Dissolution Rate Of Meloxicam Research Articles

Design of Etched- and Functionalized-Halloysite/Meloxicam Hybrids: A Tool for Enhancing Drug Solubility and Dissolution Rate.

The study focuses on the synthesis and characterization of Meloxicam-halloysite nanotube (HNT) composites as a viable approach to enhance the solubility and dissolution rate of meloxicam, a poorly water-soluble drug (BCS class II). Meloxicam is loaded on commercial and modified halloysite (acidic and alkaline etching, or APTES and chitosan functionalization) via a solution method. Several techniques (XRPD, FT-IR, 13C solid-state NMR, SEM, EDS, TEM, DSC, TGA) are applied to characterize both HNTs and meloxicam-HNT systems. In all the investigated drug-clay hybrids, a high meloxicam loading of about 40 wt% is detected. The halloysite modification processes and the drug loading do not alter the structure and morphology of both meloxicam and halloysite nanotubes, which are in intimate contact in the composites. Weak drug-clay and drug-functionalizing agent interactions occur, involving the meloxicam amidic functional group. All the meloxicam-halloysite composites exhibit enhanced dissolution rates, as compared to meloxicam. The meloxicam-halloysite composite, functionalized with chitosan, showed the best performance both in water and in buffer at pH 7.5. The drug is completely released in 4-5 h in water and in less than 1 h in phosphate buffer. Notably, an equilibrium solubility of 13.7 ± 4.2 mg/L in distilled water at 21 °C is detected, and wettability dramatically increases, compared to the raw meloxicam. These promising results can be explained by the chitosan grafting on the outer surface of halloysite nanotubes, which provides increased specific surface area (100 m2/g) disposable for drug adsorption/desorption.

Formulation and In-Vitro Evaluation of Meloxicam Solid Dispersion using Natural Polymers.

Meloxicam (MLX) is non-steroidal anti -inflammatory, poorly water soluble, highly permeable drug and the rate of its oral absorption is often controlled by the dissolution rate in the gastrointestinal tract. Solid dispersion (SD) is an effective technique for enhancing the solubility and dissolution rate of such drug.
 The present study aims to enhance the solubility and the dissolution rate of MLX by SD technique by solvent evaporation method using sodium alginate (SA), hyaluronic acid (HA), collagen and xyloglucan (XG) as gastro-protective hydrophilic natural polymers.
 Twelve formulas were prepared in different drug: polymer ratios and evaluated for their, percentage yield, drug content, water solubility, dissolution, crystal lattice using powder X-ray diffraction (PXRD) and studies and Fourier Transform Infrared Spectroscopy (FTIR) for determination the drug-polymer interaction.
 All the prepared showed improvement of drug solubility except that prepared with HA. The best result was obtained with formula SD1 (MLX: SA 1:1) that showed a high percentage yield (97), high drug content (97.4±0.05) and increase in solubility compared to solubility of pure MLX with improved dissolution rate. the PXRD study revealed the conversion of the drug to amorphous form without chemical interaction according to FTIR results

Acetone-assisted co-processing of meloxicam with amino acids for enhanced dissolution rate

Meloxicam is a widely used non-steroidal anti-inflammatory agent. However, its erratic and poor dissolution delays its onset of action. Dissolution enhancement of such medicine is essential to obtain rapid pain relief. Amino acids showed high potential to enhance the dissolution rate of drugs after co-processing. Accordingly, the objective of this work was to investigate the effect of co-processing of meloxicam with arginine, cysteine, and glycine on its crystalline structure and dissolution rate. Meloxicam was mixed with increasing molar ratios of amino acids before acetone-assisted kneading. The resulting products were examined using Fourier transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction in addition to monitoring the dissolution behavior. Combined instrumental analysis indicated salt formation with a possibility of further crystalline changes at high concentration of amino acids. Salt formation and crystalline structure modification were associated with a significant increase in the dissolution rate of meloxicam. The study introduced amino acids as potential excipients for enhanced dissolution of meloxicam after wet co-processing.

