Lornoxicam Research Articles

Emu oil enriched nanostructured lipid carriers of lornoxicam burdened polymeric gel augmented drug delivery and assisted cartilage repairing in knee osteoarthritis: In-vitro and in-vivo studies

Lornoxicam (LRX) alleviates pain and inflammation associated with knee osteoarthritis (OAS). However, inadequate solubility, short half-life, and gastrointestinal side-effects on chronic use hinder the efficacy of LRX through oral route. Therefore, in present investigation, lornoxicam loaded nanostructured lipid carriers (LRX-NLCs) were scaled-up post optimization using hot homogenization method. The optimized F14 LRX-NLCs demonstrated particle size of 172.1 ± 2.0 nm with polydispersity index (PDI) of 0.293 ± 0.01, zeta (ζ) potential of −15.5 ± 1.21 mV, entrapment efficiency of 92.85 ± 0.25 % and drug release up to 18.9 ± 1.8 % at 3 h in addition to sustained release pattern throughout 24 h. Later, F14 LRX-NLCs were amalgamated with carbopol 940 LR gel as LRX-NLCs-Gel and evaluated for pH, spreadability, drug content, rheological behavior, texture properties, ex-vivo skin permeation and retention, and dermal distribution. Furthermore, pharmacodynamic studies of LRX-NLCs-Gel disclosed a substantial diminution in pain and inflammation in addition to amended radiographic and histopathological features in monosodium iodoacetate (MIA) induced OAS in Sprague Dawley rats. LRX-NLCs-Gel exhibited a remarkable decline in the levels of pro-inflammatory cytokines such as IL-1β, TNF-α, in addition to COX-2 in knee OAS. LRX-NLCs-Gel presented an epochal decrease in synovial hyperplasia, inflammation, and ameliorated cartilage structure. In addition, omega-3, omega-6, and omega-9 fatty acids enriched emu oil might have assisted in offering synergistic activity with LRX in cartilage repairing due to suppression of the proteolytic activity of MMP-2 and MMP-9. In conclusion, LRX-NLCs-Gel may be a prospective candidate for translating the product in to a clinically viable dosage form.

Lornoxicam Solid Lipid Nanoparticle-Enriched Transdermal Gel: Development and Characterization

To develop antiinflammation and analgesic effects, scientists introduced lornoxicam (LRX) nanoemulsion, nanostructure lipid carriers, and solid lipid nanoparticles. After six months of testing at different temperatures, SLN, NLC, and NE were determined to be stable. The most prominent mechanism that was identified in case I was the diffusional release of drugs from nanoparticles and nanoemulsion, which is consistent with Fickian drug diffusion. After NE, NLC, and SLN, a gel formulation achieved the greatest rate of drug penetration via rat skin. When contrasted with the gel, nanoformulations considerably enhanced the drug’s penetration into the skin of rats. Therefore, SLN, NLC, and NE of LRX could be recommended for the relief of skin disorders characterized by inflammation and pain.

Desosomes and desimicelles − a novel vesicular and micellar system for enhanced oral delivery of poorly soluble drug: Optimization of in vitro characteristics and in vivo performance

This study introduces two innovative nanocarrier systems to improve oral drug delivery. Desosomes and desimicelles combine Deep eutectic solvent (DES) with vesicular or micellar nanosystems, respectively. These novel nanosystems integrate the DES solubilization potency for administering drugs with low aqueous solubility and the vesicular and micellar systems to bypass physiological barriers and improve poor drug bioavailability. Lornoxicam (LRX) is a BCS class II anti-inflammatory with limited aqueous solubility and rapid clearance. Desosomes and desimicelles were prepared and successfully optimized. The optimization depended on particle size, zetapotential, entrapment efficiency, and solubility. The optimized desosomes (LRX-DES-V) and desimicelles (LRX-DES-M) were pictured by transmission electron microscope. Differential scanning calorimetry (DSC) and FTIR analysis indicated the successful inclusion of LRX inside each system. Invitro LRX release profiles revealed controlled release of LRX-DES-V and LRX-DES-M, with more sustained release by the later one. In-vivo study, inflammation was induced using a carrageenan rat model, and the anti-inflammatory effect of LRX-pure, marketed product, traditional niosomes, LRX-DES-V & LRX-DES-M were determined using inhibition %, serum inflammatory cytokines, and histopathology. After 4 h of induction, LRX-DES-M (68.05%) showed a significant inhibition compared to LRX-DES-V (63.57%). LRX-DES-M also showed a better reduction in COX2, PGE2, and TNF-α (1.25-fold, 1.24-fold, and 1.36-fold inhibition), respectively, compared to LRX-DES-V. We can conclude that LRX-DES-V and LRX-DES-M showed better effects than all other groups and that LRX-DES-M might be more effective than LRX-DES-V.

