Nevirapine, the first non-nucleoside reverse transcriptase inhibitor approved for HIV-1 treatment, plays a crucial role in the prevention and therapy of acquired immunodeficiency syndrome (AIDS). However, as a biopharmaceutics classification system (BCS) class Ⅱ drug, nevirapine possesses inherent drawbacks, including low solubility and unstable bioavailability. The challenges of patient compliance associated with frequent dosing in clinical applications, as well as hepatotoxicity, skin adverse reactions, and other adverse effects, further highlight the necessity for developing novel delivery systems. This article systematically reviews the research progress in nevirapine formulation optimization, encompassing conventional formulation strategies (orodispersible tablets, solid dispersions, and cocrystals/co-amorphous systems), novel nanoscale delivery systems (polymeric nanoparticles, lipid nanoparticles, magnetic targeting nanoparticles, vesicular systems, and nanocrystals), long-acting injectables and implants among other dimensions. Nevirapine formulation research has shifted from simple solubility enhancement to targeted delivery, long-acting sustained release, and intelligent design, offering new insights to improve AIDS treatment efficacy, overcome viral reservoirs, and advance personalized therapy.

1. MadanJR,KamateVJ,DuaK,et al.Improving the solubility of nevirapine using a hydrotropy and mixed hydrotropy based solid dispersion approach[J].Polim Med,2017,47(2):83-90.DOI:10.17219/pim/77093.

2. MonschkeM,WagnerKG.Amorphous solid dispersions of weak bases with pH-dependent soluble polymers to overcome limited bioavailability due to gas tric pH variability-anin-vitroapproach[J].Int J Pharm,2019,564:162-170.DOI:10.1016/j.ijpharm.2019.04.034.

3. LiJ,YeB,GaoS,et al.The latest developments in the design and discovery of non-nucleoside reverse transcriptase inhibitors (NNRTIs) for the treatment of HIV[J].Expert Opin Drug Discov,2024,19(12):1439-1456.DOI:10.1080/17460441.2024.2415309.

4. StiegerN,CairaMR,WesselsJC,et al.Crystal form conversion of nevirapine solvates subjected to elevated temperature and humidity: a qualitative study[J].Pharmazie,2017,72(10):571-574.DOI:10.1691/ph.2017.7043.

5. RaoMRP,SapateS,SonawaneA.Pharmacotechnical evaluation by SeDeM expert system to develop orodispersible tablets[J].AAPS PharmSciTech,2022,23(5):133.DOI:10.1208/s12249-022-02285-x.

6. LavraZMM,de MedeirosFPM,da SilvaRMF,et al.Formulation, development and scale-up of fixed-dose combination tablets containing zidovudine, lamivudine and nevirapine[J].Curr HIV Res,2019,17(5):360-367.DOI:10.2174/1570162X17666190927162155.

7. Dos SantosKA,de Carvalho MoreiraLMC,Soares-SobrinhoJL,et al.New horizons in antiretroviral drug delivery systems for HIV management[J].Curr Med Chem,2025,32(21):4192-4224.DOI:10.2174/0109298673306606240802111136.

8. KuminekG,Rodríguez-HornedoN,SiedlerS,et al.How cocrystals of weakly basic drugs and acidic coformers might modulate solubility and stability[J].Chem Commun (Camb),2016,52(34):5832-5835.DOI:10.1039/c6cc00898d.

9. PanzadeP,ShendarkarG,KulkarniD,et al.Solid state characterization and dissolution enhancement of nevirapine cocrystals[J].Adv Pharm Bull,2021,11(4):772-776.DOI:10.34172/apb.2021.087.

10. Dos SantosKA,ChavesLL,NadvornyD,et al.Exploring co-amorphous formulations of nevirapine: insights from computational, thermal, and solubility analyses[J].AAPS PharmSciTech,2024,25(7):214.DOI:10.1208/s12249-024-02932-5.

11. Fotooh AbadiL,KumarP,GajbhiyeV,et al.Non-nuke HIV-1 inhibitor shuttled by mesoporous silica nanoparticles effectively slows down HIV-1 replication in infected human cells[J].Colloids Surf B Biointerfaces,2020,194:111227.DOI:10.1016/j.colsurfb.2020.111227.

12. OgunwuyiO,KumariN,SmithKA,et al.Antiretroviral drugs-loaded nanoparticles fabricated by dispersion polymerization with potential for HIV/AIDS treatment[J].Infect Dis (Auckl),2016,9:21-32.DOI:10.4137/IDRT.S38108.

13. ŽigrayováD,MikušováV,MikušP.Advances in antiviral delivery systems and chitosan-based polymeric and nanoparticulate antivirals and antiviral carriers[J].Viruses,2023,15(3):647.DOI:10.3390/v15030647.

