Polymeric Matrix-Based Transdermal Drug Delivery Systems for Brexpiprazole: A Review of Formulation Strategies, Release Kinetics, Skin Permeation, and Stability

References

[1] National Center for Biotechnology Information. PubChem Compound Summary for Brexpiprazole (CID 11171018). Bethesda (MD): National Library of Medicine; 2024.

[2] Otsuka Pharmaceutical Co. Rexulti (brexpiprazole) tablets: prescribing information. Rockville (MD): U.S. Food and Drug Administration; 2023.

[3] Citrome L. Brexpiprazole: a new dopamine D2 receptor partial agonist for the treatment of schizophrenia and major depressive disorder. Int J Clin Pract. 2015;69(9):978–997.

[4] Maeda K, Sugino H, Akazawa H, et al. Brexpiprazole I: in vitro and in vivo characterization of a novel serotonin–dopamine activity modulator. J Pharmacol Exp Ther. 2014;350(3):589–604.

[5] Prausnitz MR, Langer R. Transdermal drug delivery. Nat Biotechnol. 2008;26(11):1261–1268.

[6] Chaudhary H, Kumar V, Gupta S, et al. Transdermal drug delivery: a review. Int J Pharm Sci Res. 2018;9(1):1–15.

[7] Krishnaiah YSR. Transdermal drug delivery systems. Indian J Pharm Sci. 2010;72(5):510–520.

[8] Singh J, Tripathi KP. Transdermal drug delivery system: a review. J Pharm Res. 2019;18(2):112–121.

[9] Hadgraft J. Skin, the final frontier. Int J Pharm. 2001;224(1–2):1–18.

[10] Hadgraft J, Lane ME. Skin permeation: the years of enlightenment. Int J Pharm. 2012;435(1):2–8.

[11] Barry BW. Novel mechanisms and devices to enable successful transdermal drug delivery. Eur J Pharm Sci. 2001;14(2):101–114.

[12] Barry BW. Breaching the skin's barrier to drugs. Nat Biotechnol. 2014;22(2):165–167.

[13] Williams AC, Barry BW. Penetration enhancers. Adv Drug Deliv Rev. 2012;64:128–137.

[14] Williams AC, Walters KA, Barry BW. Chemical penetration enhancers in transdermal delivery. Pharmaceutics. 2021;13(4):543.

[15] Lane ME. Skin penetration enhancers. Int J Pharm. 2013;447(1–2):12–21.

[16] Aulton ME, Taylor KMG. Aulton's Pharmaceutics: the design and manufacture of medicines. 5th ed. London: Elsevier; 2018.

[17] Jain NK. Controlled and novel drug delivery. 4th ed. New Delhi: CBS Publishers; 2016.

[18] Bácskay I, Nemes D, Fenyvesi F, et al. Formulation and evaluation of transdermal patches prepared by solvent casting technique. Pharmaceutics. 2023;15(3):845.

[19] Rao YS, Suryanarayana MV. Formulation and evaluation of sustained release transdermal patches. Int J Pharm Sci Res. 2019;10(4):1834–1842.

[20] Kaur LP, Guleri TK. Topical gel: a recent approach for drug delivery. Asian J Biomed Pharm Sci. 2017;7(63):1–7.

[21] Rowe RC, Sheskey PJ, Quinn ME. Handbook of pharmaceutical excipients. 7th ed. London: Pharmaceutical Press; 2012.

[22] Mishra AN, Kumar A, Sharma S, et al. Drug–polymer interaction studies in transdermal systems. J Drug Deliv Sci Technol. 2018;45:234–242.

[23] Zhang Y, Liu X, Chen J, et al. Solid dispersion-based transdermal drug delivery. Drug Dev Ind Pharm. 2020;46(6):961–970.

[24] Patel D, Shah K, Patel R, et al. Development of transdermal patches of antipsychotic drugs. J Pharm Innov. 2020;15(2):155–165.

[25] Arora P, Mukherjee B. Design, development, physicochemical, and in vitro evaluation of transdermal patches containing diclofenac diethylammonium salt. J Pharm Sci. 2002;91(9):2076–2089.

[26] Patra CN, Priya R, Swain S, et al. Design and evaluation of matrix type transdermal patches. J Young Pharm. 2016;8(4):398–404.

