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Formulation Development of Sublingual Cyclobenzaprine Tablets Empowered by Standardized and Physiologically Relevant Ex Vivo Permeation Studies.

Authors :
Majid H
Puzik A
Maier T
Merk R
Bartel A
Mueller HC
Burckhardt BB
Source :
Pharmaceutics [Pharmaceutics] 2021 Sep 06; Vol. 13 (9). Date of Electronic Publication: 2021 Sep 06.
Publication Year :
2021

Abstract

Suitable ex vivo models are required as predictive tools of oromucosal permeability between in vitro characterizations and in vivo studies in order to support the development of novel intraoral formulations. To counter a lack of clinical relevance and observed method heterogenicity, a standardized, controlled and physiologically relevant ex vivo permeation model was established. This model combined the Kerski diffusion cell, process automation, novel assays for tissue integrity and viability, and sensitive LC-MS/MS analysis. The study aimed to assess the effectiveness of the permeation model in the sublingual formulation development of cyclobenzaprine, a promising agent for the treatment of psychological disorders. A 4.68-fold enhancement was achieved through permeation model-led focused formulation development. Here, findings from the preformulation with regard to pH and microenvironment-modulating excipients proved supportive. Moreover, monitoring of drug metabolism during transmucosal permeation was incorporated into the model. In addition, it was feasible to assess the impact of dosage form alterations under stress conditions, with the detection of a 33.85% lower permeation due to salt disproportionation. Integrating the coherent processes of disintegration, dissolution, permeation, and metabolization within a physiological study design, the model enabled successful formulation development for cyclobenzaprine sublingual tablets and targeted development of patient-oriented drugs for the oral cavity.

Details

Language :
English
ISSN :
1999-4923
Volume :
13
Issue :
9
Database :
MEDLINE
Journal :
Pharmaceutics
Publication Type :
Academic Journal
Accession number :
34575485
Full Text :
https://doi.org/10.3390/pharmaceutics13091409