An Update on the Contribution of Hot-melt Extrusion Technology to Novel Drug Delivery in the Twenty-first Century: Part II

Overview

Journal Expert Opin Drug Deliv

Publisher Informa Healthcare

Specialty Pharmacology

Date 2019 May 4

PMID 31046479

Citations 19

Authors

Sandeep Sarabu

Suresh Bandari

Venkata Raman Kallakunta

Roshan Tiwari

Hemlata Patil

Michael A Repka

Affiliations

Soon will be listed here.

Abstract

Introduction: Interest in hot-melt extrusion (HME) technology for novel applications is growing day by day, which is evident from several hundred publications within the last 5 years. HME is a cost-effective, solvent free, 'green' technology utilized for various formulations with low investment costs compared to conventional technologies. HME has also earned the attention of the pharmaceutical industry by the transformation of this technology for application in continuous manufacturing.

Areas Covered: Part II of the review focuses on various novel opportunities or innovations of HME such as multiple component systems (co-crystals, co-amorphous systems and salts), twin-screw granulation, semi-solids, co-extrusion, abuse deterrent formulations, solid self-emulsifying drug delivery systems, chronotherapeutic drug delivery systems, and miscellaneous applications.

Expert Opinion: HME is being investigated as an alternative technology for preparation of multicomponent systems such as co-crystals and co-amorphous techniques. Twin-screw granulation has gained increased interest in preparation of granules via twin-screw melt granulation or twin-screw granulation. This novel application of the HME process provides a promising alternate approach in the formulation of granules and solid dosage forms. However, this technology may need to be further investigated for scalability aspects of these novel applications for industrial production.

Citing Articles

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Improve Solubility and Develop Personalized Itraconazole Dosages via Forming Amorphous Solid Dispersions with Hydrophilic Polymers Utilizing HME and 3D Printing Technologies.

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References

Shi N, Wang S, Zhang Y, Huo J, Wang L, Cai J . Hot melt extrusion technology for improved dissolution, solubility and "spring-parachute" processes of amorphous self-micellizing solid dispersions containing BCS II drugs indomethacin and fenofibrate: Profiles and mechanisms. Eur J Pharm Sci. 2019; 130:78-90. DOI: 10.1016/j.ejps.2019.01.019. View

Ma X, Huang S, Lowinger M, Liu X, Lu X, Su Y . Influence of mechanical and thermal energy on nifedipine amorphous solid dispersions prepared by hot melt extrusion: Preparation and physical stability. Int J Pharm. 2019; 561:324-334. DOI: 10.1016/j.ijpharm.2019.03.014. View

Parikh T, Serajuddin A . Development of Fast-Dissolving Amorphous Solid Dispersion of Itraconazole by Melt Extrusion of its Mixture with Weak Organic Carboxylic Acid and Polymer. Pharm Res. 2018; 35(7):127. DOI: 10.1007/s11095-018-2407-4. View

Zhang F . Melt-Extruded Eudragit® FS-Based Granules for Colonic Drug Delivery. AAPS PharmSciTech. 2015; 17(1):56-67. PMC: 4766116. DOI: 10.1208/s12249-015-0357-2. View

Thompson M . Twin screw granulation - review of current progress. Drug Dev Ind Pharm. 2014; 41(8):1223-31. DOI: 10.3109/03639045.2014.983931. View

Berry D, Steed J . Pharmaceutical cocrystals, salts and multicomponent systems; intermolecular interactions and property based design. Adv Drug Deliv Rev. 2017; 117:3-24. DOI: 10.1016/j.addr.2017.03.003. View

Vo A, Feng X, Morott J, Pimparade M, Tiwari R, Zhang F . A novel floating controlled release drug delivery system prepared by hot-melt extrusion. Eur J Pharm Biopharm. 2015; 98:108-21. PMC: 4691578. DOI: 10.1016/j.ejpb.2015.11.015. View

Dumpa N, Sarabu S, Bandari S, Zhang F, Repka M . Chronotherapeutic Drug Delivery of Ketoprofen and Ibuprofen for Improved Treatment of Early Morning Stiffness in Arthritis Using Hot-Melt Extrusion Technology. AAPS PharmSciTech. 2018; 19(6):2700-2709. PMC: 6067978. DOI: 10.1208/s12249-018-1095-z. View

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. 2011; 29(3):806-17. DOI: 10.1007/s11095-011-0605-4. View

10.

Wening K, Schwier S, Stahlberg H, Galia E . Application of hot-melt extrusion technology in immediate-release abuse-deterrent formulations. J Opioid Manag. 2018; 13(6):473-484. DOI: 10.5055/jom.2017.0422. View

11.

Dierickx L, Remon J, Vervaet C . Co-extrusion as manufacturing technique for multilayer mini-matrices with dual drug release. Eur J Pharm Biopharm. 2013; 85(3 Pt B):1157-63. DOI: 10.1016/j.ejpb.2013.01.023. View

12.

Monteyne T, Adriaensens P, Brouckaert D, Remon J, Vervaet C, Beer T . Stearic acid and high molecular weight PEO as matrix for the highly water soluble metoprolol tartrate in continuous twin-screw melt granulation. Int J Pharm. 2016; 512(1):158-167. DOI: 10.1016/j.ijpharm.2016.07.035. View

13.

Mizoguchi R, Waraya H, Hirakura Y . Application of Co-Amorphous Technology for Improving the Physicochemical Properties of Amorphous Formulations. Mol Pharm. 2019; 16(5):2142-2152. DOI: 10.1021/acs.molpharmaceut.9b00105. View

14.

Tiwari R, Patil H, Repka M . Contribution of hot-melt extrusion technology to advance drug delivery in the 21st century. Expert Opin Drug Deliv. 2016; 13(3):451-64. DOI: 10.1517/17425247.2016.1126246. View

15.

Maincent J, Zhang F . Recent advances in abuse-deterrent technologies for the delivery of opioids. Int J Pharm. 2016; 510(1):57-72. DOI: 10.1016/j.ijpharm.2016.06.012. View

16.

Raman Kallakunta V, Patil H, Tiwari R, Ye X, Upadhye S, Vladyka R . Exploratory studies in heat-assisted continuous twin-screw dry granulation: A novel alternative technique to conventional dry granulation. Int J Pharm. 2018; 555:380-393. PMC: 6348896. DOI: 10.1016/j.ijpharm.2018.11.045. View

17.

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):2904-2910. DOI: 10.1002/jps.23983. View

18.

Li S, Yu T, Tian Y, Lagan C, Jones D, Andrews G . Mechanochemical Synthesis of Pharmaceutical Cocrystal Suspensions via Hot Melt Extrusion: Enhancing Cocrystal Yield. Mol Pharm. 2017; 15(9):3741-3754. DOI: 10.1021/acs.molpharmaceut.7b00979. View

19.

Schmidt A, de Waard H, Moll K, Krumme M, Kleinebudde P . Quantitative Assessment of Mass Flow Boundaries in Continuous Twin-screw Granulation. Chimia (Aarau). 2016; 70(9):604-9. DOI: 10.2533/chimia.2016.604. View

20.

Gasior M, Bond M, Malamut R . Routes of abuse of prescription opioid analgesics: a review and assessment of the potential impact of abuse-deterrent formulations. Postgrad Med. 2015; 128(1):85-96. DOI: 10.1080/00325481.2016.1120642. View