Development of oral lyophilisates containing meloxicam nanocrystals using QbD approach

Sonia Iurian, Cătălina Bogdan, Ioan Tomuță, P. Szabó-Révész, Anita Chvatal, Sorin E. Leucuța, Mirela Moldovan, Rita Ambrus

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17 Citations (Scopus)

Abstract

The aim of this study was to develop oral lyophilisates with improved meloxicam (MEL) dissolution, optimizing each step of the preparation by design of experiments. First, meloxicam nanosuspensions were prepared by high-pressure homogenization (HPH), using PVP, Poloxamer or PEG as stabilizers and were subjected to freeze-drying using mannitol as cryoprotectant. The effects of the stabilizers and cryoprotectant were assessed and an optimal formulation was generated within the Design Space where the particle sizes and the PDIs are at their lowest values. The optimal formulation was used at the preparation of oral lyophilisates. Sodium alginate (SA) and croscarmellose sodium (CCS) were tested as matrix forming agents and three different freezing regimes were applied. The formulation was optimized, choosing the polymer that yielded both high mechanical strength and fast MEL dissolution. Poloxamer led to particle size reduction down to 10.27% of the initial size, meaning 477.6 ± 7.5 nm, with a slight increase during freeze-drying process. PEG showed lower nanonizing capacity during HPH, but freeze-drying produced further diminution of the particle size. Since Poloxamer provided advanced size reduction while preserving MEL crystallinity, it was used for the optimized formulation containing 1% Poloxamer and 5% mannitol added before freeze-drying. SA showed good structural properties when compared to CCS and allowed fast MEL dissolution at low ratios. The optimal formulation contained 1.157% of SA was subjected to thermal treatment during freeze-drying. It disintegrated in 3.33 s and released 77.14% of the MEL after 2 min. The quality by design (QbD) approach for the development of pharmaceutical products ensured high quality of the dosage form and good understanding of the preparation process.

Original languageEnglish
Pages (from-to)356-365
Number of pages10
JournalEuropean Journal of Pharmaceutical Sciences
Volume104
DOIs
Publication statusPublished - Jun 15 2017

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Keywords

  • High-pressure homogenization
  • Meloxicam
  • Nanocrystals
  • Oral lyophilisates
  • Quality by design

ASJC Scopus subject areas

  • Pharmaceutical Science

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