets containing phenylpropanolamine hydrochloride prepared by hot-melt extrusion. European Journal of Pharmaceutics and Biopharmaceutics. 2001; 52(2):181-90.
33. Sarabu S, Kallakunta VR, Butreddy A, Janga KY, Ajjarapu S, Bandari S, Zhang F, Murthy SN, Repka MA. A one-step twin-screw melt granulation with gelucire 48/16 and surface adsorbent to improve the solubility of poorly soluble drugs: effect of formulation variables on dissolution and stability. AAPS PharmSciTech. 2021; 22:1-4.
34. Shaikh R, Walker GM, Croker DM. Continuous, simultaneous cocrystallization and formulation of theophylline and 4-aminobenzoic acid pharmaceutical cocrystals using twin screw melt granulation. European Journal of Pharmaceutical Sciences. 2019; 137:104981.
35. Ajjarapu S, Rangappa S, Shankar VK, Shettar A, Kumar HS, Kulkarni VI, Repka MA, Murthy SN. A rapid tool to optimize process variables for continuous manufacturing of metronidazole ointment using melt extrusion technique. AAPS PharmSciTech. 2020; 21:1-7.
36. Patil H, Tiwari RV, Repka MA. Hot-melt extrusion: from theory to application in pharmaceutical formulation. Aaps Pharmscitech. 2016; 17:20-42.
37. Shettar A, Shankar VK, Ajjarapu S, Kulkarni VI, Repka MA, Murthy SN. Development and characterization of Novel topical oil/PEG creams of voriconazole for the treatment of fungal infections. Journal of Drug Delivery Science and Technology. 2021; 66:102928.
38. Khinast J, Baumgartner R, Roblegg E. Nano-extrusion: a one-step process for manufacturing of solid nanoparticle formulations directly from the liquid phase. AAPS PharmSciTech. 2013; 14:601-4.
39. Muddineti OS, Kumari P, Ajjarapu S, Lakhani PM, Bahl R, Ghosh B, Biswas S. Xanthan gum stabilized PEGylated gold nanoparticles for improved delivery of curcumin in cancer. Nanotechnology. 2016; 27(32):325101.
40. Patil H, Kulkarni V, Majumdar S, Repka MA. Continuous manufacturing of solid lipid nanoparticles by hot melt extrusion. International journal of pharmaceutics. 2014; 471(1-2):153-6.
41. Bagde A, Patel K, Kutlehria S, Chowdhury N, Singh M. Formulation of topical ibuprofen solid lipid nanoparticle (SLN) gel using hot melt extrusion technique (HME) and determining its anti-inflammatory strength. Drug delivery and translational research. 2019; 9:816-27.
42. Matthieu G, Nina R, Sophie E J, Ewan RG M, Daniel G B, Gabriel A, Paul A D. Protein denaturation and protein: drugs interactions from intrinsic protein fluorescence measurements at the nanolitre scale. Protein Science. 2010; 19(8):1544-54.
43. Butreddy A, Janga KY, Ajjarapu S, Sarabu S, Dudhipala N. Instability of therapeutic proteins-An overview of stresses, stabilization mechanisms and analytical techniques involved in Lyophilized proteins. International journal of biological macromolecules. 2021; 167:309-25.
44. Vollrath M, Engert J, Winter G. New insights into process understanding of solid lipid extrusion (SLE) of extruded lipid implants for sustained protein delivery. European Journal of Pharmaceutics and Biopharmaceutics. 2018; 130:11-21.
230 Views | 10 Downloads
How to Cite
Dindigala AK, Kodam MRL. Application of Lipids in Hot Melt Extrusion Technology. JDDT [Internet]. 15May2023 [cited 18May2024];13(5):82-6. Available from: