A rapid method for creating drug implants: Translating laboratory-based methods into a scalable manufacturing process
Open accessAbstract
Low compliance with medication is the major cause of poor outcome in schizophrenia treatment. While surgically implantable solvent‐cast pellets were produced to improve outcome by increased compliance with medication, this process is laborious and time‐consuming, inhibiting its broader application (Siegel et al., Eur J Pharm Biopharm 2006;64:287–293). In this study, the previous fabrication process was translated to a continuous and scalable extrusion method. Extrusion processes were modified based on in vitro release studies, drug load consistency examination, and surface morphology analysis using scanning electron microscopy. Afterward, optimized haloperidol implants were implanted into rats for preliminary analysis of biocompatibility. Barrel temperature, screw speed and resulting processing pressure influenced surface morphology and drug release. Data suggest that fewer surface pores shift the mechanism from bulk to surface PLGA degradation and longer lag period. Results demonstrate that extrusion is a viable process for manufacturing antipsychotic implants. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010.
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Extrusion is a continuous process that draws a polymer-drug mixture through a die to create implants of fixed cross-sectional profile without solvent.
“Unlike solvent-casting, extrusion is a continuous process of drawing polymer-drug mixture through a die to create implants of fixed cross-sectional profile without any use of solvent.”
From Poly Lactic-co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier (2011) · cites this paper as [61]
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Cites
Melt extrusion: from process to drug delivery technology
Breitenbach, J. (2002) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/s0939-6411(02)00061-9 · Cited by 741 · see citing works
Biodegradable nanoparticles for cytosolic delivery of therapeutics
VASIR, J., & LABHASETWAR, V (2007) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2007.06.003 · Cited by 526 · see citing works
Haloperidol-loaded PLGA nanoparticles: Systematic study of particle size and drug content
Budhian, A., Siegel, S. J., & Winey, K. I. (2006) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2006.11.061 · Cited by 432 · see citing works
Self-citationWidmer, M. S., Gupta, P. K., Lu, L., Meszlenyi, R. K., Evans, G. R. D., Brandt, K., Savel, T., Gurlek, A., Patrick, C. W., & Mikos, A. G. (1998) · Biomaterials · doi:10.1016/s0142-9612(98)00099-4 · Cited by 372 · see citing works
Jiang, T., Abdel‐Fattah, W. I., & Laurencin, C. T. (2006) · Biomaterials · doi:10.1016/j.biomaterials.2006.05.025 · Cited by 285 · see citing works
Effect of drug type on the degradation rate of PLGA matrices
SIEGEL, S., KAHN, J., METZGER, K., WINEY, K., WERNER, K., & DAN, N. (2006) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2006.06.009 · Cited by 208 · see citing works
Self-citationSchnieders, J., Gbureck, U., Thulĺ, R., & Kissel, T. (2006) · Biomaterials · doi:10.1016/j.biomaterials.2006.03.032 · Cited by 170 · see citing works
Hot-Melt Extrusion for Enhanced Delivery of Drug Particles
Miller, D. A., McConville, J. T., Yang, W. P., Williams, R. O., & McGinity, J. W. (2006) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.20806 · Cited by 146 · see citing works
Relapse and rehospitalization: comparing oral and depot antipsychotics.
Schooler, N. R. (2003) · PubMed · Cited by 141 · see citing works
The case for long‐acting antipsychotic agents in the post‐CATIE era
Nasrallah, H. A. (2007) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.2006.00982.x · Cited by 135 · see citing works
The ups and downs of oral lithium dosing.
Kilts, C. D. (1998) · PubMed · Cited by 117 · see citing works
Risks versus benefits of different types of long-acting injectable antipsychotics.
McEvoy, J. P. (2006) · PubMed · Cited by 107 · see citing works
Mechanism of the hardening process for a hydroxyapatite cement
Liu, C., Shen, W. G., Gu, Y., & Hu, L. (1997) · Journal of Biomedical Materials Research · doi:10.1002/(sici)1097-4636(199704)35:1 · Cited by 100 · see citing works
Bhanji, N. H., Chouinard, G., & Margolese, H. C. (2003) · European Neuropsychopharmacology · doi:10.1016/s0924-977x(03)00109-3 · Cited by 99 · see citing works
Biodegradable polyesters for controlled release of trypanocidal drugs: In vitro and in vivo studies
Lemmouchi, Y., Schacht, E. H., Kageruka, P., Deken, R. D., Diarra, B., Diall, O., & Geerts, S. (1998) · Biomaterials · doi:10.1016/s0142-9612(98)00074-x · Cited by 81 · see citing works
Clinical review of a long-acting, injectable formulation of risperidone
Knox, E. D., & Stimmel, G. L. (2004) · Clinical Therapeutics · doi:10.1016/j.clinthera.2004.12.009 · Cited by 80 · see citing works
Weinberg, B. D., Ai, H., Blanco, E., Anderson, J. M., & Gao, J. (2006) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.30914 · Cited by 78 · see citing works
Niaz, O., & Haddad, P. M. (2007) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.2006.00980.x · Cited by 74 · see citing works
Treatment of Schizophrenia With Long-Acting Fluphenazine, Haloperidol, or Risperidone
Olfson, M., Marcus, S. C., & Ascher‐Svanum, H. (2006) · Schizophrenia Bulletin · doi:10.1093/schbul/sbm033 · Cited by 65 · see citing works
In vitro and in vivo demonstration of risperidone implants in mice
Rabin, C., Liang, Y., Ehrlichman, R. S., Budhian, A., Metzger, K. L., Majewski-Tiedeken, C., Winey, K. I., & Siegel, S. J. (2008) · Schizophrenia Research · doi:10.1016/j.schres.2007.08.003 · Cited by 64 · see citing works
Self-citationFacilitating compliance with antipsychotic medication.
