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The aim of the presented work was to design, formulate and evaluate the properties of low-acyl gellan macro beads with the potential application as carriers for oral delivery of meloxicam (MLX) in the prophylaxis of colorectal cancer. The beads were obtained by means of ionotropic gelation technique. Calcium chloride (1.0%, 9.0 × 10 -2  M) was used as the cross-linking agent. Nine different polymer, drug and surfactant (Tween ® 80) mixtures were used for production of the beads. The quantitative compositions of the mixtures were generated with the application of the Design of Experiments (DoE) modulus from the STATISTICA Software. The prepared formulations revealed 7.2-27.0% of drug loading and 29.2-50.7% drug encapsulation efficiency. It turned out that 0.5% amount of gellan gum in the mixtures was not sufficient to obtain spherical beads. The morphology and surface of the dried beads were analyzed by SEM. Raman spectra confirmed that MLX did not undergo structural changes during production of the beads. The swelling behavior and degradation of the beads were evaluated in three simulated gastrointestinal fluids at different pH (1.2; 4.5; 6.8). The MLX in vitro release studies were conducted on USP apparatus IV, working in the open loop mode. The obtained results showed that MLX release from the dried beads was pH-dependent. The formulations obtained from mixtures containing 1.0 and 1.5% of gellan may be considered as oral dosage forms for MLX, intended to omit the stomach and release the drug in the distal parts of the gastrointestinal tract.

Objective: The focus of this study was to develop and optimize in situ implant formulation of meloxicam by quality by design (QbD) principle for long-term management of musculoskeletal inflammatory disorders., Methods: The formulation was optimized by Box-Behnken design with polylactide-co-glycolide (PLGA) level (X1), N-methyl pyrrolidone level (X2) and PLGA intrinsic viscosity (X3) as the independent variables and initial burst release of drug (Y1), cumulative release (Y2), and dissolution efficiency (Y3) as the dependent variables. The formulation was physicochemically characterized by scanning electron microscopy (SEM), Fourier transform infrared (FT-IR) spectroscopy and powder X-ray diffraction (PXRD). Pharmacokinetic studies of the optimized formulation were performed on Sprague-Dawley rats., Results: Y1 was significantly affected by X2 and X3. Y2 was affected by X1 and X3 while Y3 was affected by all three independent variables employed in the formulations. Responses for the optimized formulation were in close agreement with the values predicted by the model. SEM photomicrographs indicated uniform gel formulation. No chemical interaction between the components of formulation was observed by FT-IR and meloxicam was found to be present in the amorphous form in the gel matrix as revealed by PXRD. The maximum plasma concentration (Cmax), time to achieve Cmax and area under plasma concentration curve were significantly different from those of the solution formulation used as the control. Plasma concentration of meloxicam was maintained above its IC50 concentration required for COX-2 inhibition for 23 days., Conclusion: Meloxicam in situ implant may provide long-term management of inflammatory conditions with improved patient compliance and better therapeutic index.

The objectives of this study were to prepare a powdered self-emulsified (SEDDS) formulation of meloxicam and to compare its oral bioavailability against commercial Mobic tablets. The SEDDS formulation was prepared by in situ salt formation of meloxicam in a blend of lipid excipients and aqueous tris (hydroxymethyl) aminomethane solution. The liquid SEDDS was subsequently adsorbed on silica powder and was tested for size, flow, and crystal growth. The flowability index of the powdered SEDDS was borderline acceptable. Absence of crystal growth with storage was confirmed by DSC and PXRD studies. Dissolution of meloxicam from the powdered SEDDS was >90% vs. <12% for powdered meloxicam and <80% for the commercial tablets. Stability of the powdered formulations after storage in gelatin and HPMC capsules was also evaluated to study the effect of water migration from the fill into capsule shells. Capsules softened to a different extent as a function of fill material with HPMC capsules showing greater resistance to water migration. Finally, oral bioavailability of the formulations was evaluated in beagle dogs. Powdered meloxicam SEDDS formulation showed a 1.3-fold increase in AUC vs. commercial Mobic® tablets. Overall, this study described a novel SEDDS formulation of meloxicam and outlined a systematic approach to adsorbing and testing the flow and stability behavior of powdered SEDDS formulations.

