Scale-up prospects
Long-acting versions of atovaquone are currently in pre-clinical development.
Atovaquone’s physiochemical properties including its low systemic clearance and high hydrophobicity make it a suitable candidate for long-acting injectable (LAI) formulation.
Development approaches for solid-drug nanoparticle formulations focus on attrition methods or require the generation of drug-associated nano-carriers.
However, an alternative approach may instead utilise emulsion-templated freeze drying screening to identify high drug content solid-drug particles prior to scale-up by emulsion spray drying.
Tentative equipment list for manufacturing
Not provided
Manufacturing
Researchers as part of the LONGEVITY project have developed a preclinical LAI solid-drug nanoparticle (SDN) atovaquone formulation for intramuscular admin. Initially, a library of SDNs containing atovaquone in combination with surfactant and polymer stabiliser excipients was generated, creating a range of formulations composing of 80% atovaquone, 13% polymer and 7% surfactant using FDA-approved inactive ingredients. Formulations were retained if they met the following criteria: (1) SDN average diameter <1000nm, (2) full aqueous dispersion at 0.5 mg/ml, (3) uniformity of size and drug release.
Specific analytical instrument required for characterization of formulation
Dynamic light-scattering analysis equipment (e.g. using Malvern Zetasizer Nano ZS) to measure the Z-average diameter of solid drug nanoparticles to assess formulation stability.
