Design and Optimization of a Nanoparticulate Pore Former as a Multifunctional Coating Excipient for pH Transition-Independent Controlled Release of Weakly Basic Drugs for Oral Drug Delivery

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Design and Optimization of a Nanoparticulate Pore Former as a Multifunctional Coating Excipient for pH Transition-Independent Controlled Release of Weakly Basic Drugs for Oral Drug Delivery. / Chang, Hao Han R.; Chen, Kuan; Lugtu-Pe, Jamie Anne; AL-Mousawi, Nour; Zhang, Xuning; Bar-Shalom, Daniel; Kane, Anil; Wu, Xiao Yu.

In: Pharmaceutics, Vol. 15, No. 2, 547, 2023.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Chang, HHR, Chen, K, Lugtu-Pe, JA, AL-Mousawi, N, Zhang, X, Bar-Shalom, D, Kane, A & Wu, XY 2023, 'Design and Optimization of a Nanoparticulate Pore Former as a Multifunctional Coating Excipient for pH Transition-Independent Controlled Release of Weakly Basic Drugs for Oral Drug Delivery', Pharmaceutics, vol. 15, no. 2, 547. https://doi.org/10.3390/pharmaceutics15020547

APA

Chang, H. H. R., Chen, K., Lugtu-Pe, J. A., AL-Mousawi, N., Zhang, X., Bar-Shalom, D., Kane, A., & Wu, X. Y. (2023). Design and Optimization of a Nanoparticulate Pore Former as a Multifunctional Coating Excipient for pH Transition-Independent Controlled Release of Weakly Basic Drugs for Oral Drug Delivery. Pharmaceutics, 15(2), [547]. https://doi.org/10.3390/pharmaceutics15020547

Vancouver

Chang HHR, Chen K, Lugtu-Pe JA, AL-Mousawi N, Zhang X, Bar-Shalom D et al. Design and Optimization of a Nanoparticulate Pore Former as a Multifunctional Coating Excipient for pH Transition-Independent Controlled Release of Weakly Basic Drugs for Oral Drug Delivery. Pharmaceutics. 2023;15(2). 547. https://doi.org/10.3390/pharmaceutics15020547

Author

Chang, Hao Han R. ; Chen, Kuan ; Lugtu-Pe, Jamie Anne ; AL-Mousawi, Nour ; Zhang, Xuning ; Bar-Shalom, Daniel ; Kane, Anil ; Wu, Xiao Yu. / Design and Optimization of a Nanoparticulate Pore Former as a Multifunctional Coating Excipient for pH Transition-Independent Controlled Release of Weakly Basic Drugs for Oral Drug Delivery. In: Pharmaceutics. 2023 ; Vol. 15, No. 2.

Bibtex

@article{3a3fb0765a7f417c96bd25022a89cc42,
title = "Design and Optimization of a Nanoparticulate Pore Former as a Multifunctional Coating Excipient for pH Transition-Independent Controlled Release of Weakly Basic Drugs for Oral Drug Delivery",
abstract = "Bioavailability of weakly basic drugs may be disrupted by dramatic pH changes or unexpected pH alterations in the gastrointestinal tract. Conventional organic acids or enteric coating polymers cannot address this problem adequately because they leach out or dissolve prematurely, especially during controlled release applications. Thus, a non-leachable, multifunctional terpolymer nanoparticle (TPN) made of cross-linked poly(methacrylic acid) (PMAA)-polysorbate 80-grafted-starch (PMAA-PS 80-g-St) was proposed to provide pH transition-independent release of a weakly basic drug, verapamil HCl (VER), by a rationally designed bilayer-coated controlled release bead formulation. The pH-responsive PMAA and cross-linker content in the TPN was first optimized to achieve the largest possible increase in medium uptake alongside the smallest decrease in drug release rate at pH 6.8, relative to pH 1.2. Such TPNs maintained an acidic microenvironmental pH (pHm) when loaded in ethylcellulose (EC) films, as measured using pH-indicating dyes. Further studies of formulations revealed that with the 1:2 VER:TPN ratio and 19% coating weight gain, bilayer-coated beads maintained a constant release rate over the pH transition and exhibited extended release up to 18 h. These results demonstrated that the multifunctional TPN as a pHm modifier and pH-dependent pore former could overcome the severe pH-dependent solubility of weakly basic drugs.",
keywords = "bilayer-coated beads, controlled release, microenvironmental pH modifier, multifunctional terpolymer excipient, nanogel optimization, pH-independent release, pH-responsive nanoparticles, pore former, weakly basic drug",
author = "Chang, {Hao Han R.} and Kuan Chen and Lugtu-Pe, {Jamie Anne} and Nour AL-Mousawi and Xuning Zhang and Daniel Bar-Shalom and Anil Kane and Wu, {Xiao Yu}",
note = "Funding Information: This project is supported in part by the Natural Sciences and Engineering Research Council (NSERC) Discovery grant (RGPIN-2019-07204) and equipment grants (EQPEQ 374799-09, EQPEQ 440689-13) to X.W.; and the Mitacs Accelerate Internship to H.H.R.C. with Patheon by Thermo Fisher Scientific (IT08610). Funding Information: The authors would like to thank BASF, Colorcon, and Croda for providing samples of PVP, Surelease EC, and PS 80, respectively; and to thank David Dubins, for the use of the fluid bed coater in the Patheon Pharmaceutics Teaching Laboratory; and to thank the Departmental Scholarships and Hoffman-La Roche/Rosemarie Hager Graduate Fellowship to K.C., and to thank the Dean{\textquoteright}s Fund for Ph.D. Scholarship to J.A.L.-P.; and to thank the stipendium from the government of Denmark to N.A.-M. {\textregistered} ",
year = "2023",
doi = "10.3390/pharmaceutics15020547",
language = "English",
volume = "15",
journal = "Pharmaceutics",
issn = "1999-4923",
publisher = "MDPI AG",
number = "2",

