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Current Pharmaceutical Design

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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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Review Article

Scope and Application of Hot Melt Extrusion in the Development of Controlled and Sustained Release Drug Delivery Systems

In Press, (this is not the final "Version of Record"). Available online 02 August, 2024
Author(s): Parth Joshi, G.S.N. Koteswara Rao and Bappaditya Chatterjee*
Published on: 02 August, 2024

DOI: 10.2174/0113816128299356240626114734

Price: $95

Abstract

Controlled-release drug delivery systems (CRDDS) are more beneficial than conventional immediate release (IRDDS) for reduced intake, prolonged duration of action, lesser adverse effects, higher bioavailability, etc. The preparation of CRDDS is more complex than IRDDS. The hot melt extrusion (HME) technique is used for developing amorphous solid dispersion of poorly water soluble drugs to improve their dissolution rate and oral bioavailability. HME can be employed to develop CRDDS. Sustained release delivery systems (SRDDS), usually given orally, can also be developed using HME. This technique has the advantages of using no organic solvent, converting crystalline drugs to amorphous, improving bioavailability, etc. However, the heat sensitivity of drugs, miscibility between drug-polymer, and the availability of a few polymers are some of the challenges HME faces in developing CRDDS and SRDDS. The selection of a suitable polymer and the optimization of the process with the help of the QbD principle are two important aspects of the successful application of HME. In this review, strategies to prepare SRDDS and CRDDS using HME are discussed with its applications in research.