Magnetic targeting of lornoxicam/SPION bilosomes loaded in a thermosensitive in situ hydrogel system for the management of osteoarthritis: Optimization, in vitro, ex vivo, and in vivo studies in rat model via modulation of RANKL/OPG

Osteoarthritis is a bone and joint condition characterized pathologically by articular cartilage degenerative damage and can develop into a devastating and permanently disabling disorder. This investigation aimed to formulate the anti-inflammatory drug lornoxicam (LOR) into bile salt–enriched vesicles loaded in an in situ forming hydrogel as a potential local treatment of osteoarthritis. This was achieved by formulating LOR-loaded bilosomes that are also loaded with superparamagnetic iron oxide nanoparticles (SPIONs) for intra-muscular (IM) administration to improve joint targeting and localization by applying an external magnet to the joint. A 31.22 full factorial design was employed to develop the bilosomal dispersions and the optimized formula including SPION (LSB) was loaded into a thermosensitive hydrogel. Moreover, in vivo evaluation revealed that the IM administration of LSB combined with the application of an external magnet to the joint reversed carrageen-induced suppression in motor activity and osteoprotegerin by significantly reducing the elevations in mitogen-activated protein kinases, extracellular signal-regulated kinase, and receptor activator of nuclear factor kappa beta/osteoprotegerin expressions. In addition, the histopathological evaluation of knee joint tissues showed a remarkable improvement in the injured joint tissues. The results proved that the developed LSB could be a promising IM drug delivery system for osteoarthritis management.Graphical

Principles of White Analytical Chemistry and Design of Experiments to Stability-Indicating Chromatographic Method for Simultaneous Estimation of Thiocolchicoside and Lornoxicam.

A variety of chromatographic methods have been published for the stability evaluation of thiocolchicoside and lornoxicam. Nevertheless, the development of chromatographic methods requires the use of neurotoxic and teratogenic organic solvents that are detrimental to the environment and harmful to human life. Using the principles of design of experiments (DoE), a novel white analytical chemistry-driven stability-indicating high-performance thin layer chromatographic (SI-HPTLC) method has been developed for the concurrent stability study of thiocolchicoside (THC) and lornoxicam (LNX). To protect the environment and human life, the stability-indicating HPTLC method was developed using safe organic solvents. Potential analytical method risk parameters (AMRPs) and analytical method performance attributes (AMPAs) were screened using the fractional factorial design. The response surface analysis and optimization of critical AMRPs and AMPAs was carried out using full factorial design. Navigation of the method operable design region (MODR) was used to develop the SI-HPTLC technique. The developed method was validated as per ICH (International council for harmonization) Q2(R1) guideline. The developed method's greenness was evaluated using AGREE (Analytical Procedure Greenness) tool and ESA (Eco-Scale Assessment). The Blue (B) model was used to assess the proposed method's cost and time efficiency and user-friendlyness. For the stability studies of THC and LNX, the twelve principles of WAC (White Analytical Chemistry) were used to evaluate the published and proposed chromatographic techniques. As compared to previously published chromatographic techniques for studying the stability of THC and LNX, the suggested approach was found to be more affordable, environmentally friendly, and user-friendly. Development of stability-indicating HPTLC method using a novel white analytical chemistry approach and organic solvents with low toxicity potential. Application of the developed method for analysis of the forced degraded sample and fixed-dose combinations of THC and LNX.

