The role of coatings and plasticizers compatibility in stability of advanced gastro-resistant self-emulsifying pellets designed for the delivery of volatile compounds: a combined solid-state NMR and dissolution study

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389013%3A_____%2F24%3A00600563" target="_blank" >RIV/61389013:_____/24:00600563 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14160/24:00139578

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S1773224724009948?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S1773224724009948?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.jddst.2024.106325" target="_blank" >10.1016/j.jddst.2024.106325</a>

Jazyk výsledku

angličtina

Název v původním jazyce

The role of coatings and plasticizers compatibility in stability of advanced gastro-resistant self-emulsifying pellets designed for the delivery of volatile compounds: a combined solid-state NMR and dissolution study

Popis výsledku v původním jazyce

The gastro-resistant behaviour of solid self-emulsifying drug delivery systems (S-SEDDS) represents a significant and innovative advancement in delivering poorly soluble drugs. Due to the complexity of these systems and the liquid nature of SEDDS, thorough investigation is essential. This study explored the stability of self-emulsifying (SE) pellets containing the volatile compound thymol coated with gastro-resistant Eudragit® L 30 D-55 water dispersion. The SE pellet cores, composed of Neusilin® US2 with adsorbed SEDDS (thymol, triacylglycerol, Labrasol®, and propylene glycol), microcrystalline cellulose, and chitosan, were prepared using the extrusion/spheronization method and demonstrated optimal technological properties. The 6-month stability of three coating compositions, differing in thickness and triethyl citrate (TEC) concentration in the Eudragit® L topcoat, or the application of an ethylcellulose (EC, Surelease®) sub-coat, was investigated using the combined in vitro dissolution testing and solid-state nuclear magnetic resonance (ss-NMR) for detailed structural characterization. The dissolution data of samples with Eudragit® L topcoat data showed an acceleration of thymol release in acidic conditions, preventing the SE pellets from achieving gastro-resistance. The ss-NMR analysis revealed an incompatibility between TEC and SEDDS (specifically propylene glycol), identified as a TEC phase transition to a liquid phase independent of TEC concentration. Additionally, ss-NMR analysis revealed that neat thymol negatively affected coating layer stability by promoting the plasticization of Eudragit® L. The inclusion of a 10 % Surelease® sub-coat yielded positive results, maintaining the gastro-resistant properties of SE pellets stored under 25 °C/60 % RH for 6 months. However, ss-NMR analysis confirmed ongoing TEC liquefaction after 3 and 6 months, indicating that the oleic acid and triglycerides in Surelease® as plasticizers contributed to this instability. Therefore, this formulation cannot be deemed stable, and using Surelease® as a sub-layer is only a temporary solution. Overall, while plasticizers are commonly used in pharmaceutical technology, they can introduce significant problems in S-SEDDS development, and their use in sub- or topcoats should be carefully considered or avoided. At the same time, it became evident that in-vitro dissolution testing alone cannot capture the slow processes and interactions occurring within the internal structure of these systems.

Název v anglickém jazyce

The role of coatings and plasticizers compatibility in stability of advanced gastro-resistant self-emulsifying pellets designed for the delivery of volatile compounds: a combined solid-state NMR and dissolution study

Popis výsledku anglicky

The gastro-resistant behaviour of solid self-emulsifying drug delivery systems (S-SEDDS) represents a significant and innovative advancement in delivering poorly soluble drugs. Due to the complexity of these systems and the liquid nature of SEDDS, thorough investigation is essential. This study explored the stability of self-emulsifying (SE) pellets containing the volatile compound thymol coated with gastro-resistant Eudragit® L 30 D-55 water dispersion. The SE pellet cores, composed of Neusilin® US2 with adsorbed SEDDS (thymol, triacylglycerol, Labrasol®, and propylene glycol), microcrystalline cellulose, and chitosan, were prepared using the extrusion/spheronization method and demonstrated optimal technological properties. The 6-month stability of three coating compositions, differing in thickness and triethyl citrate (TEC) concentration in the Eudragit® L topcoat, or the application of an ethylcellulose (EC, Surelease®) sub-coat, was investigated using the combined in vitro dissolution testing and solid-state nuclear magnetic resonance (ss-NMR) for detailed structural characterization. The dissolution data of samples with Eudragit® L topcoat data showed an acceleration of thymol release in acidic conditions, preventing the SE pellets from achieving gastro-resistance. The ss-NMR analysis revealed an incompatibility between TEC and SEDDS (specifically propylene glycol), identified as a TEC phase transition to a liquid phase independent of TEC concentration. Additionally, ss-NMR analysis revealed that neat thymol negatively affected coating layer stability by promoting the plasticization of Eudragit® L. The inclusion of a 10 % Surelease® sub-coat yielded positive results, maintaining the gastro-resistant properties of SE pellets stored under 25 °C/60 % RH for 6 months. However, ss-NMR analysis confirmed ongoing TEC liquefaction after 3 and 6 months, indicating that the oleic acid and triglycerides in Surelease® as plasticizers contributed to this instability. Therefore, this formulation cannot be deemed stable, and using Surelease® as a sub-layer is only a temporary solution. Overall, while plasticizers are commonly used in pharmaceutical technology, they can introduce significant problems in S-SEDDS development, and their use in sub- or topcoats should be carefully considered or avoided. At the same time, it became evident that in-vitro dissolution testing alone cannot capture the slow processes and interactions occurring within the internal structure of these systems.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10406 - Analytical chemistry

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

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

Název periodika

Journal of Drug Delivery Science and Technology

ISSN

1773-2247

e-ISSN

2588-8943

Svazek periodika

102

Číslo periodika v rámci svazku

Part A

Stát vydavatele periodika

FR - Francouzská republika

Počet stran výsledku

13

Strana od-do

106325

Kód UT WoS článku

001348172600001

EID výsledku v databázi Scopus

2-s2.0-85207775947