FORMULATION AND EVALUATION OF CLOPIDOGREL TABLET INCORPORATING DRUG NANOPARTICLES (original) (raw)
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International Journal of Pharmaceutical Sciences and Drug Research, 2020
The present research is aimed at enhancing solubility and drug dissolution of clopidogrel (CPG) used as oral antiplatelet agent by employing solid dispersion (SD) technique. Total 40 SDs formulated with drug: polymers (pluronic F127, poloxamer 407, labrafil PG, PEG 6000, gelucire 50/13), in varying ratios (1:0.5, 1:1, 1:2, 1:3, 1:4) of which CPG1 to CPG20 and CPG21 to CPG40 prepared by adopting solvent evaporation method fusion (melt) method respectively. The formulation CPG40 containing pluronic F127 as polymer showed highest solubility of 6.57±0.04 mg/ml) that is 45 folds than pure drug. Similar results reflected in the dissolution studies where CPG40 containing CPG: pluronic F127 in 1:4 ratio showed maximum % drug content, % practical yield and drug dissolution of 99.14% in 60 minutes when compared with other formulations and pure drug (32.76%) obtained by fusion melt method. From FTIR studies the optimized formulation CPG40 showed the compatibility between drug and polymers....
Journal of Applied Pharmaceutical Science, 2017
The present study was aimed to formulate nanosuspensions using high pressure homogenization (HPH), a top down technique for enhancement of dissolution rate and solubility of clopidogrel using Pluronic F127 as stabilizer. Clopidogrel is categorized as a BCS class II agent having oral bioavailability less than 50%. The formulation scheme was generated by Box-Behnken design of response surface methodology. The formulated nanosuspensions were assessed on particle size, polydispersity index, and zeta potential. Three formulations were selected based on different predicted particle size with manipulation of parameters using response optimizer. The selected formulations were checked on percentage of bias in between predicted value and observed value and evaluated based on drug content, drug entrapment efficiency and in vitro dissolution study. The formulation was optimized based on the smallest particle size and highest percentage of in vitro cumulative drug release. Formulation FF3 was selected as optimized formulation which attributed to the smallest particle size (478.1 nm) and the highest % CDR in both 0.1 N HCl (98.37%) and phosphate buffer (48.67%). The optimized formulation has shown a significant 2 folds enhancement in dissolution rate in 0.1 N HCl and 10 folds improvement in pH 6.8 phosphate buffers with 0.1% w/v Tween 80 compared to pure drug suspension.
Formulation and Evaluation of Fast Dissolving Tablets using Solid dispersion of Clopidogrel
2014
The present investigation was aimed to formulate and evaluate of fast dissolving tablets of clopidogrel bisulphate solid dispersion. The solid dispersion was prepared by fusion method using PEG 6000 as carrier in various ratios. The physio-chemical characterization of solid dispersion was carried out by various parameters like drug content, dissolution study and Differential Scanning Calorimetry. The optimized solid dispersion of clopidogrel bisulphate was used in the preparation of fast dissolving tablets by direct compression method with varying concentrations of superdisintegrants like crospovidone, crosscarmellose sodium and sodium starch glycolate. The formulations were further evaluated for pre & post compression parameters and in vitro dissolution studies. The study reveals that the formulation F3 (10% of cross povidone) is found to be the optimized formulation with 99% drug release in 60 minutes in comparison with other super disintegrants. The kinetics study shows that the ...
2017
Different formulations were made with an aim to develop stable, cost effective Clopidogrel tablets by direct compression technique. Four formulations (F1 – F4) having Primojel and xanthan gum at different concentrations level were prepared. The prepared batches of tablets were evaluated for hardness, friability, disintegration and in-vitro dissolution study. All The formulations containing combination of Primojel and Xanthan gum showed different in-vitro disintegration time and drug release.
Indo American Journal of Pharmaceutical Research, 2013
The main objective of the present study is to enable the prediction of in vivo performance of clopidogrel extended release mini-tablets in capsule by simulated In vitro bio relevant dissolution testing method. The optimized formulation evaluated for dissolution at different agitation speed shown, no significant difference in dissolution profile and the F2 value observed was 96 & 88 at 75 RPM & 125RRPM respectively in comparison to 100RPM. The formulation evaluated for dissolution under simulated pre-prandial condition and post-prandial conditions using USP dissolution apparatus -3, resulted the extent of dissolution of 82.3% and 91.5% respectively at 12 hours. A pharmacokinetic study conducted with clopidogrel extended release mini tablets, on rabbits under pre-prandial condition was deconvulted to fraction of drug absorbed, and compared for IVIV–level A correlation. The result reveals good correlations between in-vitro drug release and in-vivo drug absorption in pre-prandial state, and the F2 value observed was 73.
The main objective of the present study is to enhance the dissolution of clopidogrel bisulphate in intestinal fluids by formulating into mini-tablets with in-situ acidifying agent mini-tablets. The solubility data reveals, Clopidogrel bisulphate is freely soluble in pH 2.0 and the solubility decreases with increase in pH. Whereas, with weak acid, the solubility of clopidogrel is increased at pH 5.0 blank fed state simulated intestinal fluid and & pH 6.5 blank fasted state simulated intestinal fluid. Hence, tartaric acid is selected in the core tablet to enhance the dissolution of clopidogrel tablets at intestinal fluid pH 5.0 & pH 6.5. Formulation was evaluated with different levels of tartaric acid in core tablet. Formulation with 50mg/unit of tartaric acid showed the extent of dissolution of 100% in pH 5.0 blank fed state simulated intestinal fluid and 96% in pH 6.5 blank fasted state simulated intestinal fluid. To control the impact of humidity on degradation, a moisture protective layer is coated on core tablet with non-aqueous solvent, using conventional coating pan. The coated mini tablets are encapsulated in a hard gelatin capsule shell. The filled capsules are evaluated for description, assay, dissolution, water by KF. INTRODUCTION: Clopidogrel, an inhibitor of platelet aggregation, selectively inhibits the binding of adenosine diphosphate (ADP) to its platelet receptor and the subsequent ADP-mediated activation of the glycoprotein GPIIb/IIIa complex, thereby inhibiting platelet aggregation 1. Clopidogrel bisulfate is a white to off-white powder. It is practically insoluble in water at neutral pH but freely soluble at pH 1.0.
