Viscoelastic evaluation of topical creams containing microcrystalline cellulose/sodium carboxymethyl cellulose as stabilizer
The purpose of this study was to examine the viscoelastic properties of topical creams containing various concentrations of microcrystalline cellulose and sodium carboxymethyl cellulose (Avicel® CL-611) as a stabilizer. Avicel CL-611 was used at 4 different levels (1%, 2%, 4%, and 6% dispersion) to prepare topical creams, and hydrocortisone acetate was used as a model drug. The viscoelastic properties such as loss modulus (G), storage modulus (G), and loss tangent (tan δ) of these creams were measured using a TA Instruments AR 1000 Rheometer and compared to a commercially available formulation. Continuous flow test to determine the yield stress and thixotropic behavior, and dynamic mechanical tests for determining the linear viscosity time sweep data, were performed. Drug release from the various formulations was studied using an Enhancer TM Cell assembly. Formulations containing 1% and 2% Avicel CL-611 had relative viscosity, yield stress, and thixotropic values that were similar to those of the commercial formulation. The elastic modulus (G) of the 1% and 2% formulation was relatively high and did not cross the loss modulus (G), indicating that the gels were strong. In the commercial formulation,G increased after preshearing and broke down after 600 seconds. The strain sweep tests showed that for all formulations containing Avicel CL-611, theG was aboveG with a good distance between them. The gel strength and the predominance ofG can be ranked 6%>4%>2%. The strain profiles for the 1% and 2% formulations were similar to those of the commercial formulation. The δ values for the 1% and 2% formulations were similar, and the formulations containing 4% Avicel CL-611 had lower δ values, indicating greater elasticity. Drug release from the commercial preparation was fastest compared to the formulations prepared using Avicel CL-611, a correlation with the viscoelastic properties. It was found that viscoelastic data, especially the strain sweep profiles of products containing Avicel CL-611 1% and 2%, correlated with the commercial formulation. Rheological tests that measure the viscosity, yield stress, thixotropic behavior, other oscillatory parameters such asG andG are necessary tools in predicting performance of semisolids.
Rheological Characterization of Petrolatum Using a Controlled Stress Rheometer
The current study focuses on characterizing the rheological characteristics of different petrolatum grades using a controlled stress rheometer. Both steady-state flow and dynamic oscillatory tests were conducted on the petrolatums. The thermorheological scans were found to be the most informative and reproducible for this study. Significant differences in the structure were observed between the petrolatum grades. The structural differences were found to be most significant in the temperature range 25–35°C. The findings from this study will help in identifying the critical parameters (for e.g., temperature, mixing) during the processing and handling of such materials, which can have a direct impact on the product rheology and performance.
Pharmacokinetics of Mivacurium Isomers and Their Metabolites in Healthy Volunteers after Intravenous Bolus Administration
Background Previous studies report the pharmacokinetics of mivacurium isomers after an infusion using venous blood sampling. Although the extent of the mivacurium arterial‐venous gradient is not known, the sampling site is likely to influence mivacurium pharmacokinetic parameters because the drug is rapidly metabolized as it traverses the circulation. The objectives of this study were (1) to determine the pharmacokinetics of mivacurium isomers in healthy persons after intravenous bolus administration using intensive arterial blood sampling, and (2) to characterize the formation and elimination of mivacurium metabolites in human plasma. Methods Eight persons classified as American Society of Anesthesiologists physical status 1 or 2 who were scheduled to undergo elective surgery under balanced anesthesia received 0.15 mg/kg mivacurium chloride as an intravenous bolus. Arterial blood samples were collected every 10 s during the first 2 min and at frequent intervals for 4 h thereafter. Plasma concentrations of mivacurium isomers and their metabolites were determined by two stereoselective high‐performance liquid chromatographic methods coupled with fluorometric detection and noncompartmental pharmacokinetic parameters. Results Mean elimination half‐lives of the trans‐trans, cis‐trans, and cis‐cis isomers were 2.4, 2, and 28.5 min, respectively, with corresponding mean plasma clearances of 29.2, 45.7, and 6.7 ml [center dot] min‐1 [center dot] kg‐1. The volumes of distribution at steady state of the trans‐trans, cis‐trans, and cis‐cis isomers were 0.047, 0.054, and 0.189 l/kg, respectively. Plasma concentrations of monoester and alcohol metabolites peaked 25 s (median) after mivacurium injection, with half‐lives in the range of 90 min, except for the cis alcohol metabolite, which was only negligibly and transiently formed. Conclusions Substantial hydrolysis of mivacurium isomers by cholinesterases was confirmed by the rapid appearance of mivacurium metabolites in plasma. The intensive arterial sampling proved to be critical for the trans‐trans and cis‐trans isomers because the area under the curve between 0 and 2 min accounted for 75% and 86% of the total, respectively.