Formulation and Optimization of Floating Tablets of Clopidogrel Bisulphate Using Design of Experiments

Abstract

Objective: The present study aimed at designing of floating matrix tablet of clopidogrel bisulphate by design of experiments.Methods: The tablets were prepared by direct compression technique using hydroxypropyl methylcellulose K15 (HPMC) as a matrix polymer and sodium bicarbonate as a gas generating agent. In order to optimize the concentration of HPMC (X1) and sodium bicarbonate (X2), a 32 full factorial design was employed. The tablet formulations were evaluated for floating lag time (Y1), floating or buoyancy time (Y2), percent water uptake, and differential scanning calorimetry (DSC) and in vitro drug release (Y3).Results: The formulation variables, HPMC concentration, and sodium bicarbonate concentration exerted a significant effect on floating behavior and drug release characteristics of the tablet. The optimized formulation, with 15% sodium bicarbonate concentration and 30 % HPMC concentration resulted in 5±2.6 sec of floating lag time, 22.0±0.6 h of floating time and 42.0±0.99% of clopidogrel bisulphate release in 8 h of dissolution study. The drug release mechanism was identified as nonfickian. The water uptake studies revealed that with an increase in HPMC concentration, there was an increase in swelling index of tablet whereas higher sodium bicarbonate concentration supported the faster erosion of matrix tablets. DSC study revealed no interaction of drug and polymers. The lower percentage error between predicted and observed responses of the optimized formulation validated the design.Conclusion: The study demonstrated successful designing of floating clopidogrel bisulphate tablet with factorial design.

Development and evaluation of gastro retentive drug delivery system of monoammonium glycyrrhizinate for the management of gastric ulcer

“…Also, when exposed to the acidic medium, some amount of Ca++ ions present in the calcium alginate raft were replaced for the protons present in the acidic medium to form alginic acid. Alginic acid being slightly soluble in water, it formed a dense network which could have delayed the release of MAG Another reason for delayed release of MAG could be the presence of HPMC K15 which could have contributed to augment the formation of alginate gel, as in the presence of acidic medium HPMC forms a viscous gel thereby creating a resistant barrier for the diffusion of MAG [24].The percent release of formulated batches of raft forming tablets of MAG (F1-F17) percent is shown in Figure 8.…”

“…The time required for the raft to rise to the surface of the dissolution media was recorded as floating lag time. The total time required for the raft to float on the surface of the dissolution media was estimated as total floating time [24].…”

Electrochemical Study of Clopidogrel and its Determination in Pharmaceutical Preparations Using Square Wave Voltammetry

“…The molecular name of clopidogrel is 4,5,6,7-tetrahydrothieno[3,2-c] pyridine (Figure 1). After examining its effects in more than 30000 patients worldwide, the clinical advantage of long-term clopidogrel treatment in reducing atherothrombotic disorders is demonstrated [10,11]. Reviews of the literature indicate that UV spectrophotometry [12], high-performance liquid chromatography with ultraviolet detection [13], gas chromatography with mass spectrometry [14], and highperformance liquid chromatography with mass spectrometry [15,16] are used to quantitatively analyze clopidogrel in pharmaceutical preparations or biological liquids.…”

Bioanalytical Rp-HPLC Method Development and Validation of Clopidogrel Bisulfate in Wistar Rat Plasma and Its Application to Pharmacokinetic Study

“…Clopidogrel is a potent antiplatelet agent widely used to prevent coronary artery diseases and treat vascular thrombosis [13,14]. Its antiplatelet activity results from selective inhibition of ADP binding to the platelet receptor preventing ADP-mediated platelet responses [15,16]. Therefore, Clopidogrel should be used with caution in patients receiving other drugs that increase bleeding risk include anticoagulants, other antiplatelet, and NSAIDs [17].…”