Formulation and CCD-Based Optimization of Clonidine HCl-Loaded Microemulsion Nanoparticles for Intranasal Delivery in Anxiety Disorders
DOI:
https://doi.org/10.64261/6x43w534Keywords:
Clonidine Hydrochloride; Intranasal Delivery; Anxiety Disorders;, Sustained Drug Release; Central Composite Design Optimization.Abstract
Anxiety disorders are among the most prevalent neuropsychiatric conditions globally, often requiring long-term pharmacological management. However, the therapeutic efficacy of conventional oral treatments such as Clonidine Hydrochloride (Clonidine HCl) is limited due to extensive first-pass metabolism, suboptimal brain bioavailability, and undesirable systemic side effects. To address these challenges, the present study focused on the development and optimization of a Clonidine HCl-loaded microemulsion-based nanoparticulate system for intranasal delivery aimed at enhancing brain targeting and therapeutic performance. The formulation was prepared using isopropyl myristate as the oil phase, Tween 80 and PEG 400 as surfactant and co-surfactant, respectively, and distilled water as the aqueous phase. Pseudo-ternary phase diagrams constructed at various Smix ratios identified the 2:1 ratio as optimal for achieving a stable microemulsion region. A Central Composite Design (CCD) under Response Surface Methodology (RSM) was employed to study the effect of formulation variables on critical quality attributes including pH, viscosity, and entrapment efficiency (%EE). The optimized formulation (O1) demonstrated desirable physicochemical properties with a particle size of 281.9 nm, a polydispersity index of 0.274, and a zeta potential of –4.96 mV, indicating good colloidal stability. SEM analysis revealed spherical particles with uniform morphology, while FTIR spectra confirmed the absence of drug-excipient incompatibilities. In vitro release studies exhibited a biphasic release pattern with drug content of 99.02 ± 0.57% and 75.6% drug release in 8 hours, best fitting the Korsmeyer–Peppas model (R² = 0.9544), suggesting Fickian diffusion. Stability testing & Shelf-Life Estimation (T90) estimation confirmed the formulation’s robustness for effective anxiety treatment. These findings underscore the potential of this intranasal microemulsion-based approach as a promising platform for the efficient and sustained delivery of Clonidine HCl in the treatment of anxiety disorders.
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