Formulation of Intranasal Mucoadhesive Thermotriggered In Situ Gel Containing Mirtazapine as an Antidepressant Drug.
Mohammed Y GhazwaniRajalakshimi VasudevanGeetha KandasamyNaredla ManusriPraveen DevanandanRanadheer Chowdary PuvvadaVinoth Prabhu VeeramaniPremalatha PaulsamyKrishnaraju VenkatesanKumarappan ChidmabaramRajeshri DhurkePublished in: Gels (Basel, Switzerland) (2023)
The purpose of the present work was to develop nanoemulsion-based formulations of mirtazapine for intranasal delivery using a spray actuator to target the brain for treating depression. Research on the solubility of medications in different oils, surfactants, co-surfactants, and solvents has been done. Using pseudo-ternary phase diagrams, the various ratios of the surfactant and co-surfactant mix were computed. Thermotriggered nanoemulsion was formulated using different concentrations of poloxamer 407 (i.e., 15%, 15.5%, 16%, 16.5% up to 22%). Similarly, mucoadhesive nanoemulsion using 0.1% Carbopol and water-based plain nanoemulsions were also prepared for comparative assessment. The developed nanoemulsions were analyzed for physicochemical properties, i.e., physical appearance, pH, viscosity, and drug content. Drug-excipient incompatibility was determined by Fourier transform infrared spectral (FTIR) analysis and differential scanning calorimetry (DSC). In vitro drug diffusion studies were conducted for optimized formulations. Among the three formulations, RD1 showed the highest percentage of drug release. Ex vivo drug diffusion studies were conducted on freshly excised sheep nasal mucosa with Franz diffusion cell simulated nasal fluid (SNF) for all three formulations up to 6 h, and the thermotriggered nanoemulsion (RD1) showed 71.42% drug release with 42.64 nm particle size and a poly dispersity index of 0.354. The zeta potential was found to be -6.58. Based on the above data, it was concluded that thermotriggered nanoemulsion (RD1) has great potential to be used as an intranasal gel for treating depression in patients. It can offer great benefits by reducing dosing frequency and improving bioavailability of mirtazapine by direct nose-to-brain delivery.
Keyphrases
- drug release
- drug delivery
- end stage renal disease
- depressive symptoms
- adverse drug
- chronic kidney disease
- physical activity
- major depressive disorder
- computed tomography
- high resolution
- electronic health record
- photodynamic therapy
- emergency department
- mental health
- mesenchymal stem cells
- multiple sclerosis
- big data
- human health
- artificial intelligence
- deep learning