Bioequivalence and adhesion evaluation of transdermal clonidine following a change in excipient supplier.

OBJECTIVE: To evaluate the bioequivalence (BE), safety, tolerability, and adhesion of Oppanol® polyisobutylene (PIB)-containing transdermal therapeutic system (TTS) formulation (test treatment, T) with VistanexTM PIB-containing TTS formulation (reference treatment, R) of clonidine. METHODS: This randomized, double-blind, 2-way crossover study comprised a 7-day treatment with 0.3 mg clonidine/24 h (T1/R1), a 7-day washout, and another 7-day treatment (R1/T1) period. After a 3-day washout period, subjects used T2 and R2 (each 0.1 mg clonidine/24 h) simultaneously in the 7-day adhesion phase. Primary endpoints were AUC0-168 and Cavg. Secondary endpoints were AUC0-∞ and Cmax. Additional endpoints included adhesion properties for all phases. For the primary endpoint, the geometric mean (gMean) ratios for test/reference treatment were calculated with BE defined as 90% confidence interval (CI) between 80 and 125%. RESULTS: 58 subjects (mean age, 41.3 years) received treatment (T1/R1, n = 29; R1/T1, n = 29); 55 completed the adhesion phase. BE criteria were met for the primary and secondary endpoints. Adjusted gMean ratios for T1/R1 were 102.3% (90% CI: 95.7%, 109.4%) for AUC0-168; 104.3% (90% CI: 98.4%, 110.5%) for Cavg; 102.8% (90% CI: 97.3%, 108.6%) for AUC0-∞; and 104.0% (90% CI: 98.2%, 110.3%) for Cmax. Mean adhesion was greater than 90% for all four patch types when data from all assessment times were included. Most frequently reported adverse events were general disorders and local irritation. CONCLUSIONS: Clonidine Oppanol® PIB-containing TTS formulation was bioequivalent to VistanexTM PIB-containing TTS formulation and had similar adhesive properties. Both doses and formulations of clonidine-TTS were well tolerated.

The effect of three-dimensional morphology on the efficiency of hybrid polymer solar cells.

The efficiency of polymer solar cells critically depends on the intimacy of mixing of the donor and acceptor semiconductors used in these devices to create charges and on the presence of unhindered percolation pathways in the individual components to transport holes and electrons. The visualization of these bulk heterojunction morphologies in three dimensions has been challenging and has hampered progress in this area. Here, we spatially resolve the morphology of 2%-efficient hybrid solar cells consisting of poly(3-hexylthiophene) as the donor and ZnO as the acceptor in the nanometre range by electron tomography. The morphology is statistically analysed for spherical contact distance and percolation pathways. Together with solving the three-dimensional exciton-diffusion equation, a consistent and quantitative correlation between solar-cell performance, photophysical data and the three-dimensional morphology has been obtained for devices with different layer thicknesses that enables differentiating between generation and transport as limiting factors to performance.