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2000
Volume 15, Issue 3
  • ISSN: 2210-3031
  • E-ISSN: 2210-304X

Abstract

Background

The oral bioavailability of Dabigatran (DGT) is significantly lower due to poor aqueous solubilization and p-gp efflux.

Objective

The prime objective was to enhance the solubilization of DGT using a self-nano-emulsifying drug delivery system (SNEDDS). DGT was administered with Piperine (PRN) to increase its availability for absorption by blocking p-gp. The secondary objective was to develop an accurate analytical method for DGT and PRN.

Methods

The first-order derivative spectrophotometry for simultaneous estimation of DGT and PRN was developed and validated. The solubility of the DGT and PRN was assessed in the chosen excipients of SNEDDS. The ternary phase diagram was constructed to assess the appropriate amount of oleic acid (OA), Capmul MCM C8 EP (CAP), and Transcutol P (TP). A risk assessment matrix and Ishikawa diagram were applied to scrutinize the critical parameters affecting the quality of SNEDDS. The optimization of SNEDDS was performed using a D-optimal mixture design. The amount of OA, CAP, and TP were carefully chosen as CMAs whereas globule size, poly-dispersibility index (PDI), emulsification time, and zeta potential were chosen as critical quality attributes (CQAs). The spring and parachute theory was applied to assess the effective amount of Soluplus to reduce precipitation. The designed SNEDDS was considered for the physicochemical parameters of SNEDDS. The optimized batch was converted into a solid SNEDDS (S-SNEDDS) by adsorbing it on the appropriate adsorbent and evaluating for flow property, X-ray Diffraction (XRD), and release.

Results

The developed method was robust, accurate, and precise for estimating DGT and PRN. The solubility study reveals that OA, CAP, and TP were screened as oil, surfactant, and co-surfactant. OA, CAP, and TP in a proportion of 1:2:1 were chosen from the ternary phase diagram. The optimal region was obtained from an overlay plot. The optimal SNEDDS was able to release DGT-PRN within two hours. The negative value of zeta potential (-11.5mv) assures the stability of SNEDDS. Soluplus (3%) was screened as a parachute which inhibited the precipitation. The optimum SNEDDS was converted into solid SNEDDS by adsorbing on Neusilin (NS). The alteration in results of FTIR, DSC, and XRD confirmed the change to amorphous form. The S-SNEDDS able to release the DGT-PRN within two hours.

Conclusion

The analytical method for estimating DGT and PRN was successfully developed and validated for its linearity, accuracy, and precision. SNEDDS containing DGT-PRN were developed with better performance. The D-optimal mixture design was adequate to optimize the SNEDDS. Soluplus was able to reduce the precipitation of the drugs. NS was explored to form S-SNEDDS and converted into a stable form. The amorphous S-SNEDDS has shown higher drug release. The optimized batch can be developed at an industrial scale.

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QbD Mediated Development of Dabigatran-Piperine Loaded Smart Nanostructured System
Drug Deliv Lett 15, 298 (2025); https://doi.org/10.2174/0122103031324561250305233355
/content/journals/ddl/10.2174/0122103031324561250305233355
/content/journals/ddl/10.2174/0122103031324561250305233355
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  • Article Type:     Research Article
Keyword(s): D-optimal mixture design; Dabigatran; neusilin; piperine; SNEDDS; soluplus

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