Login Register Cart 0
Generic placeholder image

Current Drug Delivery

Editor-in-Chief

ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Long-Lasting In Situ Forming Implant Loaded with Bupivacaine: Investigation on Polymeric and Non-Polymeric Carrier and Solvent Effect

Author(s): Saeed Bazraee, Hamid Mobedi*, Arezuo Mashak and Ahmad Jamshidi

Volume 19, Issue 1, 2022

Published on: 17 June, 2021

Page: [157 - 166] Pages: 10

DOI: 10.2174/1567201818666210617102634

Price: $65

conference banner
Abstract

Introduction: Typically, in situ forming implants utilize Poly (lactide- co- glycolide) (PLGA) as carrier and N-methyl-2-pyrrolidone (NMP) as solvent. However, it is essential to develop different carriers to release various drugs in a controlled and sustained manner with economic and safety considerations.

Objective: The present study aims to evaluate the in-vitro release of Bupivacaine HCl from in situ forming systems as post-operative local anesthesia.

Methods: We used Sucrose acetate isobutyrate (SAIB), PLGA 50:50, and a mixture of them as carriers to compare the release behavior. Besides, the effect of PLGA molecular weight (RG 502H, RG 503H, and RG 504H), solvent type, and solvent concentration on the drug release profile has been evaluated. The formulations were characterized by investigating their in-vitro drug release, rheological properties, solubility, and DSC, in addition to their morphological properties. Furthermore, the Korsmeyer-Peppas and Weibull models were applied to the experimental data. Results revealed that using a mixture of SAIB and PLGA compared to using them solely can extend the Bupivacaine HCl release from 3 days to two weeks.

Results: The DSC results demonstrated the compatibility of the mixture by showing a single Tg. The formulation with NMP exhibited a higher burst release and final release in comparison with other solvents by 30% and 96%, respectively. Increasing the solvent concentration from 12% to 32% raised the drug release significantly, which confirmed the larger porosity in the morphology results. From the Korsmeyer-Peppas model, the mechanism of drug release has been predicted to be non-Fickian diffusion.

Keywords: SAIB, PLGA, local anesthetic, in situ forming implant, drug delivery systems, bioavailability.