Background: This study was designed to quantify the effects of penetration enhancers on systemic bioavailability of 0.3% meloxicam (MLX) hydroxypropylcellulose gels. Cutaneous microdialysis was also performed to assess dermis availability and to better understand the penetration process. The gels tested were a 1% oleic acid gel, a 5% menthol gel, and a control gel without penetration enhancers., Methods: To assess systemic bioavailability, three female rabbits received according to a crossover design 0.135 g/cm(2) of gel applied to a 7.5 × 7.5 cm area of their shaved back and a short (5 min) infusion of 1 mg. In each experiment, blood samples were collected serially for 36 h and analyzed by a validated HPLC method. For skin bioavailability studies, 0.135 g/cm(2) of the same gels were applied to a 1 × 2 cm area on top of a microdialysis probe previously inserted in the dermis. Dialysate samples were collected for 6 h every 30 min., Results: Systemically, the 5% menthol gel delivered 3.93 ± 0.85 mg of MLX versus the 1.41 ± 0.24 mg of the oleic acid gel. Only traces of MLX were detectable from the control gel. In dermis, substantial concentrations of MLX were detected only after the application of the menthol gel, whereas skin concentration from the control gel and the 1% oleic acid gel were always below the lowest limit of quantification (LLOQ)., Conclusions: The 5% menthol gel can possibly deliver therapeutically relevant amount of MLX in vivo. Dermis concentrations can be predictive of systemic plasma levels.

Purpose: To investigate the influence of ion pairing and chemical enhancers on the transdermal delivery of meloxicam., Method: We examined the increased permeation of meloxicam produced by ion pair formation with six organic bases, diethylamine, triethylamine, ethanolamine, diethanolamine, triethanolamine, and N-(2'-hydroxyethanol)-piperidine, and four normal permeation enhancers, oleic acid, menthol, azone, and N-methyl-2-pyrrolidone. The cumulative permeation was markedly increased in the presence of either a counter ion or chemical enhancers. In particular, we proved the formation of a meloxicam/amine ion-pair in solution by (13)C-NMR (nuclear magnetic resonance)., Results and Conclusion: The cumulative permeation was markedly increased in the presence of either a counter ion or chemical enhancers. These results suggest that the degree of enhancement possibly depends on the structure and hydrophilicity of the counter ions.

The purpose of the present study was to develop the meloxicam transdermal dosage form. The response surface methodology was used to obtain an appropriate mixed-solvent system of pH-7.4 buffer and ethanol for preparing meloxicam hydrogel. The enhancement effects of terpenes on drug precautious absorption were evaluated via in vitro and in vivo study. The result showed that the solubility of meloxicam was dependent on the pH value of buffer solution. The mixed-solvent system of pH-7.4 buffer and ethanol had a synergistic effect on the increase of drug solubility. The highest solubility was obtained in the ratio of 50/50 pH 7.4 buffer/ethanol. A series of terpenes were used as enhancer for improving the penetration rate of meloxicam. The penetration rates were significantly increased by about 70-593 fold and the lag times were shortened from 7.92 to 0.17 hr by enhancer incorporation. Among these terpenes, menthol showed the greatest effect. In vivo penetration study, the AUC(48h) was increased by about 1.7 fold by the addition of 5% menthol as enhancer.

Freeze-drying (FD) and solvent evaporation (SE) were used to prepare solid dispersions (SDs) of meloxicam (MX) in polyvinylpyrrolidone K-30 (PVP). The SDs were prepared at different ratios, namely 1:1, 1:3, and 1:5 MX:PVP weight ratio. Differential scanning calorimetry (DSC), infrared absorption spectroscopy (IR), and x-ray powder diffractometry (XPD) were utilized to characterize the physicochemical properties of the SDs. Meloxicam (MX) in the solid dispersions appeared with less crystallinity form and was present in a complete amorphous form at higher PVP ratio. Dissolution rates of MX as a pure drug, physical mixtures (PMs), and SDs indicated a marked increase of the dissolution rate of MX in presence of PVP. The increase in the dissolution rate was dependent on the ratio of PVP and the method of preparation. In addition, the permeability of the drug through standard cellophane membrane and hairless mouse skin was also evaluated. The permeation rate of MX was significantly increased in the case of SDs and was dependent on the ratio of PVP. The results were primarily due to increase wettability, the solubilization of the drug by the carrier, and formation of MX amorphous form.