Oral lyophilizates obtained using aggressive drying conditions : effect of excipients

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

Orodispersible drug formulations are a current trend in the pharmaceutical industry, mostly intended for pediatric and geriatric patients. Oral lyophilizates are solid forms, intended either to be placed in the mouth or to be dispersed (or dissolved) in water before administration. The correct excipient composition is a prerequisite to provide lyophilizates with the appropriate visual appearance and disintegration time. Typically, they are composed of binders, such as gelatin and polyvinylpyrrolidone, fillers such as sucrose, mannitol, or sorbitol, taste modifiers, colorants, sweeteners, and preservatives. The main purpose of this study was to determine the optimal excipient scaffold to ensure the proper appearance of lyophilizates that have undergone aggressive drying conditions and a disintegration time of less than 3 min. In addition to mannitol and gelatin, the most frequently used binders, PVP K25, PVP K90, glycine, croscarmellose, and hydrolyzed gelatin were investigated. The results obtained revealed that lyophilizates with only mannitol and gelatin have a disintegration time that is too long, and that replacement of gelatin with PVP K25 led to friable and cracked lyophilizates. Considering disintegration time and visual appearance, lyophilizates with a mixture of gelatin, PVP K25, and mannitol (1:2:5) formed from liquid formulations with 6% (w/w) excipients were determined to be the most suitable. As a binder, PVP K25 expresses more appropriate characteristics relating to PVP K90. Addition of croscarmellose provided lyophilizates with a shorter disintegration time, whereas glycine only had a positive effect on the elegant appearance of lyophilizate cakes. Hydrolyzed gelatin was introduced with the aim of obtaining an even shorter disintegration time and at the same time an acceptable visual appearance of lyophilizates. This was achieved by lyophilization of solutions with 15% (w/w) of excipients with a hydrolyzed gelatin:PVP K25:glycine/croscarmellose:mannitol ratio of 4:2:0.5:4.5. Such lyophilizates show the highest potential for incorporation of poorly soluble and low-dose drugs.

• Language: English
• Keywords: patient-friendly dosage forms, orodispersible dosage forms, oral lyophilizates, excipient selection, hydrolyzed gelatin, aggressive drying
• 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: 8 str.
• Numbering: Vol. 82, art. 104379
• PID: 20.500.12556/RUL-144903
• UDC: 661.12
• ISSN on article: 1773-2247
• DOI: 10.1016/j.jddst.2023.104379
• COBISS.SI-ID: 146036995
• Publication date in RUL: 22.03.2023

Record is a part of a journal

• Title: Journal of drug delivery science and technology
• Shortened title: J. drug deliv. sci. technol.
• Publisher: Elsevier
• ISSN: 1773-2247
• COBISS.SI-ID: 2045297

Licences

• License: CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
• Link: http://creativecommons.org/licenses/by-nc-nd/4.0/
• Description: The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.

Secondary language

• Language: Slovenian
• Keywords: pacientom prijazne dozirne oblike, orodisperzibilne dozirne oblike, peroralni liofilizati, izbor pomožnih snovi, hidrolizirana želatina, agresivno sušenje, farmacevtska industrija

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