Development and Characterization of Olanzapine Loaded Poly(lactide-co-glycolide) Microspheres for Depot Injection: In vitro and In vivo Release Profiles

Author(s): Fahad Pervaiz, Mahmood Ahmad, Lihong Li*, Ghulam Murtaza*

Journal Name: Current Drug Delivery

Volume 16 , Issue 4 , 2019

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Purpose: The purpose of this study was to develop a new PLGA based microsphere formulation aimed to release the olanzapine for the period of one month which will result in increased compliance.

Methods: Microspheres loaded with olanzapine were prepared using oil in water emulsion and solvent evaporation technique. The microspheres were characterized by surface morphology, shape, size, bulk density, encapsulation efficiency, and Fourier transform infrared spectrometry. In vitro release studies were performed in phosphate buffer at 37°C and in vivo studies were conducted on male Sprague- Dawley rats.

Results: The morphological results indicated that microspheres produced were having a smooth surface, spherical shape and the size in the range from 9.71 to 19.90 μm mean diameter. Encapsulation efficiency of olanzapine loaded microspheres was in the range of 78.53 to 96.12% and was affected by changing the ratio of lactic to glycolic acid in copolymer PLGA. The properties of PLGA and other formulation parameters had a significant impact on in vitro and in vivo release of drug from microspheres. In vitro release kinetics revealed that release of drug from microspheres is by both non-Fickian diffusion and erosion of PLGA polymer. In vivo data indicated an initial burst release and then sustained release depending on properties of PLGA, microsphere size, and bulk density.

Conclusion: This study indicates that microsphere formulations developed with PLGA (75:25) and PLGA (85:15) have provided a sufficient steady release of drug for at least 30 days and can be potential candidates for 30-day depot injection drug delivery of olanzapine.

Keywords: Schizophrenia, compliance, psychosis, solvent evaporation, pharmacokinetics, long-acting injections, biodegradable polymer.

