Rational Design of Self-Emulsifying Pellet Formulation of
Thymol: Technology Development Guided by Molecular-Level
Structure Characterization and Ex Vivo Testing

J 2022

Rational Design of Self-Emulsifying Pellet Formulation of Thymol: Technology Development Guided by Molecular-Level Structure Characterization and Ex Vivo Testing

MACKŮ, Jan, Kateřina KUBOVÁ, Martina URBANOVA, Jan MUSELÍK, Aleš FRANC et. al.

Basic information

Original name

Rational Design of Self-Emulsifying Pellet Formulation of Thymol: Technology Development Guided by Molecular-Level Structure Characterization and Ex Vivo Testing

Authors

MACKŮ, Jan (203 Czech Republic, belonging to the institution), Kateřina KUBOVÁ (203 Czech Republic, guarantor, belonging to the institution), Martina URBANOVA, Jan MUSELÍK (203 Czech Republic, belonging to the institution), Aleš FRANC (203 Czech Republic, belonging to the institution), Gabriela KOUTNÁ (203 Czech Republic, belonging to the institution), Miroslava PAVELKOVÁ (203 Czech Republic, belonging to the institution), David VETCHÝ (203 Czech Republic, belonging to the institution), Josef MASEK, Eliska MASKOVA and Jiri BRUS

Edition

Pharmaceutics, Basel, MDPI, 2022, 1999-4923

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30104 Pharmacology and pharmacy

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 5.400

RIV identification code

RIV/00216224:14160/22:00126642

Organization unit

Faculty of Pharmacy

DOI

http://dx.doi.org/10.3390/pharmaceutics14081545

UT WoS

000847103700001

Keywords in English

thymol; solid-state NMR; self-emulsifying pellet; rational design; structure; ex vivo testing

Abstract

V originále

The growing need for processing natural lipophilic and often volatile substances such as thymol, a promising candidate for topical treatment of intestinal mucosa, led us to the utilization of solid-state nuclear magnetic resonance (ss-NMR) spectroscopy for the rational design of enteric pellets with a thymol self-emulsifying system (SES). The SES (triacylglycerol, Labrasol (R), and propylene glycol) provided a stable o/w emulsion with particle size between 1 and 7 mu m. The ex vivo experiment confirmed the SES mucosal permeation and thymol delivery to enterocytes. Pellets W90 (MCC, Neusilin (R) US2, chitosan) were prepared using distilled water (90 g) by the M1-M3 extrusion/spheronisation methods varying in steps number and/or cumulative time. The pellets (705-740 mu m) showed mostly comparable properties-zero friability, low intraparticular porosity (0-0.71%), and relatively high density (1.43-1.45%). They exhibited similar thymol release for 6 h (burst effect in 15th min ca. 60%), but its content increased (30-39.6 mg /g) with a shorter process time. The M3-W90 fluid-bed coated pellets (Eudragit (R) L) prevented undesirable thymol release in stomach conditions (<10% for 3 h). A detailed, ss-NMR investigation revealed structural differences across samples prepared by M1-M3 methods concerning system stability and internal interactions. The suggested formulation and methodology are promising for other lipophilic volatiles in treating intestinal diseases.

Links

GA22-03187S, research and development project

Name: Racionální design částicových polysacharidových systémů pro přívod léčiv s širokým spekterem biologické aktivity k terapii sliznic (Acronym: 22-03187S)

Investor: Czech Science Foundation

MUNI/A/1251/2021, interní kód MU

Name: Vývoj a in-vivo hodnocení inovativního samoemulgujícího částicového systému s obsahem thymolu pro zlepšení podmínek hospodářského chovu králíků (Acronym: Samoemulgující thymolové pelety pro chov králíků)

Investor: Masaryk University

Citovat

MACKŮ, Jan, Kateřina KUBOVÁ, Martina URBANOVA, Jan MUSELÍK, Aleš FRANC, Gabriela KOUTNÁ, Miroslava PAVELKOVÁ, David VETCHÝ, Josef MASEK, Eliska MASKOVA and Jiri BRUS. Rational Design of Self-Emulsifying Pellet Formulation of Thymol: Technology Development Guided by Molecular-Level Structure Characterization and Ex Vivo Testing. Pharmaceutics. Basel: MDPI, 2022, vol. 14, No 8, p. 1-21. ISSN 1999-4923. Available from: https://dx.doi.org/10.3390/pharmaceutics14081545.