The use of cooling and anti-solvent precipitation technique to tailor dissolution and physicochemical properties of meloxicam for better performance

Low dissolution rate of pharmaceutical agents with poor water-solubility limits their bioavailability after oral administration. These two parameters are pivotal when a fast onset of action required which could be the case for meloxicam (MLX), an anti-inflammatory and pain reliever compound. In the present study, the effects of various solvents and method of crystallization were investigated to modify the physicochemical properties and dissolution of MLX crystals. X-ray diffractometry, infrared spectrophotometry and differential scanning calorimetry were used to investigate the crystalline characteristics of the particles. Dissolution, particle size, solubility, contact angle and morphology of crystals were also evaluated. It was found that the type of solvent and crystallization methods modified the shape of crystals from polyhedral irregular to prismatic particles. The results ruled out any polymorphic changes occurred during the processes for most samples. The dissolution rate of MLX was improved by recrystallization and the best dissolution performance was observed for crystals prepared by anti-solvent precipitation in the presence of acetone, ethanol, and propanol with a 2-3-fold increase in dissolution efficiency than that of the parent drug. This could be related to the decreased particle size, lower contact angle, improved wettability and crystalline modifications.

Improving solubility and dissolution of meloxicam by solid dispersion using hydroxypropyl methylcellulose 2910 3 cps and nicotinamide.

Background Solid dispersion (SD) represents a good method for enhancing the solubility of poorly water-soluble drugs. Meloxicam (MLX), a nonsteroidal anti-inflammatory drug has poor solubility in water. Hydroxypropyl methylcellulose (HPMC) 2910 3 cps, a hydrophilic carrier and nicotinamide (NC), a hydrotropic agent can be used as matrix of SD. The aim of this study is to investigate the effect of HPMC 2910 3 cps and NC as SD matrix on the solubility and dissolution rate of MLX. Methods The SD of MLX was prepared by solvent evaporation method using methanol as solvent. The SD formulations composed of HPMC and NC in different ratios (1:1:1, 1:1:2, 1:2:1, 1:2:2). The physical state of MLX SD were characterized by Differential Thermal Analyzer (DTA), Fourier Transform Infrared Spectroscopy, powder X-ray diffractometer (PXRD), Scanning Electron Microscopy (SEM). The solubility and dissolution of the MLX SD were also evaluated. Results The results of differential thermal analysis (DTA) showed that the melting point of MLX SD was lower than MLX further the X-ray diffractogram showed a decrease of the crystallinity of MLX in SD. Those indicated that MLX was dispersed molecularly in SD. The SD showed a widening transmission peak at 3000-3500 cm-1 which resembled the peak of pure MLX transmission. It indicated that intermolecular hydrogen bonds were formed between MLX, HPMC, and NC. The solubility and the dissolution efficiency (ED60) of SD with MLX-HPMC 2910 3 cps-NC = 1:2:1 increased 3.59 times and 1.50 times higher then MLX substance. Conclusions MLX-HPMC-NC SD system increased the solubility and dissolution of MLX. The SD with MLX-HPMC 2910 3 cps-NC ratio of 1:2:1 had the highest solubility and ED60 compared to the other SD formulas.

The Effect of an Optimized Wet Milling Technology on the Crystallinity, Morphology and Dissolution Properties of Micro- and Nanonized Meloxicam.

This article reports on the effects of a new combined wet milling technique on the physicochemical properties of meloxicam (MEL). The influence of milling time on the particle size, the crystallinity, the morphology and the dissolution rate of MEL has been studied in the presence and absence of polyvinyl alcohol (PVA) as a stabilizer agent. Micronized MEL particles were produced in aqueous medium which did not contain additive after milling for 10 min. For nanonization an additive and longer milling time were required. After particle size determination the structural and morphological characterization of the wet milled, dried products containing MEL were studied. X-ray powder diffractometry (XRPD) and differential scanning calorimetry (DSC) examinations revealed the change in the crystallinity of MEL. Scanning electron microscopy (SEM) images showed that aggregates of nanosized MEL particles were formed, regardless of the presence of PVA. The nanonized MEL crystals (D50 = 126 nm) exhibited a regular shape and a smooth surface. The increased specific surface area resulted in a high dissolution rate and concentration of free MEL. According to the results, the produced samples could be applied as a basic material (micronized MEL) and intermediate product (micronized and nanonized MEL with PVA) for the design of dosage forms.

