A dynamic mechanical method for determining the silicone elastomer solubility of drugs and pharmaceutical excipients in silicone intravaginal drug delivery rings

The silicone elastomer solubilities of a range of drugs and pharmaceutical excipients employed in the development of silicone intravaginal drug delivery rings (polyethylene glycols, norethisterone acetate, estradiol, triclosan, oleyl alcohol, oxybutynin) have been determined using dynamic mechanical analysis. The method involves measuring the concentration-dependent decrease in the storage modulus associated with the melting of the incorporated drug/excipient, and extrapolation to zero change in storage modulus. The study also demonstrates the effect of drug/excipient concentrations on the mechanical stiffness of the silicone devices at 37°C.

High speed DSC (hyper-DSC) as a tool to measure the solubility of a drug within a solid or semi-solid matrix

Conventional differential scanning calorimetry (DSC) techniques are commonly used to quantify the solubility of drugs within polymeric-controlled delivery systems. However, the nature of the DSC experiment, and in particular the relatively slow heating rates employed, limit its use to the measurement of drug solubility at the drug's melting temperature. Here, we describe the application of hyper-DSC (HDSC), a variant of DSC involving extremely rapid heating rates, to the calculation of the solubility of a model drug, metronidazole, in silicone elastomer, and demonstrate that the faster heating rates permit the solubility to be calculated under non-equilibrium conditions such that the solubility better approximates that at the temperature of use. At a heating rate of 400 degrees C/min (HDSC), metronidazole solubility was calculated to be 2.16 mg/g compared with 6.16 mg/g at 20 degrees C/min. (C) 2005 Elsevier B.V. All rights reserved.