Structure and physicochemical properties of meloxicam, a new NSAID

Luger, Peter; Daneck, Klaus; Engel, Wolfhard; Trummlitz, G.; Wagner, Karl G.

doi:10.1016/0928-0987(95)00046-1

Cited by 210 publications

(158 citation statements)

References 16 publications

Supporting

Mentioning

148

Contrasting

Unclassified

Order By: Relevance

“…7) Because oral and injectable administrations of MX are not appropriate for peptic ulcers and patient compliance, MX is suitable for development as a transdermal delivery candidate. In this study, the possibility of developing a transdermal liposomal carrier containing MX was evaluated.…”

mentioning

confidence: 99%

Menthosomes, Novel Ultradeformable Vesicles for Transdermal Drug Delivery: Optimization and Characterization

Duangjit

Obata

Sano

et al. 2012

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Menthosomes, novel deformable carriers for the enhancement of transdermal delivery are introduced in this study. Meloxicam (MX)-loaded menthosomes were formulated, and their physicochemical characteristics and skin permeability were evaluated. A two-factor spherical and second-order composite experimental design was used to prepare the formulation of the menthosomes. Ten formulations of menthosomes composed of a phospholipid as the lipid bilayer carrier, cholesterol (Chol) as a stabilizer and cetylpyridinium chloride (CPC) and L-menthol as penetration enhancers were prepared. The amounts of Chol and CPC were selected as causal factors. Physicochemical characteristics (particle size, size distribution, zeta potential, elasticity and drug content) and an in vitro skin-permeation study of meloxicam-loaded menthosomes were evaluated. The concentrations of MX that permeated the skin at 2-12 h and the flux were selected as response variables. The optimal formulation was estimated using a nonlinear response-surface method incorporating thin-plate spline interpolation. The experimental values were very close to the values predicted by the computer programs in this study. A Bayesian network analysis was applied to gain a mechanistic understanding of the relationships between causal factors and response variables.Key words menthosome; liposome; optimization; skin permeation; meloxicam; menthol For the past few decades, the use of liposomal vesicles in drug-delivery systems for skin permeation has evoked considerable interest and attracted increasing attention. Many reports focus on the use of liposomes for enhancing skin permeation of hydrophilic and lipophilic compounds, proteins and macromolecules. However, recent studies indicate that in most cases, classic liposomes are of little or no value as transdermal drug-delivery carriers because they do not penetrate skin deeply, but rather remain confined to the upper layers of the stratum corneum. Confocal microscopic studies showed that intact fluorescent labeled liposomes were not able to penetrate into the granular layers of the epidermis. 1)Since the first paper to report the effectiveness of deformable liposomes which can be used for skin delivery of drug into deep skin region was published by Cevc and Blume, 2) new categories of vesicles with high elasticity or flexibility, such as transfersomes,3) ethosomes, 4) flexosomes 5) and invasomes 6) have been introduced and developed. These vesicles mainly consist of phospholipids and an edge activator or penetration enhancer in which only a specially designed vesicle was shown to be able to allow transdermal drug delivery. Menthosomes, novel deformable carriers consist of phospholipids, surfactant and menthol were also introduced in this study. Several intensive studies suggested that the permeability of drug in liposomes and their analogues depends on their physicochemical characteristics (e.g., particle size, size distribution, zeta potential, lamellarity, elasticity, drug content, etc.), and these characteristics were dir...

show abstract

mentioning

confidence: 99%

Menthosomes, Novel Ultradeformable Vesicles for Transdermal Drug Delivery: Optimization and Characterization

Duangjit

Obata

Sano

et al. 2012

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

show abstract

“…The skin was washed with distilled water and then dried with cotton swab. The full-thickness skin of treated area was cut into small pieces with scissors and fine forceps, and sonicated for 2 h with 1 mL phosphate buffer solution pH 7.4 to extract the MX (solubility of MX in buffer pH 7.0-8.0 was 26.6-155 mg/100 mL, 1) over 20-130 times of MX in water). After centrifugation at 10000 rpm for 10 min, the clear supernatant was analysis by HPLC.…”

mentioning

confidence: 99%

Comparative Study of Novel Ultradeformable Liposomes: Menthosomes, Transfersomes and Liposomes for Enhancing Skin Permeation of Meloxicam

