Drug release from binary and ternary flexible dose combinations manufactured by drop-on-demand impregnation of mesoporous silica tablets

Abstract

Fixed-dose drug combinations (FDC) such as bi-layer tablets are known to improve treatment outcomes in polypharmacy patients thanks to better medication adherence achieved by reduced pill burden. However, the bulk manufacturing of FDCs is technically and economically viable only for such combinations where a sufficiently large patient cohort exists. The present work explores the “flexible dose combination” approach, which is based on the bulk manufacturing of placebo tablets containing mesoporous silica particles, and their subsequent impregnation by a combination of active pharmaceutical ingredients (API) at dosage strengths that can be adjusted to smaller patient cohorts or even individual patients. The present approach is based on volumetric dosing, which is generally faster and allows finer dosing steps than powder-based additive manufacturing methods. Specifically, this study investigates the potential of mesoporous silica-based tablets for the commonly prescribed triple combination of candesartan, hydrochlorothiazide, and amlodipine. Two grades of mesoporous silica were compared in terms of drug loading capacity and release kinetics for each API individually, and their binary and ternary combinations. Tablets containing Syloid 72FP showed superior performance in terms of drug release rates than tablets with custom-made mesoporous silica. The order in which the APIs were impregnated was found to be an important factor influencing drug release kinetics. The loading sequence candesartan–hydrochlorothiazide–amlodipine emerged as the best performing, enhancing amlodipine release and maintaining high release rates of hydrochlorothiazide and candesartan when compared to nanocomponent benchmarks. The findings prove that mesoporous placebo tablets loaded by the drop-on-demand method can effectively accommodate the triple drug combination, demonstrating their potential as a carrier system for flexible-dose formulations. At the same time, non-trivial API-specific dependence of drug release on the quantity and order of drug loading into the tablet was found, which must be considered when designing such formulations.

Graphical abstract: Drug release from binary and ternary flexible dose combinations manufactured by drop-on-demand impregnation of mesoporous silica tablets

Supplementary files

Transparent peer review

To support increased transparency, we offer authors the option to publish the peer review history alongside their article.

View this article’s peer review history

Article information

Article type
Paper
Submitted
12 Mar 2025
Accepted
20 Aug 2025
First published
21 Aug 2025
This article is Open Access
Creative Commons BY license

RSC Pharm., 2025, Advance Article

Drug release from binary and ternary flexible dose combinations manufactured by drop-on-demand impregnation of mesoporous silica tablets

Z. Hlavačková, D. Zůza, E. Sonntag, J. Petřík, O. Dammer and F. Štěpánek, RSC Pharm., 2025, Advance Article , DOI: 10.1039/D5PM00070J

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements