Clopidogrel Interactions: Consider while prescribing

Clopidogrel reduces the cardiovascular risks because of inhibitory action on platelets aggregation but some co-administered drugs compromise its main therapeutic effects. Clopidogrel is a prodrug and converted into active metabolite by the hepatic cytochrome P450. The active thiol metabolite inhibits the P2Y12 adenosine di-phosphate receptors and decrease the platelet aggregation processes. The activity of clopidogrel is dependent on the metabolic conversion by cytochrome P450 due to this fact proton pump inhibitors, atorvastatin and several other drugs that competitively inhibit the clopidogrel metabolism might alter its therapeutic response. Conversely other agents potentiate the clopidogrel responsiveness by inducing the cytochrome activity. Combinational drug therapy increases the risks of drug-drug interactions. The previous pharmacodynamic studies have reported clinically significant risks that are associated with combined therapy of clopidogrel with other drugs which are commonly used in coronary artery disorders. These reported studies did not demonstrate the consistent evidence for sever drug-drug interaction hazards in cardiovascular events. This review highlights the various controversies among the studies about common clopidogrel interactions when prescribed in various cardiovascular disorders to achieve targeted therapeutic outcomes. The clopidogrel is commonly prescribed in many serious disorders such as cardiovascular, hypercholesteraemia and lack of information or uncertainty may cost serious outcomes. Keywords: Clopidogrel, Interactions, Cardiovascular, Proton pump inhibitor

Formulation and in vitro evaluation of mucoadhesive controlled release matrix tablets of flurbiprofen using response surface methodology

The objective of the current study was to formulate mucoadhesive controlled release matrix tablets of flurbiprofen and to optimize its drug release profile and bioadhesion using response surface methodology. Tablets were prepared via a direct compression technique and evaluated for in vitro dissolution parameters and bioadhesive strength. A central composite design for two factors at five levels each was employed for the study. Carbopol 934 and sodium carboxymethylcellulose were taken as independent variables. Fourier transform infrared (FTIR) spectroscopy studies were performed to observe the stability of the drug during direct compression and to check for a drug-polymer interaction. Various kinetic models were applied to evaluate drug release from the polymers. Contour and response surface plots were also drawn to portray the relationship between the independent and response variables. Mucoadhesive tablets of flurbiprofen exhibited non-Fickian drug release kinetics extending towards zero-order, with some formulations (F3, F8, and F9) reaching super case II transport, as the value of the release rate exponent (n) varied between 0.584 and 1.104. Polynomial mathematical models, generated for various response variables, were found to be statistically significant (PO objetivo do presente estudo foi formular comprimidos mucoadesivos de flurbiprofeno, de liberação controlada, e otimizar o perfil da liberação do fármaco e a bioadesão, utilizando a metodologia de superfície de resposta. Prepararam-se os comprimidos via técnica de compressão direta, que foram avaliados in vitro quanto aos parâmetros de dissolução e da força bioadesiva. Planejamento com componente central para dois fatores em cinco níveis cada foi empregado para esse estudo. Carbopol 934 e carboximetilcelulose sódica foram tomados como variáveis independentes. Efetuaram-se estudos de espectroscopia por transformada de Fourier (FTIR) para observar a estabilidade do fármaco durante a compressão direta e para avaliar a interação a fármaco-polímero. Aplicaram-se vários métodos cinéticos para avaliar a liberação do fármaco dos polímeros. Gráficos de superfície de contorno e de resposta foram efetuados para retratar a relação entre as variáveis dependentes e a resposta. Os comprimidos mucoadesivos de flurbiprofeno apresentaram cinética de liberação não-fickiana, estendendo para ordem zero, para algumas formulações (F3, F8 e F9), alcançando transporte super caso II, à medida que o valor do expoente (n) de taxa de liberação variou entre 0,584 e 1,104. Modelos matemáticos polinomiais, gerados por diversas variáveis de resposta, foram estatisticamente, significativos (

Development and evaluation of biodegradable controlled release microspheres of venlafaxine

  In this study we developed and evaluated stable, biodegradable microspheres for controlled release of venlafaxine. For this purpose, polycaprolactone, a hydrophobic polymer was used in different ratios. Following are the drug to polymer ratios P1 (1:1), P2 (1:1.5), P3 (1:2), P4 (1:2.5) and P5 (1:3); employed to develop controlled release microspheres. Drug loading efficiency increased with increasing quantity of polycaprolactone. The mechanism of venlafaxine release was studied by applying First order, Zero order, Higuchi’s, Hixon-Crowell and korsmeyer-Peppas models to dissolution data. Higuchi model was found the best fit model followed by First order release. The mechanism of release was non-Fickian diffusion. All formulations showed an initial burst of 69.53%, 62.37%, 55.45%, 53.76% and 49.32% from P1, P2, P3, P4 and P5 formulations, respectively at the end of 1st h dissolution. P5 was the superior formulation in terms of reduced initial burst and after which sustained release occurred up to 8 hours. The developed microspheres were characterized by Fourier transform infra-red spectroscopy, scanning electron spectroscopy, differential scanning calorimetry and thermogravimetric analysis

Comprehensive Review on Magnetic Drug Delivery Systems: A Novel Approach for Drug Targeting