Design and dermatokinetic appraisal of lornoxicam-loaded ultrafine self-nanoemulsion hydrogel for the management of inflammation: In vitro and in vivo studies

The present study aimed to evaluate the impact of ultrafine nanoemulsions on the transdermal delivery of lornoxicam (LOR) for management of the inflammation. The transdermal administration of LORNE could increase the efficacy of LOR with a reduction in side effects. Merging the beneficial properties of ultrafine nanoemulsions and their components (penetration enhancers) can lead to good solubilization, a small droplet size, and more effective LOR carriers. Therefore, this study aims to develop and evaluate the potential use of ultrafine nanoemulsions of LOR (LORNE) to elucidate their skin targeting for the treatment of inflammation. Based on solubility and pseudo ternary phase diagram tests, ultrafine LORNE composed of Labrafil M 2125 CS, Cremophor RH40, and Transcutol HP to deliver LOR was developed and characterized for its physicochemical properties, emulsification, and in vitro release. The selected LORNE was incorporated into carbopol gel (LORNE-Gel) and examined for ex vivo skin permeation, retention, dermatokinetics, anti-inflammatory efficacy, and skin irritation. The selected LORNE12-Gel could improve skin permeation, retention, and dermatokinetic results significantly (p < 0.05) with enhanced CSkin max and AUC0-48h compared to LOR-Gel. Moreover, LORNE12-Gel showed a remarkable anti-inflammatory effect compared to LOR-Gel after topical application. No signs of skin irritation were observed following treatment, indicating the safety of LORNE12-Gel. Thus, this study demonstrated that LOR-loaded LORNE12-Gel could be promising as an efficient transdermal nanocarrier for an anti-inflammatory alternative.

Magnetic polycaprolactone microspheres: drug encapsulation and control

Targeted drug delivery (TDD) systems have several advantages, especially with drugs having toxic side effects such as lornoxicam (LX) which shows high hepatotoxicity and nephrotoxicity, especially with long-term use. This work represents an attempt to control magnetic microspheres encapsulating LX and magnetite nanoparticles (MNPs) for potential targeted drug delivery of LX. Superparamagnetic nanoparticles were fabricated via the co-precipitation method and together with LX were encapsulated into polycaprolactone (PCL) microspheres through an oil-in-water (O/W) emulsion solvent evaporation method. The effects of changing the amount of drug, MNPs, and volume of the aqueous phase were investigated by preparing several microsphere formulations. Increasing the amount of encapsulated MNPs increased the magnetization of the microspheres without affecting the morphology. Doubling the volume of the aqueous phase resulted in a higher encapsulation efficiency and drug loading; 83.9% and 10.7%, respectively, while increasing the amount of drug had a negative effect on both drug loading and encapsulation efficiency. Drug release from the microspheres was successfully achieved and showed a biphasic nature. A system of four planar coils was then used to magnetically control the movement of a cluster of capsules in a glycerin medium, as a simulation for the targeting process. The microspheres were successfully controlled to move in a U-turn path with sharp corners demonstrating their potential for TDD applications.

A novel soluble lornoxicam-sodium chelate monohydrate with improved plasticity and tabletability

Lornoxicam (LOR), a BCS II nonsteroidal anti-inflammatory drug, has been clinically utilized for moderate to severe acute pain management. However, it has poor water solubility and insufficient tabletability, leading to erratic absorption and challenge in tablet processability. This study reported a novel solid state of LOR (i.e., LOR sodium chelate monohydrate, LOR-Na·H2O) with significantly improved solubility, dissolution rate and tabletability. The prepared chelate (CCDC No.: 2125157) contains LOR-, Na+, and H2O in a molar ratio of 1:1:1, where Na+ ions bridged with O(5) of amide group, and N(2) of pyridine group on LOR-, as well as O(4) on H2O through coordination bonds. LOR-Na·H2O displayed a superior dissolution rate (5 ∼ 465 folds) than commercial LOR due to its increased wettability (contact angle: 74.5° vs 85.6°) and lower solvation free energy (∼2-fold). In addition, the significant improvement in tabletability was caused by high plasticity and deformability, which was attributed to its special interlayer gliding with weak bonding interactions across layers but strong coordination bonding interactions within layers. The novel LOR-Na·H2O with significantly enhanced pharmaceutical performance offers a promising strategy for further product development.

