mobic and Hemolysis

The aim of the present investigation was to develop a nanoemulsion (NE) gel formulation for the transdermal delivery of meloxicam (MLX) in order to ensure maximum controlled and sustained drug release capacity.. The MLX containing NE gel was prepared and characterized for particle size, zeta potential, pH, rheology, in vitro drug release, in vitro skin permeation, and in vitro hemolysis. Differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) of MLX-NE gel treated rat skin was performed to investigate the skin permeation mechanism of meloxicam from NE gel. Skin permeation potential of the developed gel formulation was assessed using confocal laser scanning microscopy (CLSM). The in vivo toxicity of MLX-NE gel was assessed by histopathological examination in rat. The rat paw edema test was performed to evaluate the anti-inflammatory activity of MLX-NE gel.. Percutaneous absorption studies demonstrated a higher permeation of meloxicam from NE gel, than the drug solution. FTIR and DSC studies supported stratum corneum lipid extraction as a possible penetration enhancer mechanism for MLX-NE gel. CLSM studies confirmed the permeation of the NE gel formulation to the deeper layers of the skin (up to 130 μm). MLX-NE gel turned out to be non-irritant, biocompatible, and provided maximum inhibition of paw edema in rats over 24 h in contrast to MLX solution.. The nanoemulsion gel formulation may hold promise as an effective alternative for the transdermal delivery of meloxicam.

Topics: Administration, Cutaneous; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Chemical Phenomena; Disease Models, Animal; Edema; Female; Gels; Hemolysis; Humans; Male; Meloxicam; Nanotechnology; Particle Size; Rats; Rheology; Skin; Skin Absorption; Surface Properties; Thiazines; Thiazoles

Meloxicam is a new non-steroidal anti-inflammatory drug (NSAID) which has potent anti-arthritic activity and a reduced potential to induce gastric irritation in animals. The present series of animal studies investigated the local and/or systemic tolerance of meloxicam formulations: intravenous, intramuscular and subcutaneous injections, eye-drops, gel and suppositories. The concentration and formulations were as intended for therapeutic use in man. An in vitro haemolysis test demonstrated that the parenteral formulation of meloxicam produced only minimal haemolysis. In comparison, NSAIDs such as piroxicam, ketoprofen and indomethacin showed comparable haemolysis only after dilution. Diclofenac and ibuprofen caused considerable haemolysis even when diluted. In all studies, the local tolerance of meloxicam was good and did not differ from placebo, even when administered daily for 4 weeks. Few abnormal histopathological findings indicative or organ toxicity were observed. There were only small, transient macroscopic changes at the site of administration, with no striking histopathological changes directly attributable to meloxicam. Intramuscular piroxicam and diclofenac, however, resulted in development of an extensive, solitary necrotic area. Other formulations tested were also very well tolerated. In conclusion, all meloxicam formulations tested exhibited excellent tissue tolerability. Therefore, meloxicam appears to be suitable for parenteral, dermal and mucosal administration.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Drug Tolerance; Female; Gels; Guinea Pigs; Hemolysis; Injections, Intramuscular; Injections, Intravenous; Injections, Subcutaneous; Male; Meloxicam; Ophthalmic Solutions; Rabbits; Rats; Suppositories; Thiazines; Thiazoles