14. AbaliSO,OnunkwoGC.Preparation andin vitro evaluation of solid-lipid nanoparticles (from Dika wax) for enhanced delivery of nevirapine in HIV/AIDS management[J].Int J Innov Sci Res Technol,2024,9(7):2520-2528.DOI:10.38124/ijisrt/IJISRT24APR1028.

15. HusseinHA,KhaphiFL,SivaramakrishnanR,et al.Recent developments in sustained-release and targeted drug delivery applications of solid lipid nanoparticles[J].J Microencapsul,2025,42(5):472-502.DOI:10.1080/02652048.2025.2495290.

16. LahkarS,Kumar DasM.Surface modified kokum butter lipid nanoparticles for the brain targeted delivery of nevirapine[J].J Microencapsul,2018,35(7-8):680-694.DOI:10.1080/02652048.2019.1573857.

17. JindalAB,BachhavSS,DevarajanPV.In situ hybrid nano drug delivery system (IHN-DDS) of antiretroviral drug for simultaneous targeting to multiple viral reservoirs: anin vivo proof of concept[J].Int J Pharm,2017,521(1-2):196-203.DOI:10.1016/j.ijpharm.2017.02.024.

18. MoghadamNH,SalehzadehS,RakhtshahJ,et al.Preparation of a highly stable drug carrier by efficient immobilization of human serum albumin (HSA) on drug-loaded magnetic iron oxide nanoparticles[J].Int J Biol Macromol,2019,125:931-940.DOI:10.1016/j.ijbiomac.2018.12.143.

19. MoghadamNH,SalehzadehS,RakhtshahJ,et al.Improving antiproliferative effect of the nevirapine on Hela cells by loading onto chitosan coated magnetic nanoparticles as a fully biocompatible nano drug carrier[J].Int J Biol Macromol,2018,118(Pt A):1220-1228.DOI:10.1016/j.ijbiomac.2018.06.144.

20. WitikaBA,WalkerRB.Preformulation characterization and identification of excipients for nevirapine loaded niosomes[J].Pharmazie,2021,76(2):77-83.DOI:10.1691/ph.2021.0137.

21. WitikaBA,WalkerRB.Development, manufacture and characterization of niosomes for the delivery for nevirapine[J].Pharmazie,2019,74(2):91-96.DOI:10.1691/ph.2019.8168.

22. PopliP,MeduriRT,SharmaT,et al.Polymeric and lipidic nanoparticles in transforming anti-HIV combinational therapy: can they turn the tide?[J].Naunyn Schmiedebergs Arch Pharmacol,2025,398(10):13153-13172.DOI:10.1007/s00210-025-04169-w.

23. YanamadalaY,MuthumulaCMR,KhareS,slet.Strategies to enhance nanocrystal formulations for overcoming physiological barriers across diverse routes of administration[J].Int J Nanomedicine,2025,20:367-402.DOI:10.2147/IJN.S494224.

24. YangX,YuB,ZhongZ,et al.Nevirapine-polycaprolactone crystalline inclusion complex as a potential long-acting injectable solid form[J].Int J Pharm,2018,543(1-2):121-129.DOI:10.1016/j.ijpharm.2018.03.043.

25. MoehrleJJ.Development of new strategies for malaria chemoprophylaxis: from monoclonal antibodies to long-acting injectable drugs[J].Trop Med Infect Dis,2022,7(4):58.DOI:10.3390/tropicalmed7040058.

26. FlexnerC.Antiretroviral implants for treatment and prevention of HIV infection[J].Curr Opin HIV AIDS,2018,13(4):374-380.DOI:10.1097/COH.0000000000000470.

27. DinhL,BlackardJT,RobertsonJ,et al.An updated overview on long-acting therapeutics for the prevention and treatment of human immunodeficiency virus (HIV) from a perspective of pharmaceutics[J].Int J Pharm,2025,670:125157.DOI:10.1016/j.ijpharm.2024.125157.

28. 刘晓娜,车丽丽,王艳名,等.奈韦拉平新剂型的研究进展[J].中国药师,2017,20(1):148-150.LiuXN,CheLL,WangYM,et al.Research progress in new dosage forms of nevirapine[J].China Pharmacist,2017,20(1):148-150.DOI:10.3969/j.issn.1008-049X.2017.01.044.

29. Kelly-HankuA,SongtaweesinWN,PalmaresML,et al.The urgency of now to end HIV vertical transmission for pregnant and breastfeeding women and their children in Asia and the Pacific[J].Lancet Reg Health West Pac,2024,53:101248.DOI:10.1016/j.lanwpc.2024.101248.