Investigation into the role of the polymer in enhancing microwave-induced in situ amorphization
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Investigation into the role of the polymer in enhancing microwave-induced in situ amorphization. / Qiang, Wei; Löbmann, Korbinian; Knopp, Matthias Manne; McCoy, Colin P.; Andrews, Gavin P.; Zhao, Min.
In: International Journal of Pharmaceutics, Vol. 609, 121157, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Investigation into the role of the polymer in enhancing microwave-induced in situ amorphization
AU - Qiang, Wei
AU - Löbmann, Korbinian
AU - Knopp, Matthias Manne
AU - McCoy, Colin P.
AU - Andrews, Gavin P.
AU - Zhao, Min
N1 - Publisher Copyright: © 2021 Elsevier B.V.
PY - 2021
Y1 - 2021
N2 - Microwave-induced in situ amorphization is an emerging technology to tackle the persistent stability issue of amorphous solid dispersions (ASDs) during manufacture and storage. The aim of this study was to introduce new effective polymeric carriers with diverse properties to microwave-induced in situ amorphization and to better understand their functions in relation to the final dissolution performance of microwaved tablets. Tablets composed of indomethacin (IND) and different polymers were compacted, stored at 75% relative humidity for at least 1 week and microwaved at 1000 W to induce amorphization. A series of polymers, polyvinylpyrrolidone/vinyl acetate copolymers (PVP/VA) of different monomer weight ratios displaying varying properties in functional group ratio, hygroscopicity, molecular weight (Mw), and glass transition temperature (Tg) of the polymer were used as model carriers. The results suggested that more than 90% of IND was amorphized after 20 mins microwaving in all 20% (w/w) drug loaded tablets except for IND:PVAc tablets presenting approx. 36% residual crystallinity. Among them, tablets composed of PVP/VA I-335 and PVP K30 achieved complete in situ amorphization upon microwaving. Further analysis indicated that the influencing factors, polymer Mw and Tg of moisture-plasticized polymer, played a major role in microwave-induced in situ amorphization. In in vitro dissolution study, ASDs containing PVP/VA I-535 with moderate hydrophilicity and 0.96 ± 1.92% IND residual crystallinity showed the most rapid and complete drug release among all formulations, presenting the most promising dissolution performance. Further study on the chemical stability of such formulation showed a statistically insignificant decrease of drug content after pre-conditioning and microwaving (P = 0.288 > 0.05).
AB - Microwave-induced in situ amorphization is an emerging technology to tackle the persistent stability issue of amorphous solid dispersions (ASDs) during manufacture and storage. The aim of this study was to introduce new effective polymeric carriers with diverse properties to microwave-induced in situ amorphization and to better understand their functions in relation to the final dissolution performance of microwaved tablets. Tablets composed of indomethacin (IND) and different polymers were compacted, stored at 75% relative humidity for at least 1 week and microwaved at 1000 W to induce amorphization. A series of polymers, polyvinylpyrrolidone/vinyl acetate copolymers (PVP/VA) of different monomer weight ratios displaying varying properties in functional group ratio, hygroscopicity, molecular weight (Mw), and glass transition temperature (Tg) of the polymer were used as model carriers. The results suggested that more than 90% of IND was amorphized after 20 mins microwaving in all 20% (w/w) drug loaded tablets except for IND:PVAc tablets presenting approx. 36% residual crystallinity. Among them, tablets composed of PVP/VA I-335 and PVP K30 achieved complete in situ amorphization upon microwaving. Further analysis indicated that the influencing factors, polymer Mw and Tg of moisture-plasticized polymer, played a major role in microwave-induced in situ amorphization. In in vitro dissolution study, ASDs containing PVP/VA I-535 with moderate hydrophilicity and 0.96 ± 1.92% IND residual crystallinity showed the most rapid and complete drug release among all formulations, presenting the most promising dissolution performance. Further study on the chemical stability of such formulation showed a statistically insignificant decrease of drug content after pre-conditioning and microwaving (P = 0.288 > 0.05).
KW - Amorphous solid dispersion
KW - Dissolution
KW - Microwave-induced in situ amorphization
KW - Moisture
KW - Polymers
U2 - 10.1016/j.ijpharm.2021.121157
DO - 10.1016/j.ijpharm.2021.121157
M3 - Journal article
C2 - 34626795
AN - SCOPUS:85117615077
VL - 609
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
SN - 0378-5173
M1 - 121157
ER -
ID: 283011378