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A comparative study between hot-melt extrusion and spray-drying for the manufacture of anti-hypertension compatible monolithic fixed-dose combination products.
Int J Pharm. 2018 Jul 10; 545(1-2):183-196.IJ

Abstract

The purpose of this work was to investigate the application of different advanced continuous processing techniques (hot melt extrusion and spray drying) to the production of fixed-dose combination (FDC) monolithic systems comprising of hydrochlorothiazide and ramipril for the treatment of hypertension. Identical FDC formulations were manufactured by the two different methods and were characterised using powder X-ray diffraction (PXRD) and modulated differential scanning calorimetry (mDSC). Drug dissolution rates were investigated using a Wood's apparatus, while physical stability was assessed on storage under controlled temperature and humidity conditions. Interestingly both drugs were transformed into their amorphous forms when spray dried, however, hydrochlorothiazide was determined, by PXRD, to be partially crystalline when hot melt extruded with either polymer carrier (Kollidon® VA 64 or Soluplus®). Hot melt extrusion was found to result in significant degradation of ramipril, however, this could be mitigated by the inclusion of the plasticizer, polyethylene glycol 3350, in the formulation and appropriate adjustment of processing temperature. The results of intrinsic dissolution rate studies showed that hot-melt extruded samples were found to release both drugs faster than identical formulations produced via spray drying. However, the differences were attributable to the surface roughness of the compressed discs in the Wood's apparatus, rather than solid state differences between samples. After a 60-day stability study spray dried samples exhibited a greater physical stability than the equivalent hot melt extruded samples.

Authors+Show Affiliations

School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin, Ireland.School of Pharmacy, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom.School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin, Ireland.School of Pharmacy, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom.School of Pharmacy, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom.School of Pharmacy, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom.School of Pharmacy, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom.School of Pharmacy, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom.School of Pharmacy, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom.School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin, Ireland. Electronic address: healyam@tcd.ie.

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

29730176

Citation

Kelleher, J F., et al. "A Comparative Study Between Hot-melt Extrusion and Spray-drying for the Manufacture of Anti-hypertension Compatible Monolithic Fixed-dose Combination Products." International Journal of Pharmaceutics, vol. 545, no. 1-2, 2018, pp. 183-196.
Kelleher JF, Gilvary GC, Madi AM, et al. A comparative study between hot-melt extrusion and spray-drying for the manufacture of anti-hypertension compatible monolithic fixed-dose combination products. Int J Pharm. 2018;545(1-2):183-196.
Kelleher, J. F., Gilvary, G. C., Madi, A. M., Jones, D. S., Li, S., Tian, Y., Almajaan, A., Senta-Loys, Z., Andrews, G. P., & Healy, A. M. (2018). A comparative study between hot-melt extrusion and spray-drying for the manufacture of anti-hypertension compatible monolithic fixed-dose combination products. International Journal of Pharmaceutics, 545(1-2), 183-196. https://doi.org/10.1016/j.ijpharm.2018.05.008
Kelleher JF, et al. A Comparative Study Between Hot-melt Extrusion and Spray-drying for the Manufacture of Anti-hypertension Compatible Monolithic Fixed-dose Combination Products. Int J Pharm. 2018 Jul 10;545(1-2):183-196. PubMed PMID: 29730176.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A comparative study between hot-melt extrusion and spray-drying for the manufacture of anti-hypertension compatible monolithic fixed-dose combination products. AU - Kelleher,J F, AU - Gilvary,G C, AU - Madi,A M, AU - Jones,D S, AU - Li,S, AU - Tian,Y, AU - Almajaan,A, AU - Senta-Loys,Z, AU - Andrews,G P, AU - Healy,A M, Y1 - 2018/05/03/ PY - 2018/03/08/received PY - 2018/04/30/revised PY - 2018/05/02/accepted PY - 2018/5/8/pubmed PY - 2018/10/16/medline PY - 2018/5/7/entrez KW - Amorphous solid dispersions KW - Continuous manufacture KW - Fixed dose combinations KW - Hot melt extrusion KW - Spray drying SP - 183 EP - 196 JF - International journal of pharmaceutics JO - Int J Pharm VL - 545 IS - 1-2 N2 - The purpose of this work was to investigate the application of different advanced continuous processing techniques (hot melt extrusion and spray drying) to the production of fixed-dose combination (FDC) monolithic systems comprising of hydrochlorothiazide and ramipril for the treatment of hypertension. Identical FDC formulations were manufactured by the two different methods and were characterised using powder X-ray diffraction (PXRD) and modulated differential scanning calorimetry (mDSC). Drug dissolution rates were investigated using a Wood's apparatus, while physical stability was assessed on storage under controlled temperature and humidity conditions. Interestingly both drugs were transformed into their amorphous forms when spray dried, however, hydrochlorothiazide was determined, by PXRD, to be partially crystalline when hot melt extruded with either polymer carrier (Kollidon® VA 64 or Soluplus®). Hot melt extrusion was found to result in significant degradation of ramipril, however, this could be mitigated by the inclusion of the plasticizer, polyethylene glycol 3350, in the formulation and appropriate adjustment of processing temperature. The results of intrinsic dissolution rate studies showed that hot-melt extruded samples were found to release both drugs faster than identical formulations produced via spray drying. However, the differences were attributable to the surface roughness of the compressed discs in the Wood's apparatus, rather than solid state differences between samples. After a 60-day stability study spray dried samples exhibited a greater physical stability than the equivalent hot melt extruded samples. SN - 1873-3476 UR - https://www.unboundmedicine.com/medline/citation/29730176/A_comparative_study_between_hot_melt_extrusion_and_spray_drying_for_the_manufacture_of_anti_hypertension_compatible_monolithic_fixed_dose_combination_products_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-5173(18)30301-6 DB - PRIME DP - Unbound Medicine ER -