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Start date: 1999Subject: search.filters.subject.Factorial design

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    Development of ibuprofen microspheres using acetylated plantain starches as polymer for sustained release
    (Springer Publications, 2018) Okunlola, A.; Ghomorai, T.
    Ibuprofen has a short half-life (1–3 h) and istypically administered 3–4 times daily with subsequent adverse side effects. A good approach to reduce these effects is the preparation of sustained-release formulations of ibuprofen. Acetylated starches form water-insoluble, acid-resistant films that can substantially retard drug release. Ibuprofen microspheres were prepared using acetylated plantain starch as sustained-release polymer. Starch obtained from unripe plantain (Musa Paradisiaca normalis) were acetylated using acetic anhydride with pyridine (degrees of substitution, DS 1.5 ± 0.05 and 2.20 ± 0.10). The starches were characterized using morphology, crystallinity, swelling, density and flow properties. Ibuprofen microspheres were prepared by quasi-emulsion solvent diffusion method, using acetylated plantain starches DS 1.5 and 2.20 in comparison to Eudragit S100. Full 32 factorial experimental design was performed with polymer type (X1), polymer: drug ratio (X2) as independent factors; microsphere size, entrapment, and quantity of drug released in 12 h (Q12) were dependent variables. The data from in vitro drug release were fitted to various kinetic models. Acetylation resulted in larger starch aggregates with disruption in crystalline order. Ibuprofen microspheres were spherical with size 5.50 ± 4.00–129.90 ± 12.97μm. Drug entrapment was 43.92 ± 4.00–79.91 ± 6.15%. Values of Q12 ranged from 20.10 ± 0.55 to 54.00 ± 5.71%. Interaction between variables X1 and X2 had positive effects on size and entrapment. Drug release fitted zero order, first order and Baker-Lonsdale kinetic models. Acetylated starch of plantain with DS 2.20 was suitable as a polymer at polymer:drug ratio 4:1 for the formulation of ibuprofen microspheres with prolonged drug release.
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    Impact of degree of substitution of acetylated ofada rice starch polymer on the release properties of nimesulide microspheres
    (IPEC-Americas Inc, 2016) Okunlola, A.; Owojori, T.
    Nimesulide microspheres were prepared by the quasi-emulsion solvent diffusion method, using acetylated starches of the indigenous Ofada rice (Oryza glaberrima Steud) with degrees of substitution (DS) 1.42 and 2.62. A full 23 factorial experimental design was performed using DS (X1), drug:polymer ratio (X2) and polymer concentration (X3) as independent factors; size, entrapment, swelling and time taken for 80% drug release (t80) were the dependent variables. Contour plots were generated and data from the in vitro release studies were fitted to various kinetic models. Nimesulide microspheres were near spherical, sizes varying from 50.91±16.22 to 74.24±24.73μm for microspheres containing starch DS 1.42 and from 21.05±4.25 to 46.10±3.85μm for starch DS 2.62. Drug entrapment was 56.75±0.45 to 98.28±2.30%. DS had the greatest effect on the size, swelling and dissolution time (p = 0.01) which was confirmed by the contour plots. The interaction between factors DS and drug:polymer ratio (X1X2) had the greatest effect on the microsphere properties (p = 0.04). Drug release was fitted into the First Order, Higuchi and Korsmeyer models. Acetylated starch of Ofada rice DS 2.62 was found more suitable for the formulation of microspheres because of reduced size and swelling, higher entrapment and prolonged drug release.
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    Characterization and evaluation of acid-modified starch of Dioscorea oppositifolia (Chinese yam) as a binder in chloroquine phosphate tablets
    (2013) Okunlola, A.; Akingbala, O.
    Chinese yam (Dioscorea oppositifolia) starch modified by acid hydrolysis was characterized and compared with native starch as a binder in chloroquine phosphate tablet formulations. The physicochemical and compressional properties (using density measurements and the Heckel and Kawakita equations) of modified Chinese yam starch were determined, and its quantitative effects as a binder on the mechanical and release properties of chloroquine phosphate were analyzed using a 23 full factorial design. The nature (X1), concentration of starch (X2) and packing fraction (X3) were taken as independent variables and the crushing strength–friability ratio (CSFR), disintegration time (DT) and dissolution time (t80) as dependent variables. Acid-modified Chinese yam starch showed a marked reduction (p<0.05) in amylose content and viscosity but increased swelling and water-binding properties. The modified starch had a faster onset and greater amount of plastic flow. Changing the binder from native to acid-modified form led to significant increases (p<0.05) in CSFR and DT but a decrease in t80. An increase in binder concentration and packing fraction gave similar results for CSFR and DT only. These results suggest that acid-modified Chinese yam starches may be useful as tablet binders when high bond strength and fast dissolution are required.