Effects of Dendrimer-Like Biopolymers on Physical Stability of Amorphous Solid Dispersions and Drug Permeability Across Caco-2 Cell Monolayers View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2018-08

AUTHORS

Monika Lavan, Gregory Knipp

ABSTRACT

The potential applications of dendrimer-like biopolymers (DLB) as stabilizing excipients for amorphous solid dispersion (ASD) of niclosamide, celecoxib, and resveratrol were evaluated based on (1) the formation and physical stability of the ASD and (2) the permeability and flux of the agents across Caco-2 cell monolayers. The evaluation was made by comparing the performance of prototype phytoglycogen derivatives (DLB1, DLB2, and DLB3) with commonly used polymers such as HPMCAS, PVPVA, and Soluplus®. PXRD was used to confirm the formation of the dispersions and detect crystallinity peaks formed during 2- and 4-week storage at 40°C/75% RH. At concentrations below 2 g/mL, the viability of Caco-2 cells remained above 80% for all DLB samples compared to untreated cells in the MTT assay. Permeability studies revealed a repeating pattern in which an increase in the initial concentration (C0) was associated with a concomitant decrease in the apparent permeability (Papp) which we theorize is due to differences in drug-polymer interactions. Niclosamide-DLB1 dispersion had the lowest flux due to a significant reduction in Papp. The high increase in the C0 of celecoxib-DLB2, however, made up for the reduction in the Papp and produced the highest flux values compared to other polymers. Resveratrol-DLB3 had a 5× reduction in Papp, but C0 increased from 25.8 to 176 μg/mL led to a higher flux compared to the crystalline drug without polymer. Collectively, these results provide a "proof-of-concept" basis to demonstrate that DLB excipients have the ability to increase apparent solubility (Solapp), most likely due to drug-binding capacity. More... »

PAGES

2459-2471

Identifiers

URI

http://scigraph.springernature.com/pub.10.1208/s12249-018-1080-6

DOI

http://dx.doi.org/10.1208/s12249-018-1080-6

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1104385598

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29869315


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