Aceclofenac

The aim of the study is to prepare solid lipid Microparticle (SLM) dispersion of aceclofenac for the treatment of inflammation and allied condition. SLM prepared by melt emulsification & solvent evaporation methods were characterized by Malvern instrument for particle size and particle size distribution and zeta potential analysis. The particle size of dispersion was further confirmed by scanning electron microscopy (SEM) studies. IR study of pure drug, Stearic acid and drug loaded solid lipid Microparticle were performed. In-vitro release study was performed on modified franz diffusion assembly which showed that drug release maximum 79.86% in 24 hours. Keywords; Aceclofenac, Solid lipid Microparticle (SLM), Microparticle, Lipid Microparticle

Aceclofenac is a non steroidal anti- inflammatory drug characterized by low solubility and high permeability which corresponds to BCS class II drug. The strategy of increasing the in vitro dissolution has the potential to enhance the oral bioavailability when using nanosized crystalline drugs. The purpose of this study was to evaluate a novel in situ micronization method avoiding any milling techniques to produce nano- or microsized drug particles by controlled crystallization to enhance the dissolution rate of poorly water-soluble drugs. Aceclofenac microcrystals were prepared by the association of the previously molecularly dispersed drug using a rapid solvent change process. The drug was precipitated in the presence of stabilizing agents, such as hydrocolloids. The obtained dispersion was spray-dried. Particle size, morphology, flow property, zeta potential and dissolution rate were analyzed. Physicochemical properties were characterized using differential scanning calorimetry and X-ray diffractometry. The obtained dispersions showed a homogeneous particle size distribution. Drugs are obtained in a mean particle size of approximately 3µm and below. A high specific surface area was created and in situ stabilized. The surface was hydrophilized because of the adsorbed stabilizer. The solubility of the drug was increased by 2 folds. Thus, a drug powder with markedly enhanced dissolution rate was obtained. In situ micronization is a suitable method for the production of micro-sized drugs. This technique can be performed continuously or discontinuously and uses only common technical equipment. Compared to milled products drug properties are optimized as all particle surfaces are naturally grown, the particle size is more uniformly distributed and the powder is less cohesive.

A simple validated high performance thin layer chromatographic method was developed for the determination of Aceclofenac in presence of its degradant. Separation of Aceclofenac from the degradant could be achieved using aluminium backed silica gel 60 F254 plate with toluene: ethyl acetate: glacial acetic acid, (6:4:0.02v/v) as mobile phase. Densitometry analysis was carried out at 282 nm. The method showed high sensitivity with good linearity over the concentration range of 0.5 – 4 µg/spot. The method was successfully applied to the analysis of pharmaceutical formulation containing Aceclofenac with excellent recovery. The LOD and LOQ were found to be 0.1 and 0.5 µg/spot. Aceclofenac was subjected to hydrolytic, oxidative, thermal and photolytic degradation. It was found that the drug was highly susceptible to acid hydrolysis. Kinetic investigation of the drug followed pseudo-first order reaction. From the Arrhenius plot the activation energy was found to be 13.19 kcal/mole. Statistical analysis revealed that the developed method is accurate and reliable. Hence it can be used for routine quality control analysis of Aceclofenac in tablet formulation.

A simple, rapid, and precise RP-HPLC method for simultaneous analysis of Losartan potassium and Atorvastatin calcium in bulk and its pharmaceutical formulations has been developed and validated. Atorvastatin was separated from losartan by using Grace Smart Altima C-18 column (25 cm × 4.6 mm, 5-μm) with a mobile phase consisting of acetonitrile: 10mM phosphate buffer (55:45 %v/v, pH 3.0) a flow rate of 1mL/min and detection wavelength at 240 nm. Aceclofenac was used as an internal standard in this method. Losartan, atorvastatin and aceclofenac were eluted with retention times of 4.85 min, 8.31min and 9.51 min respectively. The method was validated for accuracy, precision, linearity and sensitivity in accordance with ICH (Q2B) guidelines and the results of all the validation parameters were found to be within the acceptable limits. The calibration plots were linear over the concentration ranges from 200-30000ng/mL (r2 = 0.999) for both the drugs. Accuracy and precision were determined by QC sample covering low, medium, and high concentration levels. Intra and inert-day accuracy were found to be 97.16-102.57% for losartan and 97.01-103.05% for atorvastatin. The limit of quantification was found to be166ng/mL and 179ng/mL for losartan and atorvastain respectively. The method was successfully applied for the assay of the dosage form, recovery of the individual drugs from the combined tablet dosage was found to be >97% for both the drugs. From the results it is suggested that the proposed method is simple, reproducible, accurate and precise.

