Nano- & Micro-Crystallization

Integral BioSystems has internal expertise in formulating suspension-based formulations for hydrophobic compounds, particularly for ophthalmic disorders both back-of-the-eye and front-of-the-eye. If your company is considering an ophthalmic injectable with a hydrophobic compound to the back-of-the-eye or a suspension eye-drop, contact us for a discussion. 

Considerations for Ophthalmic Suspensions:

The vitreous is largely comprised of a viscous mixture of biological polymers that generate a “gel-like” consistency. The vitreous humor consists of Hyaluronic acid and GAG collagens, which is an anionic polymer with high molecular weight (~2-4 million Da) and collagen fibers that provide strength and resistance to shear forces. Hyaluronic acid is anionic and thus bears an overall negative charge.

Fluid turnover from the vitreous is quite restricted, unlike any other space in the body, where there is substantial fluid turnover. In terms of transport within the vitreous, both small molecules and large molecules are known to diffuse through the vitreous and are not restricted by the molecular size of the therapeutic.  

drug micro-crystalsIn the vitreous, the injection volume is limited to 50 microliters, using a needle gauge of 31G. Thus, the entire dose would need to be contained in 50 microliters. 

Additionally, dose regimen would need to be infrequent. Frequent injections to the back of the eye, can lead to retinal detachment and endophthalmitis. Thus, injectable sustained-release options are warranted for successful therapy to the vitreous. 

Particulates that are between 15-35 microns can be injected via 31G needles into the vitreous. The suspension is dispersed in a buffered vehicle of pH 7.4. The stability of the drug substance is unknown, as is its inherent crystallinity. In considering a suspension formulation, crystallinity of the compound and the stability of the microstructure thereof, is a critical attribute. This is due to varying polymorphs that can result, by shifting of the crystalline behavior, also resulting in inconsistencies in solubility characteristics. In a suspension formulation, the efficacy of the drug product is directly related to the rate of solubilization; the solubilization characteristics can change if the drug suspension shifts in crystalline microstructure. Thus, the suspension formulation should be characterized well, in terms of microstructure

Collaborate with Our Nano- & Micro-Crystallization Experts!

Ready to develop innovative suspension-based formulations for challenging ophthalmic disorders? Partner with Integral BioSystems to leverage our internal expertise in formulating hydrophobic compounds, specifically tailored for back-of-the-eye and front-of-the-eye applications. Let’s collaborate to overcome the unique considerations of ophthalmic suspensions, ensuring optimal efficacy and patient safety. Contact us today for a discussion on how we can elevate your ophthalmic injectable or suspension eye-drop to the next level of success!