Formulation strategies to stabilize pilocarpine hydrochloride solutions

Xerostomia (or dry mouth) is defined as a subjective complaint of dry mouth which commonly exists as a consequence of reduced salivary flow (hyposalivation). Amongst the several treatments of xerostomia, the use of systematically administered sialagogues seems to be the most promising approach. Pilocarpine (PIL) is a naturally derived compound isolated from the leaves of Pilocarpus microphyllus and Pilocarpus jaborandi, which is capable of inducing the secretion of natural saliva from the undamaged part of the salivary glands through its action on muscarinic receptors. It is a parasympathomimetic agent that acts primarily as a non-specific muscarinic acetylcholine receptor agonist with mild beta-adrenergic activity. Despite its significant efficacy, a drawback regarding PILʼs administration in the form of a solution (such as mouthwashes targeting xerostomia) is its chemical degradation due to the hydrolysis of the γ-lactone moiety and the epimerization of the α-carbon of the lactone ring. In order to overcome this limitation, commercially available products are formulated at low pH values (between 4 and 5) where the drug is almost fully ionized, leading, hence, to poor bioavailability. Therefore, the aim of the present study was to identify new strategies in order to improve PIL solution stability, and, consequently, improve its bioavailability. In this direction, the present study reveals that the chemical stability of PIL in non-aqueous solvents (i.e., glycerol and PEG-400) with or without the presence of suitable polymeric stabilizers can be considered as a promising strategy to enhance PIL solution stability.

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Artikel online veröffentlicht:
12. Dezember 2022