Design, characterization and in vivo performance of solid lipid nanoparticles (SLNs)-loaded mucoadhesive buccal tablets for efficient delivery of Lornoxicam in experimental inflammation

Lornoxicam (LRX) is a potent nonsteroidal anti-inflammatory drug (NSAID) used extensively to manage pain and inflammatory conditions. However, the drug possesses poor aqueous solubility (i.e., BCS class II) and a short half-life (3–4 h). Mucoadhesive buccal tablets containing LRX -loaded solid lipid nanoparticles (SLNs) were developed to enhance the drug solubility and bioavailability and achieve a controlled release pattern for a better anti-inflammatory effect. Different LRX-loaded SLNs were prepared using the hot homogenization /ultra-sonication technique and evaluated using size analysis and entrapment efficiency (EE%). Optimized LRX -loaded SLNs formulation showed particle size of 216 ± 7.4 nm, zeta potential of −27.3 ± 4.6 mV, and entrapment efficiency of 92.56 ± 2.3 %. Dried LRX-loaded SLNs alongside mucoadhesive polymers blend (PVP K30 /HPMC K15) were compressed to prepare the mucoadhesive buccal tablets. The tablets showed proper physicochemical properties, good mucoadhesive strength, long mucoadhesive time, suitable pH surface, good swelling capacity, and controlled drug release profile. Furthermore, Fourier transform-infrared (FTIR) spectroscopy, Powder X-Ray diffraction (PXRD), and Scanning electron microscopy (SEM) studies were carried out. The in vivo anti-inflammatory effect of pure LRX, market LRX and optimized mucoadhesive buccal tablet of LRX -loaded SLNs (T3) against carrageenan-induced models were evaluated. T3 showed a significant and early anti-inflammatory response after 1 and 2 h (63.62–77.84 % inhibition) as well as an extended effect after 4 h as compared to pure and market LRX. In parallel, T3 showed the best amelioration of PGE2, COX2, and TNF-α serum levels after 4 h of carrageenan injection.

Lornoxicam-Loaded Cubosomes: - Preparation and In vitro Characterization.

Cubosomes are nanosized structures self-assembled nanostructured materials used for controlling the release of the entrapped drug molecule. Lornoxicam (LXM) is a potent analgesic nonsteroidal anti-inflammatory (NSAID) drug with a short half-life (3-4) hours. The present study aims to prepare LXM-loaded cubosomes with well-defined morphology, particle size, PDI, high entrapment efficiency, sustained drug release, and high zeta potential value, as a transdermal drug delivery system.&#x0D; Twelve formulas of LXM-loaded cubosomal dispersions were prepared by a solvent dilution method using Glyceryl monooleate ( GMO) as polar lipid with different stabilizers as Pluronic® F127 or tween 80 and different types of hydrotrope as ethanol or propylene glycol. These formulas were evaluated for their particle size analysis &amp; PDI, E.E. %, and in-vitro drug release to select a group of the optimum formulas, that further characterized by transmission electron microscopy (TEM) and zeta potential analyzer to select the optimum dispersion. FTIR study was used to investigate the compatibility of the drug with excipients.&#x0D; The obtained results indicated that F3, composed of GMO, Pluronic® F127, ethanol, drug, and phosphate buffer solution pH 7.4 in the following per cents 7.28%, 1.82%, 8%, 2%, and 80.9% w/w, respectively, prepared in 20min agitation period, as the optimum formula for its high E.E. % (94.30±0.002%), small particle size (16.3±0.19nm), low PDI (0.06±0.02), and high zeta potential value (-65.9±0.05mV), and well-defined cubic structure. FTIR study indicated no interaction between LXM and other formulas components.&#x0D; This study's conclusion illustrated that LXM-loaded cubosomal dispersion could be considered a promising nano-carrier for transdermal drug delivery.

