Formulation of Saxagliptin Oral Films: Optimization, Physicochemical Characterization, In-Vivo Assessment, and In-Vitro Real-Time Release Monitoring via a Novel Polyaniline Nanoparticles-Based Solid-Contact Screen Printed Ion-Selective Electrode

• Published in: AAPS PharmSciTech 2024-05, Vol.25 (5), p.116, Article 116
• Main Authors: Makram, Tarek S., Eid, Sherif M., Abu-Dahab, Mohamed, AbouGhaly, Mohamed H. H., Elnahas, Osama S.
• Format: Article
• Language: English
• Subjects: Adamantane - analogs & derivatives; Adamantane - chemistry; Administration, Oral; Aniline Compounds - chemistry; Biochemistry; Biological Availability; Biomedical and Life Sciences; Biomedicine; Biotechnology; Chemistry, Pharmaceutical - methods; Dipeptides - administration & dosage; Dipeptides - chemistry; Dipeptides - pharmacokinetics; Drug Liberation; Electrodes; Humans; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - chemistry; Hypoglycemic Agents - pharmacokinetics; Hypromellose Derivatives - chemistry; Nanoparticles - chemistry; Pharmacology/Toxicology; Pharmacy; Polyvinyl Alcohol - chemistry; Research Article; Solubility; Tensile Strength
• ISSN: 1530-9932; 1530-9932
• DOI: 10.1208/s12249-024-02828-4

Oral dispersible films have received broad interest due to fast drug absorption and no first-path metabolism, leading to high bioavailability and better patient compliance. Saxagliptin (SXG) is an antidiabetic drug that undergoes first-path metabolism, resulting in a less active metabolite, so the development of SXG oral dispersible films (SXG-ODFs) improves SXG bioavailability. The formula optimisation included a response surface experimental design and the impact of three formulation factors, the type and concentration of polymer and plasticiser concentration on in-vitro disintegration time and folding endurance. Two optimised SXG-ODFs prepared using either polyvinyl alcohol (PVA) or hydroxypropyl methylcellulose were investigated. SXG-ODFs prepared with PVA demonstrated a superior rapid disintegration time, ranging from 17 to 890 s, with the fastest disintegration time recorded at 17 s. These short durations can be attributed to the hydrophilic nature of PVA, facilitating rapid hydration and disintegration upon contact with saliva. Additionally, PVA-based films displayed remarkable folding endurance, surpassing 200 folds without rupture, indicating flexibility and stability. The high tensile strength of PVA-based films further underscores their robust mechanical properties, with tensile strength values reaching up to 4.53 MPa. SXG exhibits a UV absorption wavelength of around 212 nm, posing challenges for traditional quantitative spectrophotometric analysis, so a polyaniline nanoparticles-based solid-contact screen-printed ion-selective electrode (SP-ISE) was employed for the determination of SXG release profile effectively in comparison to HPLC. SP-ISE showed a better real-time release profile of SXG-ODFs, and the optimised formula showed lower blood glucose levels than commercial tablets. Graphical Abstract