Piccinelli, M.; Homen, F.G. Gender differences in the epidemiology of affective disorders and schizophrenia; Geneva, Switzerland: World Health Organization, 1997, pp. 61-77.
Gilbert, P.L.; Harris, M.J.; McAdams, L.A.; Jeste, D.V. Neuroleptic withdrawal in schizophrenic patients: A review of the literature. Arch. Gen. Psychiatry, 1995, 52, 173-188.
Littrell, K.H.; Littrell, S.H. Therapeutic efficacy of olanzapine. J. Am. Psychiatr. Nurses Assoc., 1997, 3, S8-S13.
Shen, J.; Burgess, D.J. Drugs for Long Acting Injections and Implants. In: Jeremy, C.; Wright, D.J.B., ed. Long Acting Injections and Implants: Springer, Boston, MA. 2012, 73-91.
Nahata, T.; Saini, T. Optimization of formulation variables for the development of long acting microsphere based depot injection of olanzapine. J. Microencapsul., 2008, 25, 426-433.
Nayak, R.K.; Doose, D.R.; Nair, N. The bioavailability and pharmacokinetics of oral and depot intramuscular haloperidol in schizophrenic patients. J. Clin. Pharmacol., 1987, 27, 144-150.
Bai, Y-M.; Chen, T.; Wu, B.; Hung, C.H.; Lin, W.K.; Hu, T.M.; Lin, C.Y.; Chou, P. A comparative efficacy and safety study of long-acting risperidone injection and risperidone oral tablets among hospitalized patients: 12-week randomized, single-blind study. Pharmacopsychiatry, 2006, 39, 135-141.
Kane, J.M.; Detke, H.C.; Naber, D.; Sethuraman, G.; Lin, D.Y.; Bergstrom, R.F.; McDonnell, D. Olanzapine long-acting injection: A 24-week, randomized, double-blind trial of maintenance treatment in patients with schizophrenia. Am. J. Psychiatry, 2010, 167, 181-189.
Blanco-Príeto, M.J.; Besseghir, K.; Zerbe, O.; Andris, D.; Orsolini, P.; Heimgartner, F.; Merkle, H.P.; Gander, B. In vitro and in vivo evaluation of a somatostatin analogue released from PLGA microspheres. J. Control. Release, 2000, 67, 19-28.
Burgess, D.J.; Wright, J.C. An introduction to long acting injections and implants. In: Jeremy, C.; Wright, D.J.B., ed. Long Acting Injections and Implants: Springer, 2012, 1-9.
Perrin, D.E.; English, J.P. Polyglycolide and polylactide. In: Abraham, J.; Domb, J.K.; Wiseman, D. eds. Handbook of biodegradable polymers: Harwood Academic Publishers, Amsterdam: 1997, 3-28.
Alexis, F. Factors affecting the degradation and drug‐release mechanism of poly (lactic acid) and poly. [(lactic acid)-­‐co-­‐(glycolic acid)]. Polym. Int., 2005, 54, 36-46.
Kostanski, J.W.; Thanoo, B.; DeLuca, P.P. Preparation, characterization, and in vitro evaluation of 1-and 4-month controlled release orntide PLA and PLGA microspheres. Pharm. Dev. Technol., 2000, 5, 585-596.
Cheng, Y-H.; Illum, L.; Davis, S. A poly (D, L-lactide-co-glycolide) microsphere depot system for delivery of haloperidol. J. Control. Release, 1998, 55, 203-212.
Lewis, D. CControlled release of bioactive agents from lactide/glycolide polymers. In: Chasin, M., ed. Biodegradable Polymers as Drug Delivery Systems. Marcel Dekker, New York: 1990, 1-41.
Freitas, S.; Merkle, H.P.; Gander, B. Microencapsulation by solvent extraction/evaporation: reviewing the state of the art of microsphere preparation process technology. J. Control. Release, 2005, 102, 313-332.
D’Souza, S.; Faraj, J.A.; Giovagnoli, S.; DeLuca, P.P. Preparation, characterization, and in vivo evaluation of olanzapine poly (D, Llactide- co-glycolide) microspheres. J. Pharm, 2013, 2013
Hickey, T.; Kreutzer, D.; Burgess, D.; Moussy, F. Dexamethasone/ PLGA microspheres for continuous delivery of an anti-inflammatory drug for implantable medical devices. Biomaterials, 2002, 23, 1649-1656.
Fernández-Carballido, A.; Puebla, P.; Herrero-Vanrell, R.; Pastoriza, P. Radiosterilisation of indomethacin PLGA/PEG-derivative microspheres: Protective effects of low temperature during gamma-irradiation. Int. J. Pharm., 2006, 313, 129-135.
Zhang, Y.; Huo, M.; Zhou, J.; Zou, A.; Li, W.; Yao, C.; Xie, S. DDSolver: An add-in program for modeling and comparison of drug dissolution profiles. AAPS J., 2010, 12, 263-271.
Pervaiz, F.; Ahmad, M.; Minhas, M.U.; Sohail, M. Development and validation of reverse phase high performance chromatography method for determination of olanzapine in microsample rat plasma: Application to preclinical pharmacokinetic study. Trop. J. Pharm. Res., 2015, 14(1), 141-147.
Khang, G.; Lee, J.H.; Lee, J.W.; Cho, J.C.; Lee, H.B. Preparation and characterization of poly (lactide-co-glycolide) micro-spheres for the sustained release of AZT. Korea Polym. J., 2000, 8, 80-88.
Choi, H.S.; Seo, S-A.; Khang, G.; Rhee, J.M.; Lee, H.B. Preparation and characterization of fentanyl-loaded PLGA microspheres: in vitro release profiles. Int. J. Pharm., 2002, 234, 195-203.
Wang, Y.; Burgess, D.J. Microsphere Technologies. In: Jeremy, C.; Wright, D.J.B., ed. Long acting injections and implants. Springer, London: 2012, 167-194.
Champion, J.A.; Walker, A.; Mitragotri, S. Role of particle size in phagocytosis of polymeric microspheres. Pharm. Res., 2008, 25, 1815-1821.
Yüce, M.; Canefe, K. Indomethacin-loaded microspheres: preparation, characterization and in-vitro evaluation regarding ethylcellulose matrix material. Turk. J. Pharm. Sci., 2008, 5, 129-142.
Su, Z.; Sun, F.; Shi, Y.; Jiang, C.; Meng, Q.; Teng, L.; Li, Y. Effects of formulation parameters on encapsulation efficiency and release behavior of risperidone poly (D, L-lactide-co-glycolide) microsphere. Chem. Pharm. Bull. (Tokyo), 2009, 57, 1251-1256.
Tracy, M.; Ward, K.; Firouzabadian, L.; Wang, Y.; Dong, N.; Qian, R.; Zhang, Y. Factors affecting the degradation rate of poly (lactide-co-glycolide) microspheres in vivo and in vitro. Biomaterials, 1999, 20, 1057-1062.
Fu, X.; Ping, Q.; Gao, Y. Effects of formulation factors on encapsulation efficiency and release behaviour in vitro of huperzine A-PLGA microspheres. J. Microencapsul., 2005, 22, 705-714.
Costa, P.; Sousa, Lobo J.M. Modeling and comparison of dissolution profiles. Eur. J. Pharm. Sci., 2001, 13, 123-133.
Peppas, N. Analysis of Fickian and non-Fickian drug release from polymers. Pharm. Acta Helv., 1984, 60, 110-111.
Vismari, L.; Pires, M.L.N.; Benedito-Silva, A.A.; Calil, H.M. Bioavailability of immediate and controlled release formulations of lithium carbonate. Rev. Bras. Psiquiatr., 2002, 24, 74-79.

open access plus

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Published on: 26 December, 2018
Page: [375 - 383]
Pages: 9
DOI: 10.2174/1567201816666181227105930

Article Metrics

PDF: 57
PRC: 1