Carbon quantum dots with blue/near infrared emissions for ratiometric fluorescent lornoxicam sensing and bio-imaging.

An economical and eco-friendly hydrothermal method for the preparation of nitrogen-doped carbon quantum dots (N-CQDs) was studied with rambutan peel and lysine. The morphology, structure, and optical properties of N-CQDs were characterized by transmission electron microscopy, Fourier transform infrared spectrometry, X-ray powder diffractometer, X-ray photoelectron spectrometry, and UV spectrophotometry. The synthesized N-CQDs have excellent characteristics such as strong fluorescence, good dispersion, high stability, and excellent water solubility. The absolute fluorescence quantum yield is 1.02%, the average particle size is 1.63nm, and the maximum excitation wavelength is 340nm. The maximum emission wavelengths are 430nm and 800nm. As a quencher, lornoxicam (LNX) was used to quench the fluorescence of N-CQDs with the mechanism of inner filter effect. The fluorescence ratio of N-CQDs (F430/F800) shows a good linear relationship to the concentration of LNX. The linear range and the detection limit of LNX are 0.01‒100 and 0.003 μmol/L, respectively. An effective ratiometric fluorescence probe for the detection of LNX was constructed. The method has the advantages of low detection limit, high sensitivity, wide linear range, andcan be applied to the determination of LNX in real samples. Moreover, according to the excitation-dependent fluorescence behavior, dual-wavelength emission, and biocompatibility of N-CQDs, it has been applied to cell imaging.

BI-LAMINATED ORAL DISINTEGRATING FILM FOR DUAL DELIVERY OF PITAVASTATIN CALCIUM AND LORNOXICAM: FABRICATION, CHARACTERIZATION AND PHARMACOKINETIC STUDY

Objective: Pitavastatin calcium (PT) is an innovative drug of statins that enhances HDL-C and lowers LDL-C. However, myalgia has been reported in hyperlipidemic patients receiving statins. Therefore, co-administration of statins with NSAIDs such as Lornoxicam (LN) could be a solution to the former problem. Accordingly, this study aimed to formulate a bi-laminated oral disintegrating film (ODF) comprising PT in one layer and LN in the second one. Methods: For the formulation and optimization of PT-ODFs, a 31.21 full factorial design was carried out, where the impact of polymer type and concentration on disintegration time (DT) and % PT released after 10 min (Q10) was studied. PT-ODFs were prepared via the solvent casting method and then evaluated. One PT-ODF was chosen to represent the optimum formula according to the criteria of scoring the fastest DT and the highest Q10. The optimized PT-ODF was merged with the second film layer containing LN, forming a bi-laminated ODF named S1 that underwent an in vivo pharmacokinetic study compared to the commercially available tablets for PT (Lipidalon®) and LN (Lornoxicam®) using rats as an animal model. LC-MS/MS was used to analyze plasma drug concentrations. Results: All PT-ODFs showed acceptable outcomes. F1 scored the fastest DT (18.6±1.5 s) and the highest Q10 (91.3±3.0 %). S1 successfully recorded a maximum plasma concentration (Cmax) of 2.04 and 2.24 folds increase for PT and LN, correspondingly, compared to commercially available tablets. Conclusion: Merging PT and LN into bi-laminated ODF was promising for the fast delivery of both drugs with enhanced bioavailability.

Simultaneous Quantitation of Paracetamol and Lornoxicam in the Presence of Five Related Substances and Toxic Impurities by a Selective HPLC-DAD Method.

