Influence of ferrous sulfate on the solubility, partition coefficient, and stability of mycophenolic acid and the ester mycophenolate mofetil.

Studies were performed to (1) evaluate whether the presence of iron affected the physicochemical properties of mycophenolate mofetil (MMF) and mycophenolic acid (MPA), and (2) determine whether alteration of these properties was indicative of formation of an MMF-iron complex. The solubility, stability (chemical reactivity), and partitioning properties of MMF and MPA were evaluated over a pH range of 2-7 in the presence and absence of ferrous sulfate. In addition, the solubility and partitioning properties of MMF were assessed after the MMF drug product, CellCept capsules, was combined with an iron tablet (Fero-Gradumet, ferrous sulfate, tablets).

Sterile filtration of a parenteral emulsion.

The Syntex adjuvant formulation (SAF) containing [thr1]-muramyldipeptide in an oil-in-water emulsion has proven to be an effective adjuvant eliciting both cell-mediated and humoral immune response. As a parenteral emulsion, sterility of the final product was a concern, and various methods of achieving sterility were considered. For emulsions, most conventional sterilization methods are not viable, requiring the more cumbersome technique of sterilizing individual components and assembling/manufacturing under sterile conditions.

Formulation of vaccine adjuvant muramyldipeptides. 3. Processing optimization, characterization, and bioactivity of an emulsion vehicle.

An efficacious vaccine adjuvant which elicits both cell-mediated immunity (CMI) and humoral immune response was developed using [thr1]-Muramyldipeptide (MDP) in an oil-in-water emulsion vehicle containing poloxamer 401, polysorbate 80, and squalane. Processing optimization was performed to increase the physical stability of this adjuvant emulsion which, when prepared by conventional mixing methods, demonstrated good bioactivity but poor physical stability. Various manufacturing methods were compared with a microfluidization process, which produced the most stable and elegant emulsion vehicle.

In vitro and in vivo studies evaluating a liposome system for drug solubilization.

A liposome system was developed which demonstrates suitability as an intravenous drug carrier for a lipophilic drug compound (RS-93522, a dihydropyridine CA2+ channel blocker). An aqueous phospholipid suspension was employed as a nontoxic solubilizing vehicle for this drug. The liposome formulation, composed of a 3% mixture of dioleoylphosphatidylcholine and dioleoylphosphatidylglycerol, produced a physically and chemically stable preparation which solubilized the lipophilic drug compound at a concentration 500 times above its intrinsic aqueous solubility.