Tablet formulation studies on nimesulide and meloxicam-cyclodextrin binary systems

The objective of this work was to develop tablet formulations of nimesulide-β-cyclodextrin (NI-β-CD) and meloxicam-γ-cyclodextrin (ME-γ-CD) binary systems. In the case of nimesulide, 3 types of binary systems—physical mixtures, kneaded systems, and coevaporated systems—were studied. In the case of meloxicam, 2 types of binary systems—physical mixtures and kneaded systems—were investigated. Both drug-CD binary systems were prepared at 1∶1 and 1∶2 molar ratio (1∶1M and 1∶2M) and used in formulation studies. The tablet formulations containing drug-CD binary systems prepared by the wet granulation and direct compression methods showed superior dissolution properties when compared with the formulations of the corresponding pure drug formulations. Overall, the dissolution properties of tablet formulations prepared by the direct compression method were superior to those of tablets prepared by the wet granulation method. Selected tablet formulations showed good stability with regard to drug content, disintegration time, hardness, and in vitro dissolution properties over 6 months at 40°C±2°C and 75% relative humidity. Published: May 11, 2007     

Relationship between cyclooxygenase 1 and 2 selective inhibitors and fetal development when administered to rats and rabbits during the sensitive periods for heart development and midline closure

BACKGROUND: A review of the scientific literature suggested the occurrence of low‐level incidences of ventricular septal defect (VSD) and midline defect (MD) in rat fetuses and diaphragmatic hernia (DH), VSD, and MD in rabbit fetuses after maternal exposure to nonsteroidal anti‐inflammatory drugs (NSAIDs). Aspirin, an NSAID that irreversibly inhibits cyclooxygenase 1 (COX‐1) and COX‐2, induces DH, VSD, and MD when administered as one dose during the sensitive periods of development in rats. Unlike aspirin, other NSAIDs, including selective COX‐2 inhibitors, reversibly inhibit COX activity. To evaluate whether the dysmorphogenesis observed after maternal NSAID exposure correlates with COX‐1 or COX‐2 inhibition, a series of compounds with different capacities to inhibit COX‐1 and COX‐2 were administered to pregnant rats and rabbits during the sensitive period for heart development and midline closure. METHODS: The compounds selected, ranked from the most COX‐2 selective to the most COX‐1 selective based on COX inhibition in a human whole blood assay, were CJ‐19,209, meloxicam, diclofenac, diflunisal, ibuprofen, and ketorolac. Rat dams were treated on gestation days (GDs) 9 and 10, and rabbit does were treated on GDs 9, 10, and 11. The doses selected for evaluation represented the maximum tolerable dose for the compound, with the exception of CJ‐19,209, which was dosed at 1000 mg/kg. Fetuses were collected by cesarean section on GDs 21 and 29 for rats and rabbits, respectively, and all fetuses were examined for external and visceral developmental anomalies. RESULTS: In rabbits, diflunisal induced DH, VSD, and MD (omphalocele) and single incidences of VSD and MD (gastroschisis) were noted in the ibuprofen group; no other developmental findings were associated with treatment. In rats, ibuprofen, diflunisal, and ketorolac induced increases in the incidence of VSD. In general, the induction of developmental defects was associated with compounds that selectively inhibit COX‐1 or have a high ratio of COX‐1 to COX‐2 inhibition. CONCLUSIONS: Inhibition of COX‐1 may be involved in the disruption of heart development, whereas the selective inhibition of COX‐2 (as assessed with CJ‐19,209) appears to have no effect on heart development and midline closure in rats and rabbits. Birth Defects Research (Part B) 68:47–56, 2003. © 2003 Wiley‐Liss, Inc.     

