Development and Characterization of Coated Matrix Multiparticulate System for Milnacipran HCl Sustained Release Imbibing Design of Experiments

Author: Shekhar V. Kokate and Punit R. Rachh

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Abstract

Oral drug delivery systems are very well accepted by patients due to self-medication and its stability over other dosage forms. The formulation of sustained release product is always a challenging task and when it is employed from highly water-soluble drugs; its complexity is greatly increased. Nowadays, multi-unit particulate systems (MUPS) are gaining an interest for delivering water soluble drugs at a controlled rate. So, in the present study, coated pellets were designed for water soluble model drug Milnacipran HCl (MIL). The drug was quantified by UV spectrophotometer at 223 λmax. The core matrixpellets were prepared by Extrusion Spheronization techniques using MCC and HPMC K100M. The core pellets were further coated by Eudragit®NE based coating solution using pan coater. The coating was optimized by Box Behenken Design keeping concentration of matrix polymer (HPMCK100M) (X1), concentration of coating solution (Eudragit®NE) (X2) and %weight gain (X3) was selected as independent variables while, Q2 (Y1), Q12 (Y2), Q20 (Y3), and Aspect ratio (Y4) were taken as dependent variables. The developed pellets were characterized for various physicochemical parameters. The drug release from formulation was fitted for various drug release kinetics models. The optimized formulation was subjected for accelerated stability study as per stability guidelines by ICH. The results indicated that selected independent variables had strong impact on response which was confirmed by contour and response surface plot. SEM analysis indicated proximal spherical shape of pellets. Drug release from optimized pellets was fitting to first order release kinetics. Accelerated stability study indicated stable characteristics of optimized formulation. Developed Eudragit®NE coated pellets can be promising technology for delivering highly water-soluble drugs at a controlled rate.

Keywords

Milnacipran HCl, Eudragit NE, Coated matrix pellets, Box-behenken Design, Multi-unit particulate systems (MUPS)

Conclusion

From the results, it can be concluded that applied box Behnken design had assisted in development of coated pellets. The role of Eudragit®NE as a coating agent and HPMCK100M as matrixing agent was found to be critical in achieving desired drug release pattern. The process parameters were optimized successfully to yield pellets in near to spherical shape. The concept of use of matrixing hydrophilic polymer in core and additional coating of hydrophobic polymer over core pellet for highly water-soluble drug can be a promising approach to deliver drug in a controlled manner.

References

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How to cite this article

Shekhar V. Kokate and Punit R. Rachh (2023). Development and Characterization of Coated Matrix Multiparticulate System for Milnacipran HCl Sustained Release Imbibing Design of Experiments. Biological Forum – An International Journal, 15(1): 439-447.