Vacuum Compression Molding As a Screening Tool to Investigate Carrier Suitability for Hot-Melt Extrusion Formulations

Overview

Journal Pharmaceutics

Publisher MDPI

Date 2020 Oct 29

PMID 33114382

Citations 10

Authors

Gauri Shadambikar

Thomas Kipping

Nicole Di-Gallo

Alessandro-Giuseppe Elia

Anja-Nadine Knuttel

Daniel Treffer

Michael A Repka

Affiliations

Soon will be listed here.

Abstract

Hot-melt extrusion (HME) is the most preferred and effective method for manufacturing amorphous solid dispersions at production scale, but it consumes large amounts of samples when used for formulation development. Herein, we show a novel approach to screen the polymers by overcoming the disadvantage of conventional HME screening by using a minimum quantity of active pharmaceutical ingredient (API). Vacuum Compression Molding (VCM) is a fusion-based method to form solid specimens starting from powders. This study aimed to investigate the processability of VCM for the creation of amorphous formulations and to compare its results with HME-processed formulations. Mixtures of indomethacin (IND) with drug carriers (Parteck MXP, Soluplus Kollidon VA 64, Eudragit EPO) were processed using VCM and extrusion technology. Thermal characterization was performed using differential scanning calorimetry, and the solid-state was analyzed via X-ray powder diffraction. Dissolution studies in the simulated gastric fluid were performed to evaluate the drug release. Both technologies showed similar results proving the effectiveness of VCM as a screening tool for HME-based formulations.

Citing Articles

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References

Knopp M, Tajber L, Tian Y, Olesen N, Jones D, Kozyra A . Comparative Study of Different Methods for the Prediction of Drug-Polymer Solubility. Mol Pharm. 2015; 12(9):3408-19. DOI: 10.1021/acs.molpharmaceut.5b00423. View

Tiwari R, Patil H, Repka M . Contribution of hot-melt extrusion technology to advance drug delivery in the 21st century. Expert Opin Drug Deliv. 2016; 13(3):451-64. DOI: 10.1517/17425247.2016.1126246. View

Treffer D, Wahl P, Hormann T, Markl D, Schrank S, Jones I . In-line implementation of an image-based particle size measurement tool to monitor hot-melt extruded pellets. Int J Pharm. 2014; 466(1-2):181-9. DOI: 10.1016/j.ijpharm.2014.03.022. View

Crowley K, Zografi G . Cryogenic grinding of indomethacin polymorphs and solvates: assessment of amorphous phase formation and amorphous phase physical stability. J Pharm Sci. 2002; 91(2):492-507. DOI: 10.1002/jps.10028. View

Otsuka M, Matsumoto T, Kaneniwa N . Effect of environmental temperature on polymorphic solid-state transformation of indomethacin during grinding. Chem Pharm Bull (Tokyo). 1986; 34(4):1784-93. DOI: 10.1248/cpb.34.1784. View

Auch C, Harms M, Mader K . Melt-based screening method with improved predictability regarding polymer selection for amorphous solid dispersions. Eur J Pharm Sci. 2018; 124:339-348. DOI: 10.1016/j.ejps.2018.08.035. View

Eder S, Beretta M, Witschnigg A, Koutsamanis I, Eggenreich K, Khinast J . Establishment of a Molding Procedure to Facilitate Formulation Development for Co-extrudates. AAPS PharmSciTech. 2017; 18(8):2971-2976. DOI: 10.1208/s12249-017-0788-z. View

Kalepu S, Nekkanti V . Insoluble drug delivery strategies: review of recent advances and business prospects. Acta Pharm Sin B. 2015; 5(5):442-53. PMC: 4629443. DOI: 10.1016/j.apsb.2015.07.003. View

Nokhodchi A, Javadzadeh Y, Siahi-Shadbad M, Barzegar-Jalali M . The effect of type and concentration of vehicles on the dissolution rate of a poorly soluble drug (indomethacin) from liquisolid compacts. J Pharm Pharm Sci. 2005; 8(1):18-25. View

10.

Wlodarski K, Zhang F, Liu T, Sawicki W, Kipping T . Synergistic Effect of Polyvinyl Alcohol and Copovidone in Itraconazole Amorphous Solid Dispersions. Pharm Res. 2018; 35(1):16. DOI: 10.1007/s11095-017-2313-1. View

11.

Kyeremateng S, Pudlas M, Woehrle G . A fast and reliable empirical approach for estimating solubility of crystalline drugs in polymers for hot melt extrusion formulations. J Pharm Sci. 2014; 103(9):2847-2858. DOI: 10.1002/jps.23941. View

12.

Sakai T, Thommes M . Investigation into mixing capability and solid dispersion preparation using the DSM Xplore Pharma Micro Extruder. J Pharm Pharmacol. 2014; 66(2):218-31. DOI: 10.1111/jphp.12085. View

13.

Chiang P, Ran Y, Chou K, Cui Y, Sambrone A, Chan C . Evaluation of drug load and polymer by using a 96-well plate vacuum dry system for amorphous solid dispersion drug delivery. AAPS PharmSciTech. 2012; 13(2):713-22. PMC: 3364400. DOI: 10.1208/s12249-012-9795-2. View

14.

Agrawal A, Dudhedia M, Zimny E . Hot Melt Extrusion: Development of an Amorphous Solid Dispersion for an Insoluble Drug from Mini-scale to Clinical Scale. AAPS PharmSciTech. 2016; 17(1):133-47. PMC: 4766127. DOI: 10.1208/s12249-015-0425-7. View

15.

Cosse A, Konig C, Lamprecht A, Wagner K . Hot Melt Extrusion for Sustained Protein Release: Matrix Erosion and In Vitro Release of PLGA-Based Implants. AAPS PharmSciTech. 2016; 18(1):15-26. DOI: 10.1208/s12249-016-0548-5. View

16.

Rask M, Knopp M, Olesen N, Holm R, Rades T . Comparison of two DSC-based methods to predict drug-polymer solubility. Int J Pharm. 2018; 540(1-2):98-105. DOI: 10.1016/j.ijpharm.2018.02.002. View

17.

Lin D, Huang Y . A thermal analysis method to predict the complete phase diagram of drug-polymer solid dispersions. Int J Pharm. 2010; 399(1-2):109-15. DOI: 10.1016/j.ijpharm.2010.08.013. View

18.

Vasconcelos T, Sarmento B, Costa P . Solid dispersions as strategy to improve oral bioavailability of poor water soluble drugs. Drug Discov Today. 2007; 12(23-24):1068-75. DOI: 10.1016/j.drudis.2007.09.005. View

19.

Patil H, Tiwari R, Upadhye S, Vladyka R, Repka M . Formulation and development of pH-independent/dependent sustained release matrix tablets of ondansetron HCl by a continuous twin-screw melt granulation process. Int J Pharm. 2015; 496(1):33-41. DOI: 10.1016/j.ijpharm.2015.04.009. View

20.

Crowley M, Zhang F, Repka M, Thumma S, Upadhye S, Battu S . Pharmaceutical applications of hot-melt extrusion: part I. Drug Dev Ind Pharm. 2007; 33(9):909-26. DOI: 10.1080/03639040701498759. View