@article{2217138,
   author = {Macků, Jan and Kubová, Kateřina and Urbanova, Martina and Muselík, Jan and Franc, Aleš and Koutná, Gabriela and Pavelková, Miroslava and Vetchý, David and Masek, Josef and Maskova, Eliska and Brus, Jiri},
   article_location = {Basel},
   article_number = {8},
   doi = {http://dx.doi.org/10.3390/pharmaceutics14081545},
   keywords = {thymol; solid-state NMR; self-emulsifying pellet; rational design; structure; ex vivo testing},
   language = {eng},
   issn = {1999-4923},
   journal = {Pharmaceutics},
   title = {Rational Design of Self-Emulsifying Pellet Formulation of Thymol: Technology Development Guided by Molecular-Level Structure Characterization and Ex Vivo Testing},
   url = {https://www.mdpi.com/1999-4923/14/8/1545/htm},
   volume = {14},
   year = {2022}
}

TY  - JOUR
ID  - 2217138
AU  - Macků, Jan - Kubová, Kateřina - Urbanova, Martina - Muselík, Jan - Franc, Aleš - Koutná, Gabriela - Pavelková, Miroslava - Vetchý, David - Masek, Josef - Maskova, Eliska - Brus, Jiri
PY  - 2022
TI  - Rational Design of Self-Emulsifying Pellet Formulation of Thymol: Technology Development Guided by Molecular-Level Structure Characterization and Ex Vivo Testing
JF  - Pharmaceutics
VL  - 14
IS  - 8
SP  - 1-21
EP  - 1-21
PB  - MDPI
SN  - 19994923
KW  - thymol
KW  - solid-state NMR
KW  - self-emulsifying pellet
KW  - rational design
KW  - structure
KW  - ex vivo testing
UR  - https://www.mdpi.com/1999-4923/14/8/1545/htm
N2  - The growing need for processing natural lipophilic and often volatile substances such as thymol, a promising candidate for topical treatment of intestinal mucosa, led us to the utilization of solid-state nuclear magnetic resonance (ss-NMR) spectroscopy for the rational design of enteric pellets with a thymol self-emulsifying system (SES). The SES (triacylglycerol, Labrasol (R), and propylene glycol) provided a stable o/w emulsion with particle size between 1 and 7 mu m. The ex vivo experiment confirmed the SES mucosal permeation and thymol delivery to enterocytes. Pellets W90 (MCC, Neusilin (R) US2, chitosan) were prepared using distilled water (90 g) by the M1-M3 extrusion/spheronisation methods varying in steps number and/or cumulative time. The pellets (705-740 mu m) showed mostly comparable properties-zero friability, low intraparticular porosity (0-0.71%), and relatively high density (1.43-1.45%). They exhibited similar thymol release for 6 h (burst effect in 15th min ca. 60%), but its content increased (30-39.6 mg /g) with a shorter process time. The M3-W90 fluid-bed coated pellets (Eudragit (R) L) prevented undesirable thymol release in stomach conditions (<10% for 3 h). A detailed, ss-NMR investigation revealed structural differences across samples prepared by M1-M3 methods concerning system stability and internal interactions. The suggested formulation and methodology are promising for other lipophilic volatiles in treating intestinal diseases.
ER  -

MACKŮ, Jan, Kateřina KUBOVÁ, Martina URBANOVA, Jan MUSELÍK, Aleš FRANC, Gabriela KOUTNÁ, Miroslava PAVELKOVÁ, David VETCHÝ, Josef MASEK, Eliska MASKOVA and Jiri BRUS. Rational Design of Self-Emulsifying Pellet Formulation of Thymol: Technology Development Guided by Molecular-Level Structure Characterization and Ex Vivo Testing. \textit{Pharmaceutics}. Basel: MDPI, 2022, vol.~14, No~8, p.~1-21. ISSN~1999-4923. Available from: https://dx.doi.org/10.3390/pharmaceutics14081545.

Detailed Information on Publication Record