[1]
Vasconcelos T, Sarmento B, Costa P. Solid dispersions as strategy to improve oral bioavailability of poor water soluble drugs. Drug Discov Today 2007; 12(23-24): 1068-75.
[http://dx.doi.org/10.1016/j.drudis.2007.09.005] [PMID: 18061887]
[2]
Tekade AR, Yadav JN. A review on solid dispersion and carriers used therein for solubility enhancement of poorly water soluble drugs. Adv Pharm Bull 2020; 10(3): 359-69.
[http://dx.doi.org/10.34172/apb.2020.044] [PMID: 32665894]
[3]
Schittny A, Huwyler J, Puchkov M. Mechanisms of increased bioavailability through amorphous solid dispersions: A review. Drug Deliv 2020; 27(1): 110-27.
[http://dx.doi.org/10.1080/10717544.2019.1704940] [PMID: 31885288]
[4]
Nikam VK, Shete SK, Khapare JP. Most promising solid dispersion technique of oral dispersible tablet. Beni Suef Univ J Basic Appl Sci 2020; 9(1): 62.
[http://dx.doi.org/10.1186/s43088-020-00086-4]
[5]
Malkawi R, Malkawi WI, Al-Mahmoud Y, Tawalbeh J. Current trends on solid dispersions: Past, present, and future. Adv Pharmacol Pharm Sci 2022; 2022: 5916013.
[6]
Ziaee A, O’Dea S, Howard-Hildige A, et al. Amorphous solid dispersion of ibuprofen: A comparative study on the effect of solution based techniques. Int J Pharm 2019; 572: 118816.
[http://dx.doi.org/10.1016/j.ijpharm.2019.118816] [PMID: 31678527]
[7]
Mustafa WW, Fletcher J, Khoder M, Alany RG. Solid dispersions of gefitinib prepared by spray drying with improved mucoadhesive and drug dissolution properties. AAPS PharmSciTech 2022; 23(1): 48.
[http://dx.doi.org/10.1208/s12249-021-02187-4] [PMID: 34984564]
[8]
Dabhade D, Wadher K, Bute S, Naidu N, Umekar M, Anantwar S. Preparation and characterization of artemether solid dispersion by spray drying technique. J Drug Deliv Ther 2021; 11(2): 1-5.
[http://dx.doi.org/10.22270/jddt.v11i2.4557]
[9]
Zaini E, Fitriani L, Haqi A. Preparation and characterization of solid dispersion freeze-dried efavirenz - polyvinylpyrrolidone K-30. J Adv Pharm Technol Res 2016; 7(3): 105-9.
[http://dx.doi.org/10.4103/2231-4040.184592] [PMID: 27429930]
[10]
Ansari MT, Hussain A, Nadeem S, et al. Preparation and characterization of solid dispersions of artemether by freeze-dried method. BioMed Res Int 2015; 2015: 1-11.
[http://dx.doi.org/10.1155/2015/109563] [PMID: 26097842]
[11]
Ren Y, Mei L, Zhou L, Guo G. Recent perspectives in hot melt extrusion-based polymeric formulations for drug delivery: Applications and innovations. AAPS PharmSciTech 2019; 20(3): 92.
[http://dx.doi.org/10.1208/s12249-019-1300-8] [PMID: 30690659]
[12]
Paczkowska-Walendowska M, Miklaszewski A, Szymanowska D, Skalicka-Woźniak K, Cielecka-Piontek J. Hot melt extrusion as an effective process in the development of mucoadhesive tablets containing Scutellariae baicalensis radix extract and chitosan dedicated to the treatment of oral infections. Int J Mol Sci 2023; 24(6): 5834.
[http://dx.doi.org/10.3390/ijms24065834] [PMID: 36982908]
[13]
Lang B, McGinity JW, Williams RO III. Dissolution enhancement of itraconazole by hot-melt extrusion alone and the combination of hot-melt extrusion and rapid freezing-effect of formulation and processing variables. Mol Pharm 2014; 11(1): 186-96.
[http://dx.doi.org/10.1021/mp4003706] [PMID: 24283890]
[14]
Narala S, Komanduri N, Nyavanandi D, et al. Hard gelatin capsules containing hot melt extruded solid crystal suspension of carbamazepine for improving dissolution: Preparation and in vitro evaluation. J Drug Deliv Sci Technol 2023; 82: 104384.
[http://dx.doi.org/10.1016/j.jddst.2023.104384] [PMID: 37124158]
[15]
Narala S, Nyavanandi D, Mandati P, et al. Preparation and in vitro evaluation of hot-melt extruded pectin-based pellets containing ketoprofen for colon targeting. Int J Pharm 2023; 5: 100156.
[http://dx.doi.org/10.1016/j.ijpx.2022.100156] [PMID: 36636366]
[16]
Koutsamanis I, Roblegg E, Spoerk M. Controlled delivery via hot-melt extrusion: A focus on non-biodegradable carriers for non-oral applications. J Drug Deliv Sci Technol 2023; 81: 104289.
[http://dx.doi.org/10.1016/j.jddst.2023.104289]
[17]
Tambe S, Jain D, Agarwal Y, Amin P. Hot-melt extrusion: Highlighting recent advances in pharmaceutical applications. J Drug Deliv Sci Technol 2021; 63: 102452.
[http://dx.doi.org/10.1016/j.jddst.2021.102452]
[18]
Moseson DE, Eren A, Altman KJ, et al. Optimization of amorphization kinetics during hot melt extrusion by particle engineering: An experimental and computational study. Cryst Growth Des 2022; 22(1): 821-41.
[http://dx.doi.org/10.1021/acs.cgd.1c01306]
[19]
Vo AQ, Feng X, Morott JT, et al. A novel floating controlled release drug delivery system prepared by hot-melt extrusion. Eur J Pharm Biopharm 2016; 98: 108-21.
