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Investigating a Novel Hot Melt Extrusion-Based Drying Technique to Solidify an Amorphous Nanosuspension Using Design of Experiment Methodology.
AAPS PharmSciTech 2018; 19(8):3778-3790AP

Abstract

The hot melt extrusion (HME) technology was explored and optimized to solidify an amorphous nanosuspension using Quality by Design (QbD) methodology. A design of experiments (DoE) approach was used to perform a set of 15 experiments, varying independent variables (feed rate, input temperature, and screw speed) within a design space. Redispersibility index (RDI), moisture content, and process yield constituted the critical quality attributes (CQAs) of the experimental design. Regression analysis and ANOVA were employed to identify and estimate significant main effects and two-way interactions, and model the process of HME drying for predictive purposes. The optimized HME-dried end product was characterized for physicochemical properties using differential scanning calorimetry (DSC), X-ray powder diffractions (XRPD), polarized light microscopy (PLM), Fourier transform infrared spectroscopy (FTIR), and in vitro dissolution studies. The statistical analysis reveals feed rate and input temperature as significant independent variables, critically influencing RDI and moisture content of solidified end product. The model developed for process yield was insignificant at a p-value of 0.05. The API retained its amorphous nature after the extrusion process which was confirmed using DSC and XRPD techniques. PLM was unsuitable to differentiate and determine crystallinity of drug moiety in the presence of a semi-crystalline bulking agent, microcrystalline cellulose (MCC). In vitro dissolution study depicted solubility and dissolution enhancement for HME-dried amorphous nanosuspension in both the dissolution media which can be attributed to amorphous nature of nanosized drug particles. A well-designed study implemented by DoE aided in developing a robust and novel HME technique to dry aqueous nanosuspension.

Authors+Show Affiliations

Impel NeuroPharma, Seattle, Washington, USA. Natoli Institute for Industrial Pharmacy Research and Development at Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, New York, 11201, USA.Amneal Pharmaceuticals, Bridgewater Township, New Jersey, USA.Natoli Institute for Industrial Pharmacy Research and Development at Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, New York, 11201, USA. rutesh.dave@liu.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30280356

Citation

Gajera, Bhavin Y., et al. "Investigating a Novel Hot Melt Extrusion-Based Drying Technique to Solidify an Amorphous Nanosuspension Using Design of Experiment Methodology." AAPS PharmSciTech, vol. 19, no. 8, 2018, pp. 3778-3790.
Gajera BY, Shah DA, Dave RH. Investigating a Novel Hot Melt Extrusion-Based Drying Technique to Solidify an Amorphous Nanosuspension Using Design of Experiment Methodology. AAPS PharmSciTech. 2018;19(8):3778-3790.
Gajera, B. Y., Shah, D. A., & Dave, R. H. (2018). Investigating a Novel Hot Melt Extrusion-Based Drying Technique to Solidify an Amorphous Nanosuspension Using Design of Experiment Methodology. AAPS PharmSciTech, 19(8), pp. 3778-3790. doi:10.1208/s12249-018-1189-7.
Gajera BY, Shah DA, Dave RH. Investigating a Novel Hot Melt Extrusion-Based Drying Technique to Solidify an Amorphous Nanosuspension Using Design of Experiment Methodology. AAPS PharmSciTech. 2018;19(8):3778-3790. PubMed PMID: 30280356.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Investigating a Novel Hot Melt Extrusion-Based Drying Technique to Solidify an Amorphous Nanosuspension Using Design of Experiment Methodology. AU - Gajera,Bhavin Y, AU - Shah,Dhaval A, AU - Dave,Rutesh H, Y1 - 2018/10/02/ PY - 2018/07/15/received PY - 2018/09/17/accepted PY - 2018/10/4/pubmed PY - 2019/3/21/medline PY - 2018/10/4/entrez KW - amorphous nanosuspension KW - analysis of variance (ANOVA) KW - design of experiment KW - dissolution rate KW - hot melt extrusion KW - optimization SP - 3778 EP - 3790 JF - AAPS PharmSciTech JO - AAPS PharmSciTech VL - 19 IS - 8 N2 - The hot melt extrusion (HME) technology was explored and optimized to solidify an amorphous nanosuspension using Quality by Design (QbD) methodology. A design of experiments (DoE) approach was used to perform a set of 15 experiments, varying independent variables (feed rate, input temperature, and screw speed) within a design space. Redispersibility index (RDI), moisture content, and process yield constituted the critical quality attributes (CQAs) of the experimental design. Regression analysis and ANOVA were employed to identify and estimate significant main effects and two-way interactions, and model the process of HME drying for predictive purposes. The optimized HME-dried end product was characterized for physicochemical properties using differential scanning calorimetry (DSC), X-ray powder diffractions (XRPD), polarized light microscopy (PLM), Fourier transform infrared spectroscopy (FTIR), and in vitro dissolution studies. The statistical analysis reveals feed rate and input temperature as significant independent variables, critically influencing RDI and moisture content of solidified end product. The model developed for process yield was insignificant at a p-value of 0.05. The API retained its amorphous nature after the extrusion process which was confirmed using DSC and XRPD techniques. PLM was unsuitable to differentiate and determine crystallinity of drug moiety in the presence of a semi-crystalline bulking agent, microcrystalline cellulose (MCC). In vitro dissolution study depicted solubility and dissolution enhancement for HME-dried amorphous nanosuspension in both the dissolution media which can be attributed to amorphous nature of nanosized drug particles. A well-designed study implemented by DoE aided in developing a robust and novel HME technique to dry aqueous nanosuspension. SN - 1530-9932 UR - https://www.unboundmedicine.com/medline/citation/30280356/Investigating_a_Novel_Hot_Melt_Extrusion_Based_Drying_Technique_to_Solidify_an_Amorphous_Nanosuspension_Using_Design_of_Experiment_Methodology_ L2 - https://dx.doi.org/10.1208/s12249-018-1189-7 DB - PRIME DP - Unbound Medicine ER -