Abstract:
The objective of this study was to determination of critical manufacturing parameters (CMP) and their influences on drug release of fentanyl transdermal reservoir patches (RPs). Fentanyl as a common drug administered by RPs was used as a model for drug release testing. Drug release studies were carried out using paddle over disk (USP apparatus 5). The critical manufacturing parameters (CMP) may potentially influence on rheological properties of hydroxyethyl cellulose (HEC) gels include gelation temperature and hydration time of polymer. Rheological characterizations were examined using a spindle type rheometer with a thermostatic water pump bath. The results indicated that the viscosity and consistency of 3% gel made in 60°C was suitable for fentanyl RPs and showed desired drug release over 72 h. While the release of fentanyl from gel made in 40°C reached its maximum within 48 h. Increasing the HEC concentration or in gelation temperature, both significantly decreased the release rate of fentanyl. In contrast, the hydration time of polymer did not affect significantly on drug release. Flow curve of HEC gels showed non-Newtonian characteristics, pseudo-plasticity for 2% gel and Bingham behavior for 3% or more. Gels with 3% concentrations showed some thixotropy. The thixotropic coefficient (M) and yield value (f) were 417 mPa s and 820 dynes cm^-2.

Keywords: Fentanyl, Critical Manufacturing Parameters, Rheological Properties, Transdermal Patches, Drug Release.