Benzoyl Peroxide Solubility and Stability in Hydric Solvents

Saturated solubility and reaction rate constants for the decomposition of benzoyl peroxide in solution and suspension were determined for use in formulation development. The solvents studied included ethanol, propylene glycol, and cosolvent mixtures of PEG 400 and water. The solubility of benzoyl peroxide was inversely related to the solvent polarity, with greater solubility occurring with semipolar solvents. The stability of benzoyl peroxide in solution was dependent on the solvent, concentration of benzoyl peroxide, and temperature. The compound was least stable in PEG 400. Stability was improved when water was added to PEG 400. Similar solvent effects were observed in suspension. In benzoyl peroxide suspensions of PEG 400 and PEG 400/water blends, benzoyl peroxide stability was dependent on solubility, with improved stability occurring in blends where the benzoyl peroxide was least soluble. Thus, solution formulations of benzoyl peroxide in pharmaceutically acceptable solvents are unlikely to show good stability; however, suspension formulations should be reasonably stable if the vehicle is selected to provide low benzoyl peroxide solubility.     

The effect of glucose and copper on the stability of diatrizoic acid

Hypaque Sodium Oral Solution is used as a X-ray contrast agent. The active ingredient is diatrizoate sodium. Several bottles of drug product were found to contain elevated levels of inorganic iodide, ranging from 0.001% (w/v) to 0.036% (w/v). The USP specification is no more than 0.02% w/v. The formulation contains sucrose as a sweetener and as a viscosity modifier. It was found that elevated levels of iodide were directly related to the amount of glucose found in the formulation. Glucose is a reducing sugar which can be generated by the decomposition of sucrose. Solution stress studies containing diatrizoate sodium and varying amounts of glucose and copper were conducted at three different pH values: 6, 7 and 8 in phosphate buffer at 60 degrees C. The decomposition of diatrizoate sodium was monitored by HPLC. The greatest amount of decomposition occurred in those solutions prepared in pH 8 phosphate buffer and containing both copper and glucose. It is suggested that glucose reacts with copper to form an activated species, which reacts to displace an iodide.     

Distribution and fate of diethyl malonate and diisopropyl fluorophosphate on pig skin in vitro

The in vitro distribution and fate of [14C]diethyl malonate and [14C]diisopropyl fluorophosphate were evaluated on normal and heat-treated pig skin. The extent of hydrolysis from the skin surface, skin, and receptor fluid was determined. A significant skin-mediated hydrolysis (15-35% of applied dose) was observed for diethyl malonate in normal skin, but not in heat-treated skin. These results indicated that a heat labile process (e.g., enzymatic hydrolysis) was in part responsible for the degradation of diethyl malonate after topical application to normal skin. Heat treatment tripled the skin penetration of diisopropyl fluorophosphate and reduced the amount of recovered hydrolysis product, diisopropyl phosphoric acid. Enzymatic and spontaneous hydrolysis, as well as impurity, accounted for the presence of degradation product.