TY - JOUR
T1 - Hydrophilic and functionalized nanographene oxide incorporated faster dissolving megestrol acetate
AU - Islam, Mohammad Saiful
AU - Renner, Faradae
AU - Foster, Kimberly
AU - Oderinde, Martin S.
AU - Stefanski, Kevin
AU - Mitra, Somenath
N1 - Funding Information:
Acknowledgments: The project was partially funded from a grant from Bristol Myers Squibb. We also would like to acknowledge The Otto York Center of Environmental Engineering and Science for allowing us to characterize our sample work by using different instrumentation.
Funding Information:
Funding: This research was funded by Bristol Myers Squibb Research and Early Development, grant number 2020.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/4/1
Y1 - 2021/4/1
N2 - The aim of this work is to present an approach to enhance the dissolution of progestin medication, megestrol acetate (also known as MEGACE), for improving the dissolution rate and kinetic solubility by incorporating nano graphene oxide (nGO). An antisolvent precipitation process was investigated for nGO-drug composite preparation, where prepared composites showed crystalline properties that were similar to the pure drug but enhanced aqueous dispersibility and colloidal stability. To validate the efficient release profile of composite, in vitro dissolution testing was carried out using United States Pharmacopeia, USP-42 paddle method, with gastric pH (1.4) and intestinal pH (6.5) solutions to mimic in vivo conditions. Pure MA is practically insoluble (2 µg/mL at 37◦C). With the incorporation of nGO, it was possible to dissolve nearly 100% in the assay. With the incorporation of 1.0% of nGO, the time required to dissolve 50% and 80% of drug, namely T50 and T80, decreased from 138.0 min to 27.0 min, and the drug did not dissolve for 97.0 min in gastric media, respectively. Additionally, studies done in intestinal media have revealed T50 did not dissolve for 92.0 min. This work shows promise in incorporating functionalized nanoparticles into the crystal lattice of poorly soluble drugs to improve dissolution rate.
AB - The aim of this work is to present an approach to enhance the dissolution of progestin medication, megestrol acetate (also known as MEGACE), for improving the dissolution rate and kinetic solubility by incorporating nano graphene oxide (nGO). An antisolvent precipitation process was investigated for nGO-drug composite preparation, where prepared composites showed crystalline properties that were similar to the pure drug but enhanced aqueous dispersibility and colloidal stability. To validate the efficient release profile of composite, in vitro dissolution testing was carried out using United States Pharmacopeia, USP-42 paddle method, with gastric pH (1.4) and intestinal pH (6.5) solutions to mimic in vivo conditions. Pure MA is practically insoluble (2 µg/mL at 37◦C). With the incorporation of nGO, it was possible to dissolve nearly 100% in the assay. With the incorporation of 1.0% of nGO, the time required to dissolve 50% and 80% of drug, namely T50 and T80, decreased from 138.0 min to 27.0 min, and the drug did not dissolve for 97.0 min in gastric media, respectively. Additionally, studies done in intestinal media have revealed T50 did not dissolve for 92.0 min. This work shows promise in incorporating functionalized nanoparticles into the crystal lattice of poorly soluble drugs to improve dissolution rate.
KW - Enhanced dissolution
KW - Gastroin-testinal pH
KW - Megestrol acetate
KW - Nano graphene oxide
KW - Oral medication
KW - Paddle method
UR - http://www.scopus.com/inward/record.url?scp=85103863210&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85103863210&partnerID=8YFLogxK
U2 - 10.3390/molecules26071972
DO - 10.3390/molecules26071972
M3 - Article
C2 - 33807401
AN - SCOPUS:85103863210
SN - 1420-3049
VL - 26
JO - Molecules
JF - Molecules
IS - 7
M1 - 1972
ER -