Gel transition temperature optimisation for a new pilocarpine formulation using design of experiments methodology

Pilocarpine (PIL) is a parasympathomimetic active pharmaceutical ingredient (API) with weak beta- adrenergic action that predominantly functions as a non-specific muscarinic acetylcholine receptor agonist. It is a naturally occurring compound (tertiary alkaloid) extracted from the leaves of Pilocarpus microphyllus and Pilocarpus jaborandi. PIL’s systematic administration in the form of film-coated tablets is approved against dry mouth and xerostomia from both FDA and EMA. However, despite its high efficacy and acceptance, the systematic administration of PIL results in significant adverse events (including nausea, sweating, diarrhoea, headache, chest pain, etc.) [1]. Therefore, the preparation of a novel, buccally administrated, PIL formulation may be a significant step in an effort to lessen these side effects and increase patient compliance. Hence, the aim of the present study was to evaluate the gel transition properties of an in situ thermo-responsive PIL gel formulation using design of experiments (DoE) methodology. Specifically, a Box-Behnken experimental design was employed for evaluating the effect of three formulation factors, namely poloxamer 407 (P407), poloxamer 188 (P188) and xanthan gum (XG), on the sol-gel transition temperature (Tsol-gel) of the in situ forming PIL hydrogels. Results showed that P407 had the most significant impact in the changes induced on the sol-gel transition temperature, P188 showed a synergistic effect, whereas XG an antagonistic effect. DoE optimization suggested the use of P407, P188 and XG at concentrations of 17.95, 1.88 and 0.09% w/w, respectively, as the optimum factors’ levels for the buccally administrated PIL sol-gel formulation.

Funding This research has been co-financed by the European Regional Development Fund of the European Union and Greek national funds through the Operational Program Competitiveness, Entrepreneurship and Innovation, under the call RESEARCH – CREATE – INNOVATE (project code: T2EDK-00842).

 

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• References

• 1 Farag A.M., Holliday C., Cimmino J., Roomian T., Papas A.. Comparing the effectiveness and adverse effects of pilocarpine and cevimeline in patients with hyposalivation. Oral diseases 25 (08) 2019; 1937-1944

Publication History

Article published online:
16 November 2023