Physical Stability of and In-vitro Drug Release from Biodegradable PLGA Matrices / Friederike Bach

This work investigated different approaches to modify the release from PLGA matrices. The drug solid state in PLGA was analyzed with respect to its physical stability and impact on in-vitro drug release. Furthermore, the effect of drug particle size and the addition of a cationic excipient on the in-vitro drug release from PLGA was examined. First, the interactions between PLGA and the drugs ibuprofen, risperidone and dexamethasone were characterized. By assessing the solubility of the drugs in PLGA polymers of different grade, dexamethasone showed a lower solubility than risperidone and with up to 25 % ibuprofen exhibited the highest solubility. The examination of Hansen solubility parameters (HSPs) confirmed that the extend of interactions with PLGA was crucial for the solubility differences. The HSPs of ibuprofen and PLGA were more similar than those of dexamethasone and PLGA, leading to weaker interactions. The similarity of the risperidone HSPs to PLGA ranged in between dexamethasone and ibuprofen, which was in good accordance to the results from solubility testing. The similarity was assessed by calculating the HSP distance, Ra. The solid state stability of solid solutions and solid dispersions of the respective drugs in PLGA was characterized at ambient conditions, at 40 °C and 75 % RH and during in-vitro drug release. Films with solid solutions of all three drugs were stored under ambient conditions and dexamethasone and risperidone films remained stable over 3 month, while ibuprofen crystallized within 14 days. Polarized light microscopy and DSC suggested that ibuprofen formed a supersaturated solution in PLGA, leading to a time dependent crystallization. Storage of the films at 40 °C and 75 % RH gave a deeper insight into the crystallization mechanism of ibuprofen, denoting water uptake and the subsequent depression of glass transition temeprature as the main crystallization triggers. It is assumed that a pH decrease in the matrix contributed as well to the crystallization. The drug concentration in ....

Medienart:	E-Book

Erscheinungsjahr:	2022
Erschienen:	Berlin: Freie Universität Berlin ; 2022

Sprache:	Englisch

Weiterer Titel:	Physikalische Stabilität von und in-vitro Freisetzung aus bioabbaubaren PLGA matrices

Beteiligte Personen:	Bach, Friederike [VerfasserIn]
Hochschulschrift:	Dissertation, Berlin, Freie Universität Berlin, 2021

Links:	refubium.fu-berlin.de [kostenfrei]

BKL:	58.28 / Pharmazeutische Technologie
Themen:	Hochschulschrift

Umfang:	1 Online-Ressource

doi:	10.17169/refubium-33013
Weitere IDs:	urn:nbn:de:kobv:188-refubium-33292-5

funding:
Förderinstitution / Projekttitel:

PPN (Katalog-ID):	1788392833