HOT MELT EXTRUSION IN ENGINEERING OF DRUG COCRYSTALS: A REVIEW

ARCHANA RAJADHYAX; UJWALA SHINDE; HARITA DESAI; SHRUSHTI MANE

doi:10.22159/ajpcr.2021.v14i8.41857

Authors

ARCHANA RAJADHYAX Department of Pharmaceutics, Bombay College of Pharmacy, Mathuradas Colony, Mumbai, Maharashtra, India.
UJWALA SHINDE Department of Pharmaceutics, Bombay College of Pharmacy, Mathuradas Colony, Mumbai, Maharashtra, India.
HARITA DESAI Department of Pharmaceutics, Bombay College of Pharmacy, Mathuradas Colony, Mumbai, Maharashtra, India.
SHRUSHTI MANE Department of Pharmaceutics, Bombay College of Pharmacy, Mathuradas Colony, Mumbai, Maharashtra, India.

DOI:

https://doi.org/10.22159/ajpcr.2021.v14i8.41857

Keywords:

Crystal engineering, Cocrystallization, Solvent-free, Hot melt extrusion, Screw extruders, Synthons

Abstract

Crystal engineering technique has been widely explored in recent times to bring about changes in crystallinity which aids to achieve various goals such as solubility enhancement, stability and in vivo bioavailability without altering the chemical properties of the drug. Cocrystallisation is one of the crystal engineering approaches where the drug and an inert coformer are linked together by hydrogen bonding forming supramolecular homosynthon or heterosynthon using solvent-based or solvent-free techniques. Processing of active pharmaceutical ingredients with inert water-soluble coformers yields multicomponent crystalline cocrystals with high-performance characteristics and enhanced flow properties. Due to the emerging need of the industry for greener techniques, hot melt extrusion (HME), a continuous and solvent-free process is emerging as a field of interest in the mechanochemical synthesis of various pharmaceutical dosage forms such as solid dispersions, implants, ointments, and cocrystals. The current review emphasizes the role of HME as a cocrystallization technique for drugs to tailor-make their properties and ease of formulation. The distinct feature of HME is phase control during the process of cocrystallization. Furthermore, the selection of appropriate coformers with desirable water-solubility and stability features makes HME amenable to cocrystallization of versatile actives yielding suitable dosage forms. The application of process analytical technology further adds ease of monitoring during HME in cocrystallization approaches. Due to these salient features of HME, it can act as a prospective technique for cocrystallization of versatile drugs thus yielding dosage forms with desirable solubility and stability features.

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References

Kawabata Y, Wada K, Nakatani M, Yamada S, Onoue S. Formulation design for poorly water-soluble drugs based on biopharmaceutics classification system: Basic approaches and practical applications. Int J Pharm 2011;420:1-10.

Haltner E, Flototto T, Bock U. Biopharmaceutical Classification System. Farm Vestn 2003;54:317-18.

Kadam SV, Shinkar DM. Review on solubility enhancement technique. Int J Pharm BiolSci 2013;3:462-75.

Savjani KT, Gajjar AK, Savjani JK. Drug solubility: Importance and enhancementtechniques. ISRN Pharm 2012;2012:195727.

Loftsson T, Brewster ME. Pharmaceutical applications of cyclodextrins. 1. Drug solubilization and stabilization. J Pharm Sci 1996;85:1017-25.

Rodríguez-Spong B, Price CP, Jayasankar A, Matzger AJ, Rodríguez- Hornedo N. General principles of pharmaceutical solid polymorphism: A supramolecular perspective Adv Drug Deliv Rev 2004;56:241-74.

Rasenack N, Muller BW. Micron-Size drug particles: Common and novel micronization techniques. Pharm Dev Technol 2004;9:1-13.

Yu L. Amorphous pharmaceutical solids: Preparation, characterization and stabilization. Adv Drug Deliv Rev 2001;48:27-42.

