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Hot melt extrusion versus spray drying: hot melt extrusion degrades albendazole.
Drug Dev Ind Pharm. 2017 May; 43(5):797-811.DD

Abstract

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.

Authors+Show Affiliations

a Division of Pharmaceutics , The University of Texas at Austin , Austin , TX , USA.b DisperSol Technologies, LLC , Austin , TX , USA.a Division of Pharmaceutics , The University of Texas at Austin , Austin , TX , USA.a Division of Pharmaceutics , The University of Texas at Austin , Austin , TX , USA.a Division of Pharmaceutics , The University of Texas at Austin , Austin , TX , USA.a Division of Pharmaceutics , The University of Texas at Austin , Austin , TX , USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27616147

Citation

Hengsawas Surasarang, Soraya, et al. "Hot Melt Extrusion Versus Spray Drying: Hot Melt Extrusion Degrades Albendazole." Drug Development and Industrial Pharmacy, vol. 43, no. 5, 2017, pp. 797-811.
Hengsawas Surasarang S, Keen JM, Huang S, et al. Hot melt extrusion versus spray drying: hot melt extrusion degrades albendazole. Drug Dev Ind Pharm. 2017;43(5):797-811.
Hengsawas Surasarang, S., Keen, J. M., Huang, S., Zhang, F., McGinity, J. W., & Williams, R. O. (2017). Hot melt extrusion versus spray drying: hot melt extrusion degrades albendazole. Drug Development and Industrial Pharmacy, 43(5), 797-811. https://doi.org/10.1080/03639045.2016.1220577
Hengsawas Surasarang S, et al. Hot Melt Extrusion Versus Spray Drying: Hot Melt Extrusion Degrades Albendazole. Drug Dev Ind Pharm. 2017;43(5):797-811. PubMed PMID: 27616147.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hot melt extrusion versus spray drying: hot melt extrusion degrades albendazole. AU - Hengsawas Surasarang,Soraya, AU - Keen,Justin M, AU - Huang,Siyuan, AU - Zhang,Feng, AU - McGinity,James W, AU - Williams,Robert O,3rd Y1 - 2016/10/20/ PY - 2016/10/21/pubmed PY - 2017/6/16/medline PY - 2016/9/13/entrez KW - Albendazole KW - Flory–Huggins theory KW - amorphous solid dispersions KW - degradation KW - hot melt extrusion KW - spray drying SP - 797 EP - 811 JF - Drug development and industrial pharmacy JO - Drug Dev Ind Pharm VL - 43 IS - 5 N2 - 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. SN - 1520-5762 UR - https://www.unboundmedicine.com/medline/citation/27616147/Hot_melt_extrusion_versus_spray_drying:_hot_melt_extrusion_degrades_albendazole_ L2 - https://www.tandfonline.com/doi/full/10.1080/03639045.2016.1220577 DB - PRIME DP - Unbound Medicine ER -