  Aceclofenac is a non-steroidal anti-inflammatory, analgesic and antipyretic drug used in the treatment of rheumatic arthritis, post-traumatic pain, masculo-skeletal and joint disorder. Problem with this drug is poor solubility in water hence poor bioavailability after oral administration. The objective of the research work was to develop and evaluate mouth dissolving tablets of Aceclofenac by using sublimation technique. The sublimation technique is used to increase the porosity of the tablets in which camphor was used as subliming agents which in turn forms the porous structure on the surface of tablets after sublimation. Aspartame was used as sweetening agent. The formulated tablets were evaluated for different parameters like weight variation, hardness, friability, drug content, disintegration time, wetting time, water absorption ratio, and In-vitro dissolution studies. Based on the results, formulation F-3 & F-6 containing Crosprovidon and Kyron T-314 10% concentration as superdisintegrants showed the least wetting time of about 17 & 13 sec, disintegration time of 25 & 18 sec and drug release of about 89.13 & 99.14% within 180 sec respectively and was found to be promising and selected as the optimized formulations. From the results, it was concluded that mouth dissolving tablets with improved Aceclofenac dissolution could be prepared by sublimation of tablets containing suitable subliming agent. Key words: Aceclofenac, mouth dissolving tablets, in-vitro, sublimation technique.

  Rapid and accurate isocratic reverse phase high performance liquid chromatography method is described for simultaneous determination of aceclofenac and thiocolchicoside in the combination dosage form. The separation of two drugs was achieved on Thermo Hypersil BDS C18 (250 mm X 4.6 mm) column of 5 µm particle size. Mobile phase consisted of 42:58 of acetonitrile and buffer of pH 6 respectively. Detection was carried out at 261 nm. Thermo Hypersil BDS C18 column showed most favorable chromatographic parameters for analysis. The method was validated for system suitability, linearity, accuracy, precision, robustness and stability of sample solution. The linear range for aceclofenac and Thiocolchicoside was 25-125 μg/ml and 1-6 μg/ml respectively.

In the present work, an attempt has been made to study the sustaining release property of isolated mucilage powder of Plantago ovata by formulating the sustained release tablets of aceclofenac and comparing its efficiency with hydrophilic matrix polymer HPMC K4 M. The drug compatibility with mucilage was checked by FTIR studies and found to be intact and stable. The results of pre-compression studies revealed that they were within prescribed limits that indicate good flowing property. All the formulations were found to be within the acceptable limits of official weight variation test. In all the formulations, friability was less than 1 % indicating good mechanical resistance of tablets. Drug content was found to be within acceptable limits. The formulations were also evaluated for hardness, thickness and dissolution profile. The data of drug dissolution was fitted into kinetic models which revealed that all the formulations followed Peppas release kinetics. The results revealed that the formulation F4 showed sustained drug release up to 12 hours. It also revealed that the isolated mucilage powder of Plantago ovata showed better sustained release over HPMC K4 M. In conclusion, Plantago ovata mucilage, obtained from natural source could be used as a reliable alternative over the synthetic polymers used for sustained release formulations. Key words: Aceclofenac, Plantago ovata mucilage, HPMC K4 M, Release retardant

  The present work describes the development of stability indicating assay method for Diacerein and Aceclofenac in their combined dosage form that would provide helpful information to the manufacturers. Stress studies were conducted on the drug substance and product under the ICH prescribed stress conditions viz. hydrolysis, oxidation, humidity, photolysis, thermal stress. The separation of the drug from its degradation products, trials were made by taking acetonitrile: water, acetonitrile: phosphate buffer, acetonitrile: phosphoric acid in various blends. Separation was achieved using C-18 column and a mobile phase comprising of Acetonitrile: Phosphoric acid 0.1 M (61: 39) at a flow rate of 1.5 mL/min. The detection wavelength was 260 nm. The drug showed sufficient decomposition under alkaline hydrolysis (0.05 N NaOH), acidic hydrolysis (0.05 N HCl), neutral hydrolysis (distilled water), and oxidative hydrolysis (6% H2O2). The drug was found to be moderately sensitive to humidity studies (75 % RH), photochemical studies (UV 254 nm), and thermal studies (600C). Recovery studies were also carried out for both the drugs and the mean percent recovery were found to be 100.69 for diacerein and 99.15 for aceclofenac. Mean percent estimation in marketed formulation gave 99.63% for diacerein and 100.04% for aceclofenac. The above method was validated for accuracy, precision, ruggedness, limit of detection, limit of quantitation and was found to be satisfactory for routine analysis of diacerein and aceclofenac in their combined dosage form in the presence of their degradation products.   Key words: Aceclofenac, Diacerein, Stress Degradation, Stability Indicating, Validation