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Fabrication and Characterization of Risperidone Implants as an Extended Antipsychotic Delivery System, Exploring the Role of Excipients

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Abstract

Introduction

Implant is a promising delivery system for chronically used drugs. Excipients play an important role in physicochemical properties and more importantly drug release profile from the implant system; therefore, selecting appropriate materials in matrix formulation is an important issue.

Objective

The main purpose of the present study is to explore the role of various excipients on the physicochemical characteristic of risperidone (Ris) implants. In this study, various Ris implant formulations with polyethylene glycol (PEG) as hydrophilic and cholesterol (Chol) as hydrophobic excipients were fabricated and evaluated.

Methods

Ris implants were fabricated by casting method. Mathematical modeling was employed to explore the release mechanism of various formulations. In order to analyze the mechanical strength of implants, texture analysis was performed. The physical state of Ris in implants matrix was analyzed by differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis. Scanning electron microscopy (SEM) was used for the morphology investigation of implants. Fourier transform infrared spectroscopy (FTIR) was used to explore any changes in the chemical structure of the drug in formulation.

Results

Implant formulations with Chol showed sustained release of Ris as long as 59 days relative to 32 days with PEG. Mathematical evaluation of Ris release showed an erosion-based mechanism for implant formulations with Chol, whereas implants with PEG followed a diffusion release mechanism. Texture analysis of implants showed higher mechanical strength for the formulation with Chol. Both DSC and XRD studies confirmed partial conversion of crystalline Ris to amorphous form in formulations with Chol. The water uptake and matrix bulk erosion of implants showed lower erosion, and the water uptake for formulations with Chol in comparison to formulations with PEG. FTIR analysis showed no changes in the chemical structure of Ris in all formulations.

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References

  1. Agarwal P, Rupenthal ID. Injectable implants for the sustained release of protein and peptide drugs. Drug Discov Today. 2013;18(7):337–49.

    Article  CAS  PubMed  Google Scholar 

  2. Bourges J, Bloquel C, Thomas A, Froussart F, Bochot A, Azan F, et al. Intraocular implants for extended drug delivery: therapeutic applications. Adv Drug Deliv Rev. 2006;58(11):1182–202.

    Article  CAS  PubMed  Google Scholar 

  3. Halliday AJ, Moulton SE, Wallace GG, Cook MJ. Novel methods of antiepileptic drug delivery—polymer-based implants. Adv Drug Deliv Rev. 2012;64(10):953–64.

    Article  CAS  PubMed  Google Scholar 

  4. Dash A, Cudworth G. Therapeutic applications of implantable drug delivery systems. J Pharmacol Toxicol. 1998;40(1):1–12.

    Article  CAS  Google Scholar 

  5. Kempe S, Metz H, Pereira PG, Mäder K. Non-invasive in vivo evaluation of in situ forming PLGA implants by benchtop magnetic resonance imaging (BT-MRI) and EPR spectroscopy. Eur J Pharm Biopharm. 2010;74(1):102–8.

    Article  CAS  PubMed  Google Scholar 

  6. Lan S-F, Kehinde T, Zhang X, Khajotia S, Schmidtke DW, Starly B. Controlled release of metronidazole from composite poly-ε-caprolactone/alginate (PCL/alginate) rings for dental implants. Dent Mater. 2013;29(6):656–65.

    Article  CAS  PubMed  Google Scholar 

  7. Ho EA, Vassileva V, Allen C, Piquette-Miller M. In vitro and in vivo characterization of a novel biocompatible polymer–lipid implant system for the sustained delivery of paclitaxel. J Control Release. 2005;104(1):181–91.

    Article  CAS  PubMed  Google Scholar 

  8. Ogawa Y, Kodaka M, Okuno H. Trigger lipids inducing pH-dependent liposome fusion. Chem Phys Lipids. 2002;119(1):51–68.

    Article  CAS  PubMed  Google Scholar 

  9. Wong HL, Rauth AM, Bendayan R, Wu XY. In vivo evaluation of a new polymer-lipid hybrid nanoparticle (PLN) formulation of doxorubicin in a murine solid tumor model. Eur J Pharm Biopharm. 2007;65(3):300–8.

    Article  CAS  PubMed  Google Scholar 

  10. Sax G, Winter G. Mechanistic studies on the release of lysozyme from twin-screw extruded lipid implants. J Control Release. 2012;163(2):187–94.

