Development and Physicochemical Characterization of a Novel HPMC-Based Wound-Dressing Film Containing Betonica bulgarica: Phytochemical Profiling of the Plant Extract

Background: Betonica bulgarica Degen et Neič is an endemic Balkan species with reported antioxidant, antimicrobial, antitumor, immunomodulatory, and hypoglycemic effects. Despite its promising biological potential, its phytochemical composition remains incompletely characterized, and its application in advanced wound-healing medications has not been investigated. Therefore, the aim of the present study is to develop hydroxypropyl methylcellulose (HPMC)-based wound dressings incorporating B. bulgarica bioactive compounds as a biocompatible delivery platform with promising physical and chemical properties suitable for further biological evaluation in wound-care applications. Methods: The phytochemical composition of the extract was investigated using Ultra-High-Performance Liquid Chromatography–Mass Spectrometry (UHPLC–MS). Results: The putative analysis led to the identification of 81 compounds in positive and negative ionization mode. Predominant classes included flavonoids, phenolic acids, terpenes, organic acids, fatty acids, sugars, nucleobases and amino acids. HPMC-based films containing B. bulgarica extract were prepared and characterized with key physicochemical and mechanical properties. Mechanical evaluation demonstrated that high-molecular-weight HPMC films exhibited higher tensile strength (73 ± 9 MPa) than low-molecular-weight formulations (44 ± 8 MPa). Increasing the Betonica bulgarica extract loading up to 8.8 mg/cm2 was associated with concentration-dependent decreases in tensile strength, elongation at break, and Young’s modulus across all film types. These changes indicate an alteration of the mechanical behavior of the films, although the individual contributions of the extract and the varying PEG-to-HPMC ratio cannot be distinguished. Incorporation of Betonica bulgarica extract reduced the water vapor transmission rate (WVTR) of the HPMC films, promoting a denser polymer matrix structure. Additionally, high-molecular-weight HPMC films displayed higher WVTR values than low-molecular-weight formulations due to increased free volume within the entangled matrix. The release profiles of Betonica bulgarica extract from the HPMC films were fitted to the Korsmeyer–Peppas model using data from the first 8 h of the release study (R2 = 0.9811–0.9989). The release exponent values indicated anomalous transport behaviour for the low-MW HPMC films (n = 0.68–0.70), whereas the values obtained for the high-MW HPMC films (n = 0.404–0.438) were closer to the range commonly associated with Fickian diffusion in planar matrices. The high-MW HPMC films showed more gradual release profiles, supporting their further investigation as matrices for the delivery of plant-derived extracts. Conclusions: The findings provide further insight into the phytochemical profile of the endemic species B. bulgarica and demonstrate the feasibility of incorporating its bioactive compounds into HPMC-based wound-dressing film for future biological evaluation. The developed formulations represent a promising natural-based platform for wound-healing applications, although further studies are required to establish their therapeutic efficacy and mechanism of action.