Speaker
Abstract
Background
• Silodosin (SLD) Profile
• Highly selective α1A-adrenoreceptor antagonist prescribed for Lower Urinary
Tract Symptoms (LUTS) and Benign Prostatic Hyperplasia (BPH).
• Oral Delivery Barriers
• Low aqueous solubility & bioavailability (~32%).
• Extensive hepatic first-pass metabolism.
• Delayed therapeutic onset (Tmax 2–6 hours).
• Intranasal Route: Bypasses hepatic metabolism and enables rapid direct systemic
absorption via vascularized nasal mucosa.
• Nanomicelles (10–100 nm): Amphiphilic colloidal carriers that encapsulate
hydrophobic drugs, improving aqueous solubility, stability, and mucoadhesion.
Aim
To develop and optimize a fast-acting intranasal nano-micellar in situ gel of Silodosin designed for rapid mucosal absorption, aiming to achieve immediate systemic drug onset for the urgent relief of acute renal colic pain and prostatic spasms effectively bypassing the delayed onset and hepatic first-pass metabolism associated with conventional oral tablets.
Method
1.Dissolution & Sonication
SLD (2.5 mg) dissolve in 5ml methanol + Soluplus, Solutol HS-15 and TPGS in Methanol (5 mL), sonicated for 10 min.
2.Homogenization.
Mixed organic solutions & sonicated at 25°C to achieve uniform phase.
3.Rotary Evaporation
Evaporated solvent (45°C,600 rpm, 300 mbar, 15 min) forming a clear dry film.
4.Film Hydration
Hydrated with 10 mL distilled water at 40°C to form clear nanomicelles.
Results
Formulation optimization revealed a clear correlation between the component ratio and nanoparticle characteristics. Increasing the ratio from 1:4 to 1:10 progressively reduced the 𝑍"−Average"particle size from 74.90" nm"down to 67.30" nm"while significantly improving size homogeneity ("PDI" decreased from 0.2376to 0.1085). F4 was identified as the optimal formulation, displaying an ideal size (67.30" nm") and a highly uniform monodisperse profile ("PDI"=0.1085). The Zeta potential of F4 was measured at −4.4" mV", suggesting steric stabilization as the primary mechanism preventing particle aggregation
conclusion
Thin-film hydration successfully produced nanomicelles with optimal particle size (< 100 nm).
Formulation F4 demonstrated high monodispersity (PDI = 0.1085) and optimal particle size (67.3 nm).
The optimized formulation (F4) exhibited a slightly negative zeta potential of −𝟒.𝟒" mV" .The formulation demonstrates adequate physical stability, making it suitable for effective intranasal mucosal absorption without causing local tissue irritation.
| Has the manuscript been published | not published |
|---|---|
| Intend to be published in the IJPS ? | Yes |
