Hydroxypropyl cellulose stabilizes amorphous solid dispersions of the poorly water soluble drug felodipine

•ASDs of a poorly water soluble drug felodipine were prepared using HPC-SSL and PVP-VA.•Stability of these ASDs at various temperatures and humidity conditions was evaluated.•HPC-SSL prevented drug–polymer phase separation in the ASDs better than PVP-VA.•Felodipine remained chemically stable in both...

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Bibliographic Details
Published in:Carbohydrate polymers 2014-11, Vol.112, p.512-519
Main Authors: Sarode, Ashish L., Malekar, Swapnil A., Cote, Catherine, Worthen, David R.
Format: Article
Language:English
Subjects:
Amorphous solid dispersion
Applied sciences
Biological and medical sciences
Calorimetry, Differential Scanning
Cellulose - analogs & derivatives
Cellulose - chemistry
Cellulose and derivatives
Crystallization
Drug Compounding - methods
Drug Stability
Exact sciences and technology
Felodipine - chemistry
General pharmacology
Hot melt extrusion
Hydroxypropyl cellulose
Interaction
Medical sciences
Natural polymers
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Physicochemistry of polymers
Povidone - chemistry
Solubility
Solutions
Spectroscopy, Fourier Transform Infrared
Stability
Supersaturation
Temperature
X-Ray Diffraction
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Summary:•ASDs of a poorly water soluble drug felodipine were prepared using HPC-SSL and PVP-VA.•Stability of these ASDs at various temperatures and humidity conditions was evaluated.•HPC-SSL prevented drug–polymer phase separation in the ASDs better than PVP-VA.•Felodipine remained chemically stable in both polymer systems for 12 weeks.•Drug partitioning during biphasic dissolution was superior using HPC-SSL than PVP-VA. Overcoming the low oral bioavailability of many drugs due to their poor aqueous solubility is one of the major challenges in the pharmaceutical industry. The production of amorphous solid dispersions (ASDs) of these drugs using hydrophilic polymers may significantly improve their solubility. However, their storage stability and the stability of their supersaturated solutions in the gastrointestinal tract upon administration are unsolved problems. We have investigated the potential of a low viscosity grade of a cellulosic polymer, hydroxypropyl cellulose (HPC-SSL), and compared it with a commonly used vinyl polymer, polyvinylpyrrolidone vinyl acetate (PVP-VA), for stabilizing the ASDs of a poorly water soluble drug, felodipine. The ASDs were produced using hot melt mixing and stored under standard and accelerated stability conditions. The ASDs were characterized using differential scanning calorimetry, powder X-ray diffraction, and Fourier transform infrared spectroscopy. Drug dissolution and partitioning rates were evaluated using single- and biphasic dissolution studies. The ASDs displayed superior drug dissolution and partitioning as compared to the pure crystalline drug, which might be attributed to the formation of a drug–polymer molecular dispersion, amorphous conversion of the drug, and drug–polymer hydrogen bonding interactions. Late phase separation and early re-crystallization occurred at lower and higher storage temperatures, respectively, for HPC-SSL ASDs, whereas early phase separation, even at low storage temperatures, was noted for PVP-VA ASDs. Consequently, the partitioning rates for ASDs dispersed in HPC-SSL were greater than those of PVP-VA at lower and room temperature storage, whereas the performance of both of the ASDs was similar when stored at higher temperatures.
ISSN:0144-8617
1879-1344
DOI:10.1016/j.carbpol.2014.06.039