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Continuous production of fenofibrate solid lipid nanoparticles by hot-melt extrusion technology: a systematic study based on a quality by design approach.
AAPS J 2015; 17(1):194-205AJ

Abstract

This contribution describes a continuous process for the production of solid lipid nanoparticles (SLN) as drug-carrier systems via hot-melt extrusion (HME). Presently, HME technology has not been used for the manufacturing of SLN. Generally, SLN are prepared as a batch process, which is time consuming and may result in variability of end-product quality attributes. In this study, using Quality by Design (QbD) principles, we were able to achieve continuous production of SLN by combining two processes: HME technology for melt-emulsification and high-pressure homogenization (HPH) for size reduction. Fenofibrate (FBT), a poorly water-soluble model drug, was incorporated into SLN using HME-HPH methods. The developed novel platform demonstrated better process control and size reduction compared to the conventional process of hot homogenization (batch process). Varying the process parameters enabled the production of SLN below 200 nm. The dissolution profile of the FBT SLN prepared by the novel HME-HPH method was faster than that of the crude FBT and a micronized marketed FBT formulation. At the end of a 5-h in vitro dissolution study, a SLN formulation released 92-93% of drug, whereas drug release was approximately 65 and 45% for the marketed micronized formulation and crude drug, respectively. Also, pharmacokinetic study results demonstrated a statistical increase in Cmax, Tmax, and AUC0-24 h in the rate of drug absorption from SLN formulations as compared to the crude drug and marketed micronized formulation. In summary, the present study demonstrated the potential use of hot-melt extrusion technology for continuous and large-scale production of SLN.

Authors+Show Affiliations

Department of Pharmaceutics & Drug Delivery, University of Mississippi, University, Mississippi, 38677, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

25344439

Citation

Patil, Hemlata, et al. "Continuous Production of Fenofibrate Solid Lipid Nanoparticles By Hot-melt Extrusion Technology: a Systematic Study Based On a Quality By Design Approach." The AAPS Journal, vol. 17, no. 1, 2015, pp. 194-205.
Patil H, Feng X, Ye X, et al. Continuous production of fenofibrate solid lipid nanoparticles by hot-melt extrusion technology: a systematic study based on a quality by design approach. AAPS J. 2015;17(1):194-205.
Patil, H., Feng, X., Ye, X., Majumdar, S., & Repka, M. A. (2015). Continuous production of fenofibrate solid lipid nanoparticles by hot-melt extrusion technology: a systematic study based on a quality by design approach. The AAPS Journal, 17(1), pp. 194-205. doi:10.1208/s12248-014-9674-8.
Patil H, et al. Continuous Production of Fenofibrate Solid Lipid Nanoparticles By Hot-melt Extrusion Technology: a Systematic Study Based On a Quality By Design Approach. AAPS J. 2015;17(1):194-205. PubMed PMID: 25344439.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Continuous production of fenofibrate solid lipid nanoparticles by hot-melt extrusion technology: a systematic study based on a quality by design approach. AU - Patil,Hemlata, AU - Feng,Xin, AU - Ye,Xingyou, AU - Majumdar,Soumyajit, AU - Repka,Michael A, Y1 - 2014/10/25/ PY - 2014/07/29/received PY - 2014/09/23/accepted PY - 2014/10/26/entrez PY - 2014/10/26/pubmed PY - 2015/7/16/medline SP - 194 EP - 205 JF - The AAPS journal JO - AAPS J VL - 17 IS - 1 N2 - This contribution describes a continuous process for the production of solid lipid nanoparticles (SLN) as drug-carrier systems via hot-melt extrusion (HME). Presently, HME technology has not been used for the manufacturing of SLN. Generally, SLN are prepared as a batch process, which is time consuming and may result in variability of end-product quality attributes. In this study, using Quality by Design (QbD) principles, we were able to achieve continuous production of SLN by combining two processes: HME technology for melt-emulsification and high-pressure homogenization (HPH) for size reduction. Fenofibrate (FBT), a poorly water-soluble model drug, was incorporated into SLN using HME-HPH methods. The developed novel platform demonstrated better process control and size reduction compared to the conventional process of hot homogenization (batch process). Varying the process parameters enabled the production of SLN below 200 nm. The dissolution profile of the FBT SLN prepared by the novel HME-HPH method was faster than that of the crude FBT and a micronized marketed FBT formulation. At the end of a 5-h in vitro dissolution study, a SLN formulation released 92-93% of drug, whereas drug release was approximately 65 and 45% for the marketed micronized formulation and crude drug, respectively. Also, pharmacokinetic study results demonstrated a statistical increase in Cmax, Tmax, and AUC0-24 h in the rate of drug absorption from SLN formulations as compared to the crude drug and marketed micronized formulation. In summary, the present study demonstrated the potential use of hot-melt extrusion technology for continuous and large-scale production of SLN. SN - 1550-7416 UR - https://www.unboundmedicine.com/medline/citation/25344439/Continuous_production_of_fenofibrate_solid_lipid_nanoparticles_by_hot_melt_extrusion_technology:_a_systematic_study_based_on_a_quality_by_design_approach_ L2 - https://dx.doi.org/10.1208/s12248-014-9674-8 DB - PRIME DP - Unbound Medicine ER -