Effect of polymer type on the dissolution profile of amorphous solid dispersions containing felodipine.
Amorphous solid dispersions are used as a strategy to improve the bioavailability of poorly water-soluble compounds. When formulating with a polymer, it is important not only for the polymer to stabilize against crystallization in the solid state, but also to improve the dissolution profile through inhibiting crystallization from the supersaturated solution generated by dissolution of the amorphous material. In this study, the dissolution profiles of solid dispersions of felodipine formulated with poly(vinylpyrrolidone) (PVP), hydroxypropyl methylcellulose (HPMC) or hydroxypropyl methylcellulose acetate succinate (HPMCAS) were compared. In addition, concentration versus time profiles were evaluated for the supersaturated solutions of felodipine in the presence and absence of the polymers. HPMCAS was found to maintain the highest level of supersaturation for the greatest length of time for both the dissolution and solution crystallization experiments, whereas PVP was found to be the least effective crystallization inhibitor. All polymers appeared to reduce the crystal growth rates of felodipine at an equivalent supersaturation and this mechanism most likely contributes to the enhanced solution concentration values observed during dissolution of the amorphous solid dispersions.
Konno
Hajime
H
Pharmaceutical Research and Technology Laboratories, Astellas Pharma Inc., Japan.
Handa
Tetsurou
T
Alonzo
David E
DE
Taylor
Lynne S
LS
D003460:Crystallization; D015736:Felodipine / Q000008:administration & dosage / Q000737:chemistry*; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D011145:Polyvinyls / Q000737:chemistry; D011759:Pyrrolidines / Q000737:chemistry; D012995:Solubility; D013816:Thermodynamics
D011108:Polymers; D011145:Polyvinyls; D011759:Pyrrolidines; C505150:poly(N-vinylpyrrolidine); D065347:Hypromellose Derivatives; C048331:hydroxypropylmethylcellulose acetate succinate; D008747:Methylcellulose; D015736:Felodipine