Starch-based Pickering emulsions for topical drug delivery: A QbD approach.
Pickering emulsions are stabilized by solid particles instead of surfactants and have been widely investigated in pharmaceutical and cosmetic fields since they present less adverse effects than the classical emulsions. A quality by design (QbD) approach was applied to the production of w/o emulsions stabilized by starch. A screening design was conducted to identify the critical variables of the formula and the process affecting the critical quality properties of the emulsion (droplet size distribution). The optimization was made by establishing the Design Space, adjusting the concentration of starch and the quantity of the internal aqueous phase. The emulsion production process was, in turn, adjusted by varying the time and speed of stirring, to ensure quality and minimum variability. The stability was also investigated, demonstrating that an increase in starch concentration improves the stability of the emulsion. Rheological and mechanical studies indicated that the viscosity of the emulsions was enhanced by the addition of starch and, to a higher extent, by the presence of different lipids. The developed formulations was considered non-irritant, by an in vitro assay using human cells from skin (Df and HaCat) with the cell viability higher than 90% and, with self-preserving properties. Finally, the QbD approach successfully built quality in Pickering emulsions, allowing the development of hydrophilic drug-loaded emulsions stabilized by starch with desired organoleptic and structural characteristics. The results obtained suggest that these systems are a promising vehicle to be used in products for topical administration.
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal.
J
J
Marto
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal.
L
L
Gouveia
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal.
I M
IM
Jorge
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal.
A
A
Duarte
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal.
L M
LM
Gonçalves
Chemistry Department, University of Coimbra, Coimbra, Portugal.
S M C
SMC
Silva
Chemistry Department, University of Coimbra, Coimbra, Portugal.
F
F
Antunes
Chemistry Department, University of Coimbra, Coimbra, Portugal.
A A C C
AACC
Pais
Laboratórios Atral S.A., Castanheira do Ribatejo, Portugal.
E
E
Oliveira
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal.
A J
AJ
Almeida
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal. Electronic address: helena.ribeiro@ff.ul.pt.
H M
HM
Ribeiro
D000287:Administration, Topical; D002470:Cell Survival; D016503:Drug Delivery Systems; D015195:Drug Design; D004655:Emulsions; D005079:Excipients / Q000737:chemistry*; D006801:Humans; D008055:Lipids; D010316:Particle Size; D011208:Powders; D012212:Rheology; D012867:Skin / Q000166:cytology / Q000378:metabolism; D013213:Starch / Q000737:chemistry*; D014783:Viscosity
D004655:Emulsions; D005079:Excipients; D008055:Lipids; D011208:Powders; D013213:Starch
Pickering emulsions; Quality by design; Skin application; Starch granules