# Mesoporous Silica as an Alternative Vehicle to Overcome Solubility Limitations

## TL;DR

Researchers developed a mesoporous silica vehicle to safely administer corallopyronin A, a drug with poor solubility, in preclinical toxicology studies.

## Contribution

A novel mesoporous silica formulation was introduced to overcome solubility and tolerability issues in drug vehicle screening.

## Key findings

- The mesoporous silica vehicle enabled high-dose administration of corallopyronin A in Beagle dogs.
- The formulation achieved sufficient tolerability and high plasma concentrations.
- It provided a valuable alternative for drugs with poor aqueous solubility.

## Abstract

Toxicological studies are a part of the drug development process and the preclinical stages, for which suitable vehicles ensuring easy and safe administration are crucial. However, poor aqueous solubility of drugs complicates vehicle screening for oral administration since non-aqueous solvents are often not tolerable. In the case of the anti-infective corallopyronin A, currently undergoing preclinical investigation for filarial nematode and bacterial infections, commonly used vehicles such as polyethylene glycol 200, aqueous solutions combined with cosolvents or solubilizers, or aqueous suspension have failed due to insufficient tolerability, solubility, or the generation of a non-homogeneous suspension. To this end, the aim of the study was to establish an alternative approach which offers suitable tolerability, dissolution, and ease of handling. Thus, a corallopyronin A-mesoporous silica formulation was successfully processed and tested in a seven-day toxicology study focused on Beagle dogs, including a toxicokinetic investigation on day one. Sufficient tolerability was confirmed by the vehicle control group. The vehicle enabled high-dose levels resulting in a low-, middle-, and high-dose of 150, 450, and 750 mg/kg. Overall, it was possible to achieve high plasma concentrations and exposures, leading to a valuable outcome of the toxicology study and establishing mesoporous silica as a valuable contender for challenging drug candidates.