Hot melt extrusion versus spray drying: hot melt extrusion degrades albendazole.
The purpose of this study was to enhance the dissolution properties of albendazole (ABZ) by the use of amorphous solid dispersions. Phase diagrams of ABZ-polymer binary mixtures generated from Flory-Huggins theory were used to assess miscibility and processability. Forced degradation studies showed that ABZ degraded upon exposure to hydrogen peroxide and 1 N NaOH at 80 °C for 5 min, and the degradants were albendazole sulfoxide (ABZSX), and ABZ impurity A, respectively. ABZ was chemically stable following exposure to 1 N HCl at 80 °C for one hour. Thermal degradation profiles show that ABZ, with and without Kollidon®VA 64, degraded at 180 °C and 140 °C, respectively, which indicated that ABZ could likely be processed by thermal processing. Following hot melt extrusion, ABZ degraded up to 97.4%, while the amorphous ABZ solid dispersion was successfully prepared by spray drying. Spray-dried ABZ formulations using various types of acids (methanesulfonic acid, sulfuric acid and hydrochloric acid) and polymers (Kollidon®VA 64, Soluplus®and Eudragit®E PO) were studied. The spray-dried ABZ with methanesulfonic acid and Kollidon®VA 64 substantially improved non-sink dissolution in acidic media as compared to bulk ABZ (8-fold), physical mixture of ABZ:Kollidon®VA 64 (5.6-fold) and ABZ mesylate salt (1.6-fold). No degradation was observed in the spray-dried product for up to six months and less than 5% after one-year storage. In conclusion, amorphous ABZ solid dispersions in combination with an acid and polymer can be prepared by spray drying to enhance dissolution and shelf-stability, whereas those made by melt extrusion are degraded.
a Division of Pharmaceutics , The University of Texas at Austin , Austin , TX , USA.
Soraya
S
Hengsawas Surasarang
b DisperSol Technologies, LLC , Austin , TX , USA.
Justin M
JM
Keen
a Division of Pharmaceutics , The University of Texas at Austin , Austin , TX , USA.
Siyuan
S
Huang
a Division of Pharmaceutics , The University of Texas at Austin , Austin , TX , USA.
Feng
F
Zhang
a Division of Pharmaceutics , The University of Texas at Austin , Austin , TX , USA.
James W
JW
McGinity
a Division of Pharmaceutics , The University of Texas at Austin , Austin , TX , USA.
Robert O
RO
Williams
D015766:Albendazole / Q000031:analogs & derivatives* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003890:Desiccation / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods*; D004355:Drug Stability; D005615:Freezing; D006358:Hot Temperature; D006851:Hydrochloric Acid / Q000737:chemistry; D008698:Mesylates / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D011109:Polymethacrylic Acids / Q000737:chemistry; D011145:Polyvinyls / Q000737:chemistry; D011205:Povidone / Q000737:chemistry; D012995:Solubility; D013464:Sulfuric Acids / Q000737:chemistry
D004337:Drug Carriers; D008698:Mesylates; D011108:Polymers; D011109:Polymethacrylic Acids; D011145:Polyvinyls; D013464:Sulfuric Acids; C572167:polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; C045880:methanesulfonic acid; D011092:Polyethylene Glycols; C518398:Eudragit E PO; D015766:Albendazole; D011205:Povidone; C027186:albendazole sulfoxide; C033158:sulfuric acid; D006851:Hydrochloric Acid
Albendazole; Flory–Huggins theory; amorphous solid dispersions; degradation; hot melt extrusion; spray drying