Development of Novel High Density Gastroretentive Multiparticulate Pulsatile Tablet of Clopidogrel Bisulfate Using Quality by Design Approach

Abstract

Myocardial infarction, i.e., heart attack, is a fatal condition which is on the increase all over the world. It is reported that a large number of heart attack occur in morning hours which are attributable to platelet aggregation. Chronotherapy at this stage can be crucial. Clopidogrel bisulfate (CLB) is an antiplatelet agent and has become a drug of choice for prevention of heart attack. It is soluble in acidic pH and has a narrow absorption window. So, its long residence time in stomach is desirable. Therefore, a novel high density tablet was developed comprising multiparticulate pellets with pulsatile release necessary to maintain chronotherapy of heart attack. The pellets were prepared by extrusion-spheronization and coated in fluidized bed processor with different coating material to achieve pulsatile release. The size, shape of pellets, and drug release were evaluated. High density tablet containing coated pellets was formulated and evaluated for retention in stomach. Quality by design tools was used to design and optimize the processes. Timed release observed by dissolution study showed lag time of 6 h followed by burst release of drug up to 94% in 1 h. Density of tablets was found to be 2.2 g cm which is more than gastric fluid. In vivo x-ray studies in rabbit revealed 8 h of gastric retention of tablet at the bottom of the stomach. Thus, CLB high density pulsatile system looks to open up a window of opportunity for developing formulations with drugs that are stable in gastric region and needed chronotheraupetic activity.

QbD Based Optimization of Curcumin Nanoemulsion: DoE and Cytotoxicity Studies

“…DoE is an excellent tool wherein we systematically manipulate factors according to a pre specified design. [16][17][18][19][20][21][22] DoE also reveals relationships between input factors and output responses. In the current study, the concentration of Smix and concentration of oil were the input parameters (independent variables) while the zeta potential, particle size and PDI were output parameters (dependent variables).…”

“…15 QbD has been successfully used for development of number of NEs. 16 The aim of the present study was to develop and optimize an oil o/w NE for CUR in order to overcome poor solubility of the drug. As NEs are thermodynamically unstable; a QbD based optimization design was applied in order to obtain a stable and robust NE with improved stability as well as efficacy.…”

Gastroretentive Technologies in Tandem with Controlled-Release Strategies: A Potent Answer to Oral Drug Bioavailability and Patient Compliance Implications

“…Excipients that are commonly used to ensure a sufficiently high density of these systems include barium sulphate, zinc oxide, iron oxide, iron powder, and titanium dioxide. Usually, the dosage forms reported in the literature are high-density pellets or tablets [126,127].…”

“…Desai et al developed a novel multiparticulate pulsatile high-density tablet containing clopidogrel. The aim was to prepare tablets that would be retained in the stomach for 7-8 h and release the drug after a predetermined lag time [126]. Iron oxide was used as the density-increasing agent and high-density pellets were prepared using extrusion and spheronisation, followed by their compression into tablets.…”

Mechanically Robust Gastroretentive Drug-Delivery Systems Capable of Controlling Dissolution Behaviors of Coground β-Lapachone

“…Various types of GRDDS with different gastroretentive mechanisms have been investigated, such as floating [4], high-density [5], muco-adhesive [6], raft-forming [7], magnetic [8], and expandable systems [9]. The most extensively explored types of GRDDS are floating or expandable systems.…”