« Previous Next »
Graphical Abstract

[1]
Bruschi, M.L. Strategies to modify the drug release from pharmaceutical systems; Woodhead Publishing, 2015.
[2]
Osmani, R.A.; Bhosale, R.R.; Ghodake, P.P. In-situ forming parenteral drug delivery: A new-fangled loom in therapeutics. Am. J. Pharm. Heal. Res., 2014, 2.
[3]
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.
[http://dx.doi.org/10.1016/j.jconrel.2013.08.024] [PMID: 24001947]
[4]
Musmade, N.; Jadhav, A.; Moin, P. An overview of in situ gel forming implants: Current approach towards alternative drug delivery system. J. Biol. Chem. Chronicles, 2019, 5, 14-21.
[http://dx.doi.org/10.33980/jbcc.2019.v05i01.003]
[5]
Mitra, A.K.; Kwatra, D.; Vadlapudi, A.D. Drug Delivery (book); Jones & Bartlett Publishers, 2014.
[6]
Jivawala, R.; Goyani, M. A novel approach to deliver therapeutic agents using in situ forming implants based on solvent induced phase separation technique for long term controlled release. Int. J. Adv. Res. Rev., 2017, 2, 50-62.
[7]
Li, Y.; Shi, X. In vitro and in vivo evaluation of lidocaine hydrochloride-loaded injectable poly (lactic-co-glycolic acid) implants. Curr. Drug Deliv., 2018, 15(10), 1411-1416.
[http://dx.doi.org/10.2174/1567201815666180912123137] [PMID: 30207229]
[8]
Bode, C.; Kranz, H.; Siepmann, F.; Siepmann, J. In-situ forming PLGA implants for intraocular dexamethasone delivery. Int. J. Pharm., 2018, 548(1), 337-348.
[http://dx.doi.org/10.1016/j.ijpharm.2018.07.013] [PMID: 29981408]
[9]
Parent, M.; Clarot, I.; Gibot, S.; Derive, M.; Maincent, P.; Leroy, P.; Boudier, A. One-week in vivo sustained release of a peptide formulated into in situ forming implants. Int. J. Pharm., 2017, 521(1-2), 357-360.
[http://dx.doi.org/10.1016/j.ijpharm.2017.02.046] [PMID: 28232200]
[10]
Kempe, S.; Mäder, K. In situ forming implants -an attractive formulation principle for parenteral depot formulations. J. Control. Release, 2012, 161(2), 668-679.
[http://dx.doi.org/10.1016/j.jconrel.2012.04.016] [PMID: 22543012]
[11]
Koocheki, S.; Madaeni, S.S.; Niroomandi, P. Development of an enhanced formulation for delivering sustained release of buprenorphine hydrochloride. Saudi Pharm. J., 2011, 19(4), 255-262.
[http://dx.doi.org/10.1016/j.jsps.2011.05.001] [PMID: 23960766]
[12]
Khuphe, M.; Thornton, P.D. Poly (hydroxy acid) nanoparticles for the encapsulation and controlled release of doxorubicin. Macromol. Chem. Phys., 2018, 219, 1800352.
[http://dx.doi.org/10.1002/macp.201800352]
[13]
Basu, A.; Domb, A.J. Recent advances in polyanhydride based biomaterials. Adv. Mater., 2018, 30(41), e1706815.
[http://dx.doi.org/10.1002/adma.201706815] [PMID: 29707879]
[14]
Behar-Cohen, F. Recent advances in slow and sustained drug release for retina drug delivery. Expert Opin. Drug Deliv., 2019, 16(7), 679-686.
[http://dx.doi.org/10.1080/17425247.2019.1618829] [PMID: 31092046]
[15]
Dual drug delivery of curcumin and niclosamide using PLGA nanoparticles for improved therapeutic effect on breast cancer cells. J. Polym. Res., 2020, 27, 133.
[http://dx.doi.org/10.1007/s10965-020-02092-7]
[16]
Li, H.; Xu, Y.; Tong, Y.; Dan, Y.; Zhou, T.; He, J.; Liu, S.; Zhu, Y. Sucrose acetate isobutyrate as an in situ forming implant for sustained release of local anesthetics. Curr. Drug Deliv., 2019, 16(4), 331-340.
[http://dx.doi.org/10.2174/1567201816666181119112952] [PMID: 30451111]
[17]
Guo, J.; Wang, J.; Cai, C.; Xu, J.; Yu, H.; Xu, H.; Xing, T. The anti-melanoma efficiency of the intratumoral injection of cucurbitacin-loaded sustained release carriers: In situ-forming implants. AAPS PharmSciTech, 2015, 16(4), 973-985.
[http://dx.doi.org/10.1208/s12249-015-0292-2] [PMID: 25609378]
[18]
Pandya, Y.; Sisodiya, D.; Dashora, K. ATRIGEL®, implants and controlled released drug delivery system. Int. J. Biopharm., 2014, 5, 208-213.
[19]
Tant, M.R. Biopharmaceutic and pharmacokinetic studies of sucrose acetate isobutyrate as an excipient for oral drug delivery; East Tennessee State University, 2011.
[20]
Cheng, T.L.; Murphy, C.M.; Ravarian, R.; Dehghani, F.; Little, D.G.; Schindeler, A. Bisphosphonate-adsorbed ceramic nanoparticles increase bone formation in an injectable carrier for bone tissue engineering. J. Tissue Eng., 2015, 6, 2041731415609448.
[http://dx.doi.org/10.1177/2041731415609448] [PMID: 26668709]
[21]
Lu, Y.; Yu, Y.; Tang, X. Sucrose acetate isobutyrate as an in situ forming system for sustained risperidone release. J. Pharm. Sci., 2007, 96(12), 3252-3262.
[http://dx.doi.org/10.1002/jps.21091] [PMID: 17721936]
[22]
Lin, X.; Yang, S.; Gou, J.; Zhao, M.; Zhang, Y.; Qi, N.; He, H.; Cai, C.; Tang, X.; Guo, P. A novel risperidone-loaded SAIB-PLGA mixture matrix depot with a reduced burst release: Effects of solvents and PLGA on drug release behaviors in vitro in vivo. J. Mater. Sci. Mater. Med., 2012, 23(2), 443-455.
[http://dx.doi.org/10.1007/s10856-011-4521-2] [PMID: 22170300]
[23]
Chandrasekaran, A.R.; Jia, C.Y.; Theng, C.S. In vitro studies and evaluation of metformin marketed tablets-Malaysia. J. Appl. Pharm. Sci., 2011, 1, 214.
[24]
Shapourgan, M.; Mobedi, H.; Sheikh, N.; Behnamghader, A.; Mashak, A. Leuprolide acetate release study from γ-irradiated PLGA-based in situ forming system. Curr. Drug Deliv., 2017, 14(8), 1170-1177.
[http://dx.doi.org/10.2174/1567201814666170329104047] [PMID: 28530536]
[25]
Astaneh, R.; Moghimi, H.R.; Erfan, M.; Mobedi, H. Formulation of an injectable implant for peptide delivery and mechanistic study of the effect of polymer molecular weight on its release behavior. Daru, 2006, 14, 65-70.
[26]
Jain, R.A.; Rhodes, C.T.; Railkar, A.M.; Malick, A.W.; Shah, N.H. Controlled delivery of drugs from a novel injectable in situ formed biodegradable PLGA microsphere system. J. Microencapsul., 2000, 17(3), 343-362.
[http://dx.doi.org/10.1080/026520400288319] [PMID: 10819422]
[27]
Jahanmir, G.; Chau, Y. Mathematical models of drug release from degradable hydrogels. Biomedical Applications of Nanoparticles; Elsevier, 2019, pp. 233-269.
[http://dx.doi.org/10.1016/B978-0-12-816506-5.00002-4]
[28]
Rahimi, M.; Mobedi, H.; Behnamghader, A. In situ-forming PLGA implants loaded with leuprolide acetate/β-cyclodextrin complexes: Mathematical modelling and degradation. J. Microencapsul., 2016, 33(4), 355-364.
[http://dx.doi.org/10.1080/02652048.2016.1194905] [PMID: 27530523]
[29]
Mircioiu, C.; Voicu, V.; Anuta, V.; Tudose, A.; Celia, C.; Paolino, D.; Fresta, M.; Sandulovici, R.; Mircioiu, I. Mathematical modeling of release kinetics from supramolecular drug delivery systems. Pharmaceutics, 2019, 11(3), 140.
[http://dx.doi.org/10.3390/pharmaceutics11030140] [PMID: 30901930]
[30]
Paolino, D.; Tudose, A.; Celia, C.; Di Marzio, L.; Cilurzo, F.; Mircioiu, C. Mathematical models as tools to predict the release kinetic of fluorescein from lyotropic colloidal liquid crystals. Materials (Basel), 2019, 12(5), 5.
[http://dx.doi.org/10.3390/ma12050693] [PMID: 30813650]

Rights & Permissions Print Cite
Article Metrics
20
1
© 2024 Bentham Science Publishers | Privacy Policy