This research describes the simultaneous quantitation of paracetamol (PRM) and lornoxicam (LRX) with five of their related substances and toxic impurities, including, 4-nitrophenol (NTP), 4-aminophenol (AMP), 4-chloroacetanilide (CAC), N-phenylacetamide (NPA), and 2-aminopyridine (APD) using a specific HPLC-diode array detector (DAD) method. The chromatographic separation involves the use of a XTerra C18 column as the stationary phase and a mobile phase consisting of acetonitrile and 0.025 M phosphate buffer (pH 6). The separation was performed using gradient elution mode at 1.0 mL/min flow rate and detection at 260 nm for the determination of PRM and LRX. For detecting PRM and LRX in the presence of their toxic impurities, 270 nm was used. Validation of the suggested HPLC method was accomplished with regard to linearity, ranges, detection and quantitation limits, robustness, accuracy, precision, and specificity. Excellent resolution of the mixture components was accomplished at retention times 4.2, 4.8, 7.4, 11.1, 13.5, 14.7, and 15.3 min for APD, AMP, PRM, NPA, LRX, NTP, and CAC, respectively. Linearity was established for PRM and LRX within concentration ranges of 10-100 and 10-60 µg/mL, respectively. The correlation coefficients obtained were >0.9997. The suggested method was confirmed to be a specific stability-indicating through the selective separation of PRM and LRX from their related substances, degradants, and impurities. The proposed method was successfully utilized for the sensitive and selective determination of PRM and LRX in their pharmaceutical formulation. To the best of our knowledge, this is the first impurity profiling assay method for this combination in the presence of five of their toxic related substances and impurities. Taking into consideration that at least two of the studied impurities (AMP and APD) are actually reported degradation products for the main drugs, the suggested method can be considered stability-indicating as well.

Formulation and optimization of lornoxicam-loaded bilosomes using 23 full factorial design for the management of osteoarthritis in rats: Modulation of MAPK/Erk1 signaling pathway

The objective of this study was to formulate and evaluate Lornoxicam (LOX) loaded bilosomes for effective treatment of osteoarthrotis. Lornoxicam bilosomes were formulated using thin film hydration method. A 23 full factorial design was employed to evaluate the effect of different formulation variables. Three independent variables were studied; bile salt type (X1), drug amount (X2) and lipid: bile salt ratio (X3). The dependent responses were; entrapment efficiency (Y1: EE %), vesicles size (Y2: VS) and zeta potential (Y3: ZP). Design Expert® software was utilized to statistically optimize formulation variables. The vesicles revealed high LOX encapsulation efficiency ranging from 56.01 ± 3.26 to 82.70 ± 1.80% whereas vesicle size ranged from 94.04 ± 6.5 to 292.5 ± 5.3 nm. High negative zeta potential values indicated good stability of the prepared formulations. The optimized vesicles exhibited spherical morphology under transmission electron microscopy (TEM). LOX release from bilosomes was biphasic and the release pattern followed Higuchi's model. In-vivo studies confirmed the efficiency of LOX bilosomes in treatment of osteoarthritis by improving locomotor activity and coordination, inhibiting pro-inflammatory cytokines; IL-6, and NF-κβ as well as blocking mitogen-activated protein kinases (MAPKs)/extracellular signal-regulated kinase (ERK) pathway. Moreover, in-vivo histopathological studies of knee joint tissues treated with LOX bilosomal formulations showed a reduction in inflammatory cells infiltration with average synovial lining and average articular cartilage. The results revealed that the developed LOX bilosomes could be a promising drug delivery system to be used in the treatment of osteoarthritis.

Formulation and evaluation of taste masked oral disintegrating tablets of lornoxicam

Orally disintegrating tablets (ODT) disintegrate quickly with saliva when administered into the oral cavity and taken without water or chewed. ODT are easy to take for children and the elderly, who may experience difficultly in taking ordinary oral preparations such as tablets, capsules, and powders. The ODT threes substantial benefits for the patient (or elder) who cannot swallow (Dysphagia), or who is not permitted water intake due to disease. The reason of the current research was to prepare taste masking oral disintegrating tablets of poorly soluble lornoxicam (LXM) by direct compression technique using Kyron T-114 (cation exchange resin) as a taste masking agent. With in various ratios the Drug-resin of 1:4 was established to present best taste masking. The superdisintegrants used in formulation are croscarmellose sodium and cross povidone. Among these croscarmellose sodium demonstrated superior drug release. The tablets were evaluated for friability, weight variation, wetting time, hardness, disintegration time and uniformity of content. Optimized formulations were evaluated for in vitro dissolution test. Amongst all the formulations F-6 was found to be most successful tablets prepared by this technique had disintegration time of 30sec and % CDR 94.78 within 30min. Hence, this advance can be utilized for taste masking of bitter pharmaceutical ingredients leading to superior patient compliance.&#x0D; Keywords: Oral disintegration tablets, Lornoxicam, Kyron T-114, Superdisintegrants, Direct Compression.