Subramanian S, Zaworotko MJ. Manifestations of noncovalent bonding in the solid state. 6. [H 4 (Cyclam)] 4+ (Cyclam = 1,4,8,11-Tetraazacyclotetradecane) as a template for crystal engineering of network hydrogen-bonded solids. Can J Chem 1995;73:414-24.

Parkin IP. Supramolecular Chemistry. In: Applied Organometallic Chemistry. Hoboken, New Jersey: John Wiley and Sons Ltd.; 2001. p. 236.

Blagden N, de Matas M, Gavan PT, York P. Crystal engineering of active pharmaceutical ingredients to improve solubility and dissolution rates. Adv Drug Deliv Rev 2007;59:617-30.

Desiraju GR. Supramolecular synthons in crystal engineering a new organic synthesis. Angew Chem 1995;34:2311-27.

Fukte SR, Wagh MP, Rawat S. Coformer selection: An important tool in cocrystal formation. Int J Pharm Pharm Sci 2014;6:9-14.

Dirksen JA, Ring TA. Fundamentals of crystallization: Kinetic effects on particle size distributions and morphology. Chem Eng Sci 1991;46:2389-427.

Adhiyaman R, Basu SK. Crystal modification of dipyridamole using different solvents and crystallization conditions. Int J Pharm 2006;321:27-34.

Nokhodchi A, Bolourtchian N, Dinarvand R. Crystal modification of phenytoin using different solvents and crystallization conditions. Int J Pharm 2003;250:85-97.

Paradkar A, Maheshwari M, Kamble R, Grimsey I, York P. Design and evaluation of celecoxib porous particles using melt sonocrystallization. Pharm Res 2006;23:1395-400.

Manish M, Harshal J, Anant P. Melt sonocrystallization of ibuprofen: Effect on crystal properties. Eur J Pharm Sci 2005;25:41-8.

Hu J, Johnston KP, Williams RO. Nanoparticle engineering processes for enhancing the dissolution rates of poorly water soluble drugs. Drug Dev Ind Pharm 2004;30:233-45.

Trask AV, Motherwell WD, Jones W. Solvent-Drop grinding: Green polymorph control of cocrystallisation. Chem Commun 2004;4:890-91.

Karagianni A, Malamatari M, Kachrimanis K. Pharmaceutical cocrystals: New solid phase modification approaches for the formulation of Apis. Pharmaceutics 2018;10:1-30.

Douroumis D, Ross SA, Nokhodchi A. Advanced methodologies for cocrystal synthesis. Adv Drug Deliv Rev 2017;117:178-95.

Sopyan I, Fudholi A, Muchtaridi M, Puspitasari I. A simple effort to enhance solubility and dissolution rate of simvastatin using cocrystallization. Int J Pharm Pharm Sci 2016;8:342-6.

Repka MA, Shah S, Lu J, Maddineni S, Morott J, Patwardhan K, et al. Melt extrusion: Process to product. Exp Opin Drug Deliv 2012;9:105-25.

Repka MA, Langley N, Dinunzio JC. Melt extrusion: Materials, technology and drug product design. In: Repka MA, Langley N, JD, editors. AAPS Advances in the Pharmaceutical Sciences Series. 9th ed. New York: Springer; 2013. p. 3-46.

Maniruzzaman M, Boateng JS, Snowden MJ, Douroumis D. A review of hot-melt extrusion: Process technology to pharmaceutical products. ISRN Pharm 2012;2012:436763.

Breitenbach J. Melt Extrusion: From process to drug delivery technology. Eur J Pharm Biopharm 2002;54:107-17.

Chokshi HZ. Hot-Melt extrusion technique: A review. Iran J Pharm Res 2004;3:3-16.

Patil H, Tiwari RV, Repka MA. Hot-melt extrusion: From theory to application in pharmaceutical formulation. AAPS PharmSciTech 2016;17:20-42.

Andrews GP, Margetson DN, Jones DS, McAllister MS, Diak OA. Hot- Melt Extrusion: an emerging drug delivery technology. Pharm Technol Eur 2009;21:24-7.

