Study on Optimization of Wet Milling Process for the Development of Albendazole Containing Nanosuspension with Improved Dissolution

Authors

  • Viktor Fülöp
    Affiliation
    Department of Pharmaceutics, Faculty of Pharmacy, Semmelweis University, H-1092 Budapest, Hőgyes Endre Street 7., Hungary
  • Géza Jakab
    Affiliation
    Department of Pharmaceutics, Faculty of Pharmacy, Semmelweis University, H-1092 Budapest, Hőgyes Endre Street 7., Hungary
  • Bence Tóth
    Affiliation
    Department of Pharmaceutics, Faculty of Pharmacy, Semmelweis University, H-1092 Budapest, Hőgyes Endre Street 7., Hungary
  • Emese Balogh
    Affiliation
    Department of Pharmaceutics, Faculty of Pharmacy, Semmelweis University, H-1092 Budapest, Hőgyes Endre Street 7., Hungary
  • István Antal
    Affiliation
    Department of Pharmaceutics, Faculty of Pharmacy, Semmelweis University, H-1092 Budapest, Hőgyes Endre Street 7., Hungary
https://doi.org/10.3311/PPch.15569

Abstract

The main objective of this work was to show the potential of the optimization of top-down wet planetary bead milling process parameters (milling speed, process time and size of the milling medium) by Design Of Experiments (DOE) approach for the development of albendazole (ABZ) containing nanosuspension with improved dissolution. In addition, the influence of process parameters (capacity of milling container, applied volume of milling beads, size of the milling medium, milling speed, milling time) on ABZ polymorphic transition has also been investigated. The optimized, milled formula yielded ~ 145.39 times reduction in mean particle size (182.200 ± 1.3130 nm) compared to unmilled dispersion, which demonstrated 13.50 times gain in mean dissolution rate value compared to the unmilled dispersion in medium at pH = 1.2. No lag time values were observed in the dissolution kinetics of the nanosuspension in comparison with the unmilled samples. Moreover, maximal mean solubility value was also improved by 1.45 times compared to the unmilled suspension, in medium at pH = 6.8, supporting the significance of the Ostwald-Freundlich equation. Diffraction pattern comparisons have indicated a polymorphic transition of albendazole to Form II, which was more pronounced in smaller container at high milling speed values and prolonged operations.

Keywords:

albendazole nanosuspension, wet media milling, dissolution improvement, Powder X-Ray Diffractometry (PXRD), Design Of Experiments (DOE)

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Published Online

2020-07-24

How to Cite

Fülöp, V., Jakab, G., Tóth, B., Balogh, E., Antal, I. “Study on Optimization of Wet Milling Process for the Development of Albendazole Containing Nanosuspension with Improved Dissolution”, Periodica Polytechnica Chemical Engineering, 64(4), pp. 401–420, 2020. https://doi.org/10.3311/PPch.15569

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