Controlled Precipitation (CP) is a novel process which can provide highly controllable particle size, continuous production, as well as flexibility of amorphous or crystalline forms of the API while achieving high drug loading.

Controlled Precipitation Process Advantages: Morphology capabilities Crystalline or amorphous Enhanced bioavailability and dissolution Controllable particle size Choice of excipient Highly potent APIs Proprietary   Diagram

Rogers, T.L., et al., Pharma .Res., 21:2048-2057 (2004)

Case Study: Controlled Precipitation of Cyclosporine A

CsA is a cyclic undecapeptide used for immunosuppression in organ transplantation patients, autoimmune diseases, and chronic and inflammatory conditions (e.g. asthma). It is highly lipophilic and very poorly water soluble (log P of 4.3; solubility of 7.3 mcg/mL in water). The delivery of therapeutic effective amounts of CsA to lung tissue with oral or parenteral formulations can cause severe renal and liver toxicity. Additionally, the bioavailability of oral CsA formulations has been highly variable in clinical trials.

GOAL: TO ACHIEVE HIGH SUPERSATURATION WITH ENHANCED LUNG DELIVERY AND SYSTEMIC LEVELS BELOW TOXIC LIMITS

Study Details

• Formulation of CsA and Polysorbate 80 (10:1)
• Amorphous nanoparticle aqueous dispersion of CsA generated for pulmonary delivery
• Achievement of aerosols delivered to mice via nebulization (8.4 mg/ml CsA)