title: Implementation of quality by design principles in the development of microsponges as drug delivery carriers: Identification and optimization of critical factors using multivariate statistical analyses and design of experiments studies.
abstract: Microsponges drug delivery system (MDDC) was prepared by double emulsion-solvent-diffusion technique using rotor-stator homogenization. Quality by design (QbD) concept was implemented for the development of MDDC with potential to be incorporated into semisolid dosage form (gel). Quality target product profile (QTPP) and critical quality attributes (CQA) were defined and identified, accordingly. Critical material attributes (CMA) and Critical process parameters (CPP) were identified using quality risk management (QRM) tool, failure mode, effects and criticality analysis (FMECA). CMA and CPP were identified based on results obtained from principal component analysis (PCA-X&Y) and partial least squares (PLS) statistical analysis along with literature data, product and process knowledge and understanding. FMECA identified amount of ethylcellulose, chitosan, acetone, dichloromethane, span 80, tween 80 and water ratio in primary/multiple emulsions as CMA and rotation speed and stirrer type used for organic solvent removal as CPP. The relationship between identified CPP and particle size as CQA was described in the design space using design of experiments - one-factor response surface method. Obtained results from statistically designed experiments enabled establishment of mathematical models and equations that were used for detailed characterization of influence of identified CPP upon MDDC particle size and particle size distribution and their subsequent optimization.
authors.affiliation: Institute of Pharmaceutical Technology, Faculty of Pharmacy, University of Ss. Cyril & Methodius, Majka Tereza 47, 1000 Skopje, Macedonia; Center of Pharmaceutical Nanotechnology, Faculty of Pharmacy, University of Ss. Cyril & Methodius, Majka Tereza 47, 1000 Skopje, Macedonia. Electronic address: msimonoska@ff.ukim.edu.mk.
authors.forename: Maja
authors.initials: M
authors.lastname: Simonoska Crcarevska
authors.affiliation: Institute of Applied Chemistry and Pharmaceutical Analysis, Faculty of Pharmacy, University of Ss. Cyril & Methodius, Majka Tereza 47, 1000 Skopje, Macedonia.
authors.forename: Aneta
authors.initials: A
authors.lastname: Dimitrovska
authors.affiliation: Institute of Pharmaceutical Technology, Faculty of Pharmacy, University of Ss. Cyril & Methodius, Majka Tereza 47, 1000 Skopje, Macedonia; Center of Pharmaceutical Nanotechnology, Faculty of Pharmacy, University of Ss. Cyril & Methodius, Majka Tereza 47, 1000 Skopje, Macedonia.
authors.forename: Nadica
authors.initials: N
authors.lastname: Sibinovska
authors.affiliation: Institute of Pharmaceutical Technology, Faculty of Pharmacy, University of Ss. Cyril & Methodius, Majka Tereza 47, 1000 Skopje, Macedonia; Center of Pharmaceutical Nanotechnology, Faculty of Pharmacy, University of Ss. Cyril & Methodius, Majka Tereza 47, 1000 Skopje, Macedonia.
authors.forename: Kristina
authors.initials: K
authors.lastname: Mladenovska
authors.affiliation: Institute of Pharmaceutical Technology, Faculty of Pharmacy, University of Ss. Cyril & Methodius, Majka Tereza 47, 1000 Skopje, Macedonia; Center of Pharmaceutical Nanotechnology, Faculty of Pharmacy, University of Ss. Cyril & Methodius, Majka Tereza 47, 1000 Skopje, Macedonia.
authors.forename: Renata
authors.initials: R
authors.lastname: Slavevska Raicki
authors.affiliation: Institute of Pharmaceutical Technology, Faculty of Pharmacy, University of Ss. Cyril & Methodius, Majka Tereza 47, 1000 Skopje, Macedonia; Center of Pharmaceutical Nanotechnology, Faculty of Pharmacy, University of Ss. Cyril & Methodius, Majka Tereza 47, 1000 Skopje, Macedonia.
authors.forename: Marija
authors.initials: M
authors.lastname: Glavas Dodov
mesh_terms: D000096:Acetone / Q000737:chemistry; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D015195:Drug Design; D006601:Hexoses / Q000737:chemistry; D006851:Hydrochloric Acid / Q000737:chemistry; D016018:Least-Squares Analysis; D008752:Methylene Chloride / Q000737:chemistry; D015999:Multivariate Analysis; D011136:Polysorbates / Q000737:chemistry; D025341:Principal Component Analysis
chemical_list: D004337:Drug Carriers; D006601:Hexoses; D011136:Polysorbates; C018665:sorbitan monooleate; D000096:Acetone; D008752:Methylene Chloride; C013517:ethyl cellulose; D002482:Cellulose; D006851:Hydrochloric Acid
keywords: Microsponges; Partial least squares; Principal component analysis; Quality by design; Response surface method; Semisolid dosage form