Twin-Screw WT. Extrusion and screw design. In: Ghebre-Sellassie I, Martin CE, Zhang F, Dinunzio J, editor. Pharmaceutical Extrusion Technology. New York: Marcel Dekker; 2003. p. 69-98.

Thakkar R, Pillai A, Ashour EA, Repka MA. Systematic screening of pharmaceutical polymers for hot melt extrusion processing: A Comprehensive review. Int J Pharm 2020;576:1-45.

Kolter K, Karl M, Gryczke A. Physico-chemical characteristics processability. In: Hot-melt Extrusion with Basf Pharma Polymers. Germany: BASF the Chemical Company; 2012. p. l03-23.

Gilbert M. Relation of structure to thermal and mechanical properties. In: Brydson’s Plastics Materials. 8th ed. Amsterdam, Netherlands: Elsevier; 2016. p. 59-73.

Shah S, Maddineni S, Lu J, Repka MA. Melt Extrusion with poorly soluble drugs. Int J Pharm 2013;453:233-52.

Balani K, Verma V, Agarwal A, Narayan R. Physical, thermal, and mechanical properties of polymers. In: Balani K, Verma V, Agarwal A, editors. Biosurfaces: A Materials Science and Engineering Perspective. Hoboken, New Jersey: John Wiley and Sons, Inc.; 2015. p. 329-44.

Hancock BC, Zografi G. Characteristics and significance of the amorphous state in pharmaceutical systems. J Pharm Sci 1997;86:1-12.

Follonier N, Doelker E, Cole ET. Evaluation of Hot-Melt extrusion as a new technique for the production of polymer-based pellets for sustained release capsules containing high loadings of freely soluble drugs. Drug Dev Ind Pharm 1994;20:1323-339.

Aitken-Nichol C, Zhang F, McGinity JW. Hot Melt Extrusion of acrylic films. Pharm Res 1996;13:804-8.

De Brabander C, Van Den Mooter G, Vervaet C, Remon JP. Characterization of Ibuprofen as a nontraditional plasticizer of ethyl cellulose. J Pharm Sci 2002;91:1678-85.

Six K, Berghmans H, Leuner C, Dressman J, Van Werde K, Mullens J, et al. Characterization of solid dispersions of itraconazole and hydroxypropylmethylcellulose prepared by melt extrusion, Part II. Pharm Res 2003;20:1047-54.

Verreck G, Six K, Van den Mooter G, Baert L, Peeters J, Brewster ME. Characterization of solid dispersions of itraconazole and hydroxypropylmethylcellulose prepared by melt extrusion Part I. Int J Pharm 2003;251:65-74.

Lakshman JP, Cao Y, Kowalski J, Serajuddin AT. Application of Melt extrusion in the development of a physically and chemically stable high-energy amorphous solid dispersion of a poorly water-soluble drug. Mol Pharm 2008;5:994-1002.

Kazarian SG. Polymer processing with supercritical fluids. Polym Sci Ser C 2000;42:78-101.

Kiran E. Polymer formation, modifications and processing in or with supercritical fluids. In: Kiran E, editor. Supercritical Fluids. Dordrecht: Springer; 1994. p. 541-8.

Chiou JS, Barlow JW, Paul DR. Plasticization of glassy polymers by CO2. J Appl Polym Sci 1985;30:2633-42.

Verreck G, Decorte A, Li H, Tomasko D, Arien A, Peeters J, et al. The effect of pressurized carbon dioxide as a plasticizer and foaming agent on the hot melt extrusion process and extrudate properties of pharmaceutical polymers. J Supercrit Fluids 2006;38:383-91.

Gajda M, Nartowski KP, Pluta J, Karolewicz B. Continuous, one-step synthesis of pharmaceutical cocrystals via Hot melt extrusion from neat to matrix-assisted processing state of the art. Int J Pharm 2019;558:426-40.

Thiry J, Krier F, Evrard B. A review of pharmaceutical extrusion: Critical process parameters and scaling-up. Int J Pharm 2015;479:227-40.

Martin C. Twin Screw extruders as continuous mixers for thermal processing: A technical and historical perspective. AAPS PharmSciTech 2016;17:3-19.