Marder, S. R. (1998) · PubMed · Cited by 57 · see citing works
Surgically Implantable Long-term Antipsychotic Delivery Systems for the Treatment of Schizophrenia
Siegel, S. J. (2002) · Neuropsychopharmacology · doi:10.1016/s0893-133x(01)00426-2 · Cited by 53 · see citing works
Self-citationLuan, X., & Bodmeier, R. A. (2006) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2005.12.010 · Cited by 48 · see citing works
Bhardwaj, R., & Blanchard, J. D. (1997) · Journal of Controlled Release · doi:10.1016/s0168-3659(96)01544-1 · Cited by 38 · see citing works
Desai, K. G. H., Mallery, S. R., & Schwendeman, S. P. (2007) · Pharmaceutical Research · doi:10.1007/s11095-007-9430-1 · Cited by 38 · see citing works
Release of diclofenac sodium from polylactide-co-glycolide 80/20 rods
Viitanen, P., Suokas, E. O., Törmälä, P., & Ashammakhi, N. A. (2006) · Journal of Materials Science Materials in Medicine · doi:10.1007/s10856-006-0601-0 · Cited by 24 · see citing works
Identification of psoralen loaded PLGA microspheres in rat skin by light microscopy
Gomes, A. J., Lunardi, C. N., Lunardi, L. O., Pitol, D. L., & Machado, A. E. H. (2007) · Micron · doi:10.1016/j.micron.2007.06.015 · Cited by 21 · see citing works
Metzger, K. L., Shoemaker, J. M., Kahn, J. B., Maxwell, C. R., Liang, Y., Tokarczyk, J., Kanes, S., Hans, M. L., Lowman, A. M., Dan, N. R., et al. (2006) · Psychopharmacology · doi:10.1007/s00213-006-0616-8 · Cited by 21 · see citing works
Self-citationPatient Attitudes towards Surgically Implantable, Long-Term Delivery of Psychiatric Medicine
Irani, F., Dankert, M. E., Brensinger, C. M., Bilker, W. B., Nair, S., Kohler, C. G., Kanes, S., Turetsky, B. I., Moberg, P. J., Ragland, J. D., et al. (2003) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300385 · Cited by 20 · see citing works
Self-citationRegenthal, R., Künstler, U., Junhold, U., & Preiss, R. (1997) · International Clinical Psychopharmacology · doi:10.1097/00004850-199709000-00002 · Cited by 9 · see citing works
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Makadia, H. K., & Siegel, S. J. (2011) · Polymers · doi:10.3390/polym3031377 · Cited by 4,816 · see citing works
“The resulting extrudate is then cooled and solidified before cutting into desired lengths for implants or other applications [61].”
BackgroundSelf-citationPLGA: a Unique Polymer for Drug Delivery
Kapoor, D. N., Bhatia, A., Kaur, R., Sharma, R., Kaur, G., & Dhawan, S. (2015) · Therapeutic Delivery · doi:10.4155/tde.14.91 · Cited by 618 · see citing works
Immunotoxicity Considerations for Next Generation Cancer Nanomedicines
Hannon, G., Lysaght, J., Liptrott, N. J., & Prina‐Mello, A. (2019) · Advanced Science · doi:10.1002/advs.201900133 · Cited by 81 · see citing works
Poly(lactic‐co‐glycolic acid) devices: Production and applications for sustained protein delivery
Lee, P. W., & Pokorski, J. K. (2018) · Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology · doi:10.1002/wnan.1516 · Cited by 76 · see citing works
Drug eluting implants in pharmaceutical development and clinical practice
Johnson, A. R., Forster, S. P., White, D. E., Terife, G., Lowinger, M. B., Teller, R. S., & Barrett, S. E. (2020) · Expert Opinion on Drug Delivery · doi:10.1080/17425247.2021.1856072 · Cited by 53 · see citing works
Drug-Eluting Nasal Implants: Formulation, Characterization, Clinical Applications and Challenges
Parikh, A. R., Anand, U., Ugwu, M. C., Feridooni, T., Massoud, E. A. S., & Agu, R. U. (2014) · Pharmaceutics · doi:10.3390/pharmaceutics6020249 · Cited by 48 · see citing works
Poly(lactic- co -glycolic acid) (PLGA) matrix implants
Sequeira, J. A. D., Paiva‐Santos, A. C., Serra, J. P., Veiga, F., & Ribeiro, A. J. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-813665-2.00010-7 · Cited by 39 · see citing works
Maturavongsadit, P., Paravyan, G., Kovářová, M., García, J. V., & Benhabbour, S. R. (2020) · International Journal of Pharmaceutics X · doi:10.1016/j.ijpx.2020.100068 · Cited by 26 · see citing works
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Pothupitiya, J. U., Zheng, C., & Saltzman, W. M. (2022) · Expert Opinion on Drug Delivery · doi:10.1080/17425247.2022.2131768 · Cited by 27 · see citing works
