Transdermal co-delivery of glucosamine sulfate and diacerein for the induction of chondroprotection in experimental osteoarthritis.

The aim of this work was to develop a transdermal delivery system consisting of a glucosamine sulfate-laden xanthan hydrogel containing a nanoemulsion-loaded diacerein. The system was intended to prevent cartilage degradation typical of osteoarthritis. The nanoemulsion, made of soybean oil as the oil phase; soybean lecithin, Tween 80, and poloxamer 407 as surfactants; and propylene glycol as cosurfactant, was formed within the hydrogel. The hydrodynamic diameter of the nanoemulsion globules was 81.95 ± 0.256 nm with 0.285 ± 0.036 of PDI value and the zeta potential value of the formulation was 39.33 ± 0.812 mV. CryoSEM and TEM studies revealed the uniform morphology of the vehicle. A rheological study exposed the nanoemulsion-loaded hydrogel as a thixotropic system. Satisfactory storage stability under ICH conditions was established by the zeta potential and rheological studies. Furthermore, skin biocompatibility of the hydrogel was ascertained on the basis of skin irritation study. Additionally, the diffusion of the drugs across rat skin followed a controlled non-Fickian anomalous steady mechanism. Following in vivo administration in experimental osteoarthritis, the transdermal hydrogel showed a reduction in tumor necrosis factor-alpha, C-reactive protein, high mobility group box protein, and monocyte chemoattractant protein-1. Finally, histopathological analysis of the animals showed satisfactory chondroprotection in the in vivo study. In conclusion, the developed transdermal systems showed a potential against the progression of experimental osteoarthritis.

Accentuated transdermal application of glucosamine sulphate attenuates experimental osteoarthritis induced by monosodium iodoacetate.

Osteoarthritis is a chronic degenerative joint disease causing pain and disability. Glucosamine sulphate is a well known oral supplement for its treatment. The present pioneering study provides an overview of the accentuated transdermal delivery of glucosamine sulphate through the optimized gel formulation with guar gum and sodium carboxymethyl cellulose (Na-CMC). Response surface methodology based on the three-level three-factor central composite design provided the optimum concentration of guar gum, Na-CMC and glycerol for a maximum flux. The transdermal characterization, ex vivo permeation study and in vivo study were performed with optimized gel formulation. The factorial design predicted the optimum values of guar gum, Na-CMC and glycerol which were 418.53 mg, 444.97 mg and 2322.4 mg respectively for 25 g of the gel. This optimized gel demonstrated the maximum flux, i.e., 1047.46 µg cm-2 h-1. The optimized gel showed satisfactory results with respect to drug uniformity, pH, stability, rheological properties, zeta potential, drug-excipient compatibility and skin irritation. The release of the drug from the optimized transdermal gel followed the controlled first order Fickian (non-steady) release pattern. The in vivo study was carried out in a rat model of osteoarthritis induced by monosodium iodoacetate damaging the tibial plateau. In this study the optimized formulation effectively reduced the symptoms like reduction in swelling of the knee joint, gross changes in digitized radio images and morphological and histopathological alterations. Additionally the changes in the release pattern of the proinflammatory cytokine tumor necrosis factor-α illustrated the efficacy of the transdermal gel for the treatment of experimental osteoarthritis. Thus the optimized gel was found to be a unique potential vehicle for transdermal application of glucosamine sulphate which effectively attenuates the experimental osteoarthritis.

Novel Starch-PVA Polymer for Microparticle Preparation and Optimization Using Factorial Design Study.

The aim of our present work was to optimize the ratio of a very novel polymer, starch-polyvinyl alcohol (PVA), for controlled delivery of Ornidazole. Polymer-coated drug microparticles were prepared by emulsion method. Microscopic study, scanning electron microscopic study, and atomic force microscopic study revealed that the microparticles were within 10 micrometers of size with smooth spherical shape. The Fourier transform infrared spectroscopy showed absence of drug polymer interaction. A statistical 3(2) full factorial design was used to study the effect of different concentration of starch and PVA on the drug release profile. The three-dimensional plots gave us an idea about the contribution of each factor on the release kinetics. Hence this novel polymer of starch and polyvinyl alcohol can be utilized for control release of the drug from a targeted delivery device.

A comparative study of two separate analytical techniques for the simultaneous determination of diclofenac sodium and diacerein from combined dosage form

ABSTRACT Diclofenac sodium (DS) and diacerein (DC) have emerged as a potential combination therapy for the treatment of knee osteoarthritis. Therefore a validated analytical method is essential for the simultaneous estimation of both from combined dosage form. A ratio derivative spectrophotometric and a chromatographic technique have been developed for the simultaneous determination of DS and DC. The quantification was done at 263.00 nm for DC and 304.50 nm for DS in the first method, whereas 257 nm for DC and at 274 nm for DS for LC-DAD analysis in chromatographic method using acetate buffer and methanol as the mobile phase at a flow-rate 0.50 mL/min. Both of these methods are found to be linear in the concentration range under study with r2 value 0.999 and 0.996 for DS and DC respectively in ratio derivative spectroscopy and 0.998 and 0.999 for DS and DC respectively in LC-DAD study. Both of these methods are found to be accurate and precise, though greater robustness and precision is observed with chromatographic analysis over the ratio derivative spectroscopy. Statistically there was no significant difference between proposed ratio derivative spectrophotometric and LC-DAD methods.