    Article  CAS  PubMed  Google Scholar 

  11. Kreye F, Siepmann F, Willart J, Descamps M, Siepmann J. Drug release mechanisms of cast lipid implants. Eur J Pharm Biopharm. 2011;78(3):394–400.

    Article  CAS  PubMed  Google Scholar 

  12. Sax G, Kessler B, Wolf E, Winter G. In-vivo biodegradation of extruded lipid implants in rabbits. J Control Release. 2012;163(2):195–202.

    Article  CAS  PubMed  Google Scholar 

  13. Siepmann J, Siepmann F. Mathematical modeling of drug release from lipid dosage forms. Int J Pharm. 2011;418(1):42–53.

    Article  CAS  PubMed  Google Scholar 

  14. Raghuveer K, Hammond E. The influence of glyceride structure on the rate of autoxidation. J Am Oil Chem Soc. 1967;44(4):239–43.

    Article  CAS  PubMed  Google Scholar 

  15. Fang J-L, Vaca CE, Valsta LM, Multanen M. Determination of DNA adducts of malonaldehyde in humans: effects of dietary fatty acid composition. Carcinogenesis. 1996;17(5):1035–40.

    Article  CAS  PubMed  Google Scholar 

  16. Williams G, Caldwell J, Armstrong D, Bartsch H, Bevan R, Browne R, et al. Multicenter study to assess potential hazards from exposure to lipid peroxidation products in soya bean oil from Trilucent™ breast implants. Regul Toxicol Pharmacol. 2009;53(2):107–20.

    Article  CAS  PubMed  Google Scholar 

  17. Parent M, Nouvel C, Koerber M, Sapin A, Maincent P, Boudier A. Plga in situ implants formed by phase inversion: critical physicochemical parameters to modulate drug release. J Control Release. 2013;172(1):292–304.

    Article  CAS  PubMed  Google Scholar 

  18. Peterson HB, Curtis KM. Long-acting methods of contraception. N Engl J Med. 2005;353(20):2169–75.

    Article  CAS  PubMed  Google Scholar 

  19. Kreye F, Siepmann F, Siepmann J. Drug release mechanisms of compressed lipid implants. Int J Pharm. 2011;404(1):27–35.

    Article  CAS  PubMed  Google Scholar 

  20. Desai KGH, Mallery SR, Schwendeman SP. Effect of formulation parameters on 2-methoxyestradiol release from injectable cylindrical poly (DL-lactide-co-glycolide) implants. Eur J Pharm Biopharm. 2008;70(1):187–98.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Wang F, Saidel GM, Gao J. A mechanistic model of controlled drug release from polymer millirods: effects of excipients and complex binding. J Control Release. 2007;119(1):111–20.

    Article  CAS  PubMed  Google Scholar 

  22. Herrmann S, Winter G, Mohl S, Siepmann F, Siepmann J. Mechanisms controlling protein release from lipidic implants: effects of PEG addition. J Control Release. 2007;118(2):161–8.

    Article  CAS  PubMed  Google Scholar 

  23. Wang PY. Palmitic acid as an excipient in implants for sustained release of insulin. Biomaterials. 1991;12(1):57–62.

    Article  CAS  PubMed  Google Scholar 

  24. Wang F, Blanco E, Ai H, Boothman DA, Gao J. Modulating β‐lapachone release from polymer millirods through cyclodextrin complexation. J Pharm Sci. 2006;95(10):2309–19.

    Article  CAS  PubMed  Google Scholar 

  25. Pfrieger FW. Role of cholesterol in synapse formation and function. Biochim Biophys Acta. 2003;1610(2):271–80.

    Article  CAS  PubMed  Google Scholar 

  26. Dzeletovic S, Breuer O, Lund E, Diczfalusy U. Determination of cholesterol oxidation products in human plasma by isotope dilution-mass spectrometry. Anal Biochem. 1995;225(1):73–80.

    Article  CAS  PubMed  Google Scholar 

  27. Khan MZI, Tucker IG, Opdebeeck JP. Cholesterol and lecithin implants for sustained release of antigen: release and erosion in vitro, and antibody response in mice. Int J Pharm. 1991;76(1):161–70.

