Study on Mechanism for Amorphous Drug Stabilization Using Gelucire 50/13

Abstract

Methods of preparation and application of amorphous form are well established but it is equally important to note that devitrification of amorphous drugs has limited their applications. Present study was performed to investigate mechanism for amorphous drug stabilization using Gelucire in comparison with polyvinylpyrrolidone (PVP). Etoricoxib and celecoxib were taken as model drugs for this study, as etoricoxib has only proton accepting site for hydrogen bonding in comparison with celecoxib, which has both proton accepting and donating site. Solid dispersion of celecoxib with polyvinylpyrrolidone and Gelucire was prepared by spray drying and meltgranulation technique respectively. X-ray powder diffractometry and differential scanning calorimetry were used to study the physical state of the drug. Dissolution studies were performed to differentiate dissolution performance. Stability study samples were evaluated for physical state of the drug and dissolution performance. An IR study in correlation with molecular modeling was carried out to study the mechanism for stabilization. Dissolution of melt-granulation of amorphous celecoxib was improved significantly as compared to amorphous celecoxib and Celecoxib-PVP solid dispersion. Melt-granulation with lipid seemed to be more dominant than amorphization of drug for improving dissolution. Stability data revealed that PVP was significantly advantageous for amorphous form stabilization whereas Gelucire failed in case of Celecoxib. In contrast to this, our previous study revealed the stabilization ability of Gelucire for amorphous etoricoxib. Molecular modeling and IR studies revealed that H-bonding was predominant mechanism for stabilization. Out of two proposed mechanism for amorphous drug stabilization by lipids, H-bonding ability is more dominant than immobilization of molecule in lipid matrix.

Gelucire-Based Nanoparticles for Curcumin Targeting to Oral Mucosa: Preparation, Characterization, and Antimicrobial Activity Assessment

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“…Because it exhibits unique compositions with surfactants, cosurfactants, and lipid phases, it has interesting properties such as emulsification, drug solubility enhancement, and granule formation acting as lipid matrix in drug delivery systems. 19 Gelucires R are generally recognized as safe. 20 Its incorporation in lipid nanocarriers can prove to be helpful in increasing drug loading of lipophilic compounds as well as it can help stabilization of the lipid nanosystem.…”

Food Nanoscience and Nanotechnology

“…Other emulsifiers can be used in the stabilization of structured nanosized systems such as: monoglycerides of hydrogenated palm oil (Martini and Herrera, 2008), Tween 20 (Xin et al 2013) and Gelucires (Shimpi et al 2009;Tsai et al 2012) …”

Preparation, Characterization, and Evaluation of Anti-Inflammatory Activity of Etoricoxib Loaded Soluplus® Nanocomposites

“…Insptite of powerful analgesic and anti-inflammatory potential [17,18], ECB exhibits a delayed rate of absorption [17]. Therefore, efforts were made to improve the physicochemical properties of ECB using solid dispersion [19][20][21], drug amorphization [22][23][24], cyclodextrin complexation [25,26] and spherical crystallization technique [27]. In this article, the formation of nanocomposites of ECB were attempted with Soluplus ® to evaluate it for physicochemical properties as well as anti-inflammatory activity.…”