Flow‐injection analysis for meloxicam based on tris(2,2′‐bipyridine) ruthenium(II)–Ce(IV) chemiluminescent system

It was found that meloxicam could enhance the chemiluminescence (CL) of the tris(2,2'‐bipyridine) ruthenium(II)–Ce(IV) system in the medium of sulfate acid. Based on this phenomenon a new flow‐injection system with chemiluminescent detection has been proposed for determination of meloxicam. Under optimum conditions, meloxicam had a good linear relationship with the CL intensity in the concentration range of 6.0  10^?4 to 1.0 µg/mL and the detection limit was 3.7 × 10^?4 µg/mL. The proposed method was applied to detect meloxicam in tablets and a satisfactory recovery was obtained. The possible mechanism for this CL system is also discussed in this paper. Copyright © 2009 John Wiley & Sons, Ltd.     

Adsorption of meloxicam on porous calcium silicate: Characterization and tablet formulation

The purpose of the present study was characterization of microparticles obtained by adsorption of poorly water soluble drug, meloxicam, on a porous silicate carrier Florite RE (FLR) and development of a tablet formulation using these microparticles, with improved drug dissolution properties. The study also reveals the use of FLR as a pharmaceutical excipient. Meloxicam was adsorbed on the FLR in 2 proportions (1∶1 and 1∶3), by fast evaporation of solvent from drug solution containing dispersed FLR. Drug adsorbed FLR microparticles were evaluated for surface topography, thermal analysis, X-ray diffraction properties, infrared spectrum, residual solvent, micromeritic properties, drug content, solubility, and dissolution studies. Microparticles showed bulk density in the range of 0.10 to 0.12 g/cm³. Dissolution of drug from microparticles containing 1∶3, drug∶FLR ratio was faster than microparticles containing 1∶1, drug∶FLR ratio. These microparticles were used for formulating directly compressible tablets. Prepared tablets were compared with a commercial tablet. All the prepared tablets showed acceptable mechanical properties. Disintegration time of prepared tablets was in the range of 18 to 38 seconds, and drug dissolution was much faster in both acidic and basic medium from prepared tablets as compared with commercial tablet. The results suggest that FLR provides a large surface area for drug adsorption and also that a reduction in crystallinity of drug occurs. Increase in surface area and reduction in drug crystallinity result in improved drug dissolution from microparticles. Published: December 7, 2005     

Effects of a local anaesthetic and NSAID in castration of piglets,on the acute pain responses,growth and mortality

The present study addresses the questions whether on-farm use of local anaesthesia with lidocaine leads to a reduction in pain responses during castration, and whether the non-steroidal anti-inflammatory drug meloxicam improves technical performance after castration of piglets. Five treatments were included in the study: (1) castration without anaesthesia or analgesia (CAST), (2) castration after local anaesthesia with lidocaine (LIDO), (3) castration after administration of meloxicam (MELO), (4) castration after lidocaine and meloxicam (L + M) and (5) sham castration (SHAM). To reduce litter influences, each treatment was present in each of the 32 litters (n = 32 per treatment). During castration, vocalizations were recorded continuously. Blood samples were collected 15 min before and 20 min after castration for determination of plasma levels of total cortisol, glucose, lactate and creatine kinase (CK). Mortality was registered and piglets were weighed several times to calculate growth. Several aspects of vocalizations during castration showed consistent and significantly different levels in CAST compared with LIDO, L + M and SHAM. CAST piglets squealed longer, louder and higher. Vocalizations of MELO piglets most resembled those of CAST. An increase in cortisol was seen in all treatments. However, in SHAM piglets this increase was significantly lower than in the other treatments. LIDO piglets showed a significantly smaller increase in plasma cortisol levels compared with CAST and MELO. L + M piglets differed significantly only from the SHAM group. Lactate levels differed significantly between LIDO and MELO, the level in LIDO being decreased after castration. In the other treatments an increase was measured. No treatment effects were found in plasma glucose and CK levels, nor in growth and mortality of the piglets. In conclusion, on the basis of vocalizations and plasma cortisol, local anaesthesia with lidocaine reduces pain responses in piglets during castration. A positive effect of meloxicam on technical performance was not found.