mobic and betadex

The purpose of this research was to develop an inclusion complex of meloxicam (MEL)/β-cyclodextrin (β-CD) incorporated into an orally disintegrating tablet (ODT), using statistical analysis to optimize the ODT formulation based on a quality by design (QbD) approach. MEL/β-CD complexation was performed by kneading, co-precipitation and spray drying methods under different molar ratios. Fourier transform infrared spectroscopy, X-ray diffraction and thermal analysis were utilized to evaluate the complexes. A central composite design (α = 2) was applied to optimize and assess the influence of Primojel, Primellose and crushing strength (CS) as independent variables on tablet friability, disintegration behavior, wicking properties and drug release. The spray drying method induced formation of an amorphous complex and enhanced solubility and drug release of MEL. Furthermore, a QbD-based statistical analysis was successfully utilized to optimize the ODT formulation. Primojel, Primellose and CS showed unique main effects and interactions at different levels. CS was the dominant factor, affecting friability, disintegration behavior and drug release, while wicking properties were affected by Primojel and its interaction with Primellose. Therefore, according to the overlay plot, CS was dominant factor in determining the optimum region based on a QbD approach.

Topics: Administration, Oral; Analysis of Variance; beta-Cyclodextrins; Drug Compounding; Drug Liberation; Hardness; Meloxicam; Solubility; Tablets; Thiazines; Thiazoles; Water; X-Ray Diffraction

The objective of the present work was to develop inclusion complexes of meloxicam with β-cyclodextrin- and β-cyclodextrin-based nanosponges to enhance their solubility and stability and to prolong release using different methods that included physical mixing, kneading and sonication. Particle size, zeta potential, encapsulation efficiency, stability study results, in vitro and in vivo drug release study results, FTIR, DSC and XRPD were used as characterization parameters. SEM (Scanning Electron Microscope) studies revealed that the particle sizes of the inclusion complexes of meloxicam were within the range of 350 ± 5.69-765 ± 13.29 nm. The zeta potentials were sufficiently high to obtain stable formulations. In vitro and in vivo release studies revealed the controlled release of meloxicam from the nanosponges for 24h. The interaction of the meloxicam with the nanosponges was confirmed by FTIR and DSC. A XRPD study revealed that the crystalline nature of meloxicam was changed to an amorphous form due to the complexation with the nanosponges. A stability study revealed that the meloxicam nanosponges were stable. Therefore, β-cyclodextrin-based nanosponges represent a novel approach for the controlled release of meloxicam for anti-inflammatory and analgesic effects.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; beta-Cyclodextrins; Calorimetry, Differential Scanning; Female; In Vitro Techniques; Male; Meloxicam; Microscopy, Electron, Scanning; Nanostructures; Particle Size; Powder Diffraction; Rats; Rats, Wistar; Solubility; Spectroscopy, Fourier Transform Infrared; Thiazines; Thiazoles

The association rate constant and dissociation rate constant are important parameters of the drug-cyclodextrin supermolecule systems, which determine the dissociation of drugs from the complex and the further in vivo absorption of drugs. However, the current studies of drug-cyclodextrin interactions mostly focus on the thermodynamic parameter of equilibrium constants (K). In this paper, a method based on quantitative high performance affinity chromatography coupled with mass spectrometry was developed to determine the apparent dissociation rate constant (k(off,app)) of drug-cyclodextrin supermolecule systems. This method was employed to measure the k(off,app) of meloxicam and acetaminophen. Firstly, chromatographic peaks of drugs and non-retained solute (uracil) on β-cyclodextrin column at different flow rates were acquired, and the retention time and variance values were obtained via the fitting the peaks. Then, the plate heights of drugs (H(R)) and uracil (H(M,C)) were calculated. The plate height of theoretical non-retained solute (H(M,T)) was calculated based on the differences of diffusion coefficient and the stagnant mobile phase mass transfer between drugs and uracil. Finally, the k(off,app) was calculated from the slope of the regression equation between (H(R)-H(M,T)) and uk/(1+k)2, (0.13 ± 0.00) s(-1) and (4.83 ± 0.10) s(-1) for meloxicam and acetaminophen (control drug), respectively. In addition, the apparent association rate constant (k(on,app)) was also calculated through the product of K (12.53 L x mol(-1)) and k(off,app). In summary, it has been proved that the method established in our study was simple, efficiently fast and reproducible for investigation on the kinetics of drug-cyclodextrin interactions.