}

RIS

TY - JOUR

T1 - Design and Optimization of a Nanoparticulate Pore Former as a Multifunctional Coating Excipient for pH Transition-Independent Controlled Release of Weakly Basic Drugs for Oral Drug Delivery

AU - Chang, Hao Han R.

AU - Chen, Kuan

AU - Lugtu-Pe, Jamie Anne

AU - AL-Mousawi, Nour

AU - Zhang, Xuning

AU - Bar-Shalom, Daniel

AU - Kane, Anil

AU - Wu, Xiao Yu

N1 - Funding Information: This project is supported in part by the Natural Sciences and Engineering Research Council (NSERC) Discovery grant (RGPIN-2019-07204) and equipment grants (EQPEQ 374799-09, EQPEQ 440689-13) to X.W.; and the Mitacs Accelerate Internship to H.H.R.C. with Patheon by Thermo Fisher Scientific (IT08610). Funding Information: The authors would like to thank BASF, Colorcon, and Croda for providing samples of PVP, Surelease EC, and PS 80, respectively; and to thank David Dubins, for the use of the fluid bed coater in the Patheon Pharmaceutics Teaching Laboratory; and to thank the Departmental Scholarships and Hoffman-La Roche/Rosemarie Hager Graduate Fellowship to K.C., and to thank the Dean’s Fund for Ph.D. Scholarship to J.A.L.-P.; and to thank the stipendium from the government of Denmark to N.A.-M. ®

PY - 2023

Y1 - 2023

N2 - Bioavailability of weakly basic drugs may be disrupted by dramatic pH changes or unexpected pH alterations in the gastrointestinal tract. Conventional organic acids or enteric coating polymers cannot address this problem adequately because they leach out or dissolve prematurely, especially during controlled release applications. Thus, a non-leachable, multifunctional terpolymer nanoparticle (TPN) made of cross-linked poly(methacrylic acid) (PMAA)-polysorbate 80-grafted-starch (PMAA-PS 80-g-St) was proposed to provide pH transition-independent release of a weakly basic drug, verapamil HCl (VER), by a rationally designed bilayer-coated controlled release bead formulation. The pH-responsive PMAA and cross-linker content in the TPN was first optimized to achieve the largest possible increase in medium uptake alongside the smallest decrease in drug release rate at pH 6.8, relative to pH 1.2. Such TPNs maintained an acidic microenvironmental pH (pHm) when loaded in ethylcellulose (EC) films, as measured using pH-indicating dyes. Further studies of formulations revealed that with the 1:2 VER:TPN ratio and 19% coating weight gain, bilayer-coated beads maintained a constant release rate over the pH transition and exhibited extended release up to 18 h. These results demonstrated that the multifunctional TPN as a pHm modifier and pH-dependent pore former could overcome the severe pH-dependent solubility of weakly basic drugs.

AB - Bioavailability of weakly basic drugs may be disrupted by dramatic pH changes or unexpected pH alterations in the gastrointestinal tract. Conventional organic acids or enteric coating polymers cannot address this problem adequately because they leach out or dissolve prematurely, especially during controlled release applications. Thus, a non-leachable, multifunctional terpolymer nanoparticle (TPN) made of cross-linked poly(methacrylic acid) (PMAA)-polysorbate 80-grafted-starch (PMAA-PS 80-g-St) was proposed to provide pH transition-independent release of a weakly basic drug, verapamil HCl (VER), by a rationally designed bilayer-coated controlled release bead formulation. The pH-responsive PMAA and cross-linker content in the TPN was first optimized to achieve the largest possible increase in medium uptake alongside the smallest decrease in drug release rate at pH 6.8, relative to pH 1.2. Such TPNs maintained an acidic microenvironmental pH (pHm) when loaded in ethylcellulose (EC) films, as measured using pH-indicating dyes. Further studies of formulations revealed that with the 1:2 VER:TPN ratio and 19% coating weight gain, bilayer-coated beads maintained a constant release rate over the pH transition and exhibited extended release up to 18 h. These results demonstrated that the multifunctional TPN as a pHm modifier and pH-dependent pore former could overcome the severe pH-dependent solubility of weakly basic drugs.

KW - bilayer-coated beads

KW - controlled release

KW - microenvironmental pH modifier

KW - multifunctional terpolymer excipient

KW - nanogel optimization

KW - pH-independent release

KW - pH-responsive nanoparticles

KW - pore former

KW - weakly basic drug

U2 - 10.3390/pharmaceutics15020547

DO - 10.3390/pharmaceutics15020547

M3 - Journal article

C2 - 36839869

AN - SCOPUS:85149144256

VL - 15

JO - Pharmaceutics

JF - Pharmaceutics

SN - 1999-4923

IS - 2

M1 - 547

ER -

ID: 339334341