Cargando…

DoE-Assisted Development of a Novel Glycosaminoglycan-Based Injectable Formulation for Viscosupplementation

The aim of the present work was the development of a novel glycosaminoglycan (GAG)-based injectable formulation intended for intra-articular administration that should best mimic the healthy synovial fluid. Hyaluronic acid (HA) was chosen among GAG polymers, since it is the most abundant component o...

Descripción completa

Detalles Bibliográficos
Autores principales: Cicognani, Marta, Rossi, Silvia, Vecchi, Gabriele, Giori, Andrea Maria, Ferrari, Franca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407620/
https://www.ncbi.nlm.nih.gov/pubmed/32698313
http://dx.doi.org/10.3390/pharmaceutics12070681
_version_ 1783567663550693376
author Cicognani, Marta
Rossi, Silvia
Vecchi, Gabriele
Giori, Andrea Maria
Ferrari, Franca
author_facet Cicognani, Marta
Rossi, Silvia
Vecchi, Gabriele
Giori, Andrea Maria
Ferrari, Franca
author_sort Cicognani, Marta
collection PubMed
description The aim of the present work was the development of a novel glycosaminoglycan (GAG)-based injectable formulation intended for intra-articular administration that should best mimic the healthy synovial fluid. Hyaluronic acid (HA) was chosen among GAG polymers, since it is the most abundant component of the synovial fluid. A DoE (Design of Experiment) approach was used for the development of a formulation containing two HA (very high (VHMW) and low (LMW) molecular weight) grades. The rationale for this choice is that so far, no commercial product based on a single HA grade or even on binary HA mixture possesses optimal viscoelastic properties in comparison with healthy synovial fluid. A full factorial design was chosen to investigate the influence of concentration and relative fraction of the two polymer grades (retained as factors of the model) on formulation functional (viscosity and viscoelastic) properties, which are considered response variables. Thanks to the DoE approach, the composition of the optimized HA formulation was found. The addition to such formulation of an injectable grade fat-free soy phospholipid, which was rich in phosphatidylcholine (PC), resulted in improved lubrication properties. The final HA + PC formulation, packaged in pre-filled sterile syringes, was stable in long-term and accelerated ICH (International Council for Harmonisation) storage conditions. The overall results pointed out the formulation suitability for further steps of pharmaceutical developments, namely for the passage to pilot scale.
format Online
Article
Text
id pubmed-7407620
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-74076202020-08-12 DoE-Assisted Development of a Novel Glycosaminoglycan-Based Injectable Formulation for Viscosupplementation Cicognani, Marta Rossi, Silvia Vecchi, Gabriele Giori, Andrea Maria Ferrari, Franca Pharmaceutics Article The aim of the present work was the development of a novel glycosaminoglycan (GAG)-based injectable formulation intended for intra-articular administration that should best mimic the healthy synovial fluid. Hyaluronic acid (HA) was chosen among GAG polymers, since it is the most abundant component of the synovial fluid. A DoE (Design of Experiment) approach was used for the development of a formulation containing two HA (very high (VHMW) and low (LMW) molecular weight) grades. The rationale for this choice is that so far, no commercial product based on a single HA grade or even on binary HA mixture possesses optimal viscoelastic properties in comparison with healthy synovial fluid. A full factorial design was chosen to investigate the influence of concentration and relative fraction of the two polymer grades (retained as factors of the model) on formulation functional (viscosity and viscoelastic) properties, which are considered response variables. Thanks to the DoE approach, the composition of the optimized HA formulation was found. The addition to such formulation of an injectable grade fat-free soy phospholipid, which was rich in phosphatidylcholine (PC), resulted in improved lubrication properties. The final HA + PC formulation, packaged in pre-filled sterile syringes, was stable in long-term and accelerated ICH (International Council for Harmonisation) storage conditions. The overall results pointed out the formulation suitability for further steps of pharmaceutical developments, namely for the passage to pilot scale. MDPI 2020-07-20 /pmc/articles/PMC7407620/ /pubmed/32698313 http://dx.doi.org/10.3390/pharmaceutics12070681 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cicognani, Marta
Rossi, Silvia
Vecchi, Gabriele
Giori, Andrea Maria
Ferrari, Franca
DoE-Assisted Development of a Novel Glycosaminoglycan-Based Injectable Formulation for Viscosupplementation
title DoE-Assisted Development of a Novel Glycosaminoglycan-Based Injectable Formulation for Viscosupplementation
title_full DoE-Assisted Development of a Novel Glycosaminoglycan-Based Injectable Formulation for Viscosupplementation
title_fullStr DoE-Assisted Development of a Novel Glycosaminoglycan-Based Injectable Formulation for Viscosupplementation
title_full_unstemmed DoE-Assisted Development of a Novel Glycosaminoglycan-Based Injectable Formulation for Viscosupplementation
title_short DoE-Assisted Development of a Novel Glycosaminoglycan-Based Injectable Formulation for Viscosupplementation
title_sort doe-assisted development of a novel glycosaminoglycan-based injectable formulation for viscosupplementation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407620/
https://www.ncbi.nlm.nih.gov/pubmed/32698313
http://dx.doi.org/10.3390/pharmaceutics12070681
work_keys_str_mv AT cicognanimarta doeassisteddevelopmentofanovelglycosaminoglycanbasedinjectableformulationforviscosupplementation
AT rossisilvia doeassisteddevelopmentofanovelglycosaminoglycanbasedinjectableformulationforviscosupplementation
AT vecchigabriele doeassisteddevelopmentofanovelglycosaminoglycanbasedinjectableformulationforviscosupplementation
AT gioriandreamaria doeassisteddevelopmentofanovelglycosaminoglycanbasedinjectableformulationforviscosupplementation
AT ferrarifranca doeassisteddevelopmentofanovelglycosaminoglycanbasedinjectableformulationforviscosupplementation