    Article  CAS  Google Scholar 

  28. Marder SR, Meibach RC. Risperidone in the treatment of schizophrenia. Am J Psych. 1994.

  29. Rabin C, Liang Y, Ehrlichman R, Budhian A, Metzger K, Majewski-Tiedeken C, et al. In vitro and in vivo demonstration of risperidone implants in mice. Schizophr Res. 2008;98(1):66–78.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Ritger PL, Peppas NA. A simple equation for description of solute release I. Fickian and non-Fickian release from non-swellable devices in the form of slabs, spheres, cylinders or discs. J Control Release. 1987;5(1):23–36.

    Article  CAS  Google Scholar 

  31. Huang J, Wigent RJ, Bentzley CM, Schwartz JB. Nifedipine solid dispersion in microparticles of ammonio methacrylate copolymer and ethylcellulose binary blend for controlled drug delivery: effect of drug loading on release kinetics. Int J Pharm. 2006;319(1):44–54.

    Article  CAS  PubMed  Google Scholar 

  32. Higuchi T. Mechanism of sustained‐action medication. Theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J Pharm Sci. 1963;52(12):1145–9.

    Article  CAS  PubMed  Google Scholar 

  33. Siepmann J, Siepmann F. Mathematical modeling of drug delivery. Int J Pharm. 2008;364(2):328–43.

    Article  CAS  PubMed  Google Scholar 

  34. Cheng L, Guo S, Wu W. Characterization and in vitro release of praziquantel from poly (ɛ-caprolactone) implants. Int J Pharm. 2009;377(1):112–9.

    Article  CAS  PubMed  Google Scholar 

  35. Opdebeeck J, Tucker I. A cholesterol implant used as a delivery system to immunize mice with bovine serum albumin. J Control Release. 1993;23(3):271–9.

    Article  CAS  Google Scholar 

  36. Rahman Z, Zidan AS, Khan MA. Risperidone solid dispersion for orally disintegrating tablet: its formulation design and non-destructive methods of evaluation. Int J Pharm. 2010;400(1):49–58.

    Article  CAS  PubMed  Google Scholar 

  37. Rahman Z, Zidan AS, Khan MA. Non-destructive methods of characterization of risperidone solid lipid nanoparticles. Eur J Pharm Biopharm. 2010;76(1):127–37.

    Article  CAS  PubMed  Google Scholar 

  38. Silva AC, Kumar A, Wild W, Ferreira D, Santos D, Forbes B. Long-term stability, biocompatibility and oral delivery potential of risperidone-loaded solid lipid nanoparticles. Inter J Pharm. 2012;436(1):798–805.

    Article  CAS  Google Scholar 

  39. Sattanathan P, Babu JM, Vyas K, Reddy R, Rajan S, Sudhakar P. Structural studies of impurities of risperidone by hyphenated techniques. J Pharm Biopharm Anal. 2006;40(3):598–604.

    Article  CAS  Google Scholar 

  40. Hu Z, Liu Y, Yuan W, Wu F, Su J, Jin T. Effect of bases with different solubility on the release behavior of risperidone loaded PLGA microspheres. Colloids Surf B:Biointerfaces. 2011;86(1):206–11.

    Article  CAS  PubMed  Google Scholar 

  41. Daniel JSP, Veronez IP, Rodrigues LL, Trevisan MG, Garcia JS. Risperidone–solid-state characterization and pharmaceutical compatibility using thermal and non-thermal techniques. Thermochim Acta. 2013.

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Acknowledgments

The authors would like to acknowledge the Iranian National Science Foundation (INSF) for the grant No 89004212.

Conflict of Interest

The authors report no conflict of interest.

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Authors and Affiliations

  1. Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 14399-56131, Iran

    Ebrahim Saadat & Farid A. Dorkoosh

  2. Department of pharmaceutics, Azad University, Tehran, Iran

    Asieh Abdollahi

  3. Medical Biomaterial Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Farid A. Dorkoosh

Authors
  1. Ebrahim Saadat
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  2. Asieh Abdollahi
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  3. Farid A. Dorkoosh
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Correspondence to Farid A. Dorkoosh.

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Saadat, E., Abdollahi, A. & Dorkoosh, F.A. Fabrication and Characterization of Risperidone Implants as an Extended Antipsychotic Delivery System, Exploring the Role of Excipients. J Pharm Innov 10, 118–129 (2015). https://doi.org/10.1007/s12247-015-9212-y

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  • DOI: https://doi.org/10.1007/s12247-015-9212-y

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