An in situ-forming, solid lipid/PLGA hybrid implant for long-acting antipsychotics
Dong, S., Wang, S., Zheng, C., Liang, W., & Huang, Y. (2011) · Soft Matter · doi:10.1039/c1sm05310h · Cited by 26 · see citing works
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Manchanda, S., Das, N., Chandra, A., Bandyopadhyay, S., & Chaurasia, S. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-814487-9.00002-8 · Cited by 17 · see citing works
Eluu, S. C., Obayemi, J. D., Salifu, A. A., Yiporo, D., Oko, A. O., Aina, T., Oparah, J. C., Ezeala, C. C., Etinosa, P. O., Ugwu, C. M., et al. (2024) · Scientific Reports · doi:10.1038/s41598-023-50656-6 · Cited by 15 · see citing works
Polymeric implants with drug-releasing capabilities: a mapping review of laboratory research
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Utomo, E., Stewart, S. A., Picco, C. J., Domínguez‐Robles, J., & Larrañeta, E. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-821749-8.00012-4 · Cited by 14 · see citing works
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Fiedler, T., Belova, I. V., Murch, G. E., Roether, J. A., & Boccaccini, A. R. (2012) · Computational Materials Science · doi:10.1016/j.commatsci.2012.04.043 · Cited by 12 · see citing works
Asmus, L. R., Gurny, R., & Möller, M. (2011) · The International Journal of Artificial Organs · doi:10.5301/ijao.2011.6392 · Cited by 9 · see citing works
Kumar, S., Singh, S., Quadir, S. S., Joshi, G., Chouhan, M., Puri, D., & Choudhary, D. K. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-18915-9.00004-5 · Cited by 8 · see citing works
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Shuwisitkul, D. (2011) · Universitätsbibliothek der FU Berlin Hochschulschriftenstelle u. Dokumentenserver · doi:10.17169/refubium-8515 · Cited by 8 · see citing works
Chintha, V., & Rajendra, W. (2021) · Natural Product Research · doi:10.1080/14786419.2020.1869968 · Cited by 7 · see citing works
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Lu, Y., Essadki-Aittaji, I., Gao, J., Abraham, A. M., Anjani, Q. K., Cobo-González, A. B., Iglesías-Martín, F., Vora, L. K., Millán, M., Larrañeta, E., et al. (2025) · Expert Opinion on Drug Delivery · doi:10.1080/17425247.2025.2549847 · Cited by 5 · see citing works
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Gowda, G. S., Das, S., & Nanjegowda, R. B. (2017) · Asian Journal of Psychiatry · doi:10.1016/j.ajp.2017.03.035 · Cited by 5 · see citing works
Zeeshan, F., Tabbassum, M., Jørgensen, L., & Medlicott, N. J. (2017) · AAPS PharmSciTech · doi:10.1208/s12249-017-0883-1 · Cited by 5 · see citing works
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Prakash Raj, K., Kathiresan, K., & Pandian, P. L. (2021) · Journal of Evolution of Medical and Dental Sciences · doi:10.14260/jemds/2021/416 · Cited by 1 · see citing works
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Gomes, C. M. (2020) · doi:10.17760/d20397587
- Authors
- Wang, C., Wang, W., Meyer, R. F., Liang, Y., Winey, K. I., & Siegel, S. J.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Siegel, Steven J.
- Venue
- Journal of Biomedical Materials Research Part B: Applied Biomaterials
- Publisher
- Wiley
- Published
- 2010-04-02
- Volume
- 93B
- Issue
- 2
- Pages
- 562-572
- ISSN
- 1552-4973 (ISSN-L)
- 1552-4981
- PMC
- PMC3049914
- OpenAlex
- W2118031005
- Cited by
- 33
- References
- 30
- Citations by year
- 2025: 1 · 2024: 2 · 2022: 2 · 2021: 5 · 2020: 6 · 2019: 3 · 2018: 2 · 2017: 2 · 2016: 1 · 2015: 1 · 2014: 1 · 2012: 3
- FWCI
- 1.56
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Biomedical Materials Research Part B Applied Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01MH074672)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- extrusion, scalable fabrication, PLGA, haloperidol, schizophrenia, medication adherence, surface morphology, drug release, biocompatibility, processing pressure, barrel temperature, screw speed
- MeSH terms
- Animals, Drug Implants, Haloperidol, Schizophrenia, Antipsychotic Agents, Rats
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