Moradiya HG, Islam MT, Halsey S, Maniruzzaman M, Chowdhry BZ, Snowden MJ, et al. Continuous cocrystallisation of carbamazepine and trans-cinnamic acid via melt extrusion processing. Cryst Eng Commun 2014;16:3573-83.

Paradkar A, Dhumal RS, Kelly AL, York P, Coates PD. Cocrystallization and simultaneous agglomeration using hot melt extrusion. Pharm Res 2010;27:2725-33.

Reitz E, Podhaisky H, Ely D, Thommes M. Residence time modeling of hot melt extrusion processes. Eur J Pharm Biopharm 2013;85:1200-5.

Medina C, Daurio D, Nagapudi K, Alvarez-Nunez F. Manufacture of pharmaceutical cocrystals using twin screw extrusion: A solvent-less and scalable process. J Pharm Sci 2010;99:1693-6.

Moradiya H, Islam MT, Woollam GR, Slipper IJ, Halsey S, Snowden MJ, et al. Continuous cocrystallization for dissolution rate optimization of a poorly water soluble drug Cryst Growth Des 2014;14:189-98.

Moradiya HG, Islam MT, Scoutaris N, Halsey SA, Chowdhry BZ, Douroumis D. Continuous manufacturing of high quality pharmaceutical cocrystals integrated with process analytical tools for in-line process control. Cryst Growth Des 2016;16:3425-34.

Karimi-Jafari M, Padrela L, Walker GM, Croker DM. Creating cocrystals: A review of pharmaceutical cocrystal preparation routes and applications. Cryst Growth Des 2018;18:6370-87.

Walsh D, Serrano DR, Worku ZA, Madi AM, O’Connell P, Twamley B, et al. Engineering of pharmaceutical cocrystals in an excipient matrix: Spray drying versus hot melt extrusion. Int J Pharm 2018;551:241-56.

Bak A, Gore A, Yanez E, Stanton M, Tufekcic S, Syed R, et al. The cocrystal approach to improve the exposure of a water-insoluble compound: AMC 517 sorbic acid cocrystal characterization and pharmacokinetics. J Pharm Sci 2008;97:3942-56.

Anant P, Adrian K, Phil C, Peter Y. Method and Product WO 2010/013035 A1; 2010.

Kulkarni C, Wood C, Kelly AL, Gough T, Blagden N, Paradkar A. Stoichiometric control of cocrystal formation by solvent free continuous cocrystallization (sfcc). Cryst Growth Des 2015;15:5648-51.

Mohammad MA, Alhalaweh A, Velaga S ZP. Hansen solubility parameter as a tool to predict cocrystal formation. Int J Pharm 2011;407:63-71.

Li S, Yu T, Tian Y, Lagan C, Jones DS, Andrews GP. Mechanochemical synthesis of pharmaceutical cocrystal suspensions via Hot melt extrusion: Enhancing cocrystal yield. Mol Pharm 2018;15:3741-54.

Li S, Yu T, Tian Y, McCoy CP, Jones DS, Andrews GP. Mechanochemical synthesis of pharmaceutical cocrystal suspensions via Hot melt extrusion: Feasibility studies and physicochemical characterization. Mol Pharm 2016;13:3054-68.

Hasa D, Carlino E, Jones W. Polymer-assisted grinding, a versatile method for polymorph control of cocrystallization. Cryst Growth Des 2016;16:1772-9.

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;103:2904-10.

Gajda M, Nartowski KP, Pluta J, 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.

Hitzer P, Bauerle T, Drieschner T, Ostertag E, Paulsen K, van Lishaut H, et al. Process Analytical techniques for hot-melt extrusion and their application to amorphous solid dispersions. Anal Bioanal Chem 2017;409:4321-33.

Wesholowski J, Prill S, Berghaus A, Thommes M. Inline UV/Vis spectroscopy as PAT tool for hot-melt extrusion. Drug Deliv Transl Res 2018;8:1595-603.