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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22340%2F25%3A43933663" target="_blank" >RIV/60461373:22340/25:43933663 - isvavai.cz</a>

Výsledek na webu

<a href="http://DOI" target="_blank" >http://DOI</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/d5pm00070j" target="_blank" >10.1039/d5pm00070j</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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 &quot;flexible dose combination&quot; 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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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 &quot;flexible dose combination&quot; 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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

20402 - Chemical process engineering

Projekt

<a href="/cs/project/EH22_008%2F0004607" target="_blank" >EH22_008/0004607: Nové technologie pro translační výzkum ve farmaceutických vědách /NETPHARM</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

RSC Pharmaceutics

ISSN

2976-8713

e-ISSN

2976-8713

Svazek periodika

2

Číslo periodika v rámci svazku

6

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

12

Strana od-do

nestránkováno

Kód UT WoS článku

001565412600001

EID výsledku v databázi Scopus

—