Topics: Acetaminophen; beta-Cyclodextrins; Chromatography, Affinity; Drug Interactions; Kinetics; Mass Spectrometry; Meloxicam; Thermodynamics; Thiazines; Thiazoles

Ion exchange resins have ability to exchange their counter ions for ionized drug in the surrounding medium, yielding "drug resin complex." Cyclodextrin can be applied for enhancement of drug solubility and stability.. Cyclodextrin inclusion complex of poorly water-soluble NSAIDs, i.e. meloxicam and piroxicam, was characterized and its novel application for improving drug loading onto an anionic exchange resin, i.e. Dowex® 1×2, was investigated.. β-Cyclodextrin (β-CD) and hydroxypropyl β-cyclodextrin (HP-β-CD) were used for the preparation of inclusion complex with drugs in solution state at various pH. The inclusion complex was characterized by phase solubility, continuous variation, spectroscopic and electrochemistry methods. Then, the drug with and without cyclodextrin were equilibrated with resin at 1:1 and 1:2 weight ratio of drug and resin.. Solubility of the drugs was found to increase with increasing cyclodextrin concentration and pH. The increased solubility was explained predominantly due to the formation of inclusion complex at low pH and the increased ionization of drug at high pH. According to characterization studies, the inclusion complex was successfully formed with a 1:1 stoichiometry. The presence of cyclodextrin in the loading solution resulted in the improvement of drug loading onto resin.. Enhancing drug loading onto ion-exchange resin via the formation of cyclodextrin inclusion complex is usable in the development of ion-exchange based drug delivery systems, which will beneficially reduce the use of harmful acidic or basic and organic chemicals.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Anti-Inflammatory Agents, Non-Steroidal; beta-Cyclodextrins; Cyclodextrins; Drug Carriers; Drug Compounding; Drug Stability; Electric Conductivity; Excipients; Hydrogen-Ion Concentration; Hydrophobic and Hydrophilic Interactions; Ion Exchange Resins; Kinetics; Meloxicam; Models, Molecular; Piroxicam; Resins, Synthetic; Sequestering Agents; Solubility; Thiazines; Thiazoles

The aim of this study was to prepare fast-dissolving tablets of meloxicam after its complexation with β-cyclodextrin (β-CD) and to investigate the effect of using different superdisintegrants on the disintegration and release of meloxicam from the tablets. A complex of meloxicam with β-CD was prepared by spray drying and then compressed in the form of tablets utilizing the direct compression technique. Three superdisintegrants were employed at various levels - sodium starch glycolate, croscarmellose sodium, and crospovidone. Co-spray dried micro-crystalline cellulose and mannitol (Avicel HFE-102) were used as diluents in the tablets. Prior to compression, the pre-compression parameters showed satisfactory flow properties. Post-compression parameters showed that all tablet formulations had acceptable mechanical properties. Wetting and disintegration times were prolonged by increasing the level of sodium starch glycolate in the tablets. This was attributed to the formation of a viscous gel layer around the tablets by sodium starch glycolate whereas this effect was not observed with croscarmellose sodium and crospovidone. Dissolution studies showed fast release of meloxicam except in tablets containing a high level of sodium starch glycolate. Complexation of meloxicam with β-CD significantly improved the solubility of the drug and improved the mechanical properties of tablets produced by direct compression.

