IMPLEMENTING CENTRAL COMPOSITE DESIGN FOR THE FABRICATION OF SELECTIVE SEROTONIN RE-UPTAKE INHIBITOR BASED IN SITU FORMING BIODEGRADABLE DRUG DELIVERY SYSTEM

SRUTHI S.; GOPINATH S.; MERITON STANLEY A.; SATHEESH KUMAR S.; RISHAANTH M.

doi:10.22159/ijap.2025v17i3.53413

Authors

SRUTHI S. Department of Pharmaceutics, Sri Ramachandra Institute of Higher Education and Research (DU), Porur, Chennai, India https://orcid.org/0000-0002-2889-5833
GOPINATH S. Department of Pharmaceutics, Sri Ramachandra Institute of Higher Education and Research (DU), Porur, Chennai, India
MERITON STANLEY A. Department of Community Medicine, Sri Ramachandra Medical College and Research Institute, SRIHER (DU), Porur, Chennai, India https://orcid.org/0000-0001-6437-9070
SATHEESH KUMAR S. Department of Pharmaceutics, SNS college of Pharmacy and Health Sciences, SNS Kalvinagar, Kurumbalayam, Saravanampatti, Coimbatore, India https://orcid.org/0000-0002-8573-8797
RISHAANTH M. Department of Pharmaceutics, Sri Ramachandra Institute of Higher Education and Research (DU), Porur, Chennai, India https://orcid.org/0009-0005-7811-8708

DOI:

https://doi.org/10.22159/ijap.2025v17i3.53413

Keywords:

Major depressive disorder (MDD), Biodegradable polymeric implant, Chronic Illness, Optimization, Central composite design, Fluvoxamine maleate

Abstract

Objective: The current study aims to develop and optimize an injectable fluvoxamine-loaded biodegradable implant utilizing PLGA 50:50 as the polymer and PEG 6000 as the surfactant to tailor depression therapy.

Methods: A systematic preformulation study assessed the physical and chemical properties of Fluvoxamine, including solubility, melting point, and compatibility through FTIR, DSC, and PXRD. A central composite design was used to optimize the implant formulation, evaluating critical parameters such as drug release profiles at 2 and 6 h. Surface morphology was analyzed using SEM to confirm the structural integrity of the implants.

Results: Studies on preformulation validated the stability and compatibility of the medication. Central Composite design showed that an increment of PEG concentration demonstrated a significant negative effect on Y1 response, while PLGA concentration had a positive impact on Y2. The optimized formulation showed experimental values of 2.60% for the initial burst after 2 h and 19.96% for the release after 6 h. SEM analysis revealed uniform implant morphology, supporting consistent drug delivery.

Conclusion: An optimized Fluvoxamine-loaded biodegradable implant formulation with minimum burst release and maximum sustained release was developed as an innovative solution for MDD management, addressing the challenges of conventional therapies. This approach offers improved bioavailability, patient compliance, and therapeutic outcomes, paving the way for advanced treatment strategies in depression management.

References

Sabic D, Sabic A, Bacic Becirovic A. Major depressive disorder and difference between genders. Mater Sociomed. 2021;33(2):105-8. doi: 10.5455/msm.2021.33.105-108, PMID 34483737.

Yuan S, MA T, Zhang YN, Wang N, Baloch Z, MA K. Novel drug delivery strategies for antidepressant active ingredients from natural medicinal plants: the state of the art. J Nanobiotechnology. 2023;21(1):391. doi: 10.1186/s12951-023-02159-9, PMID 37884969.

Roy Byrne PP, Davidson KW, Kessler RC, Asmundson GJ, Goodwin RD, Kubzansky L. Anxiety disorders and comorbid medical illness. Gen Hosp Psychiatry. 2008;30(3):208-25. doi: 10.1016/j.genhosppsych.2007.12.006, PMID 18433653.

Huang X, Brazel CS. On the importance and mechanisms of burst release in matrix controlled drug delivery systems. J Control Release. 2001;73(2-3):121-36. doi: 10.1016/s0168-3659(01)00248-6, PMID 11516493.

Dankert ME, Brensinger CM, Ralph LN, Seward DA, Bilker WB, Siegel SJ. Psychiatric health care provider attitudes towards implantable medication. Psychiatry Res. 2010;177(1-2):167-71. doi: 10.1016/j.psychres.2008.12.012, PMID 20378184.

Makadia HK, Siegel SJ. Poly lactic co glycolic acid (PLGA) as biodegradable controlled drug delivery carrier. Polymers (Basel). 2011;3(3):1377-97. doi: 10.3390/polym3031377, PMID 22577513.

Demyttenaere K, Mesters P, Boulanger B, Dewe W, Delsemme MH, Gregoire J. Adherence to treatment regimen in depressed patients treated with amitriptyline or fluoxetine. J Affect Disord. 2001;65(3):243-52. doi: 10.1016/s0165-0327(00)00225-1, PMID 11511404.

