Title:Long-term Stabilization of Aqueous Doxycycline Formulations, in Mucoadhesive Hydrogels for Treatment of Oral Mucosal Conditions
VOLUME: 17 ISSUE: 3
Author(s):Venu G.R. Patlolla, William P. Holbrook, Sveinbjorn Gizurarson* and Thordis Kristmundsdottir
Affiliation:Faculty of Pharmaceutical Sciences, University of Iceland, Hofsvallagata 53, 107 Reykjavik, Faculty of Odontology, University of Iceland, Vatnsmýrarvegi 16, 101 Reykjavík, Faculty of Pharmaceutical Sciences, University of Iceland, Hofsvallagata 53, 107 Reykjavik, Faculty of Pharmaceutical Sciences, University of Iceland, Hofsvallagata 53, 107 Reykjavik
Keywords:Stability, doxycycline, in situ, oral mucosal, drug delivery, mucoadhesive hydrogels.
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.
