The main objective of this thesis project was to identify a mixture composed of Chlorhexidine and fatty acids with a melting point close to body temperature, to be used for the treatment of oral infections. All the aforementioned components possess antibacterial properties, so their combination allows for a synergistic effect, enhancing therapeutic efficacy. Once the most suitable mixture was identified, the work focused on developing a pharmaceutical formulation, specifically a gel membrane intended for the treatment of oral infections, particularly periodontitis. In the initial phase, I worked on the chemical-physical characterization of the raw materials to verify their purity and stability. Analyses were performed on Chlorhexidine, chitosan, and fatty acids (capric acid (C10), lauric acid (C12), and myristic acid (C14)) using various analytical techniques, including thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), infrared spectroscopy (FT-IR), and X-ray diffraction (XRD). Subsequently, physical mixtures (nine) of Chlorhexidine and fatty acids in different molar ratios were prepared by mixing with a mortar and pestle and using ice to facilitate the collection of the mixture. The analyses conducted on these mixtures revealed their inadequacy concerning the project’s objectives. Therefore, salts of Chlorhexidine and fatty acids with a stoichiometric ratio of 1:2 were prepared and subsequently used to formulate new mixtures, for a total of nine combinations. These salts and the corresponding mixtures were subjected to further analyses, particularly by DSC, FT-IR, and hot-stage microscopy. The results obtained led to the selection of two optimal eutectic mixtures: one consisting of 10% salt (Chlorhexidine + capric acid, C10) and 90% capric acid (C10), and another composed of 10% salt (Chlorhexidine + lauric acid, C12) and 90% lauric acid (C12). DSC analysis of these mixtures showed a single endothermic peak during heating and an exothermic peak during cooling, confirming the formation of eutectic mixtures with a melting point compatible with body temperature. Before creating the final pharmaceutical form, the excipients were selected, and their respective quantities and behavior were examined through DSC analysis to verify their response to heating. The selected eutectic mixtures were then used as the active ingredient for the formulation of a mucoadhesive gel intended for oral application. The obtained gels were subsequently subjected to mucoadhesion studies to improve their adherence to the gingival mucosa, a crucial characteristic for prolonging the release of the active ingredient and optimizing therapeutic efficacy. Finally, the mucoadhesive gel was heated to obtain a gel membrane, a formulation aimed at overcoming the limitations of conventional pharmaceutical formulations in the oral cavity. Again, DSC analyses were conducted to examine the behavior and stability of the mixtures within the pharmaceutical formulation, to ensure their efficacy and safety for clinical use. The preliminary results obtained are very promising regarding both the stability of the gel and its adhesion properties.
Il principale obiettivo di questo progetto di tesi è stato l'identificazione di una miscela composta da Clorexidina e acidi grassi avente temperatura di fusione prossima a quella corporea da utilizzare per il trattamento delle infezioni del cavo orale. Tutti i componenti sopra citati possiedono proprietà antibatteriche, quindi la loro combinazione permette di ottenere un effetto sinergico, utile per migliorare l’efficacia terapeutica. Una volta individuata la miscela più adatta, il lavoro si è concentrato sulla realizzazione di una formulazione farmaceutica, in particolare una membrana di gel, destinata al trattamento delle infezioni orali, con particolare riferimento alla parodontite. In una fase iniziale, mi sono occupato della caratterizzazione chimico-fisica delle materie prime per verificarne la purezza e la stabilità. Sono state eseguite analisi sulla Clorexidina, sul chitosano, e sugli acidi grassi (acido caprico (C10), acido laurico (C12) e acido miristico (C14)) utilizzando diverse tecniche analitiche, tra cui l'analisi termogravimetrica (TGA), la calorimetria differenziale a scansione (DSC), la spettroscopia infrarossa (FT-IR) e la diffrattometria a raggi X (XRD). Successivamente, sono state preparate miscele fisiche (nove) di Clorexidina e acidi grassi in vari rapporti molari, tramite miscelazione con mortaio e pestello e l'ausilio di ghiaccio per facilitare la raccolta della miscela. Le analisi condotte su queste miscele hanno evidenziato la loro inadeguatezza rispetto agli obiettivi del progetto. Di conseguenza, sono stati preparati dei sali di Clorexidina e acidi grassi con un rapporto stechiometrico di 1:2, i quali sono stati successivamente impiegati per formulare nuove miscele, per un totale di nove combinazioni. Questi sali e le relative miscele sono stati sottoposti a ulteriori analisi, in particolare mediante DSC, FT-IR e hot stage microscopy. I risultati ottenuti hanno portato alla selezione di due miscele eutettiche ottimali: una composta dal 10% di sale (Clorexidina + acido caprico, C10) e dal 90% di acido caprico (C10), e un'altra composta dal 10% di sale (Clorexidina + acido laurico, C12) e dal 90% di acido laurico (C12). L'analisi DSC di queste miscele ha mostrato un singolo picco endotermico in fase di riscaldamento e un picco esotermico in fase di raffreddamento, confermando la formazione di miscele eutettiche con un punto di fusione compatibile con la temperatura corporea. Prima della realizzazione della forma farmaceutica finale, sono stati selezionati gli eccipienti e determinati i rispettivi quantitativi e il loro comportamento è stato esaminato tramite analisi DSC per verificare la loro risposta al riscaldamento. Le miscele eutettiche selezionate sono state poi impiegate come principio attivo per la formulazione di un gel mucoadesivo destinato all’applicazione orale. I gel ottenuti sono stati successivamente sottoposti a studi di mucoadesione per migliorarne l'aderenza alla mucosa gengivale, una caratteristica cruciale per prolungare il rilascio del principio attivo e ottimizzare l'efficacia terapeutica. Infine, il gel mucoadesivo è stato sottoposto a riscaldamento per ottenere una membrana di gel, un formulato che mira a superare le limitazioni delle formulazioni farmaceutiche convenzionali nel cavo orale. Anche in questo caso, sono state condotte analisi DSC per esaminare il comportamento e la stabilità delle miscele all'interno della formulazione farmaceutica, al fine di garantire la loro efficacia e sicurezza per l'uso clinico. I risultati preliminari ottenuti sono molto promettenti sia per quanto riguarda la stabilità del gel sia per quanto riguarda l’aderenza.
Caratterizzazione chimico-fisica di miscele di clorexidina e acidi grassi ad attività antibatterica per la preparazione di gel di membrana mucoadesivi.
MAREI ELMITWALLI ELBAYOUMI BAYOUMI, AHMED
2023/2024
Abstract
The main objective of this thesis project was to identify a mixture composed of Chlorhexidine and fatty acids with a melting point close to body temperature, to be used for the treatment of oral infections. All the aforementioned components possess antibacterial properties, so their combination allows for a synergistic effect, enhancing therapeutic efficacy. Once the most suitable mixture was identified, the work focused on developing a pharmaceutical formulation, specifically a gel membrane intended for the treatment of oral infections, particularly periodontitis. In the initial phase, I worked on the chemical-physical characterization of the raw materials to verify their purity and stability. Analyses were performed on Chlorhexidine, chitosan, and fatty acids (capric acid (C10), lauric acid (C12), and myristic acid (C14)) using various analytical techniques, including thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), infrared spectroscopy (FT-IR), and X-ray diffraction (XRD). Subsequently, physical mixtures (nine) of Chlorhexidine and fatty acids in different molar ratios were prepared by mixing with a mortar and pestle and using ice to facilitate the collection of the mixture. The analyses conducted on these mixtures revealed their inadequacy concerning the project’s objectives. Therefore, salts of Chlorhexidine and fatty acids with a stoichiometric ratio of 1:2 were prepared and subsequently used to formulate new mixtures, for a total of nine combinations. These salts and the corresponding mixtures were subjected to further analyses, particularly by DSC, FT-IR, and hot-stage microscopy. The results obtained led to the selection of two optimal eutectic mixtures: one consisting of 10% salt (Chlorhexidine + capric acid, C10) and 90% capric acid (C10), and another composed of 10% salt (Chlorhexidine + lauric acid, C12) and 90% lauric acid (C12). DSC analysis of these mixtures showed a single endothermic peak during heating and an exothermic peak during cooling, confirming the formation of eutectic mixtures with a melting point compatible with body temperature. Before creating the final pharmaceutical form, the excipients were selected, and their respective quantities and behavior were examined through DSC analysis to verify their response to heating. The selected eutectic mixtures were then used as the active ingredient for the formulation of a mucoadhesive gel intended for oral application. The obtained gels were subsequently subjected to mucoadhesion studies to improve their adherence to the gingival mucosa, a crucial characteristic for prolonging the release of the active ingredient and optimizing therapeutic efficacy. Finally, the mucoadhesive gel was heated to obtain a gel membrane, a formulation aimed at overcoming the limitations of conventional pharmaceutical formulations in the oral cavity. Again, DSC analyses were conducted to examine the behavior and stability of the mixtures within the pharmaceutical formulation, to ensure their efficacy and safety for clinical use. The preliminary results obtained are very promising regarding both the stability of the gel and its adhesion properties.| File | Dimensione | Formato | |
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https://hdl.handle.net/20.500.14239/28511