Tags

Type your tag names separated by a space and hit enter

Characterization and stability of solid dispersions based on PEG/polymer blends.
Int J Pharm. 2010 May 10; 390(2):165-73.IJ

Abstract

Solid dispersions were prepared by a melting method from the water-insoluble model drugs carbamazepine and nifedipine and polyethylene glycol 1500 (PEG 1500) or 1:1 mixtures of PEG 1500 and the polymers polyvinylpyrrolidone (PVP 30, PVP 12), polyvinylpyrrolidone-co-vinylacetate (PVPVA) and Eudragit EPO (Eudragit) in order to combine advantages of the different carrier polymers (recrystallization inhibition, processability and stability). The solid dispersions were characterized by dissolution, powder X-ray diffractometry and microscopy directly after preparation and after storage for 3 and 6 months at 25 degrees C/0% relative humidity (RH) or 3 months at 40 degrees C/75% RH. More than 80% drugs were released from all solid dispersions within 20min. The dissolution rate of carbamazepine decreased in the order of PEG 1500>PEG 1500/Eudragit>PEG 1500/PVP 30>PEG 1500/PVPVA>PEG 1500/PVP 12. The dissolution rank order was not directly correlated to the amorphous/crystalline state of the drugs, but rather to the properties of the PEG 1500/polymer compositions. Nifedipine was released in the order of PEG 1500>PEG 1500/PVPVA>PEG 1500/PVP 30>PEG 1500/PVP 12>PEG 1500/Eudragit. Amorphous nifedipine was present in all PEG 1500/polymer dispersions except in pure PEG 1500 solid dispersion. The significant increase in dissolution rate of PEG 1500 solid dispersions was due to the reduced crystallinity of the drug and the excellent solubilisation properties of PEG 1500. After 6 months storage at 25 degrees C/0% RH, the solid dispersions released both drugs in the order PEG 1500/PVPVA>PEG 1500/PVP 30>PEG 1500/PVP 12>PEG 1500/Eudragit>PEG 1500. The stabilized amorphous state of the drug resulted in stable dissolution profiles of PEG 1500/PVPVA, PEG 1500/PVP 30 and PEG 1500/PVP 12 when compared to the PEG 1500 solid dispersions, which contained a higher amount of crystalline drug. The solid dispersions with PEG 1500/PVPVA or PEG 1500/PVP stored for 3 months at 40 degrees C/75% RH showed phase separation due to the hygroscopic properties of the polymers. The influence of 10% (w/w) of the solubilisers polyoxyl 40 hydrogenated castor oil (Cremophor), macrogol-15-hydroxystearate (Solutol) and fatty alcohol alkoxylate (Pluronic) on the dissolution rate and the physical state of the drug was significant.

Authors+Show Affiliations

College of Pharmacy, Freie Universität Berlin, Kelchstrasse 31, 12169 Berlin, Germany.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20132875

Citation

Bley, Heike, et al. "Characterization and Stability of Solid Dispersions Based On PEG/polymer Blends." International Journal of Pharmaceutics, vol. 390, no. 2, 2010, pp. 165-73.
Bley H, Fussnegger B, Bodmeier R. Characterization and stability of solid dispersions based on PEG/polymer blends. Int J Pharm. 2010;390(2):165-73.
Bley, H., Fussnegger, B., & Bodmeier, R. (2010). Characterization and stability of solid dispersions based on PEG/polymer blends. International Journal of Pharmaceutics, 390(2), 165-73. https://doi.org/10.1016/j.ijpharm.2010.01.039
Bley H, Fussnegger B, Bodmeier R. Characterization and Stability of Solid Dispersions Based On PEG/polymer Blends. Int J Pharm. 2010 May 10;390(2):165-73. PubMed PMID: 20132875.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Characterization and stability of solid dispersions based on PEG/polymer blends. AU - Bley,Heike, AU - Fussnegger,Bernd, AU - Bodmeier,Roland, Y1 - 2010/02/10/ PY - 2009/09/24/received PY - 2010/01/16/revised PY - 2010/01/26/accepted PY - 2010/2/6/entrez PY - 2010/2/6/pubmed PY - 2010/7/20/medline SP - 165 EP - 73 JF - International journal of pharmaceutics JO - Int J Pharm VL - 390 IS - 2 N2 - Solid dispersions were prepared by a melting method from the water-insoluble model drugs carbamazepine and nifedipine and polyethylene glycol 1500 (PEG 1500) or 1:1 mixtures of PEG 1500 and the polymers polyvinylpyrrolidone (PVP 30, PVP 12), polyvinylpyrrolidone-co-vinylacetate (PVPVA) and Eudragit EPO (Eudragit) in order to combine advantages of the different carrier polymers (recrystallization inhibition, processability and stability). The solid dispersions were characterized by dissolution, powder X-ray diffractometry and microscopy directly after preparation and after storage for 3 and 6 months at 25 degrees C/0% relative humidity (RH) or 3 months at 40 degrees C/75% RH. More than 80% drugs were released from all solid dispersions within 20min. The dissolution rate of carbamazepine decreased in the order of PEG 1500>PEG 1500/Eudragit>PEG 1500/PVP 30>PEG 1500/PVPVA>PEG 1500/PVP 12. The dissolution rank order was not directly correlated to the amorphous/crystalline state of the drugs, but rather to the properties of the PEG 1500/polymer compositions. Nifedipine was released in the order of PEG 1500>PEG 1500/PVPVA>PEG 1500/PVP 30>PEG 1500/PVP 12>PEG 1500/Eudragit. Amorphous nifedipine was present in all PEG 1500/polymer dispersions except in pure PEG 1500 solid dispersion. The significant increase in dissolution rate of PEG 1500 solid dispersions was due to the reduced crystallinity of the drug and the excellent solubilisation properties of PEG 1500. After 6 months storage at 25 degrees C/0% RH, the solid dispersions released both drugs in the order PEG 1500/PVPVA>PEG 1500/PVP 30>PEG 1500/PVP 12>PEG 1500/Eudragit>PEG 1500. The stabilized amorphous state of the drug resulted in stable dissolution profiles of PEG 1500/PVPVA, PEG 1500/PVP 30 and PEG 1500/PVP 12 when compared to the PEG 1500 solid dispersions, which contained a higher amount of crystalline drug. The solid dispersions with PEG 1500/PVPVA or PEG 1500/PVP stored for 3 months at 40 degrees C/75% RH showed phase separation due to the hygroscopic properties of the polymers. The influence of 10% (w/w) of the solubilisers polyoxyl 40 hydrogenated castor oil (Cremophor), macrogol-15-hydroxystearate (Solutol) and fatty alcohol alkoxylate (Pluronic) on the dissolution rate and the physical state of the drug was significant. SN - 1873-3476 UR - https://www.unboundmedicine.com/medline/citation/20132875/Characterization_and_stability_of_solid_dispersions_based_on_PEG/polymer_blends_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-5173(10)00092-X DB - PRIME DP - Unbound Medicine ER -