In vitro evaluation of mucoadhesive vaginal tablets of antifungal drugs prepared with thiolated polymer and development of a new dissolution technique for vaginal formulations

The main objective of this work was to develop antifungal matrix tablet for vaginal applications using mucoadhesive thiolated polymer. Econazole nitrate (EN) and miconazole nitrate (MN) were used as antifungal drugs to prepare the vaginal tablet formulations. Thiolated poly(acrylic acid)-cysteine (PAA-Cys) conjugate was synthesized by the covalent attachment of L-cysteine to PAA with the formation of amide bonds between the primary amino group of L-cysteine and the carboxylic acid group of the polymer. Vaginal mucoadhesive matrix tablets were prepared by direct compression technique. The investigation focused on the influence of modified polymer on water uptake behavior, mucoadhesive property and release rate of drug. Thiolated polymer increased the water uptake ratio and mucoadhesive property of the formulations. A new simple dissolution technique was developed to simulate the vaginal environment for the evaluation of release behavior of vaginal tablets. In this technique, daily production amount and rate of the vaginal fluid was used without any rotational movement. The drug release was found to be slower from PAA-Cys compared to that from PAA formulations. The similarity study results confirmed that the difference in particle size of EN and MN did not affect their release profile. The release process was described by plotting the fraction released drug versus time and n fitting data to the simple exponential model: M(t)/M(∞)=kt(n). The release kinetics were determined as Super Case II for all the formulations prepared with PAA or PAA-Cys. According to these results the mucoadhesive vaginal tablet formulations prepared with PAA-Cys represent good example for delivery systems which prolong the residence time of drugs at the vaginal mucosal surface.     

Effect of processing consitions on the development of morphology in clay nanoparticle filled nylon 6 fibers

The effect of melt temperature on the phase behavior and preferential orientation development in Nylon 6/montmorillonite nanocomposites were investigated at melt spinning temperatures ranging from 230° to 250°C. The fibers were found to exhibit mostly γ crystalline form that is typical of Nylon 6 filled with montmorillonite nanoparticles. At higher take-up speeds α-crystals begin to appear in the crystalline phase. The presence of nanoparticles was found to impart substantial chain orientation levels even at low to moderate take up speeds reaching a plateau at moderate take up speeds. This was attributed to the increased spin line stress in the presence of nanoparticles that increase the overall viscosity due to their large contact areas with the polymer chains. This increased spinline tension was found to cause fiber breakup at moderate speeds. Increasing melt temperature from 230° to 250°C alleviated this problem.     

Structure‐dependent conductivity and microhardness of metal‐filled PVC composites

Metal‐filled composites of a commercial PVC (polyvinyl chloride) powder (mean particle size d_p ≈ 100 microns) and a metal powder (mean particle size d_f about 100 microns for copper, Cu, and about 10 microns for nickel, Ni) prepared by mechanical mixing in a ball mill, subsequent hot‐pressing at 443 K and rapid cooling to 300 K, were characterized by the room‐temperature measurements of electrical conductivity σ, density ρ and microhardness H. The sudden jumps of about 17 orders of magnitude followed by a much slower growth up to the limiting filler fraction ϕ* on the log σ vs. ϕ plots are the evidence for the onset of percolation transitions, at filler volume contents ϕ_c1 = 0.05 and 0.04 for PVC/Cu and PVC/Ni, respectively. For both systems, the values of H exhibited an initial steep increase up to ϕ_c2 = 0.07, followed by an apparent plateau extending up to ϕ = 0.18. However, drastic differences in the patterns of composition dependence of H were observed at higher metal loadings, i.e., a continuous increase of H up to the leveling‐off at ϕ* for PVC/Cu, in contrast to a sudden drop of H at ϕ = 0.20 and subsequent slow increase for PVC/Ni. For both composites the apparent density ρ′ of a polymer matrix remained the same as that of the neat PVC in the composition interval ϕ < 0.20, while at ϕ* > 0.20 a precipitous drop of ρ₁ was observed due to the formation of polymer‐free voids between filler particles (crowding effect) as ϕ approaches ϕ*. The observed effects were analyzed in terms of a tentative model envisaging cross‐overs from “dilute suspension regime” to “semi‐dilute suspension regime” in the concentration range ϕ_c1 to ϕ_c2, and from “semi‐dilute suspension regime” to “concentrated suspension regime” above ϕ = 0.20. Different behavior in this latter regime was explained by intrinsic differences in the structure of conductive infinite clusters between mixtures of particles of about the same size (PVC/Cu) and of widely different sizes (PVC/Ni).