Possible solutions include: 15% Solutol HS 15 + 10% Cremophor EL + 35% PEG400 + 40% Water.

HPMC-related solutions include: 0.5% HPMC/Saline water, 0.5% HPMC/0.2% Tween-80 in Saline water.

HPMCAS currently has no recommendations.

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1) 0.5% CMC-Na (suspending vehicle) What it is: carboxymethylcellulose sodium — classic aqueous suspending agent for poorly soluble drugs.Feasibility: Good for producing a suspension at 8 mg/mL if olorofim is poorly water-soluble (i.e., you’ll have dispersed particles rather than a true molecular solution). 0.5% w/v CMC provides acceptable viscosity for gavage and helps keep particles suspended during dosing.Practical tips: Include a wetting/surfactant aid (e.g., 0.1% Tween-80 or 0.2% polysorbate) to improve dispersion/wetting of hydrophobic particles. Micronize drug (sieving / milling) to 5–10 min.Notes: micronize drug to

For oral olorofim (8 mg/mL, 20 mL gavage), the safest, non-toxic solubilizing options are:

0.5% CMC-Na → good for suspension, safe and widely used in rodents.

PEG 300 + saline (1:1) → enhances solubility, generally well tolerated at gavage volumes.

HPMCAS / HPMC-AS → better for solid dispersions than simple gavage; useful if you plan a pre-formulated dosage form, but less practical for direct dosing.

👉 For your case, start with 0.5% CMC-Na or PEG 300:saline; reserve HPMCAS/HPMC-AS for advanced formulations.

• Target concentration: 8 mg/mL
• Dose volume: 20 mL
• Drug required per gavage = 8 mg/mL × 20 mL = 160 mg (per animal)

Option A — 0.5% CMC-Na suspension (recommended first choice for repeated dosing)

Good for: safe, non-toxic suspension vehicle; widely used in rodents; low systemic interaction.

Prepare a single 20 mL dose

Notes / safety

• CMC-Na 0.5% is well tolerated orally in rodents.
• Suspension will not solubilize the drug — measure delivered content by HPLC on the prepared suspension to confirm actual mg/mL (recommended).
• Keep at room temp for immediate use; if storing short-term, refrigerate and re-suspend before use. Discard after 24–48 hrs unless stability data say otherwise.
• Run a pilot (n=3) to check tolerability and observe for regurgitation/aspiration.

Option B — PEG 300 : Saline (1:1) solution (higher solubilizing power; use with caution)

Good for: improved solubility and faster absorption. Use for single-dose PK or when suspension homogeneity is a problem.

Prepare a single 20 mL dose

Notes / safety

• PEG 300 is generally tolerated for single gavage in rodents at common volumes, but species and volume limits vary. Always check local institutional guidance.
• Avoid repeated high-percentage PEG dosing without tolerability data.
• For chronic dosing prefer lower PEG fraction or alternate vehicle (e.g., dilute PEG further or use Captisol/Cyclodextrin).
• Assay final solution by HPLC if possible. Run pilot tolerability (n=3) and check body weight, behavior, and liver enzymes if you plan repeat dosing.

Option C — HPMC-AS (HPMCAS) / HPMC-AS-based solid dispersion (for pre-formulated solid oral dosage)

Good for: solid oral formulations (tablets/capsules) or suspensions made from an ASD. Not suited to direct gavage without prior formulation (requires spray-drying / HME).

Practical note: if you want a translational test of an ASD, produce a small-scale spray-dried ASD (e.g., drug:HPMCAS 1:2–1:4 w/w) then suspend the milled ASD in 0.5% CMC for gavage. Expect improved exposure but stability/processing required.

General practical & safety checklist (must do before dosing)

Quick comparison (summary)

• 0.5% CMC-Na — safest for repeat dosing, suspension, low systemic interaction. Best first-line.
• PEG 300:Saline (1:1) — better solubilization and likely higher systemic exposure; use for single-dose PK or when suspension fails. Monitor for PEG-related effects.
• HPMCAS/HPMC-AS — best for real formulation development (ASD), not for quick gavage without formulation work