SIMULTANEOUS ESTIMATION OF LORNOXICAM AND PARACETAMOL IN COMBINED TABLET DOSAGE FORM USING REVERSE PHASE HIGH- PERFORMANCE LIQUID CHROMATOGRAPHY METHOD

Using simple, precise, and accurate reversed-phase high-performance liquid chromatography (RP-HPLC) method, the synchronous of lornoxicam (LOR) and paracetamol (PCM) in the unite dosage form in the tablet has been established and confirmed. Acetonitrile: methanol: water is the mobile phase of the RP-HPLC method (pH adjusted with orthophosphoric acid), pH 3.8 (50:30:20 v/v/v), a diode array detector tuned to 290 nm was used to detect the signal. For LOR and PCM, chromatographic technique linearity was obtained in the concentration, ranges of 2-40 and 8–150 g/mL, respectively. In HPLC techniques, the recoveries were in the range of 99.85 0.0642 percent for LOR and 99.73 0.187 percent for PCM. Both approaches may be used to analyze the medicines in a pharmaceutical formulation regularly. The results of the analysis were statistically verified. KEYWORDS: linearity, validation, oxicam, N-methyl Aspartate

Amelioration of physicochemical, pharmaceutical, and pharmacokinetic properties of lornoxicam by cocrystallization with a novel coformer

Objective The present study was aimed to prepare and characterize new cocrystals of lornoxicam (LORX), a BCS class II drug employing 1,3-dimethyl urea (DMU) as a coformer to improve physicochemical, pharmaceutical, and pharmacokinetic performance. Methods A screening study was conducted by employing three techniques viz. neat grinding, liquid-assisted grinding (LAG), and solvent evaporation (SE) using different drug–coformer molar ratios (1:1, 1:2, and 1:3). Samples were characterized by DSC, PXRD, ATR-FTIR, SEM, intrinsic dissolution rate (IDR) studies, compressional studies, and pharmacokinetic studies. In vitro dissolution and stability studies (25 °C/60%RH and 40 °C/75%RH for three months) were carried out for cocrystal tablets. Results LAG and SE were found successful in ratio 1:3 and IDR showed approximately 28- and 19-fold increase, respectively in 0.1 N HCl (pH 1.2) and buffer (pH 7.4) as compared to pure LORX. The cocrystal exhibited good tabletability and was ∼2.5 times that of LORX at 6000 Psi. Dissolution profiles of tablets of cocrystal increased (56% and 100% at pH 1.2 and 7.4, respectively in contrast to those of physical mixture (PhyMix) (∼35% and ∼10%) and pure LORX (∼17% and ∼7%) within 60 min. The Cmax and AUC0–∞ for the selected cocrystal were significantly increased (p < 0.05) which was 2.4 and 2.5 times, respectively, that of LORX in a single dose oral pharmacokinetic study executed in rabbits. Tablets of cocrystal were found stable at both conditions. Conclusion The study indicates that cocrystallization with DMU can concomitantly improve tabletability, dissolution rate, and in vivo performance of dissolution limited drug LORX.

Bilosomes as Promising Nanovesicular Carriers for Improved Transdermal Delivery: Construction, in vitro Optimization, ex vivo Permeation and in vivo Evaluation.

