Tags

Type your tag names separated by a space and hit enter

Application of film-casting technique to investigate drug-polymer miscibility in solid dispersion and hot-melt extrudate.
J Pharm Sci. 2015 Jul; 104(7):2142-52.JP

Abstract

Determination of drug-polymer miscibility is critical for successful development of solid dispersions. This report details a practical method to predict miscibility and physical stability of drug with various polymers in solid dispersion and, especially, in melt extrudates by applying a film-casting technique. Mixtures of itraconazole (ITZ) with hydroxypropylmethylcellulose phthalate (HPMCP), Kollidon(®) VA 64, Eudragit(®) E PO, and Soluplus(®) were film-casted, exposed to 40°C/75% RH for 1 month and then analyzed using differential scanning calorimetry (DSC), powder X-ray diffractometry, and polarized light microscopy (PLM). ITZ had the highest miscibility with HPMCP, being miscible at drug to polymer ratio of 6:4 (w/w). There was a downward trend of lower miscibility with Soluplus(®) (miscible at 3:7, w/w, and a few microcrystals present at 4:6, w/w), Kollidon(®) VA 64 (2:8, w/w) and Eudragit(®) E PO (<1:9, w/w). PLM was found more sensitive to detect drug crystallization than DSC and powder X-ray diffractometry. There was general correlation between results of film casting and hot-melt extrusion (HME) using a twin screw extruder. For ITZ-Soluplus(®) mixtures, HME at 4:6 (w/w) resulted in a single phase, whereas drug crystallization was observed at higher drug load. HME of ITZ-Kollidon(®) VA 64 mixtures also correlated well with the miscibility predicted by film casting.

Authors+Show Affiliations

College of Pharmacy and Health Sciences, St. John's University, Queens, New York, 11439.College of Pharmacy and Health Sciences, St. John's University, Queens, New York, 11439.College of Pharmacy and Health Sciences, St. John's University, Queens, New York, 11439.Catalent Pharma Solutions, Somerset, New Jersey, 08873.Catalent Pharma Solutions, Somerset, New Jersey, 08873.College of Pharmacy and Health Sciences, St. John's University, Queens, New York, 11439.

Pub Type(s)

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

Language

eng

PubMed ID

25917333

Citation

Parikh, Tapan, et al. "Application of Film-casting Technique to Investigate Drug-polymer Miscibility in Solid Dispersion and Hot-melt Extrudate." Journal of Pharmaceutical Sciences, vol. 104, no. 7, 2015, pp. 2142-52.
Parikh T, Gupta SS, Meena AK, et al. Application of film-casting technique to investigate drug-polymer miscibility in solid dispersion and hot-melt extrudate. J Pharm Sci. 2015;104(7):2142-52.
Parikh, T., Gupta, S. S., Meena, A. K., Vitez, I., Mahajan, N., & Serajuddin, A. T. (2015). Application of film-casting technique to investigate drug-polymer miscibility in solid dispersion and hot-melt extrudate. Journal of Pharmaceutical Sciences, 104(7), 2142-52. https://doi.org/10.1002/jps.24446
Parikh T, et al. Application of Film-casting Technique to Investigate Drug-polymer Miscibility in Solid Dispersion and Hot-melt Extrudate. J Pharm Sci. 2015;104(7):2142-52. PubMed PMID: 25917333.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Application of film-casting technique to investigate drug-polymer miscibility in solid dispersion and hot-melt extrudate. AU - Parikh,Tapan, AU - Gupta,Simerdeep Singh, AU - Meena,Anuprabha K, AU - Vitez,Imre, AU - Mahajan,Nidhi, AU - Serajuddin,Abu T M, Y1 - 2015/04/27/ PY - 2014/12/22/received PY - 2015/02/28/revised PY - 2015/03/16/accepted PY - 2015/4/29/entrez PY - 2015/4/29/pubmed PY - 2016/3/12/medline KW - amorphous KW - crystallization KW - drug-polymer miscibility KW - film casting KW - hot-melt extrusion KW - itraconazole KW - polarized light microscopy KW - polymer KW - solid dispersion KW - thermal analysis SP - 2142 EP - 52 JF - Journal of pharmaceutical sciences JO - J Pharm Sci VL - 104 IS - 7 N2 - Determination of drug-polymer miscibility is critical for successful development of solid dispersions. This report details a practical method to predict miscibility and physical stability of drug with various polymers in solid dispersion and, especially, in melt extrudates by applying a film-casting technique. Mixtures of itraconazole (ITZ) with hydroxypropylmethylcellulose phthalate (HPMCP), Kollidon(®) VA 64, Eudragit(®) E PO, and Soluplus(®) were film-casted, exposed to 40°C/75% RH for 1 month and then analyzed using differential scanning calorimetry (DSC), powder X-ray diffractometry, and polarized light microscopy (PLM). ITZ had the highest miscibility with HPMCP, being miscible at drug to polymer ratio of 6:4 (w/w). There was a downward trend of lower miscibility with Soluplus(®) (miscible at 3:7, w/w, and a few microcrystals present at 4:6, w/w), Kollidon(®) VA 64 (2:8, w/w) and Eudragit(®) E PO (<1:9, w/w). PLM was found more sensitive to detect drug crystallization than DSC and powder X-ray diffractometry. There was general correlation between results of film casting and hot-melt extrusion (HME) using a twin screw extruder. For ITZ-Soluplus(®) mixtures, HME at 4:6 (w/w) resulted in a single phase, whereas drug crystallization was observed at higher drug load. HME of ITZ-Kollidon(®) VA 64 mixtures also correlated well with the miscibility predicted by film casting. SN - 1520-6017 UR - https://www.unboundmedicine.com/medline/citation/25917333/Application_of_film_casting_technique_to_investigate_drug_polymer_miscibility_in_solid_dispersion_and_hot_melt_extrudate_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-3549(15)30038-1 DB - PRIME DP - Unbound Medicine ER -