In situ gelling formulation based on methylcellulose/pectin system for oral-sustained drug delivery to dysphagic patients

Abstract

Background: Oral-sustained release gel formulations with suitable rheological properties have been proposed as a means of improving the compliance of dysphagic and geriatric patients who have difficulties with handling and swallowing oral dosage forms. Aim: We have modified the rheological and release properties of thermally reversible methylcellulose solutions by admixture with pectin, the gelation of which is ion-responsive, with the aim of formulating an in situ gelling vehicle suitable for oral-sustained drug delivery. Method: Gels formed by solutions containing methylcellulose (1.0–2.0%) and pectin (0.5–2.0%) were assessed for suitable gel strength, and in vitro and in vivo release of paracetamol. Results: Addition of 1.5% pectin to a 2.0% methylcellulose formulation containing 20% d-sorbitol and calcium ions in complexed form increased the gel strength and provided a formulation with a suitable viscosity for ease of swallowing by dysphagic patients. Gels formed in situ after oral administration of this formulation retained their integrity in the rat stomach for sufficient time for sustained release to be achieved. In vitro release of paracetamol from methylcellulose, pectin, and methylcellulose/pectin gels was diffusion-controlled. Plasma levels of paracetamol after oral administration to rats (gastric pH 2.6 and 5.5) of a solution including 2.0% methylcellulose/1.5% pectin showed improved sustained release compared with that from both 2.0% methylcellulose and 1.5% pectin solutions. Conclusions: The addition of suitable concentrations of pectin to methylcellulose solutions produces in situ gelling formulations with suitable viscosity for administration to dysphagic patients and improved sustained release characteristics.

Keywords::

• Methylcellulose
• pectin
• oral drug delivery
• controlled release
• dysphagia
• gels
• paracetamol

Acknowledgements

The authors are grateful to Dr. Hiroyasu Kokubo of Shin-Etsu Chemical Co., Ltd. for the kind gift of methylcellulose.

Declaration of interest

This work was supported in part by “High-Tech Research Center” Project for Private Universities: matching fund subsidy was from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and Grant-in-Aid for the 2009–2010 Research Project of the Research Institute of Personalized Health Sciences, Health Sciences University of Hokkaido. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper.