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Physicochemical characterization of hot melt extruded bicalutamide-polyvinylpyrrolidone solid dispersions.
J Pharm Sci. 2010 Mar; 99(3):1322-35.JP

Abstract

Solid molecular dispersions of bicalutamide (BL) and polyvinylpyrrolidone (PVP) were prepared by hot melt extrusion technology at drug-to-polymer ratios of 1:10, 2:10, and 3:10 (w/w). The solid-state properties of BL, physical mixtures of BL/PVP, and hot melt extrudates were characterized using differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD), Raman, and Fourier transform infrared (FTIR) spectroscopy. Drug dissolution studies were subsequently conducted on hot melt extruded solid dispersions and physical mixtures. All hot melt extrudates had a single T(g) between the T(g) of amorphous BL and PVP indicating miscibility of BL with PVP and the formation of solid molecular dispersions. PXRD confirmed the presence of the amorphous form of BL within the extrudates. Conversely, PXRD patterns recorded for physical mixtures showed sharp bands characteristic of crystalline BL, whereas DSC traces had a distinct endotherm at 196 degrees C corresponding to melting of crystalline BL. Further investigations using DSC confirmed solid-state plasticization of PVP by amorphous BL and hence antiplasticization of amorphous BL by PVP. Experimentally observed T(g) values of physical mixtures were shown to be significantly higher than those calculated using the Gordon-Taylor equation suggesting the formation of strong intermolecular interactions between BL and PVP. FTIR and Raman spectroscopy were used to investigate these interactions and strongly suggested the presence of secondary interaction between PVP and BL within the hot melt extrudates. The drug dissolution properties of hot melt extrudates were enhanced significantly in comparison to crystalline BL and physical mixtures. Moreover, the rate and extent of BL release were highly dependent on the amount of PVP present within the extrudate. Storage of the extrudates confirmed the stability of amorphous BL for up to 12 months at 20 degrees C, 40% RH whereas stability was reduced under highly humid conditions (20 degrees C, 65% RH). Interestingly, BL recrystallization after storage under these conditions had no effect on the dissolution properties of the extrudates.

Authors+Show Affiliations

The Drug Delivery and Biomaterials Group, School of Pharmacy, Medical Biology Centre, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, UK. g.andrews@qub.ac.ukNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

19798757

Citation

Andrews, Gavin P., et al. "Physicochemical Characterization of Hot Melt Extruded Bicalutamide-polyvinylpyrrolidone Solid Dispersions." Journal of Pharmaceutical Sciences, vol. 99, no. 3, 2010, pp. 1322-35.
Andrews GP, AbuDiak OA, Jones DS. Physicochemical characterization of hot melt extruded bicalutamide-polyvinylpyrrolidone solid dispersions. J Pharm Sci. 2010;99(3):1322-35.
Andrews, G. P., AbuDiak, O. A., & Jones, D. S. (2010). Physicochemical characterization of hot melt extruded bicalutamide-polyvinylpyrrolidone solid dispersions. Journal of Pharmaceutical Sciences, 99(3), 1322-35. https://doi.org/10.1002/jps.21914
Andrews GP, AbuDiak OA, Jones DS. Physicochemical Characterization of Hot Melt Extruded Bicalutamide-polyvinylpyrrolidone Solid Dispersions. J Pharm Sci. 2010;99(3):1322-35. PubMed PMID: 19798757.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Physicochemical characterization of hot melt extruded bicalutamide-polyvinylpyrrolidone solid dispersions. AU - Andrews,Gavin P, AU - AbuDiak,Osama A, AU - Jones,David S, PY - 2009/10/3/entrez PY - 2009/10/3/pubmed PY - 2010/4/3/medline SP - 1322 EP - 35 JF - Journal of pharmaceutical sciences JO - J Pharm Sci VL - 99 IS - 3 N2 - Solid molecular dispersions of bicalutamide (BL) and polyvinylpyrrolidone (PVP) were prepared by hot melt extrusion technology at drug-to-polymer ratios of 1:10, 2:10, and 3:10 (w/w). The solid-state properties of BL, physical mixtures of BL/PVP, and hot melt extrudates were characterized using differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD), Raman, and Fourier transform infrared (FTIR) spectroscopy. Drug dissolution studies were subsequently conducted on hot melt extruded solid dispersions and physical mixtures. All hot melt extrudates had a single T(g) between the T(g) of amorphous BL and PVP indicating miscibility of BL with PVP and the formation of solid molecular dispersions. PXRD confirmed the presence of the amorphous form of BL within the extrudates. Conversely, PXRD patterns recorded for physical mixtures showed sharp bands characteristic of crystalline BL, whereas DSC traces had a distinct endotherm at 196 degrees C corresponding to melting of crystalline BL. Further investigations using DSC confirmed solid-state plasticization of PVP by amorphous BL and hence antiplasticization of amorphous BL by PVP. Experimentally observed T(g) values of physical mixtures were shown to be significantly higher than those calculated using the Gordon-Taylor equation suggesting the formation of strong intermolecular interactions between BL and PVP. FTIR and Raman spectroscopy were used to investigate these interactions and strongly suggested the presence of secondary interaction between PVP and BL within the hot melt extrudates. The drug dissolution properties of hot melt extrudates were enhanced significantly in comparison to crystalline BL and physical mixtures. Moreover, the rate and extent of BL release were highly dependent on the amount of PVP present within the extrudate. Storage of the extrudates confirmed the stability of amorphous BL for up to 12 months at 20 degrees C, 40% RH whereas stability was reduced under highly humid conditions (20 degrees C, 65% RH). Interestingly, BL recrystallization after storage under these conditions had no effect on the dissolution properties of the extrudates. SN - 1520-6017 UR - https://www.unboundmedicine.com/medline/citation/19798757/Physicochemical_characterization_of_hot_melt_extruded_bicalutamide_polyvinylpyrrolidone_solid_dispersions_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-3549(15)32734-9 DB - PRIME DP - Unbound Medicine ER -