Experimental design for the formulation and optimization of novel cross-linked oilispheres developed for in vitro site-specific release of<Emphasis Type="Italic">Mentha piperita</Emphasis> oil |
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Authors: | Wilbert Sibanda Viness Pillay Michael P Danckwerts Alvaro M Viljoen Sandy van Vuuren Riaz A Khan |
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Institution: | 1Department of Pharmacy and Pharmacology, Medical School, University of the Witwatersrand, 2193 Johannesburg, South Africa ;2College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, 32307 Tallahassee, FL |
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Abstract: | A Plackett-Burman design was employed to develop and optimize a novel crosslinked calcium-aluminum-alginatepectinate oilisphere
complex as a potential system for the in vitro site-specific release ofMentha piperita, an essential oil used for the treatment of irritable bowel syndrome. The physicochemical and textural properties (dependent
variables) of this complex were found to be highly sensitive to changes in the concentration of the polymers (0%–1.5% wt/vol),
crosslinkers (0%–4% wt/vol) and crosslinking reaction times (0.5–6 hours) (independent variables). Particle size analysis
indicated both unimodal and bimodal populations with the highest frequency of 2 mm oilispheres. Oil encapsulation ranged from
6 to 35 mg/100 mg oilispheres. Gravimetric changes of the crosslinked matrix indicated significant ion sequestration and loss
in an exponential manner, while matrix erosion followed Higuchi's cube root law. Among the various measured responses, the
total fracture energy was the most suitable optimization objective (R
2 =0.88, Durbin-Watson Index=1.21%, Coefficient of Variation (CV)=33.21%). The Lagrangian technique produced no significant
differences (P>.05) between the experimental and predicted total fracture energy values (0.0150 vs 0.0107 J). Artificial Neural Networks,
as an alternative predictive tool of the total fracture energy, was highly accurate (final mean square error of optimal network
epoch≈0.02). Fused-coated optimized oilispheres produced a 4-hour lag phase followed by zero-order kinetics (n>0.99), whereby
analysis of release data indicated that diffusion (Fickian constantk
1=0.74 vs relaxation constantk
2=0.02) was the predominant release mechanism. |
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