Zolmitriptan Intranasal Spanlastics for Enhanced Migraine Treatment; Formulation Parameters Optimized via Quality by Design Approach

Zolmitriptan is a potent second-generation triptan prescribed for migraine attacks. It suffers low bioavailability (40%) after oral administration due to the hepatic first-pass metabolism. Spanlastics are surfactant-based elastic vesicular drug carrier systems. This study aimed to design and optimize intranasal spanlastic formulations as an alternative approach that directly targets brain delivery, enhancing its bioavailability and avoiding the first-pass effect. The quality by design approach was applied to correlate the formulation parameters (Span 60 and Tween 80 concentrations) and critical quality attributes (entrapment efficiency (EE%) and particle size). Spanlastic formulations were designed based on response surface central composite design and prepared via an ethanol injection method. Designed formulations were characterized by EE% and particle size measurements to select the optimized formula (with a combination of small particle size and high EE%). The optimized formula was further subjected to transmission electron microscopy, zeta potential measurement and ex vivo permeation study. The optimized formulation showed a particle size of 117.5 nm and EE% of 45.65%, with a low percentage of error between the observed and predicted values. Seventy percent of zolmitriptan was permeated through the nasal membrane within 30 min, and it completely permeated within 2 h with a significantly higher steady-state flux compared to plain gel. This study introduced a successful and promising intranasal formulation suitable for further brain delivery analysis.

Download Full-text

Application of quality by design approach to optimize process and formulation parameters of rizatriptan loaded chitosan nanoparticles

Journal of Advanced Pharmaceutical Technology amp Research ◽

10.4103/2231-4040.157983 ◽

2015 ◽

Vol 6 (3) ◽

pp. 88 ◽

Cited By ~ 6

Author(s):

AjinathEknath Shirsat ◽

SohanS Chitlange

Keyword(s):

Quality By Design ◽

Chitosan Nanoparticles ◽

Design Approach ◽

Quality By Design Approach ◽

Formulation Parameters

Download Full-text

Resveratrol Nanocrystal Incorporated into Mesoporous Material: Rational Design and Screening through Quality-by-Design Approach

Nanomaterials ◽

10.3390/nano12020214 ◽

2022 ◽

Vol 12 (2) ◽

pp. 214

Author(s):

Ahmad Ainurofiq ◽

Yuniawan Hidayat ◽

Eva Y. P. Lestari ◽

Mayasri M. W. Kumalasari ◽

Syaiful Choiri

Keyword(s):

Particle Size ◽

Rational Design ◽

Quality By Design ◽

Drug Loading ◽

Fractional Factorial ◽

Design Approach ◽

Grape Seeds ◽

Screening Process ◽

Screening Design ◽

Quality By Design Approach

Bioflavonoids from grape seeds feature powerful antioxidant and immunostimulant activities, but they present problems related to solubility and bioavailability. Nanocrystal (NC) incorporated into a mesoporous carrier is a promising strategy to address these issues. However, the preparation of this formulation involves the selection of factors affecting its critical quality attributes. Hence, this study aimed to develop an NC formulation incorporating resveratrol into a soluble mesoporous carrier based on rational screening design using a systematic and continuous development process, the quality-by-design paradigm. A mesoporous soluble carrier was prepared by spray-drying mannitol and ammonium carbonate. The NC was obtained by introducing the evaporated solvent containing a drug/polymer/surfactant and mesoporous carrier to the medium. A 26−2 fractional factorial design (FFD) approach was carried out in the screening process to understand the main effect factors. The type and concentration of polymer and surfactant, resveratrol loading, and solvent were determined on the NC characteristics. The results indicated that drug loading, particle size, and solubility were mainly affected by RSV loading, PEG concentration, and Kolliphor EL concentration. The polymer contributed dominantly to reducing the particle size and enhancing solubility in this screening design. The presence of surfactants in this system made it possible to prolong the supersaturation process. According to the 26−2 FFD, the factors selected to be further developed using a statistical technique according to the quality-by design-approach, Box Behnken Design, were Kolliphor EL, PEG400, and RSV loading.

Download Full-text