Enavail’s Rapid Freezing (RF) technology uses a cryogenic substrate to create stable dry powders of drug compositions. Highly porous, amorphous, nanostructured morphologies enhance dissolution and thereby improve bioavailability for BCS Class II and IV drugs. With no introduction of heat into the process, RF eliminates premature thermal degradation of APIs –a critical benefit for labile proteins and peptides.

Rapid Freezing Process Advantages: Amorphous morphology Enhanced bioavailability and dissolution Capability of producing dry active forms of       labile proteins Highly potent APIs Proprietary   Diagram

Overhoff, K.A., et al., Eur. J. of Pharma . and Biopharma., 65:57-67 (2007)

Case Study 1: Rapid Freezing Engineering of Tacrolimus (TAC)

TAC is a hydrophobic macrolide antibiotic used as a potent immunosuppressant for treatment of transplanted organ rejection as well as different immunological diseases such as pulmonary fibrosis and bronchiolar asthma. It has 10 to 100 times more potent immunosuppressive properties compared to similar drugs and is currently available in both an intravenous and oral dosage forms. However, these dosage forms are either poorly tolerated or provide erratic absorption with mean oral bioavailability reported to be 25%, ranging from 4 to 93%.

GOAL: TO ACHIEVE HIGH SUPERSATURATION ENABLING IMPROVED BIOAVAILABILITY IN AN ORAL FORMULATION

Study Details

Formulation of TAC and Sodium Dodecyl Sulfate (SDS), Poly (vinyl alcohol) (PVA), or Poloxamer 407 (P407)

Amorphous oral formulation generated of TAC

Overhoff, K.A., et al., Pharma. Res., 25:167-175 (2008)

Overhoff, K.A., et al., Pharma. Res., 25:167-175 (2008)

Case Study 2: Rapid Freezing Engineering of Itraconazole (ITZ)

Itraconazole, a broad-spectrum antifungal drug for both prophylaxis and treatment of invasive fungal infections, has extremely low aqueous solubility (estimated at approximately 1 ng/mL at neutral pH, with a calculated log P of 6.2). Currently marketed products show low oral absorption and considerably varied pharmacokinetics in patients. Itraconazole levels of greater than 0.5 mcg/g in lung tissue or 0.5 mcg /mL in blood are generally required for adequate treatment of invasive fungal infections.

GOAL: TO ACHIEVE HIGH SUPERSATURATION ENABLING IMPROVED BIOAVAILABILITY IN AN ORAL FORMULATION

Study Details

ITZ and Cellulose Acetate Phthalate (1:2) formulation

Amorphous formulation of ITZ generated for oral delivery

Enavail process resulted in ~15 times higher surface area than micronized ITZ (45m2/g)

DiNunzio, J.C., et al., Molec. Pharma., 5:968-980 (2008).

DiNunzio, J.C., et al., Molec. Pharma., 5:968-980 (2008).