Development of mucoadhesive vaginal films with metronidazole using Poly(2-ethyl-2-oxazoline) – Polycarbophil blends via hot melt extrusion

Mucoadhesive vaginal films are increasingly regarded as a versatile platform for local drug delivery, offering prolonged mucosal retention, ease of administration, and enhanced bioavailability. In this study, vaginal films based on blends of poly(2-ethyl-2-oxazoline) (POZ) and polycarbophil (PC) were developed and characterized, incorporating metronidazole as a poorly soluble antimicrobial drug. The films were prepared using hot-melt extrusion. Their physicochemical and mechanical properties, mucoadhesive performance, and ex vivo retention on the mucosal surface were studied. Particular attention was given to the effects of polymer ratio and plasticizer content on these characteristics.

Key findings revealed that incorporating polycarbophil into POZ-based films significantly enhanced mucoadhesive strength, particularly in formulations containing glycerol as a plasticizer, which provided improved flexibility and adhesion. In ex vivo studies using sheep vaginal mucosa, POZ/PC films exhibited strong retention, with the POZ/PC (80:20) formulation showing significantly longer adhesion under simulated physiological fluid flow. Differential scanning calorimetry analysis confirmed partial amorphization of metronidazole in the films, reducing its crystallinity from 100 % to ∼ 65–70 %. Additionally, the films provided sustained drug release and demonstrated notable antimicrobial activity against S. aureus and E. coli.

Highlights

• Mucoadhesive vaginal films were made from poly(2-ethyl-2-oxazoline)/polycarbophil blends via hot-melt extrusion.
• Strong interactions between poly(2-ethyl-2-oxazoline) and polycarbophil improved miscibility and film stability.
• Metronidazole was incorporated in a partially amorphous form to enhance its release from the films.
• Polycarbophil increased mucoadhesion and retention, especially when glycerol was included as a plasticizer.
• Films showed sustained metronidazole release and activity against S. aureus and E. coli.

 

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Materials

Poly(2-ethyl-2-oxazoline) (POZ, MW ∼ 50 kDa, Sigma-Aldrich, Gillingham, UK) was used as the primary film-forming polymer due to its thermoplastic and hydrophilic nature. Polycarbophil (PC, Lubrizol Advanced Materials Europe, Belgium) served as a mucoadhesive agent. Glycerol (GL, ≥99.5 %, Sigma-Aldrich, UK) and polyethylene glycol 1500 (PEG 1500, Merck, Germany) were used as plasticizers. Sodium fluorescein (NaFl), metronidazole (MTZ, as a model poorly soluble antimicrobial drug), bovine serum albumin (BSA), glucose, urea, lactic acid, and acetic acid; all these chemicals were of analytical grade and obtained from Sigma-Aldrich (UK). A cellulose dialysis membrane tube (molecular weight cut-off 14 kDa) was obtained from Sigma-Aldrich (Gillingham, UK) was used for drug release experiments.

Marzhan K. Akhmetova, Guzel K. Abilova, Aknaz B. Duisengali, Tomiris A. Nurlybaeva, Sanimai S. Uzakbaeva, Galiya S. Irmukhametova, Amirbek Z. Bekeshev, Vitaliy V. Khutoryanskiy,
Development of mucoadhesive vaginal films with metronidazole using Poly(2-ethyl-2-oxazoline) – Polycarbophil blends via hot melt extrusion,
European Polymer Journal, Volume 237, 2025, 114175, ISSN 0014-3057,
https://doi.org/10.1016/j.eurpolymj.2025.114175.