Cargando…
Co-crystals as a new approach to multimodal analgesia and the treatment of pain
Pain is highly prevalent, but frequently untreated or under-treated, and health care professionals are faced with a range of treatment challenges. Multimodal therapy is recommended and can be achieved using open combinations (ie, concomitant administration) of individual agents, fixed-dose combinati...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6732512/ https://www.ncbi.nlm.nih.gov/pubmed/31564960 http://dx.doi.org/10.2147/JPR.S208082 |
_version_ | 1783449825056915456 |
---|---|
author | Almansa, Carmen Frampton, Christopher S Vela, José Miguel Whitelock, Steve Plata-Salamán, Carlos R |
author_facet | Almansa, Carmen Frampton, Christopher S Vela, José Miguel Whitelock, Steve Plata-Salamán, Carlos R |
author_sort | Almansa, Carmen |
collection | PubMed |
description | Pain is highly prevalent, but frequently untreated or under-treated, and health care professionals are faced with a range of treatment challenges. Multimodal therapy is recommended and can be achieved using open combinations (ie, concomitant administration) of individual agents, fixed-dose combinations (FDCs), or multimodal agents (ie, single agents with multiple mechanisms of action). Co-crystallization of active pharmaceutical ingredients (APIs) offers another approach, with the potential to provide drugs with unique properties and advantages for therapeutic applications compared to combinations. API–API co-crystals are single-entity forms that offer a unique possibility of improving the physicochemical properties of both constituent APIs, as well as permitting their synchronous release. Consequently, this may positively impact on their pharmacokinetic (PK) properties and profiles, providing a potential advantage over FDCs and translating into improved clinical efficacy and safety profiles. We report here a revision of the literature concerning API–API co-crystals for the treatment of pain. It becomes apparent that identifying APIs with complementary mechanisms of action that can be adequately co-crystallized in an appropriate molecular ratio applicable for therapeutic use is challenging. In addition, API–API co-crystals normally result in a mere increased exposure of an API without defined clinical benefits (since, to maintain the benefit-risk, the dose needs to be proportionally reduced to adjust for the increased exposure). An exception to this is the co-crystal of tramadol-celecoxib (CTC), that represents a unique concept in co-crystal technology. In CTC neither of its three active components that have complementary mechanisms of action (ie, the two enantiomers of tramadol and celecoxib) show increased exposure levels versus commercially available single-entity reference products, but rather show a change in their PK profile with potential clinical advantages. CTC is in Phase III clinical development for the treatment of pain. |
format | Online Article Text |
id | pubmed-6732512 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-67325122019-09-27 Co-crystals as a new approach to multimodal analgesia and the treatment of pain Almansa, Carmen Frampton, Christopher S Vela, José Miguel Whitelock, Steve Plata-Salamán, Carlos R J Pain Res Review Pain is highly prevalent, but frequently untreated or under-treated, and health care professionals are faced with a range of treatment challenges. Multimodal therapy is recommended and can be achieved using open combinations (ie, concomitant administration) of individual agents, fixed-dose combinations (FDCs), or multimodal agents (ie, single agents with multiple mechanisms of action). Co-crystallization of active pharmaceutical ingredients (APIs) offers another approach, with the potential to provide drugs with unique properties and advantages for therapeutic applications compared to combinations. API–API co-crystals are single-entity forms that offer a unique possibility of improving the physicochemical properties of both constituent APIs, as well as permitting their synchronous release. Consequently, this may positively impact on their pharmacokinetic (PK) properties and profiles, providing a potential advantage over FDCs and translating into improved clinical efficacy and safety profiles. We report here a revision of the literature concerning API–API co-crystals for the treatment of pain. It becomes apparent that identifying APIs with complementary mechanisms of action that can be adequately co-crystallized in an appropriate molecular ratio applicable for therapeutic use is challenging. In addition, API–API co-crystals normally result in a mere increased exposure of an API without defined clinical benefits (since, to maintain the benefit-risk, the dose needs to be proportionally reduced to adjust for the increased exposure). An exception to this is the co-crystal of tramadol-celecoxib (CTC), that represents a unique concept in co-crystal technology. In CTC neither of its three active components that have complementary mechanisms of action (ie, the two enantiomers of tramadol and celecoxib) show increased exposure levels versus commercially available single-entity reference products, but rather show a change in their PK profile with potential clinical advantages. CTC is in Phase III clinical development for the treatment of pain. Dove 2019-09-04 /pmc/articles/PMC6732512/ /pubmed/31564960 http://dx.doi.org/10.2147/JPR.S208082 Text en © 2019 Almansa et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Review Almansa, Carmen Frampton, Christopher S Vela, José Miguel Whitelock, Steve Plata-Salamán, Carlos R Co-crystals as a new approach to multimodal analgesia and the treatment of pain |
title | Co-crystals as a new approach to multimodal analgesia and the treatment of pain |
title_full | Co-crystals as a new approach to multimodal analgesia and the treatment of pain |
title_fullStr | Co-crystals as a new approach to multimodal analgesia and the treatment of pain |
title_full_unstemmed | Co-crystals as a new approach to multimodal analgesia and the treatment of pain |
title_short | Co-crystals as a new approach to multimodal analgesia and the treatment of pain |
title_sort | co-crystals as a new approach to multimodal analgesia and the treatment of pain |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6732512/ https://www.ncbi.nlm.nih.gov/pubmed/31564960 http://dx.doi.org/10.2147/JPR.S208082 |
work_keys_str_mv | AT almansacarmen cocrystalsasanewapproachtomultimodalanalgesiaandthetreatmentofpain AT framptonchristophers cocrystalsasanewapproachtomultimodalanalgesiaandthetreatmentofpain AT velajosemiguel cocrystalsasanewapproachtomultimodalanalgesiaandthetreatmentofpain AT whitelocksteve cocrystalsasanewapproachtomultimodalanalgesiaandthetreatmentofpain AT platasalamancarlosr cocrystalsasanewapproachtomultimodalanalgesiaandthetreatmentofpain |