Formulation and evaluation of orally disintegrating clopidogrel tablets
Brazilian Journal of Pharmaceutical Sciences, 2016
Recent advances in drug delivery systems have aimed to achieve better patient compliance. One of these advances is the formulation of orally disintegrating tablets (ODTs) that dissolve instantaneously, releasing drugs within a few seconds without the need of water. The main objective of this paper was to prepare and develop ODTs of clopidogrel. The ODTs were prepared by direct compression. The effect of three superdisintegrants, namely crospovidone, croscarmellose sodium, and sodium starch glycolate, using three different disintegration times on the dissolution rate was investigated. The prepared tablets were evaluated for hardness, friability, disintegration time and in vitro drug release. Furthermore, the interaction of clopidogrel with the formulation excipients was studied using differential scanning calorimetry (DSC). DSC studies revealed that there were no interactions between the drug and the excipients used. All tablets had hardness values in the range 4.0-5.2 kp and friabil...
Formulation Development and Evaluation of Clopidogrel Fast Dissolving Tablets
The main objective of the present research work is to formulate the Clopidogrel Fast Dissolving tablets. Clopidogrel, an antiplatelet drug, belongs to BCS Class-II and used to control Heart attack, Hypertension by inhibiting Platelet activation and aggregation .The Fast Dissolving tablets of Clopidogrel were prepared employing different concentrations of Crospovidone and Croscarmellose sodium in different combinations as a Superdisintegrant by Direct Compression technique using 3 2 factorial design. The concentration of Crospovidone and Croscarmellose sodium was selected as independent variables, X 1 and X 2 respectively whereas, wetting time, Disintegration time, t 50% , t 90% were selected as dependent variables. Totally nine formulations were designed and evaluated for hardness, friability, thickness, Assay, Wetting time, Disintegration time, and in-vitro drug release. From the Results it was concluded that all the formulation were found to be with in the Pharmacopoeial limits and the in-vitro dissolution profiles of all formulations were fitted into different Kinetic models, the statistical parameters like intercept (a), slope (b) and regression coefficient (r) were calculated. Polynomial equations were developed for Wetting time, Disintegration time, t 50% , t 90%. Validity of developed polynomial equations was verified by designing 2 check point formulations (C 1 , C 2). According to SUPAC guidelines, the formulation (F 5) containing combination of 15% Crospovidone and 15% Croscarmellose, is the most similar formulation (similarity factor f 2 =91.3936, dissimilarity factor f 1 = 1.203& No significant difference, t=-0.00062) to marketed product (PLAVIX-75). The selected formulation (F 1) follows First order, Higuchi's kinetics, mechanism of drug release found to be Fickian Diffusion (n= 0.226).
International Journal of Pharmaceutical Sciences and Medicine (IJPSM), 2024
Cardiovascular diseases (CVDs) are a major cause of global morbidity and mortality, necessitating effective therapeutic strategies. Clopidogrel, an antiplatelet drug, is crucial for preventing thrombotic events but suffers from poor aqueous solubility, affecting its bioavailability. This study investigates the enhancement of clopidogrel's solubility through its inclusion in β-cyclodextrin complexes prepared by the solvent evaporation method. Saturation solubility studies demonstrated that the complexes significantly improved solubility, with values of 4.5 µg/ml for formulation F1, 7.7 µg/ml for F5, and 6.2 µg/ml for F9. Tablet formulations incorporating these complexes were evaluated for physicochemical properties, including angle of repose (21.56° to 49.85°), bulk density (0.48 to 0.694 g/cm³), tapped density (0.625 to 0.834 g/cm³), Carr’s Index (16.67% to 29.09%), and Hausner’s ratio (1.2 to 1.44). Hardness ranged from 4.34 ± 0.26 kg/cm² to 6.75 ± 0.25 kg/cm², with friability between 0.2% and 0.5%. Disintegration times varied from 42 to 58 seconds. In-vitro drug release studies in 0.1 N HCl revealed that formulation F9 achieved a release of 44.89% at 2 minutes, 67.71% at 4 minutes, 84.13% at 6 minutes, and 93.21% at 8 minutes. These findings suggest that β-cyclodextrin significantly enhances clopidogrel’s solubility and dissolution, potentially improving its clinical efficacy and patient outcomes.
Development of Microemulsion for Solubility Enhancement of Clopidogrel
2016
Clopidogrel, an inhibitor of platelet aggregation, selectively inhibits the binding of adenosine diphosphate (ADP) to its platelet receptor and the subsequent ADP-mediated activation of the glycoprotein GPIIb/IIIa complex, thereby inhibiting platelet aggregation. Oral bioavailability of clopidogrel is very low (less than 50%), due to its poor water solubility. The aim of this investigation was to design and develop a microemulsion formulation of clopidogrel for enhancing its solubility, and hence its oral bioavailability. For this purpose, initially, solubility of clopidogrel was determined in various vehicles. Next, pseudo-ternary phase diagrams were constructed to identify the microemulsion existing zone. Solubility study was also performed for optimization of formulation. The optimized microemulsion formulation was characterized for its transparency, droplet size, zeta potential, viscosity, conductivity, % assay, and phase separation study. Particle size and zeta potential of the...