Jain N, Verma A, Jain N. Preformulation studies of niosomal gel containing dipivefrin hydrochloride for antiglaucomatic activity. Int J Pharm Pharm Sci. 2024;16(2):17-23. doi: 10.22159/ijpps.2024v16i2.49174.

Ambati T, Nizampuram V, Selvaganesh S, SR, Nesappan T. Efficacy of copper oxide nanoparticles using Piper longum and piper betle. Bioinformation. 2023;19(9):964-70. doi: 10.6026/97320630019964, PMID 37928485.

Hattali Ws Al, Samuel BA, Philip AK. Enhancing fluconazole solubility and bioavailability through solid dispersion techniques: evaluation of polyethylene glycol 6000 and sodium carboxymethylcellulose systems using fiber optics. Int J Pharm Pharm Sci. 2024;16(12):51-9. doi: 10.22159/ijpps.2024v16i12.52739.

Rojek B, Wesolowski M. DSC supported by factor analysis as a reliable tool for compatibility study in pharmaceutical mixtures. J Therm Anal Calorim. 2019;138(6):4531-9. doi: 10.1007/s10973-019-08223-7.

Majumdar R, Kar PK. Biosynthesis characterization and anthelmintic activity of silver nanoparticles of clerodendrum infortunatum isolate. Sci Rep. 2023;13(1):7415. doi: 10.1038/s41598-023-34221-9, PMID 37150767.

Avachat AM, Kapure SS. Asenapine maleate in situ forming biodegradable implant: an approach to enhance bioavailability. Int J Pharm. 2014;477(1-2):64-72. doi: 10.1016/j.ijpharm.2014.10.006, PMID 25305379.

Hatefi A, Amsden B. Biodegradable injectable in situ forming drug delivery systems. J Control Release. 2002;80(1-3):9-28. doi: 10.1016/s0168-3659(02)00008-1, PMID 11943384.

Ahmed TA, Alharby YA, El Helw AR, Hosny KM, El Say KM. Depot injectable atorvastatin biodegradable in situ gel: development optimization in vitro and in vivo evaluation. Drug Des Dev Ther. 2016 Jan 20;10:405-15. doi: 10.2147/DDDT.S98078, PMID 26855565.

Nadendla RR, Priyanka PV. Optimizing transdermal patch formulation for enhanced delivery of rivaroxaban: a comprehensive design of experiments approach. Int J Pharm Pharm Sci. 2024;16(12):8-20. doi: 10.22159/ijpps.2024v16i12.51075.

Rebbapragada D, Kalyanaraman R. Statistical optimization of medium components by plackett burman design and response surface methodology for enhanced antioxidant activity by xylaria feejeensis HMJAU22039. Int J Pharm Pharm Sci. 2016;8(11):159. doi: 10.22159/ijpps.2016v8i11.14257.

Rezaeian Shiadeh SN, Hadizadeh F, Khodaverdi E, Gorji Valokola M, Rakhshani S, Kamali H. Injectable in-situ forming depot based on PLGA and PLGA-PEG-PLGA for sustained release of risperidone: in vitro evaluation and pharmacokinetics in rabbits. Pharmaceutics. 2023;15(4):1229. doi: 10.3390/pharmaceutics15041229, PMID 37111714.

Farooqui P, Gude R. Formulation development and optimisation of fast dissolving buccal films loaded glimepiride solid dispersion with enhanced dissolution profile using central composite design. Int J Pharm Pharm Sci. 2023;15(6):35-54. doi: 10.22159/ijpps.2023v15i6.47992.

Ghaderi F, Nemati M, Siahi Shadbad MR, Valizadeh H, Monajjemzadeh F. Thermal stability and kinetic study of fluvoxamine stability in binary samples with lactose. Adv Pharm Bull. 2017;7(1):43-51. doi: 10.15171/apb.2017.006, PMID 28507936.

Choi MJ, Woo MR, Choi HG, Jin SG. Effects of polymers on the drug solubility and dissolution enhancement of poorly water-soluble rivaroxaban. Int J Mol Sci. 2022;23(16):9491. doi: 10.3390/ijms23169491, PMID 36012748.

Zhang X, Yang L, Zhang C, Liu D, Meng S, Zhang W. Effect of polymer permeability and solvent removal rate on in situ forming implants: drug burst release and microstructure. Pharmaceutics. 2019;11(10):520. doi: 10.3390/pharmaceutics11100520, PMID 31658642.

Ahmed TA, Alharby YA, El Helw AR, Hosny KM, El Say KM. Depot injectable atorvastatin biodegradable in situ gel: development optimization in vitro and in vivo evaluation. Drug Des Dev Ther. 2016;10:405-15. doi: 10.2147/DDDT.S98078, PMID 26855565.

Bode C, Kranz H, Kruszka A. In situ forming PLGA implants: how additives affect swelling and drug release. J Drug Deliv Sci Technol. 2019 Oct;53:101180. doi: 10.1016/j.jddst.2019.101180.