Duangjit

Obata

Sano

et al. 2014

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

In the present study, novel ultradeformable liposomes (menthosomes; MTS), deformable liposomes (transfersomes; TFS) and conventional liposomes (CLP) were compared in their potential for transdermal delivery of meloxicam (MX). MTS, TFS and CLP were investigated for size, size distribution, zeta potential, elasticity, entrapment efficiency and stability. In vitro skin permeation using hairless mice skin was evaluated. Vesicular morphology was observed under freeze-fractured transmission electron microscopy (FF-TEM). Intrinsic thermal properties were performed using differential scanning calorimetry (DSC) and X-ray diffraction. The skin permeation mechanism was characterized using confocal laser scanning microscopy (CLSM). The results indicated that the difference in physicochemical characteristics of MTS, TFS and CLP affected the skin permeability. MTS and TFS showed higher flux of MX than CLP. CLSM image showed deformable vesicles mechanism for delivery of MX across the hairless mice skin. Our study suggested that ultradeformable and deformable liposomes (MTS and TFS) had a potential to use as transdermal drug delivery carriers for MX.Key words menthosome; transfersome; liposome; skin permeation; meloxicam; menthol Meloxicam (MX), a cyclooxygenase-2 inhibitor nonsteroidal anti-inflammatory drug (NSAID), is used to treat rheumatoid arthritis, osteoarthritis and other joint diseases. The injectable and oral administrations of NSAID drugs are not appropriate for needle-phobia and peptic ulcer patients. Moreover, the major limitation of MX is its low aqueous solubility (0.012 mg/mL in water and 0.086×10 −2 mg/mL in 0.1 M HCl) 1) with log P 1.91 and 0.07 at pH 5.0 and 7.4, respectively. MX delays its absorption from gastrointestinal tract (GI) and its prolonged use is associated with the incidence of GI side effects (bellyache, indigestion, ulceration and bleeding).2) If MX could be delivered without incidence of these limitations, MX administration would become safer and more acceptable. MX is suitable for development as a transdermal delivery candidate.Transdermal drug delivery or skin delivery has become a global priority because the conventional drug administration is associated with numerous limitations. Liposomes are one of potential strategies that utilize for skin delivery of hydrophilic drugs, 3) lipophilic drugs, 4) protein 5) and macromolecule.6) Although last decades, some design of conventional liposomes are of little or no value as carriers for transdermal drug delivery, but rather remain confined to the upper layer of the stratum corneum. However, recent approaches in vesicular modulating drug delivery through skin have resulted in many designs of novel vesicular carriers e.g., deformable liposomes (transfersomes), 7) niosomes, 8) ethosomes, 9) invasomes, 10) flexosomes 11) and menthosomes. 12) Transfersomes are the first generation of elastic vesicles introduced by Cevc and Blune 7) and consist mainly of phospholipids and an edge activator or a single-chain surfactant which having a high radius of curv...

show abstract

“…DZG analogues have been reported to possess a broad range of biological activities like antioxidant, anticancer, anti-inflammatory, antidepressant, antimalarial, antifungal, etc. 19 The thiazole nucleus is a common motif presently found in several FDA-approved drugs, such as the nonsteroidal antiinflammatory drug meloxicam 20 and the tyrosine kinase inhibitor dasatinib. 21 Recently, Meissner et al have demonstrated the structure−activity relationships (SAR) of novel series of 2-aminothiazole analogues as effective antimycobacterial agents, 22 and Carradori et al have reported microwaveassisted method for the synthesis of substituted-thiazolyl hydrazines.…”

mentioning

confidence: 99%

Dehydrozingerone Inspired Styryl Hydrazine Thiazole Hybrids as Promising Class of Antimycobacterial Agents

Hampannavar

Karpoormath

Palkar

et al. 2016

ACS Med. Chem. Lett.

View full text Add to dashboard Cite

Series of styryl hydrazine thiazole hybrids inspired from dehydrozingerone (DZG) scaffold were designed and synthesized by molecular hybridization approach. In vitro antimycobacterial activity of synthesized compounds was evaluated against Mycobacterium tuberculosis H 37 Rv strain. Among the series, compound 6o exhibited significant activity (MIC = 1.5 μM; IC 50 = 0.48 μM) along with bactericidal (MBC = 12 μM) and intracellular antimycobacterial activities (IC 50 = <0.098 μM). Furthermore, 6o displayed prominent antimycobacterial activity under hypoxic (MIC = 46 μM) and normal oxygen (MIC = 0.28 μM) conditions along with antimycobacterial efficiency against isoniazid (MIC = 3.2 μM for INH-R1; 1.5 μM for INH-R2) and rifampicin (MIC = 2.2 μM for RIF-R1; 6.3 μM for RIF-R2) resistant strains of Mtb. Presence of electron donating groups on the phenyl ring of thiazole moiety had positive correlation for biological activity, suggesting the importance of molecular hybridization approach for the development of newer DZG clubbed hydrazine thiazole hybrids as potential antimycobacterial agents. KEYWORDS: Antimycobacterial activity, bactericidal, dehydrozingerone, NIAID, thiazole T uberculosis (TB) is a chronic necrotizing bacterial infection caused by Mycobacterium tuberculosis (Mtb), which has been a bane of humanity for thousands of years and remains as one of the rampant health problems in the world. TB is an ancient enemy, and current threat that has been ranked among the foremost killers of the 21st century. 1According to a World Health Organization (WHO) report, around 9 million people were found infected and around 1.5 million casualties occurred because of TB. Besides, the life threatening strains of MDR-TB (Multi Drug Resistance Tuberculosis) are appearing, some of which can lead to high mortality rate (e.g., 72−89%) with death occurring in short period (4−16 weeks).2 In 2013 around 480,000 affirmative cases of MDR-TB were witnessed.3 India, China, the Russian Federation, and South Africa have almost 60% of the world's cases of MDR-TB. In addition, the risk becomes even greater if the person is coinfected with the HIV (human immunodeficiency virus). 4 The global resurgence of TB and development of drug resistance necessitates for an imperative attention of medicinal chemists to develop innovative antimycobacterial agents as no new classes of anti-TB agents have been developed since the introduction of rifampin in to clinical practice in 1960s.It is well-known fact that trans-cinnamic acid analogues have recently drawn back the intentness of medicinal chemists due to their admirable pharmacological properties like antioxidant,

show abstract

Structure and physicochemical properties of meloxicam, a new NSAID

Cited by 210 publications

References 16 publications

Menthosomes, Novel Ultradeformable Vesicles for Transdermal Drug Delivery: Optimization and Characterization

Menthosomes, Novel Ultradeformable Vesicles for Transdermal Drug Delivery: Optimization and Characterization

Comparative Study of Novel Ultradeformable Liposomes: Menthosomes, Transfersomes and Liposomes for Enhancing Skin Permeation of Meloxicam

Dehydrozingerone Inspired Styryl Hydrazine Thiazole Hybrids as Promising Class of Antimycobacterial Agents

Contact Info

Product

Resources

About