Combining the benefits of nanocrystals (high stability and dissolution rate) and amorphous dispersions (high supersaturation) in a dosage form capable of higher drug loading and faster formulation design.
Solid State Stability
We control the chemistry of our hydrogels to spontaneously transform an API into nanocrystals within the mesh of the three-dimensional covalently cross-linked polymer network.
Hydrogels decompose into solubility enhancing polymers while releasing nanocrystalline API, which improve the dissolution rate and solubility above levels that either can achieve independently.
High Drug Loading
Hydrogels are initially composed by as little as 10% (by volume) polymer and can be made to swell to further increase the remaining volume of nanopores to load with API.
See more details in our peer-reviewed publication in the journal Small.
A Platform Technology
Current formulation techniques (e.g., nanocrystals, amorphous dispersions, and lipid formulations or LBDDS) to improve drug solubility are effective for compounds with specific combinations of physical properties (e.g., melt temperature and lipophilicity or LogP). In many cases, a given API falls within the region where multiple formulations and manufacturing methods (e.g., HME, hot melt extrusion, and SDD, spray dried dispersions) may be effective, which requires extensive formulation studies to determine the best option.
In contrast, hydrogels can serve as an effective delivery vehicle for essentially any compound due to their chemical versatility. As a result, hydrogels can dramatically simplify the formulation development process. Their robust mechanical properties make hydrogels uniquely capable of transforming lipid formulations and liquid APIs into oral solid dosages. Further, the solution processing utilized for drug loading is a preferred approach for handling highly potent drugs (HPAPIs) as opposed to powder processing.
An Excipient and a Final Dosage Form
Nano-templated hydrogels are pre-formed oral dosages that simplify drug product design and manufacturing to accelerate clinical translation and improve performance.
Due to the sensitive dependence of critical processing parameters (CPPs) on critical material attributes (CMAs) and their combined influence on the desired critical quality attributes (CQAs), each process that a drug product is exposed to during manufacturing (see the figure above) must be designed and qualified using an extensive quality by design (QbD) process.
Since several processes are required to produce tablets using currently available solubility enhancing formulations, a "fit-for-purpose" dosage is used in early stage development to minimize the investment into potentially failed APIs then converted into a commercially viable tablet during clinical trials.
Hydrogels as pre-formed tablets avoid the need for excipient compatibility studies and therefore drastically accelerate early stage formulation design. The minimal impact of process parameters of drug product performance avoids significant manufacturing modifications and can significantly accelerate scale-up and process validation required for clinical translation.
Despite their versatility and simplicity, hydrogels are capable of improving the solubility and controlling the release profile through their polymer chemistry before and after decomposing upon ingestion. The result is a stable dosage form that achieves immediate release up to high levels of supersaturation in physiologically relevant media. These release profiles are consistent despite varying from 30% to 60% by weight of drug substance.