For small molecule parenteral formulation development, the interplay between solubility, local tolerance and systemic toxicity is key for a successful formulation development needing a minimum of resources and time. Our DPS experts have a significant experience in developing parenteral small molecule products and a track-record of bringing products to the clinic and the market.
Small molecules are often characterized by very low aqueous solubility, and this is the first challenge for delivering small molecules parentally. However when focusing only on solubility and stability during formulation development, there is a risk of detecting local tolerance limitations, systemic toxicity or hypersensitivity issues during preclinical testing, making a later reformulation necessary. Our parenteral formulation experts have an extensive track record in balancing these challenges so that reformulation is avoided.
The feasibility of different solubilisation techniques is systematically verified based on a formulation decision tree, which considers e.g. charge modification by pH adjustment, micellarisation, co-solvency, cyclodextrin-chelation, emulsification. Freeze drying is also proposed when appropriate. Complex drug dosage forms such as emulsions or liposomes are taken into consideration when no more straightforward techniques are possible, since these approaches entail significantly more resources and costs.
Our DPS experts have a significant experience in developing parenteral small molecule products and a track-record of bringing products to the clinic and the market.
The panel of drug product services for small molecule parenteral development includes:
- Optimized pre-formulation studies focussing on parenteral dosage forms
- Stress-testing (sensitivity towards oxygen, metal-ions, light, heat)
- In-silico evaluation of pre-formulation data and proposal of formulation types with high likelihood of success
- Comprehensive high throughput solubility studies
- In vitro haemolysis of heparinised human blood and miscibility with plasma as surrogate markers of local tolerance
- ICH stability studies
- In-use compatibility studies