Hypromellose acetate succinate based amorphous solid dispersions via hot melt extrusion: Effect of drug physicochemical properties

Sandeep Sarabu; Venkata Raman Kallakunta; Suresh Bandari; Amol Batra; Vivian Bi; Thomas Durig; Feng Zhang; Michael A Repka

doi:10.1016/j.carbpol.2020.115828

Hypromellose acetate succinate based amorphous solid dispersions via hot melt extrusion: Effect of drug physicochemical properties

Carbohydr Polym. 2020 Apr 1:233:115828. doi: 10.1016/j.carbpol.2020.115828. Epub 2020 Jan 10.

Authors

Sandeep Sarabu¹, Venkata Raman Kallakunta², Suresh Bandari³, Amol Batra⁴, Vivian Bi⁵, Thomas Durig⁶, Feng Zhang⁷, Michael A Repka⁸

Affiliations

¹ Department of Pharmaceutics and Drug Delivery, The University of Mississippi University, 38677, USA. Electronic address: ssarabu@go.olemiss.edu.
² Department of Pharmaceutics and Drug Delivery, The University of Mississippi University, 38677, USA. Electronic address: vkallaku@go.olemiss.edu.
³ Department of Pharmaceutics and Drug Delivery, The University of Mississippi University, 38677, USA. Electronic address: sbandari@olemiss.edu.
⁴ Ashland Specialty Ingredients, Wilmington, DE 19808, USA. Electronic address: amol_batra@ashland.com.
⁵ Ashland Specialty Ingredients, Wilmington, DE 19808, USA. Electronic address: vbi@ashland.com.
⁶ Ashland Specialty Ingredients, Wilmington, DE 19808, USA. Electronic address: tdurig@ashland.com.
⁷ College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA. Electronic address: feng.zhang@austin.utexas.edu.
⁸ Department of Pharmaceutics and Drug Delivery, The University of Mississippi University, 38677, USA; Pii Center for Pharmaceutical Innovation and Instruction, The University of Mississippi University 38677, USA. Electronic address: marepka@olemiss.edu.

Abstract

In this study, the impact of drug and hydroxypropyl methylcellulose acetate succinate (HPMCAS) grades physicochemical properties on extrusion process, dissolution and stability of the hot melt extruded amorphous solid dispersions (ASDs) of nifedipine and efavirenz was investigated. Incorporation of drugs affected the extrusion temperature required for solid dispersion preparation. Differential scanning calorimetry and powder X-ray diffraction studies confirmed the amorphous conversion of the drugs in the prepared formulations. The amorphous nature of ASDs was unchanged after 3 months of stability testing at 40 °C and 75% relative humidity. The dissolution efficiency of the ASDs was dependent on the log P of the drug. The inhibitory effect of HPMCAS on drug precipitation was dependent on the hydrophobic interactions between drug and polymer, polymer grade, and dose of the drug. The dissolution efficiency and dissolution rate of the ASDs were dependent on the log P of the drug and solubility and hydrophilicity of the polymer grade respectively. The inhibitory effect of HPMCAS on drug precipitation was dependent on the hydrophobic interactions between drug and polymer, polymer grade, and the dissolution dose of the drug.

Keywords: Efavirenz; HME; HPMCAS; Nifedipine; Solid dispersions; Supersaturation.

MeSH terms

Acetates / chemistry
Alkynes
Benzoxazines / chemistry*
Cyclopropanes
Drug Compounding / methods
Drug Liberation
Drug Stability
Excipients / chemistry*
Hot Melt Extrusion Technology
Hot Temperature
Hypromellose Derivatives / chemistry*
Methylcellulose / analogs & derivatives
Methylcellulose / chemistry
Nifedipine / chemistry*
Solubility
Succinates / chemistry

Substances

Acetates
Alkynes
Benzoxazines
Cyclopropanes
Excipients
Succinates
Hypromellose Derivatives
hydroxypropylmethylcellulose acetate succinate
Methylcellulose
Nifedipine
efavirenz

Grants and funding

P30 GM122733/GM/NIGMS NIH HHS/United States