(7) (PDF) Nanoformulated Eudragit lopinavir and preliminary release of its loaded suppositories

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Research articleNanoformulated Eudragit lopinavir and preliminary release of itsloaded suppositoriesLebogang Katata-Serua,*, Babatunde Moses Ojoa, Omotunde Okubanjob, Rebeccah Soremekunc,Oluwole Samuel AremuaaDepartment of Chemistry, Faculty of Natural and Agricultural Sciences, North-West University, Mmabatho, Mafikeng, 2735, South AfricabDepartment of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, University of Lagos, PMB 12003, Lagos, NigeriacDepartment of Clinical Pharmacy and Biopharmacy, Faculty of Pharmacy, University of Lagos, PMB 12003, Lagos, NigeriaARTICLE INFOKeywords:EudragitNanoparticlesSuppositoriesMelt fusion methodHIV paediatricChemistryAnalytical chemistryOrganic chemistryPharmaceutical chemistryHealth sciencesABSTRACTThe development of novel paediatrics formulations is critical towards achieving the UNAIDS 90-90-90 targets.According to the latest UNAIDS reports, the availability of antiretrovirals (ARVs) for children has increasedsignificantly, from 49% in 2015 to 53% in 2017. However, this percentage is considerably lower than the 80% forpregnant women that are currently on treatment. Therefore, there is still an urgent need for an alternative child-friendly delivery system. Lopinavir (LPV) is a protease inhibitorfirst-line HIV treatment drugs but suffers fromlow aqueous solubility, bitter state, short half-life leading to a limited dissolution and variable bioavailabilityupon oral administration. This work focused on the fabrication and characterization of a delivery system entailingEudragit RSPO-LPV nanoparticles loaded suppositories in two different bases to improve the bioavailability andovercome the problem encountered through oral administration emanating from poor solubility. The preparednanoparticles by nanoprecipitation method were characterized and compounded into suppositories in fattibaseand polyethylene glycol (PEG) bases using a melt fusion method. The suppositories were stored at 5 and 25C,and were sampled at 0, 4, 8, 12 weeks. The samples were assessed by particle size, entrapment efficiency (EE),zeta potential and polydispersity index (PDI) variations. The preliminaryin vitrorelease studies were analysed byHPLC. The nanoparticles have an average particle size of 191 nm with spherical morphology, entrapment effi-ciency, polydispersity index and zeta potential of 79.00.5%, 0.224, and 25.870.41 mV respectively. Thesurface analysis of the nanoparticles with FTIR, SEM, PXRD and TGA indicated that the drug was truly encap-sulated without any interaction. Thein vitrorelease studies showed that a better release was observed in sup-positories formulated with PEG than the fattibase by having higher drug concentration released. Hence, this rectalformulation might serve as an alternative for paediatric HIV treatment upon further investigation.1. IntroductionHuman immunodeficiency virus (HIV) is regarded as a major globalepidemic and a serious threat to public health, especially in manydeveloping countries (Lloyd-Sherlock et al., 2014). The recent statisticsshowed that 36.9 million people were living with HIV, 35.1 millionadults and 1.8 million children, respectively (UNAIDS, 2018). PaediatricHIV infection in children remains a significant health issue globally(Newell et al., 2004). Although, the survival of HIV-infected children hasimproved with increased access of 51% receiving treatment at the end of2017 when compared to 80% of HIV-infected pregnant women ontreatments (UNAIDS, 2018). These populations of children on treatmentwere still not acceptable when compared to the ratio of infected children,which is high. Therefore, drastic actions must be taken into cognizance inimproving paediatric HIV treatment in order to meet the millenniumdevelopment goal of 90–90–90 target of eradicating HIV prevalence by2030 (Joint United Nations Programme on HIV/AIDS (UNAIDS), 2017).One of the foremost leading components of highly active antiretro-viral therapy (HAART) applied for the treatment of HIV infections in bothadults and children is LPV. LPV, as depicted inFigure 1, is a potentprotease inhibitor (Maartens et al., 2014;Khan et al., 2019). It iscurrently being used, as a combination therapy with ritonavir (RTV) withlimited oral route therapy challenges (Pham et al., 2016). This currenttreatment which is based on oral administrations, has been shown to* Corresponding author.E-mail address:Lebo.Seru@nwu.ac.za(L. Katata-Seru).Contents lists available atScienceDirectHeliyonjournal homepage:www.cell.com/heliyonhttps://doi.org/10.1016/j.heliyon.2020.e03890Received 14 November 2019; Received in revised form 4 January 2020; Accepted 28 April 20202405-8440/©2020 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Heliyon 6 (2020) e03890