In depth analysis of pilocarpine-carbomer molecular interactions via molecular dynamics simulations

Pilocarpine (PIL) is a cholinergic agonist of natural origin used in the treatment of glaucoma and dry mouth. A major formulation-related drawback for this drug is its high chemical degradation in the presence of water (due to hydrolysis and epimerization). One way to overcome this limitation is to prepare hydrogel complexes of the API with carbomer (CRB) [1]. In this case, the formation of strong molecular interactions between the API and CBR are responsible for keeping the latter stable when exposed to an aqueous environment. Hence, in order to gain a further insight into PIL-CRB stabilization process, the present study attempts to unravel the nature of these interactions with the aid of molecular dynamics (MD) simulations. In this direction, a PIL-CRB amorphous assembly was initially prepared containing 10% w/w of the API. After equilibration, the well relaxed assembly was subjected to long run (10 ns) MD simulations. A similar procedure was also followed for the neat API, containing 20 molecules of PIL, and the neat copolymer, containing a 30-monomer chain. The final 3.0 ns of the trajectory were used for computing the cohesive energy (Ecoh) and solubility parameter (δ) for each compound, and for calculating the respective radial distribution functions. Results confirmed, on a theoretical basis, the formation of significant intermolecular interactions between the drug and the copolymer, which can be considered as responsible for APIʼs stabilization in the presence of aqueous environments. These results were in good agreement with experimental data (using ATR-FTIR).

Publikationsverlauf

Artikel online veröffentlicht:
12. Dezember 2022

• Reference

• 1 Zoppi A, Linck YG, Monti GA. et al. Studies of pilocarpine : carbomer intermolecular interactions. Int J Pharm 2012; 427 (02) 252-259