[http://dx.doi.org/10.1016/j.ejpb.2015.11.015] [PMID: 26643801]
[20]
Bezerra GSN, de Lima TAM, Colbert DM, Geever J, Geever L. Formulation and evaluation of fenbendazole extended-release extrudes processed by hot-melt extrusion. Polymers 2022; 14(19): 4188.
[http://dx.doi.org/10.3390/polym14194188] [PMID: 36236135]
[21]
Muhindo D, Ashour EA, Almutairi M, Repka MA. Development and evaluation of raloxifene hydrochloride-loaded subdermal implants using hot-melt extrusion technology. Int J Pharm 2022; 622: 121834.
[http://dx.doi.org/10.1016/j.ijpharm.2022.121834] [PMID: 35597391]
[22]
Zhang S, Meng X, Wang Z, et al. Engineering hot-melt extruded solid dispersion for controlled release of hydrophilic drugs. Eur J Pharm Sci 2017; 100: 109-15.
[http://dx.doi.org/10.1016/j.ejps.2017.01.009] [PMID: 28087352]
[23]
Simões MF, Pinto RMA, Simões S. Hot-melt extrusion: A roadmap for product development. AAPS PharmSciTech 2021; 22(5): 184.
[http://dx.doi.org/10.1208/s12249-021-02017-7] [PMID: 34142250]
[24]
Patil H, Tiwari RV, Repka MA. Hot-melt extrusion: From theory to application in pharmaceutical formulation. AAPS PharmSciTech 2016; 17(1): 20-42.
[http://dx.doi.org/10.1208/s12249-015-0360-7] [PMID: 26159653]
[25]
Deshkar S, Rathi M, Zambad S, Gandhi K. Hot melt extrusion and its application in 3d printing of pharmaceuticals. Curr Drug Deliv 2021; 18(4): 387-407.
[http://dx.doi.org/10.2174/1567201817999201110193655] [PMID: 33176646]
[26]
Li S, Tian Y, Jones DS, Andrews GP. Optimising drug solubilisation in amorphous polymer dispersions: Rational selection of hot-melt extrusion processing parameters. AAPS PharmSciTech 2016; 17(1): 200-13.
[http://dx.doi.org/10.1208/s12249-015-0450-6] [PMID: 26729536]
[27]
Schittny A, Ogawa H, Huwyler J, Puchkov M. A combined mathematical model linking the formation of amorphous solid dispersions with hot-melt-extrusion process parameters. Eur J Pharm Biopharm 2018; 132: 127-45.
[http://dx.doi.org/10.1016/j.ejpb.2018.09.011] [PMID: 30240820]
[28]
Alshetaili A, Alshahrani SM, Almutairy BK, Repka MA. Hot melt extrusion processing parameters optimization. Processes 2020; 8(11): 1516.
[http://dx.doi.org/10.3390/pr8111516]
[29]
Matić J, Paudel A, Bauer H, Garcia RAL, Biedrzycka K, Khinast JG. Developing HME-based drug products using emerging science: A fast-track roadmap from concept to clinical batch. AAPS PharmSciTech 2020; 21(5): 176.
[http://dx.doi.org/10.1208/s12249-020-01713-0] [PMID: 32572701]
[30]
Maniruzzaman M, Nokhodchi A. Continuous manufacturing via hot-melt extrusion and scale up: Regulatory matters. Drug Discov Today 2017; 22(2): 340-51.
[http://dx.doi.org/10.1016/j.drudis.2016.11.007] [PMID: 27866007]
[31]
Adepu S, Ramakrishna S. Controlled drug delivery systems: Current status and future directions. Molecules 2021; 26(19): 5905.
[http://dx.doi.org/10.3390/molecules26195905] [PMID: 34641447]
[32]
Sawant KP, Fule R, Maniruzzaman M, Amin PD. Extended release delivery system of metoprolol succinate using hot-melt extrusion: Effect of release modifier on methacrylic acid copolymer. Drug Deliv Transl Res 2018; 8(6): 1679-93.
[http://dx.doi.org/10.1007/s13346-018-0545-1] [PMID: 29948916]
[33]
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.
[http://dx.doi.org/10.3390/pharmaceutics13020213] [PMID: 33557076]
[34]
Yang Y, Shen L, Li J, Shan W. 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.
[http://dx.doi.org/10.1080/03639045.2017.1287715] [PMID: 28128647]
[35]
Balogh A, Farkas B, Domokos A, 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.
[http://dx.doi.org/10.1016/j.eurpolymj.2017.08.032]
[36]
Qi S, Gryczke A, Belton P, Craig DQM. Characterisation of solid dispersions of paracetamol and EUDRAGIT®E prepared by hot-melt extrusion using thermal, microthermal and spectroscopic analysis. Int J Pharm 2008; 354(1-2): 158-67.
[http://dx.doi.org/10.1016/j.ijpharm.2007.11.048] [PMID: 18242020]
[37]
Li Q, Wen H, Jia D, et al. Preparation and investigation of controlled-release glipizide novel oral device with three-dimensional printing. Int J Pharm 2017; 525(1): 5-11.
[http://dx.doi.org/10.1016/j.ijpharm.2017.03.066] [PMID: 28377316]
[38]
Yi S, Wang J, Lu Y, et al. Novel hot melt extruded matrices of hydroxypropyl cellulose and amorphous felodipine-plasticized hydroxypropyl methylcellulose as controlled release systems. AAPS PharmSciTech 2019; 20(6): 219.
[http://dx.doi.org/10.1208/s12249-019-1435-7] [PMID: 31201583]
[39]
Kachrimanis K, Nikolakakis I. Polymers as formulation excipients for hot-melt extrusion processing of pharmaceuticals. Handbook of Polymers for Pharmaceutical Technologies. (1st ed.). Wiley 2015; pp. 121-49.
[http://dx.doi.org/10.1002/9781119041412.ch5]
