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A Package of Established Analytical Tools to Investigate the Solid-State Alteration of Lipid-Based Excipients
Published on: August 9, 2022
Formulation and evaluation of a protein-loaded solid dispersions by non-destructive methods
Ziyaur Rahman1, Ahmed S Zidan, Mansoor A Khan
1Division of Product Quality and Research, Center of Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
The AAPS Journal
|February 4, 2010
Summary
This study developed solid dispersion formulations of cyclosporine (CyA) using polyethylene glycol (PEG-6000) to improve drug dissolution. Non-destructive methods like Near Infrared Chemical Imaging (NIR-CI) accurately predicted drug and carrier content in the novel formulations.
Area of Science:
- Pharmaceutical Sciences
- Drug Delivery Systems
- Materials Science
Background:
- Cyclosporine (CyA) exhibits poor aqueous solubility, limiting its therapeutic efficacy.
- Solid dispersion (SD) technology offers a promising approach to enhance the dissolution rate of poorly soluble drugs.
- Polyethylene glycol (PEG-6000) is a widely used carrier in SD formulations due to its biocompatibility and ability to improve drug solubility.
Purpose of the Study:
- To develop and characterize solid dispersion (SD) formulations of cyclosporine (CyA) using polyethylene glycol (PEG-6000).
- To enhance the dissolution rate of CyA through SD formulation.
- To establish a non-destructive method for predicting both CyA and PEG-6000 content in the SD formulations.
Main Methods:
- SD formulations were prepared using the solvent evaporation technique with varying CyA and PEG-6000 ratios.
- Characterization involved dissolution testing, SEM, DSC, FTIR, PXRD, NIR, and NIR-CI.
- Chemometric analysis, including Principal Component Analysis (PCA) and Partial Least Squares (PLS) regression, was applied to spectral data (NIR and PXRD).
Main Results:
- Dissolution studies showed significantly enhanced CyA release from SD formulations compared to pure CyA.
- DSC indicated a decrease in PEG-6000 crystallinity within the SD formulations.
- FTIR confirmed the absence of chemical interactions between CyA and PEG-6000.
- NIR-CI and multivariate analysis of PXRD data demonstrated the homogeneity of the SD matrix.
- PLS models achieved high accuracy (2.10% to 5.35%) for predicting CyA and PEG-6000 content.
Conclusions:
- Solid dispersion formulation with PEG-6000 effectively enhances cyclosporine dissolution.
- Non-destructive techniques, particularly NIR and PXRD coupled with chemometrics, provide a reliable and accurate method for characterizing SD formulations and quantifying drug and carrier content.
- This approach offers a valuable tool for quality control and development of novel drug delivery systems.
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