Influence of the Freeze-Drying Process on the Physicochemical and Biological Properties of Pre-heated Amphotericin B Micellar Systems
Journal Title: AAPS PharmSciTech - Year 2014, Vol 15, Issue 3
Abstract
The moderate heat treatment of amphotericin B (AmB) in its micellar form (M-AmB) results in superaggregates (H-AmB) that present a substantially lower toxicity and similar activity. The aim of this work was to evaluate the H-AmB behavior after a freeze-drying process. H-AmB and M-AmB micelles were evaluated before and after freeze-drying concerning their physicochemical and biological properties by spectrophotometry and activity/toxicity assay, respectively. Four concentrations of M-AmB and H-AmB were studied aiming to correlate their aggregation state and the respective biological behavior: 50 mg L−1, 5 mg L−1, 0.5 mg L−1, and 0.05 mg L−1. Then, potassium leakage and hemoglobin leakage from red blood cells were used to evaluate the acute and chronic toxicity, respectively. The efficacy of M-AmB and H-AmB formulations was assessed by potassium leakage from Candida albicans and by the broth microdilution method. After heating, in addition to an evident turbidity, a slight blueshift from 327 to 323 nm was also observed at the concentrations of 50 and 5 mg L−1 for H-AmB. Additionally, an increase in the absorbance at 323 nm at the concentration of 0.5 mg L−1 was detected. Concerning the toxicity, H-AmB caused significantly lower hemoglobin leakage than M-AmB. These results were observed for H-AmB before and after freeze-drying. However, there was no difference between H-AmB and M-AmB concerning their activity. Accordingly, the freeze-drying cycle did not show any influence on the behavior of heated formulations, highlighting the suitability of such a method to produce a new AmB product with a long shelf life and with both greater efficiency and less toxicity.
Authors and Affiliations
Scheyla D. V. S. Siqueira, Miguel A. Silva-Filho, Christian A. Silva, Ivonete B. Araújo, Acarilia E. Silva, Matheus F. Fernandes-Pedrosa, Anselmo G. Oliveira, E. Sócrates T. Egito
Keywords
Related Articles
- EP ID EP682386
- DOI 10.1208/s12249-014-0085-z
- Views 105
- Downloads 0
Investigating Transdermal Delivery of Vitamin D3
Transdermal delivery of therapeutic amounts of vitamin D3 is proposed to overcome its variable oral bioavailability, especially for people who suffer from fat malabsorption. The main challenge for this delivery route is...
Quality-by-Design: Are We There Yet?
In 2012, the Quality-by-Design and Product Performance Focus Group of AAPS conducted a survey to assess the state of adoption and perception of Quality-by-Design (QbD). Responses from 149 anonymous individuals from indus...
A New Extrudable Form of Hypromellose: AFFINISOL™ HPMC HME
The online version of this article (doi:10.1208/s12249-015-0395-9) contains supplementary material, which is available to authorized users.
Investigation of Thermal and Viscoelastic Properties of Polymers Relevant to Hot Melt Extrusion, IV: Affinisol™ HPMC HME Polymers
Most cellulosic polymers cannot be used as carriers for preparing solid dispersion of drugs by hot melt extrusion (HME) due to their high melt viscosity and thermal degradation at high processing temperatures. Three HME-...
Comparison of Univariate and Multivariate Models of 13C SSNMR and XRPD Techniques for Quantification of Nimodipine Polymorphs
The focus of the present investigation was to explore the use of solid-state nuclear magnetic resonance (13C ssNMR) and X-ray powder diffraction (XRPD) for quantification of nimodipine polymorphs (form I and form II) cry...