Magnetic drug delivery systems have been emerged as a prominent technique for site-specific targeting of various pharmacological agents throughout the last few decades. With the support of a magnetic field, it avoids reticuloendothelial system and directs the drugs to reach the target precisely. Magnetic carriers like nanoparticles, microspheres, liposomes and emulsion have been found advantageous of the fact that they reduces the free drug concentration in the blood and to minimize the adverse effects provoked by these drugs. It has made the most crucial tumor targeting possible without damaging the healthy tissues. In this review, we will summarize the facts about magnetic drug delivery systems comprehensively

A comparative bioavailability study of aceclofenac products in healthy human subjects

This study was conducted to compare the bioavailability of two branded formulations of aceclofenac and to evaluate their pharmacokinetic behavior. For bioequivalence study of two formulations of aceclofenac; drug A and drug B were administered to 18 healthy human volunteers using a two-treatment, two-way cross over study design in a randomized fashion. For the determination of aceclofenac plasma concentration, validated HPLC method with UV-visible detector, 20 µl injecting loop and C18 analytical column were used. The lower limit of detection is 0.0195µg/ml and quantitation range is 0.039, 0.078, 0.156, 0.312, 0.625, 1.25, 2.5, 5, 10 and 20µg/ml. Different pharmacokinetic parameter were determined including Tmax, T1/2, Cmax, AUC0-t, AUC0-?, vd, ke for two formulations of aceclofenac in plasma. After log-transformation of plasma data for bioequivalence Cmax, AUC0-t and AUCt-? were tested. The Cmax values of 7.69 ± 0.14221µg/ml and 6.82 ± 0.13411µg/ml were attained in 3.14 ± 0.0801 h and 2.94 ± 0.1878 h for drug A and Drug B, respectively. AUC0-t was 45332.79 ± 2096.770µg.h/ml and 43842.56 ± 1046.954µg.h/ml, respectively. AUC0-? was 45329.97±2138.871µg.h/ml and 43589.97 ± 1039.78 µg.h/ml for drug A and Drug B, respectively. The t1/2 values were found to be 3.14 ± 0.080 h and 3.01 ± 0.024 h for drug A and Drug B

Fabrication and Evaluation of Rosuvastatin Calcium Fast- Disintegrating Tablets Using β-Cyclodextrin and Superdisintegrants

Purpose: To formulate fast-disintegrating tablets (FDT) of rosuvastatin calcium (RST) using β- cyclodextrin (CD) and different superdisintegrants to enhance their solubility.Methods: A total of 15 FDT formulations of RST were prepared using three different techniques. The FDTs were evaluated for micromeritic properties, as well as by Fourier transform infrared spectroscopy (FTIR), thermal analysis, disintegration time (DT), dissolution rate, powder x-ray diffraction (XRDP), scanning electron microscopy (SEM) and stability studies.Results: XRDP showed that RST was changed from crystalline to amorphous form. SEM images revealed the presence of small microscopic pores that enhanced water penetration and provided rapid dissolution rate compared with the pure drug. There was maximum release of drug (99 %) from F4 formulation containing solid dispersion of RST, CD and superdisintegrants. DT and wetting time were 25 s (p = 0.032) and 33 s (p = 0.023), respectively, for F4 formulation. In vitro dispersion time was also lowest for F4 at 23 s (p = 0.023). FTIR and DSC studies also confirmed complex formation of drug with CD and superdisintegrants.Conclusion: FDT is a suitable strategy to enhance the dissolution rate of RST and thus is an effective tool to improve bioavailability of poorly water soluble drugs.Keywords: Solubility, β-cyclodextrin, Kyron, Polymer, Rosuvastatin, Fast-disintegrating tablet

Using Carbomer-Based Hydrogels for Control the Release Rate of Diclofenac Sodium: Preparation and In Vitro Evaluation

The aim of the current research work was to prepare Car934-g-poly(acrylic acid) hydrogels by the free-radical polymerization technique. Various concentrations of carbopol, acrylic acid and ethylene glycol dimethacrylate were employed for the fabrication of Car934-g-poly(acrylic acid) hydrogels. Fourier-transform infrared spectroscopy (FTIR), Thermogravimetric analysis (TGA), Differential scanning calorimetry (DSC), Scanning electron microscope (SEM) and Powder X-ray diffractometry (PXRD) studies were performed to know the structural arrangement, thermal stability, physical appearance and amorphous network of developed hydrogels. FTIR analysis revealed that carbopol reacted with acrylic acid during the process of polymerization and confirmed the grafting of acrylic acid over the backbone of carbopol. TGA and DSC studies showed that developed hydrogels were thermally stable. Surface morphology was analyzed by SEM, which confirmed a porous network of hydrogels. PXRD analysis indicated that crystallinity of the drug was reduced by the amorphous network of hydrogels. Furthermore, swelling studies for all developed hydrogels were performed at both media, i.e., pH 1.2 and 7.4, and higher swelling was exhibited at pH 7.4. Sol–gel analysis was performed to evaluate the soluble unreacted part of the fabricated hydrogels. Similarly, an in-vitro study was conducted for all hydrogel formulations at both acidic (pH 1.2) and basic (pH 7.4) mediums, and a greater drug release was observed at pH 7.4. Different kinetics such as zero-order, first-order, the Higuchi model and the Korsmeyer–Peppas model were applied to know the mechanism of release order of drugs from the hydrogels