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A Rapid Tool to Optimize Process Variables for Continuous Manufacturing of Metronidazole Ointment Using Melt Extrusion Technique

  • Research Article
  • Theme: Pharmaceutical Thermal Processing - An Update
  • Published:
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Abstract

The use of hot-melt extrusion (HME) technique in the preparation of semi-solid products offers several advantages over conventional processes. However, the optimization of the technique for preparation of semi-solid pharmaceuticals is challenging due to involvement of ingredients with different physical properties. Hence, a simple tool to optimize the mixing of ingredients that results in a target ratio and drug content uniformity is utmost important. In this study, a handheld colorimeter has been explored to optimize the process variables of twin screw processor for preparation of hydrophilic PEG-based ointment. The process parameters which were optimized with use of handheld colorimeter have been used for preparation of polyethylene glycol–based metronidazole ointment. The metronidazole ointment prepared by twin screw processor was compared with commercially available metronidazole gel for in vitro release testing and ex vivo permeation. The flux, ex vivo bioavailability, and Tmax of polyethylene glycol-based metronidazole ointment was found to be similar to that of marketed metronidazole gel.

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Abbreviations

HME:

Hot-melt extrusion

T max :

Time at which maximum flux was attained

PEG:

Polyethylene glycol

Do/Di :

Outer diameter to inner diameter ratio

HPLC:

High-performance liquid chromatography

PDA:

Photodiode array

LOQ:

Limit of quantification

rpm:

Revolutions per minute

WoA:

Work of adhesion

PBS:

Phosphate-buffered saline

IVRT:

In vitro release testing

L :

Lightness value

cp:

Centipoise

API:

Active pharmaceutical ingredient

J max :

Maximum flux

AUC0–24 :

Area under the curve of flux versus time plot

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Funding

We thank the technical support and the generous grant support from Steer America, Uniontown, OH, for this project.

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Authors and Affiliations

  1. Department of Pharmaceutics of Drug Delivery, University of Mississippi, University Park, Oxford, Mississippi, USA

    Srinivas Ajjarapu, Srinath Rangappa, Vijay Kumar Shankar, Abhishek Shettar, Micheal A Repka & S. Narasimha Murthy

  2. Pharmaceutics, KLE University’s College of Pharmacy, Bangalore, Karnataka, India

    H.N. Shiva Kumar

  3. Pharmaceutics, Institute for Drug Delivery and Biomedical Research (IDBR), Bengaluru, Karnataka, India

    H.N. Shiva Kumar & S. Narasimha Murthy

  4. Pharmaceutical Development Center, STEERLife India Pvt. Ltd., Bengaluru, Karnataka, India

    Vijay I. Kulkarni

Authors
  1. Srinivas Ajjarapu
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  2. Srinath Rangappa
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  7. Micheal A Repka
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  8. S. Narasimha Murthy
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Correspondence to S. Narasimha Murthy.

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Guest Editors: Feng Zhang, Michael Repka and Suresh Bandari

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Ajjarapu, S., Rangappa, S., Shankar, V.K. et al. A Rapid Tool to Optimize Process Variables for Continuous Manufacturing of Metronidazole Ointment Using Melt Extrusion Technique. AAPS PharmSciTech 21, 273 (2020). https://doi.org/10.1208/s12249-020-01808-8

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