Topics: Anti-Inflammatory Agents, Non-Steroidal; beta-Cyclodextrins; Carboxymethylcellulose Sodium; Cellulose; Excipients; Mannitol; Meloxicam; Povidone; Solubility; Starch; Tablets; Thiazines; Thiazoles; Time Factors

Meloxicam (an oxicam derivative), a relatively new cyclo-oxygenase inhibitor, is a member of enolic acid group of non-steroidal anti-inflammatory drugs. It is generally used in the treatment of rheumatoid arthritis, osteoarthritis and other joint pains. Meloxicam is practically insoluble in water (8µg/ml), which directly influences the C(max), T(max), as well as the bioavailability of the drug. In the present study, an attempt has been made to improve the dissolution of Meloxicam by preparation of its solid dispersion using β-cyclodextrin blended with various water soluble polymer carriers i.e., HPMC (methocel IH), methylcellulose (400cps), PVP K30, HPMC (K(4)M), HPMC (50cps). It is reported that when small amount of water soluble polymer is added to β-cyclodextrin, its nature of solubilization significantly increases due to increase in the apparent complex stability constant. Phase solubility studies were carried out to evaluate the solubilizing power of β-cyclodextrin along with various water soluble polymers. The solid dispersion was prepared and formulated into tablets and suspension, which were evaluated on the basis of various official tests. All the studies suggest that formulations of Meloxicam utilizing solid dispersion technique significantly enhances solubility (90 µg/ml) of the drug and results in superior formulations of the drug by using β-cyclodextrin blended with 0.12% w/w HPMC (Methocel IH). Ternary complexation is a valuable tool for solubility enhancement of drugs.

Topics: beta-Cyclodextrins; Biological Availability; Cyclooxygenase Inhibitors; Excipients; Hydrogen-Ion Concentration; Hypromellose Derivatives; Meloxicam; Methylcellulose; Polyvinyls; Pyrrolidines; Solubility; Solvents; Tablets; Thiazines; Thiazoles

The aim of the present study was to evaluate and compare the analgesic activity and serum levels of meloxicam (CAS 71125-38-7) after administration of meloxicam associated with beta-cyclodextrin (BCD, CAS 7585-39-9) and unmodified meloxicam. The analgesic activity was measured using the plantar test (rats) and the writhing test (mice). In the plantar test, BCD-meloxicam (3 mg/kg and 10 mg/kg orally) showed higher analgesic activity than corresponding doses of meloxicam alone; in the writhing test BCD-meloxicam (7 mg/kg and 15 mg/kg orally) showed stronger analgesic activity than unmodified meloxicam. Serum levels of meloxicam were significantly higher, at 0.5 h and 1 h after administration of BCD-meloxicam orally than those of unmodified meloxicam (both dosed at 10 mg/kg). The present results suggest that association with beta-cyclodextrin increases the analgesic activity of meloxicam. This may be due to an icreased systemic bioavailability of meloxicam after oral administration of its complex with beta-cyclodextrin.

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; beta-Cyclodextrins; Carrageenan; Hyperalgesia; Male; Meloxicam; Mice; Pain; Pain Measurement; Rats; Rats, Wistar; Thiazines; Thiazoles; Veins

