Long-term Stabilization of Aqueous Doxycycline Formulations, in Mucoadhesive Hydrogels for Treatment of Oral Mucosal Conditions

Author(s): Venu G.R. Patlolla, William P. Holbrook, Sveinbjorn Gizurarson*, Thordis Kristmundsdottir

Journal Name: Current Drug Discovery Technologies

Volume 17 , Issue 3 , 2020

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Graphical Abstract:


Abstract:

Background: The main aim of this work was to develop stable (>2 years) doxycycline formulation, at clinically relevant concentrations and using clinically relevant formulation. Doxycycline has a MMP- inhibitory effects that is important for the treatment of various oral mucosal conditions. Therefore, protecting doxycycline from degradation in aqueous formulation requires halting or prevention of oxidation and epimerisation of the active compound.

Methods: Stabilizing excipients were intuitively put together to enhance the stability as a cumulative effort. A total of 30 hydrogels were compared with different types and concentrations of stability enhancing excipients, pH, storage temperatures (4, 25 and 40°C) and mucoadhesive polymers. The duration of the study was from day 1 and up to 58 months. The gelation temperature was adjusted below the actual body temperature. The complexation efficiency between the doxycycline and HPβCD was studied using the DSC, FTIR and XRPD.

Results: The majority of formulations at 4°C were highly stable by the end of 58 months and their stabilities were improved at all 3 temperatures.

Conclusion: In conclusion, it is possible to prevent doxycycline from both oxidation and epimerization in an aqueous formulation, for up to 5 years.

Keywords: Stability, doxycycline, in situ, oral mucosal, drug delivery, mucoadhesive hydrogels.

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VOLUME: 17
ISSUE: 3
Year: 2020
Published on: 15 July, 2020
Page: [376 - 386]
Pages: 11
DOI: 10.2174/1570163816666190222193902
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