Application of quality by design principles to the development of oral lyophilizates containing olanzapine

Bjelošević Žiberna, Maja (author), Ahlin Grabnar, Pegi (author)

Oral lyophilizates are intended for application to the oral cavity or for dispersing in water. The purposes of this research were: (i) to set up the quality by design approach in the development of oral lyophilizates for drug incorporation; and (ii) to evaluate the established approach by comparing its outcomes with experimentally obtained results. Within the knowledge space, properties about drugs, excipients, and the lyophilization process were acquired, followed by the determination of critical quality attributes via risk identification. Risks were assessed by failure mode and effective analysis, which recognized critical material attributes, i.e., type, concentration, particle size, solubility of drug and excipients, while as main critical process parameters, cooling rate, shelf temperature, and chamber pressure during drying were pointed out. Additionally, design space was established using the Minitab$^®$ 17 software and valued with an 88.69% coefficient of determination. A detailed comparison between the model and experimental results revealed that the proposed optimal compositions match in the total concentration of excipients (6%, w/w) in the pre-lyophilized liquid formulation, among which mannitol predominates. On the other hand, a discrepancy regarding the presence of gelatin was detected. The conclusion was that the set model represents a suitable onset toward optimization of drug-based oral lyophilizates development, preventing unnecessary investment of time and resources.

• Language: English
• Keywords: oral lyophilizate, lyophilization, quality by design, disintegration time, Minitab$^®$
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2023
• Number of pages: 16 str.
• Numbering: Vol. 15, iss. 7, art. 1967
• PID: 20.500.12556/RUL-148360
• UDC: 542.47:661.12
• ISSN on article: 1999-4923
• DOI: 10.3390/pharmaceutics15071967
• COBISS.SI-ID: 160781059
• Publication date in RUL: 18.08.2023

Record is a part of a journal

• Title: Pharmaceutics
• Shortened title: Pharmaceutics
• Publisher: MDPI
• ISSN: 1999-4923
• COBISS.SI-ID: 517949977

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: peroralni liofilizati, liofilizacija, kakovost po zasnovi, čas razpadanja, Minitab$^®$, sušenje, farmacevtska tehnologija

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: P1-0189
• Name: Farmacevtska tehnologija: od dostavnih sistemov učinkovin do terapijskih izidov zdravil pri otrocih in starostnikih

• Funder: ARRS - Slovenian Research Agency
• Project number: L1-3160
• Name: Razvoj visokokoncentriranih proteinskih formulacij in vrednotenje kinetike absorpcije po subkutani aplikaciji