title: Adaptation of the quality by design concept in early pharmaceutical development of an intranasal nanosized formulation.
abstract: Regulatory science based pharmaceutical development and product manufacturing is highly recommended by the authorities nowadays. The aim of this study was to adapt regulatory science even in the nano-pharmaceutical early development. Authors applied the quality by design (QbD) concept in the early development phase of nano-systems, where the illustration material was meloxicam. The meloxicam nanoparticles produced by co-grinding method for nasal administration were studied according to the QbD policy and the QbD based risk assessment (RA) was performed. The steps were implemented according to the relevant regulatory guidelines (quality target product profile (QTPP) determination, selection of critical quality attributes (CQAs) and critical process parameters (CPPs)) and a special software (Lean QbD Software(®)) was used for the RA, which represents a novelty in this field. The RA was able to predict and identify theoretically the factors (e.g. sample composition, production method parameters, etc.) which have the highest impact on the desired meloxicam-product quality. The results of the practical research justified the theoretical prediction. This method can improve pharmaceutical nano-developments by achieving shorter development time, lower cost, saving human resource efforts and more effective target-orientation. It makes possible focusing the resources on the selected parameters and area during the practical product development.
authors.affiliation: Institute of Drug Regulatory Affairs, University of Szeged, Faculty of Pharmacy, Szeged, Hungary. Electronic address: edina.pallagi@pharm.u-szeged.hu.
authors.forename: Edina
authors.initials: E
authors.lastname: Pallagi
authors.affiliation: Department of Pharmaceutical Technology, University of Szeged, Faculty of Pharmacy, Szeged, Hungary. Electronic address: arita@pharm.u-szeged.hu.
authors.forename: Rita
authors.initials: R
authors.lastname: Ambrus
authors.affiliation: Department of Pharmaceutical Technology, University of Szeged, Faculty of Pharmacy, Szeged, Hungary. Electronic address: revesz@pharm.u-szeged.hu.
authors.forename: Piroska
authors.initials: P
authors.lastname: Szabó-Révész
authors.affiliation: Institute of Drug Regulatory Affairs, University of Szeged, Faculty of Pharmacy, Szeged, Hungary. Electronic address: csoka@pharm.u-szeged.hu.
authors.forename: Ildikó
authors.initials: I
authors.lastname: Csóka
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics; D002460:Cell Line; D002626:Chemistry, Pharmaceutical; D004304:Dosage Forms; D004339:Drug Compounding; D015195:Drug Design; D006801:Humans; D008297:Male; D000077239:Meloxicam; D053758:Nanoparticles / Q000008:administration & dosage*; D010316:Particle Size; D011786:Quality Control; D051381:Rats; D017207:Rats, Sprague-Dawley; D018570:Risk Assessment; D012984:Software; D012995:Solubility; D013843:Thiazines / Q000008:administration & dosage / Q000493:pharmacokinetics; D013844:Thiazoles / Q000008:administration & dosage / Q000493:pharmacokinetics
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004304:Dosage Forms; D013843:Thiazines; D013844:Thiazoles; D000077239:Meloxicam
keywords: Early development QbD; Meloxicam nanoparticles; Nasal administration; Quality by design; Regulatory pharmacy; Risk assessment