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.

Content Provider	Europe PMC
Author	Chang, Hao Han R. Chen, Kuan Lugtu-Pe, Jamie Anne AL-Mousawi, Nour Zhang, Xuning Bar-Shalom, Daniel Kane, Anil Wu, Xiao Yu
Editor	Lai, Wing-Fu
Copyright Year	2023
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.
Journal	Pharmaceutics
Volume Number	15
PubMed Central reference number	PMC9964771
Issue Number	2
PubMed reference number	36839869
e-ISSN	19994923
DOI	10.3390/pharmaceutics15020547
Language	English
Publisher	MDPI
Publisher Date	2023-02-07
Access Restriction	Open
Rights License	Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). © 2023 by the authors.
Subject Keyword	multifunctional terpolymer excipient controlled release microenvironmental pH modifier pore former pH-responsive nanoparticles nanogel optimization weakly basic drug bilayer-coated beads pH-independent release
Content Type	Text
Resource Type	Article
Subject	Pharmaceutical Science