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Fusion production of solid dispersions containing a heat-sensitive active ingredient by hot melt extrusion and Kinetisol dispersing.
Eur J Pharm Biopharm. 2010 Feb; 74(2):340-51.EJ

Abstract

Many techniques for the production of solid dispersions rely on elevated temperatures and prolonged material residence times, which can result in decomposition of temperature-sensitive components. In this study, hydrocortisone was used as a model temperature-sensitive active ingredient to study the effect of formulation and processing techniques as well as to characterize the benefits of KinetiSol Dispersing for the production of solid dispersions. Preformulation studies were conducted using differential scanning calorimetry and hot stage microscopy to identify optimum carriers for the production of amorphous solid dispersions. After identification, solid dispersions were prepared by hot melt extrusion and KinetiSol Dispersing, with material characterized by X-ray diffraction, dissolution and potency testing to evaluate physicochemical properties. Results from the preformulation studies showed that vinylacetate:vinylpyrrolidone (PVPVA) copolymer allowed for hydrocortisone dissolution within the carrier at temperatures as low as 160 degrees C, while hydroxypropyl methylcellulose required temperatures upward of 180 degrees C to facilitate solubilization. Low substituted hydroxypropyl cellulose, a high glass transition temperature control, showed that the material was unable to solubilize hydrocortisone. Manufacturing process control studies using hot melt extruded compositions of hydrocortisone and PVPVA showed that increased temperatures and residence times negatively impacted product potency due to decomposition. Using KinetiSol Dispersing to reduce residence time and to facilitate lower temperature processing, it was possible to produce solid dispersions with improved product potency. This study clearly demonstrated the importance of carrier selection to facilitate lower temperature processing, as well as the effect of residence time on product potency. Furthermore, KinetiSol Dispersing provided significant advantages over hot melt extrusion due to the reduced residence times and lower required processing temperatures. This allowed for the production of solid dispersions with enhanced product potency.

Authors+Show Affiliations

Division of Pharmaceutics, The University of Texas at Austin, 1 University Station A1920, Austin, TX 78712, United States. james.dinunzio@mail.utexas.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19818402

Citation

Dinunzio, James C., et al. "Fusion Production of Solid Dispersions Containing a Heat-sensitive Active Ingredient By Hot Melt Extrusion and Kinetisol Dispersing." European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, vol. 74, no. 2, 2010, pp. 340-51.
Dinunzio JC, Brough C, Hughey JR, et al. Fusion production of solid dispersions containing a heat-sensitive active ingredient by hot melt extrusion and Kinetisol dispersing. Eur J Pharm Biopharm. 2010;74(2):340-51.
Dinunzio, J. C., Brough, C., Hughey, J. R., Miller, D. A., Williams, R. O., & McGinity, J. W. (2010). Fusion production of solid dispersions containing a heat-sensitive active ingredient by hot melt extrusion and Kinetisol dispersing. European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, 74(2), 340-51. https://doi.org/10.1016/j.ejpb.2009.09.007
Dinunzio JC, et al. Fusion Production of Solid Dispersions Containing a Heat-sensitive Active Ingredient By Hot Melt Extrusion and Kinetisol Dispersing. Eur J Pharm Biopharm. 2010;74(2):340-51. PubMed PMID: 19818402.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fusion production of solid dispersions containing a heat-sensitive active ingredient by hot melt extrusion and Kinetisol dispersing. AU - Dinunzio,James C, AU - Brough,Chris, AU - Hughey,Justin R, AU - Miller,Dave A, AU - Williams,Robert O,3rd AU - McGinity,James W, Y1 - 2009/10/07/ PY - 2009/06/10/received PY - 2009/09/09/revised PY - 2009/09/17/accepted PY - 2009/10/13/entrez PY - 2009/10/13/pubmed PY - 2010/5/25/medline SP - 340 EP - 51 JF - European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V JO - Eur J Pharm Biopharm VL - 74 IS - 2 N2 - Many techniques for the production of solid dispersions rely on elevated temperatures and prolonged material residence times, which can result in decomposition of temperature-sensitive components. In this study, hydrocortisone was used as a model temperature-sensitive active ingredient to study the effect of formulation and processing techniques as well as to characterize the benefits of KinetiSol Dispersing for the production of solid dispersions. Preformulation studies were conducted using differential scanning calorimetry and hot stage microscopy to identify optimum carriers for the production of amorphous solid dispersions. After identification, solid dispersions were prepared by hot melt extrusion and KinetiSol Dispersing, with material characterized by X-ray diffraction, dissolution and potency testing to evaluate physicochemical properties. Results from the preformulation studies showed that vinylacetate:vinylpyrrolidone (PVPVA) copolymer allowed for hydrocortisone dissolution within the carrier at temperatures as low as 160 degrees C, while hydroxypropyl methylcellulose required temperatures upward of 180 degrees C to facilitate solubilization. Low substituted hydroxypropyl cellulose, a high glass transition temperature control, showed that the material was unable to solubilize hydrocortisone. Manufacturing process control studies using hot melt extruded compositions of hydrocortisone and PVPVA showed that increased temperatures and residence times negatively impacted product potency due to decomposition. Using KinetiSol Dispersing to reduce residence time and to facilitate lower temperature processing, it was possible to produce solid dispersions with improved product potency. This study clearly demonstrated the importance of carrier selection to facilitate lower temperature processing, as well as the effect of residence time on product potency. Furthermore, KinetiSol Dispersing provided significant advantages over hot melt extrusion due to the reduced residence times and lower required processing temperatures. This allowed for the production of solid dispersions with enhanced product potency. SN - 1873-3441 UR - https://www.unboundmedicine.com/medline/citation/19818402/Fusion_production_of_solid_dispersions_containing_a_heat_sensitive_active_ingredient_by_hot_melt_extrusion_and_Kinetisol_dispersing_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0939-6411(09)00286-0 DB - PRIME DP - Unbound Medicine ER -