Hydrogel formulations for biologicals
Hydrogels are, from a commercial perspective especially because of their ease of production, attractive sustained-release systems for high potent immunoglobulins with short circulation half-lives. Hydrogel formulations can reduce the dosing frequency while maintaining therapeutically relevant drug concentrations locally as well as systemically. However, hydrogels have only limited loading capacities and release hydrophilic immunoglobulins typically within hours or days, whereas weeks or months would be more preferable. Despite an evident medical need, the call for novel depot formulations seems to go unheard. This special report explores sought-after hydrogel properties, discusses arguments for using established versus novel excipients and provides selected examples for hydrogel formulations of biologicals that have proceeded into clinical development.
Conclusion & future perspective
To conclude this brief spotlight on hydrogel formulations for biologicals, it appears that although substantial progress in the development of hydrogel technologies has been made, the commercialization of hydrogel formulations for sc. delivery remains challenging. There is no shortage of innovative academic hydrogel formulations , which encompass ever more features such as self-healing properties , responsive hydrogels to, for example, hyaluronidases or metalloproteases or hydrogels, which release their content by activating a trigger, for example, ultrasound. For the near future, however, the predominant formulation options for biologicals remain liquid and lyophilized formulations, which are administered iv. or sc. To widen the spectrum of proteins that could benefit when formulated in a hydrogel, the release period of hydrogels for hydrophilic molecules needs to be prolonged. To achieve this, additional diffusion barriers could be engineered into the matrix. To improve the drug loading capacity one could envision formulating amorphous solid or crystalline proteins instead of liquid solutions. These efforts as well as efforts for developing responsive hydrogels or triggered-release hydrogels need to come with as little complexity to the manufacturing procedure as possible and ideally without the use of novel excipients, organic solvents or heat. Success or failure of a next generation hydrogel formulation for biologicals will also depend on the success of suitable molecule formats, for example, high potent immunoglobulins and/or formats with short plasma half-lives. Further factors that drive the progress of hydrogel formulations are developments in global pharma markets and healthcare cost, as well as the competitive situation of biologicals and biosimilars, which may foster the progress from biosimilars to ‘biobetters’.