PurposeThe goal of this research was to enhance the transdermal delivery of lornoxicam (LX), using nanovesicular carriers composed of the bile salt sodium deoxycholate (SDC), soybean phosphatidyl choline (SPC) and a permeation enhancer limonene.MethodsThin-film hydration was the technique employed for the fabrication using a Box–Behnken design with three central points. The investigated factors were SPC molar concentration, SDC amount in mg and limonene percentage (%). The studied responses were percent entrapment efficiency (%EE), particle size (PS), polydispersity index (PDI), zeta potential (ZP), and in vitro drug release (after 2, 10 h). In order to obtain the optimum formula, numerical optimization by Design-Expert® software was used. Electing the optimized bilosomal formula was based on boosting %EE, ZP (as absolute value) and in vitro drug release, taking in consideration diminishing PS and PDI. Further assessment of the selected formula was achieved by transmission electron microscopy (TEM), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), stability testing, ex vivo skin permeation and deposition. The in vivo pharmacodynamics activities of the optimized formula were examined on male rats and mice and compared to that of the oral market product.ResultsThe optimized bilosomal formula demonstrated to be nonirritant, with noticeably enhanced anti-inflammatory and antinociceptive activities. Superior in vivo permeation was proved by confocal laser scanning microscopy (CLSM).ConclusionThe outcomes demonstrated that bilosomes could improve transdermal delivery of lornoxicam.

LORNOXICAM-LOADED NANOSPONGES FOR CONTROLLED ANTI-INFLAMMATORY EFFECT: IN VITRO/IN VIVO ASSESSMENT

Objective: To design a controlled topical delivery system of lornoxicam (LX) in order to enhance skin permeation and treatment efficacy. Nanosponges were selected as a novel carrier for this purpose.&#x0D; Methods: Nanosponges were formulated via the emulsion solvent evaporation method using ethyl cellulose (polymer) and polyvinyl alcohol (surfactant). Nanosponge dispersions were characterized for colloidal properties, entrapment efficiency and in vitro release study. The nanosponge formulation (LS1) was then incorporated into carboxymethyl cellulose sodium hydrogels and evaluated for pH, viscosity and in vitro drug release. Skin irritation was evaluated, and anti-inflammatory activity was assessed via rat hind paw edema method.&#x0D; Results: Nanosponges were in the nano-sized range and attained a uniform round shape with a spongy structure. LS1exhibited the highest LX release after 6 h, so it was incorporated as hydrogel. Formulated hydrogels showed acceptable physicochemical parameters (pH, drug content and rheological properties). Skin irritation testing proved LX-loaded nanosponge hydrogel formulation (G1) to be non-irritant. In vivo study revealed an enhanced anti-inflammatory activity of G1 for 6 h (p&lt;0.001).&#x0D; Conclusion: The developed nanosponge hydrogel is an efficient nanocarrier for improved and controlled topical delivery of LX.

Direct Injection Microemulsion HPLC Method for Simultaneous Determination of Morphine, Tramadol and Lornoxicam in Biological Fluids Using Monolithic Column

&lt;P&gt;Objective: A rapid and environmental friendly microemulsion liquid chromatographic method was developed for simultaneous quantification of morphine (MOR), tramadol (TRA) and lornoxicam (LOR) in biological fluids. &lt;/P&gt;&lt;P&gt; Methods: Microemulsion used in this study was an aqueous solution containing sodium dodecyl sulfate (0.12 M), n-propanol (10%), ethyl acetate (0.75%), tri-ethyl amine (0.3%), orthophosphoric acid (0.15 %) and the pH was adjusted to 3.0 with orthophosphoric acid. Chromatographic separation was carried out on a monolithic C18 column and a mobile phase flow rate of 1.0 mL min−1 was applied throughout the analysis. The data was monitored using UV-detection mode at a wavelength of 220 nm. &lt;/P&gt;&lt;P&gt; Results: Under the optimized conditions, all the studied drugs were well resolved and completely eluted within 6 min. The proposed method was linear over the concentration ranges of 0.5−100, 0.75−125 and 0.25−50 μg mL−1; limits of detection of 0.074, 0.086 and 0.056 μgmL−1 and limits of quantification of 0.21, 0.28 and 0.12 were recorded for TRA, LOR, and MOR, respectively. The developed method was fully validated according to the ICH guidelines. The method was successfully utilized to estimate the tested analytes in plasma and urine samples, which were directly injected into the chromatographic system after suitable dilution with the microemulsion. &lt;/P&gt;&lt;P&gt; Conclusion: The developed method is considered to be very efficient to analyze the cited drugs in different biological fluids with low running costs and short analysis time.&lt;/P&gt;