Recrystallized agglomerated meloxicam: evaluation of anti-nociceptive effect

Meloxicam (Mel) is a non steroidal anti-inflammatory drug belonging to BCS class II category. Hence, its pharmacological effect is affected by its low water solubility. The aim of this study was to improve the solubility and dissolution rate of meloxicam. Mel was recrystallized into spherical agglomerates (SA) with or without different polymers (PEG 4000, Inutec SP1, PVP k30, Pluronic F127 and HPsCD) at three different concentrations (0.0125, 0. 025 and 0.05 % w/v) using quasi emulsion solvent diffusion (QESD) and neutralization techniques (NT). Mel SA containing low concentration level of polymer (0.0125 % w/v) showed highest solubility and dissolution rate enhancement compared to pure Mel. DSC and IR outcome showed no chemical alteration in the recrystallized drug. DSC and PXRD studies showed that crystallinity of Mel was retained in all of the prepared SA (although slightly reduced compared to pure Mel). The anti-nociceptive effect of F2 (QESD) and F29 (NT) (showing highest dissolution in simulated gastric fluid) was assessed in mice using acetic acid induced abdominal writhing in comparison to pure drug. The selected formulae showed significantly higher analgesic activity in comparison to the pure drug and the control.

Improving Dissolution of Meloxicam Using Solid Dispersions

Meloxicam is a poorly water soluble non steroidal anti-inflammatory drug and antipyretic agent. The aim of the present work was to investigate the effect of different types of carriers on in vitro dissolution of meloxicam. Meloxicam solid dispersions were prepared by physical mixing, co-grinding and solvent evaporation methods with polyethylene glycol (PEG) 6000. The effect of solubilization by sodium lauryl sulphate (SLS) was also studied. The dissolution was determined by USP XXVII Apparatus I, using phosphate buffer with a pH of 7.4 as the dissolution medium. The maximum in vitro dissolution of meloxicam, i.e. 97.45% in 60 min, was observed for solid dispersions containing meloxicam (150 mg), PEG 6000 (350 mg) and SLS (75 mg) prepared by solvent evaporation method containing a sum of 3 g of Lactose and MCC (4:1) as additives. The general trend indicated that there was an increase in dissolution rate for solid dispersions containing the solubilizer SLS. The best-fit model indicating the mechanism of dissolution from the formulation showing the highest release for was found to be Higuchi matrix release (r=0.9774, b=13.042, a=2.4798). Infra red spectroscopy (IR) indicated that meloxicam in solid dispersions showed physical entrapment. The increased in dissolution rate of meloxicam by solid dispersion technique may be due to increase wettability and hydrophilic nature of carrier.

The effect of β-cyclodextrin on the solubility and dissolution rate of meloxicam and investigation of the driving force for complexation using molecular modeling

The aim of this study was to investigate the effect of β-cyclodextrin (β-CD) on the solubility and dissolution rate of meloxicam. The methods that were employed to prepare meloxicam–β-cyclodextrin complexes were physical mixture, kneaded dispersion, and spray drying. Spray drying method was found to be the best to form a true inclusion complex. Complexes were characterized by thermal analysis, X-ray diffractometry (XRD), and Fourier transform infrared (FT-IR) spectroscopy. The apparent stability constant of the complex, Kc, calculated from the slope and intercept of the AL solubility diagram was found to be 429.73, 259.96, 183.31, and 36.50 L mol−1 at pH 2, 3, 6.5, and 10.3, respectively. The dissolution rate of meloxicam from the complexes was higher than from meloxicam alone. Molecular modeling was also used to investigate the interaction between meloxicam and β-CD. The dominant driving force for the complexation was evidently Van der Waals force with very little electrostatic contribution.

Enhancement of the Dissolution and Permeation Rates of Meloxicam by Formation of Its Freeze-dried Solid Dispersions in Polyvinylpyrrolidone K-30

ABSTRACTFreeze-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.

Tablet formulation containing meloxicam and β-cyclodextrin: Mechanical characterization and bioavailability evaluation

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.