Nanoformulated Eudragit lopinavir and preliminary release of its loaded suppositories

Abstract

The 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 increased significantly, from 49% in 2015 to 53% in 2017. However, this percentage is considerably lower than the 80% for pregnant 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 inhibitor first-line HIV treatment drugs but suffers from low aqueous solubility, bitter state, short half-life leading to a limited dissolution and variable bioavailability upon oral administration. This work focused on the fabrication and characterization of a delivery system entailing Eudragit RSPO-LPV nanoparticles loaded suppositories in two different bases to improve the bioavailability and overcome the problem encountered through oral administration emanating from poor solubility. The prepared nanoparticles by nanoprecipitation method were characterized and compounded into suppositories in fattibase and polyethylene glycol (PEG) bases using a melt fusion method. The suppositories were stored at 5 and 25 °C, 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 preliminary in vitro release studies were analysed by HPLC. The nanoparticles have an average particle size of 191 nm with spherical morphology, entrapment efficiency, polydispersity index and zeta potential of 79.0 ± 0.5%, 0.224, and 25.87 ± 0.41 mV respectively. The surface analysis of the nanoparticles with FTIR, SEM, PXRD and TGA indicated that the drug was truly encapsulated without any interaction. The in vitro release studies showed that a better release was observed in suppositories formulated with PEG than the fattibase by having higher drug concentration released. Hence, this rectal formulation might serve as an alternative for paediatric HIV treatment upon further investigation.

Keywords: Analytical chemistry; Chemistry; Eudragit; HIV paediatric; Health sciences; Melt fusion method; Nanoparticles; Organic chemistry; Pharmaceutical chemistry; Suppositories.

Figure 1

The chemical structure of lopinavir.

Figure 2

Diagrammatic representation of the preparation of Eudragit RSPO-LPV suppositories.

Figure 3

Particle size distribution by intensity as a function of particle size for Eudragit RSPO-nanoparticles.

Figure 4

SEM micrograph of Eudragit RSPO-LPV nanoparticles.

Figure 5

FTIR spectrum of (a) Eudragit RSPO-LPV nanoparticles, (b) LPV, (c) Eudragit RSPO.

Figure 6

XRD results where the y-axis represents counts per second and x-axis is theta degree; (a) Eudragit RSPO-LPV nanoparticles, (b) LPV, (c) Eudragit RSPO.

Figure 7

TGA curves where the y-axis represents heat flow (w/g) and the x-axis is the temperature (^oC); (a) Eudragit RSPO-LPV nanoparticles, (b) LPV, (c) Eudragit RSPO.

Figure 8

DSC thermograms where y-axis represents heat flow (w/g) and x-axis is the temperature (^oC); (a) Eudragit RSPO-LPV nanoparticles, (b) LPV, (c) Eudragit RSPO.

Figure 9

a. Stability results of Eudragit RSPO- LPV NPs in terms of mean particle size, entrapment efficiency (EE), zeta potential and polydispersity index (PDI) stored at 5 °C for 12 weeks. b. Stability results of the Eudragit RSPO- LPV NPs in terms of mean particle size, entrapment efficiency (EE), zeta potential and polydispersity index (PDI) stored at 25 °C and 60% ± 5% RH for 12 weeks.

Figure 10

The release studies profile where the y-axis represents percentage drug release and the x-axis is time (minutes); (a) Fattibase suppositories (b) LPV, (c) Eudragit RSPO-LPV nanoparticles, (d) PEG suppositories.