[40]
dos Santos J, da Silva GS, Velho MC, Beck RCR. Eudragit®: A versatile family of polymers for hot melt extrusion and 3d printing processes in pharmaceutics. Pharmaceutics 2021; 13(9): 1424.
[http://dx.doi.org/10.3390/pharmaceutics13091424] [PMID: 34575500]
[41]
Kaur G, Grewal J, Jyoti K, Jain UK, Chandra R, Madan J. Oral controlled and sustained drug delivery systems. Drug Targeting and Stimuli Sensitive Drug Delivery Systems. Elsevier 2018; pp. 567-626.
[http://dx.doi.org/10.1016/B978-0-12-813689-8.00015-X]
[42]
Owusu-Ware SK, Boateng JS, Chowdhry BZ, Antonijevic MD. Glassy state molecular mobility and its relationship to the physico-mechanical properties of plasticized hydroxypropyl methylcellulose (HPMC) films. Int J Pharm X 2019; 1: 100033.
[http://dx.doi.org/10.1016/j.ijpx.2019.100033] [PMID: 31528853]
[43]
Fan W, Zhang X, Zhu W, Di L. The preparation of curcumin sustained-release solid dispersion by hot-melt extrusioni II. Optimization of preparation process and evaluation in vitro and in vivo. J Pharm Sci 2020; 109(3): 1253-60.
[http://dx.doi.org/10.1016/j.xphs.2019.11.020] [PMID: 31794699]
[44]
Zhu W, Fan W, Zhang X, Gao M. Sustained-release solid dispersion of high-melting-point and insoluble resveratrol prepared through hot melt extrusion to improve its solubility and bioavailability. Molecules 2021; 26(16): 4982.
[http://dx.doi.org/10.3390/molecules26164982] [PMID: 34443569]
[45]
Lu J, Obara S, Liu F, Fu W, Zhang W, Kikuchi S. Melt extrusion for a high melting point compound with improved solubility and sustained release. AAPS PharmSciTech 2018; 19(1): 358-70.
[http://dx.doi.org/10.1208/s12249-017-0846-6] [PMID: 28741140]
[46]
Ijaz QA, Latif S, Shoaib Q, et al. Preparation and characterization of ph-independent sustained-release tablets containing hot melt extruded solid dispersions of clarithromycin. AAPS PharmSciTech 2021; 22(8): 275.
[http://dx.doi.org/10.1208/s12249-021-02115-6] [PMID: 34773162]
[47]
Song Y, Wang L, Yang P, et al. Physicochemical characterization of felodipine-kollidon VA64 amorphous solid dispersions prepared by hot-melt extrusion. J Pharm Sci 2013; 102(6): 1915-23.
[http://dx.doi.org/10.1002/jps.23538] [PMID: 23580396]
[48]
Stewart S, Domínguez-Robles J, Donnelly R, Larrañeta E. Implantable polymeric drug delivery devices: Classification, manufacture, materials, and clinical applications. Polymers 2018; 10(12): 1379.
[http://dx.doi.org/10.3390/polym10121379] [PMID: 30961303]
[49]
Pons-Faudoa FP, Ballerini A, Sakamoto J, Grattoni A. Advanced implantable drug delivery technologies: Transforming the clinical landscape of therapeutics for chronic diseases. Biomed Microdevices 2019; 21(2): 47.
[http://dx.doi.org/10.1007/s10544-019-0389-6] [PMID: 31104136]
[50]
Noreen S, Maqbool I, Madni A. Dexamethasone: Therapeutic potential, risks, and future projection during COVID-19 pandemic. Eur J Pharmacol 2021; 894: 173854.
[http://dx.doi.org/10.1016/j.ejphar.2021.173854] [PMID: 33428898]
[51]
Li D, Guo G, Fan R, 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.
[http://dx.doi.org/10.1016/j.ijpharm.2012.11.019] [PMID: 23178216]
[52]
Cossé A, König C, Lamprecht A, Wagner KG. Hot melt extrusion for sustained protein release: Matrix erosion and in vitro release of PLGA-based implants. AAPS PharmSciTech 2017; 18(1): 15-26.
[http://dx.doi.org/10.1208/s12249-016-0548-5] [PMID: 27193002]
[53]
Tran PHL, Tran TTD, Park JB, Lee BJ. Controlled release systems containing solid dispersions: Strategies and mechanisms. Pharm Res 2011; 28(10): 2353-78.
[http://dx.doi.org/10.1007/s11095-011-0449-y] [PMID: 21553168]
[54]
Maincent J, Williams RO. Sustained-release amorphous solid dispersions. Drug Deliv Transl Res 2018; 8(6): 1714-25.
[http://dx.doi.org/10.1007/s13346-018-0494-8] [PMID: 29498004]
[55]
Thakral S, Thakral NK. Prediction of drug-polymer miscibility through the use of solubility parameter based Flory-Huggins interaction parameter and the experimental validation: PEG as model polymer. J Pharm Sci 2013; 102(7): 2254-63.
[http://dx.doi.org/10.1002/jps.23583] [PMID: 23649486]
[56]
Alshahrani SM, Lu W, Park JB, et al. Stability-enhanced hot-melt extruded amorphous solid dispersions via combinations of Soluplus® and HPMCAS-HF. AAPS PharmSciTech 2015; 16(4): 824-34.
[http://dx.doi.org/10.1208/s12249-014-0269-6] [PMID: 25567525]
[57]
Samsoen S, Dudognon É, Le Fer G, Fournier D, Woisel P, Affouard F. Impact of the polymer dispersity on the properties of curcumin/polyvinylpyrrolidone amorphous solid dispersions. Int J Pharm 2024; 653: 123895.
[http://dx.doi.org/10.1016/j.ijpharm.2024.123895] [PMID: 38346598]

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