[27] Verma P, Singh S, Yadav K, et al. Statistical optimization of matrix transdermal patches. J Drug Deliv Sci Technol. 2022;67:102961.

[28] Sharma A, Gupta R, Mehta P, et al. QbD-based optimization of polymeric transdermal patches. Drug Dev Ind Pharm. 2024;50(1):45–58.

[29] Zidan AS, Rahman Z. Quality by Design in pharmaceutical development. AAPS PharmSciTech. 2015;16(4):771–781.

[30] Liu X, Wang Y, Zhao L, et al. Polymer composite transdermal systems for enhanced drug permeation. Int J Pharm. 2023;634:122640.

[31] International Council for Harmonisation. ICH Q1A(R2): stability testing of new drug substances and products. Geneva: ICH; 2003.

[32] International Council for Harmonisation. ICH Q2(R1): validation of analytical procedures. Geneva: ICH; 2005.

[33] Zhao K, Li M, Sun Q, et al. Stability evaluation of polymeric transdermal patches. J Pharm Sci. 2021;110(7):2589–2598.

[34] Wokovich AM, Prodduturi S, Doub WH, et al. Transdermal drug delivery system regulatory considerations. AAPS J. 2006;8(4):E687–E700.

[35] Remington JP. Remington: the science and practice of pharmacy. 23rd ed. London: Pharmaceutical Press; 2020.

[36] Sweetman SC. Martindale: the complete drug reference. 39th ed. London: Pharmaceutical Press; 2017.

[37] United States Pharmacopeial Convention. United States Pharmacopeia–National Formulary (USP–NF). Rockville (MD): USP Convention; 2023.

@article{1722285,
      author = {Amit Kumar, Dharmendra Kumar, Vedant Kumar Prajapati},
      title = {Polymeric Matrix-Based Transdermal Drug Delivery Systems for Brexpiprazole: A Review of Formulation Strategies, Release Kinetics, Skin Permeation, and Stability},
      journal = {Iconic Research And Engineering Journals},
      year = {2026},
      volume = {10},
      number = {2},
      pages = {1078-1095},
      issn = {2456-8880},
      url = {https://www.irejournals.com/formatedpaper/1722285.pdf},
      abstract = {Brexpiprazole is a second-generation atypical antipsychotic and serotonin–dopamine activity modulator approved for schizophrenia and as adjunctive therapy in major depressive disorder. Although the molecule is well absorbed after oral dosing, its clinical use in chronic psychiatric disease is constrained by the well-documented problem of poor long-term medication adherence, by fluctuations in plasma concentration associated with once-daily oral regimens, and by the practical difficulties of sustained tablet-taking in this patient population. Its very long elimination half-life makes it an attractive candidate for a delivery system that maintains steady systemic exposure with minimal user intervention. The present review critically examines the rationale, scientific principles, formulation strategies, and evaluation framework for a polymeric matrix-based transdermal drug delivery system (TDDS) of brexpiprazole. The structure and barrier properties of the skin, the principal pathways of percutaneous transport, and the quantitative descriptors of permeation are discussed in relation to the physicochemical profile of the drug. Matrix-type patch architecture, film-forming polymers, plasticizers, and chemical permeation enhancers are reviewed alongside solubility-enhancement strategies appropriate to a lipophilic, poorly water-soluble molecule. The role of the solvent-casting technique and its critical process parameters, the in-vitro release and ex-vivo permeation testing framework, mathematical modelling of release kinetics, and the application of Design of Experiments (DoE) and Quality-by-Design (QbD) principles for systematic optimization are described. Stability considerations under International Council for Harmonisation (ICH) conditions and local skin tolerability are also addressed. The review concludes that a rationally engineered polymeric matrix patch, optimized through DoE and supported by mechanistic release–permeation correlation and ICH-compliant stability data, represents a scientifically sound route toward improving adherence and therapeutic consistency in long-term brexpiprazole therapy.},
      keywords = {Brexpiprazole, Transdermal Drug Delivery System, Polymeric Matrix Patch, Controlled Release, Skin Permeation, Solvent Casting, Design of Experiments, Quality-By-Design, Release Kinetics, Stability Evaluation, Antipsychotic Adherence.},
      month = {August},
      doi = {https://doi.org/10.64388/IREV10I2-1722285}
  }