Synthesis of novel interpenetrated network for ocular co-administration of timolol maleate and dorzolamide hydrochloride drugs

Evangelia Balla; Alexandra Zamboulis; Panagiotis Klonos; Apostolos Kyritsis; Panagiotis Barmpalexis; Dimitrios Ν Bikiaris

doi:10.1016/j.ijpharm.2023.123439

Synthesis of novel interpenetrated network for ocular co-administration of timolol maleate and dorzolamide hydrochloride drugs

Int J Pharm. 2023 Nov 5:646:123439. doi: 10.1016/j.ijpharm.2023.123439. Epub 2023 Sep 22.

Authors

Evangelia Balla¹, Alexandra Zamboulis¹, Panagiotis Klonos², Apostolos Kyritsis³, Panagiotis Barmpalexis⁴, Dimitrios Ν Bikiaris⁵

Affiliations

¹ Laboratory of Polymer Chemistry and Technology, Department of Chemistry, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece.
² Laboratory of Polymer Chemistry and Technology, Department of Chemistry, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece; Department of Physics, National Technical University of Athens, Zografou Campus, 15780 Athens, Greece.
³ Department of Physics, National Technical University of Athens, Zografou Campus, 15780 Athens, Greece.
⁴ Laboratory of Pharmaceutical Technology, Department of Pharmacy, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece.
⁵ Laboratory of Polymer Chemistry and Technology, Department of Chemistry, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece. Electronic address: dbic@chem.auth.gr.

PMID: 37742821
DOI: 10.1016/j.ijpharm.2023.123439

Abstract

In the present work, novel interpenetrated networks (IPNs) of [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide) (SBMA) and poly(vinyl alcohol) (PVA) were prepared for the ocular co-administration of timolol maleate (TIM) and dorzolamide hydrochloride (DORZ), two drugs widely used for the treatment of glaucoma. The successful polymerization of SBMA, in the presence of PVA, led to the formation of semi-interpenetrated pSBMA-PVA networks (IPNs), in the form of sponges, exhibiting intrinsic antimicrobial properties attributed to SBMA. Fourier-transform infrared spectroscopy (FTIR) was utilized to confirm the successful synthesis of the IPNs. Further assessments, including contact angle and water sorption measurements, highlighted their significant hydrophilicity, a feature that makes them suitable for ocular applications. Differential scanning calorimetry (DSC) measurements indicated that PVA serves as a plasticizer, while an assessment of the water sorption capacity of these materials suggested that although the incorporation of PVA results in slightly less hydrophilic materials, the prepared sponges still remain sufficiently hydrophilic for ocular use. Following their characterization, the optimal pSBMA-PVA IPN was used to encapsulate TIM and DORZ. Irritation tests, performed using the HET-CAM method, confirmed that the drug-loaded sponges were safe and potentially well-tolerated for ophthalmic use. Finally, the co-release study for the two drugs revealed a sustained release pattern in both cases, while drug release from the sponges was primarily controlled by diffusion.

Keywords: Co-delivery; Dorzolamide hydrochloride; Drug delivery; Interpenetrated polymeric networks; Timolol maleate.