The ultra-flexible lipid vesicles, the elastic liposomes bearing meloxicam-beta-cyclodextrin complex were prepared for its topical administration with the aim of simultaneously exploiting the favorable properties of both the carriers. The prepared meloxicam-beta-cyclodextrin complex was evaluated using DSC, XRD and FT-IR, which indicates the formation of inclusion complex in a molar ratio of 1:2 of meloxicam and beta-cyclodextrin (beta-CD). The elastic liposomes were prepared by conventional rotary evaporation method and characterized for various parameters such as vesicle shape and surface morphology, size and size distribution, entrapment efficiency, elasticity, stability and in-vitro release pattern. Permeability studies of meloxicam and meloxicam-beta-cyclodextrin complex, as such or incorporated in elastic liposomes performed both across artificial membranes and rat skin highlighted a favorable effect of cyclodextrin on drug permeation rate, due to its solubilizing action. Moreover skin-permeation enhancer property of elastic liposomes has been evidenced. Skin permeation potential of the developed formulation was assessed using confocal laser scanning microscopy (CLSM), which revealed an enhanced permeation of the formulation to the deeper layers of the skin (up to 160 microm) following channel like pathways. Skin permeation profile of elastic liposomal formulation bearing meloxicam-beta-cyclodextrin complex was observed and the investigations revealed an enhanced transdermal flux (12.48+/-0.9 microg/cm(2)/h) and decreased lag time (0.7 h) for meloxicam. The obtained flux was nearly 1.4 and 9.1 times higher than elastic liposomal formulation bearing meloxicam and plain drug solution, respectively (P<0.005). The results indicate that the elastic liposomes may be promising vehicles for the transdermal delivery of meloxicam.

Topics: Administration, Cutaneous; Animals; beta-Cyclodextrins; Calorimetry, Differential Scanning; Cyclooxygenase 2 Inhibitors; Drug Carriers; Drug Compounding; Drug Stability; Elasticity; Liposomes; Meloxicam; Microdialysis; Particle Size; Rats; Rats, Hairless; Rats, Sprague-Dawley; Skin Absorption; Solubility; Spectroscopy, Fourier Transform Infrared; Thiazines; Thiazoles; X-Ray Diffraction

The objective of this work was to develop tablet formulations of nimesulide-beta-cyclodextrin (NI-beta-CD) and meloxicam-gamma-cyclodextrin (ME-gamma-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 degrees C +/- 2 degrees C and 75% relative humidity.

Topics: beta-Cyclodextrins; Chemistry, Pharmaceutical; Drug Stability; gamma-Cyclodextrins; Meloxicam; Solubility; Sulfonamides; Tablets; Thiazines; Thiazoles

The purpose of this research was to evaluate beta-cyclodextrin (beta-CD) as a vehicle, either singly or in blends with lactose (spray-dried or monohydrate), for preparing a meloxicam tablet. Aqueous solubility of meloxicam in presence of beta-CD was investigated. The tablets were prepared by direct compression and wet granulation techniques. The powder blends and the granules were evaluated for angle of repose, bulk density, compressibility index, total porosity, and drug content. The tablets were subjected to thickness, diameter, weight variation test, drug content, hardness, friability, disintegration time, and in vitro dissolution studies. The effect of beta-CD on the bioavailability of meloxicam was also investigated in human volunteers using a balanced 2-way crossover study. Phase-solubility studies indicated an A(L)-type diagram with inclusion complex of 1:1 molar ratio. The powder blends and granules of all formulations showed satisfactory flow properties, compressibility, and drug content. All tablet formulations prepared by direct compression or wet granulation showed acceptable mechanical properties. The dissolution rate of meloxicam was significantly enhanced by inclusion of beta-CD in the formulations up to 30%. The mean pharmacokinetic parameters (C(max), K(e), and area under the curve [AUC](0-infinity)) were significantly increased in presence of beta-CD. These results suggest that beta-CD would facilitate the preparation of meloxicam tablets with acceptable mechanical properties using the direct compression technique as there is no important difference between tablets prepared by direct compression and those prepared by wet granulation. Also, beta-CD is particularly useful for improving the oral bioavailablity of meloxicam.

Topics: Adult; beta-Cyclodextrins; Biological Availability; Chemistry, Pharmaceutical; Cross-Over Studies; Humans; Male; Mechanics; Meloxicam; Solubility; Tablets; Thiazines; Thiazoles

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; beta-Cyclodextrins; Cyclodextrins; Edema; Intestinal Mucosa; Male; Meloxicam; Rats; Rats, Wistar; Stomach Ulcer; Thiazines; Thiazoles