This study investigates the correlation between the structural and release properties of solid lipid microparticles (MPs) of tristearin containing 5 % w/w of four different liquid additives used as crystal modifiers: isopropyl myristate (IM), ethyl oleate (EO), oleic acid (OA) and medium chain triglycerides (MCT). All additives accelerated the conversion of the unstable alpha-form of tristearin, formed after the MPs manufacturing, to the stable beta-polymorph and the transformation was completed within 24 h (for IM and EO) or 48 h (for OA and MCT). The kinetic of polymorphic transition at 25 degrees C was investigated by simultaneous synchrotron SAXS/WAXS and DSC analysis after melting and subsequent cooling of the lipid mixture. After crystallization in the alpha-phase, additives accelerate the solid-solid phase transformation to beta-tristearin. SAXS data showed that two types of structural modifications occurred on MPs during storage: compaction of the crystal packing (slight decrease in lamellar thickness) and crystal growth (increased number of stacked lipid lamellae). The release behavior of a model hydrophilic drug (caffeine) at two different amounts (15 % and 30 %) from MPs was studied in water and biorelevant media simulated the gastric and intestinal environment. It was particularly significant that the introduction of IM, EO and MCT were able to prolong the drug release in water, passing from a diffusion-based Higuchi kinetics to a perfect zero-order kinetic. Moreover, the overall release profiles were higher in biorelevant media, where erosion/digestion of MPs was observed. After 6 months, a moderate but statistically significant change in release profile was observed for the MPs with IM and EO, which can be correlated with the timedependent structural alterations (i.e. larger average crystallite size) of these formulations; while MPs with OA or MCT displayed stable release profiles. These findings help to understand the correlation between release behavior, polymorphism and supramolecular-level structural modification of lipid formulations containing crystal modifiers.

Bertoni S., Simone E., Sangiorgi S., Albertini B., Passerini N. (2024). The use of polymorphic state modifiers in solid lipid microparticles: The role of structural modifications on drug release performance. EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 192, 1-12 [10.1016/j.ejps.2023.106650].

The use of polymorphic state modifiers in solid lipid microparticles: The role of structural modifications on drug release performance

Bertoni S.
Primo
;
Sangiorgi S.;Albertini B.
Penultimo
;
Passerini N.
Ultimo
2024

Abstract

This study investigates the correlation between the structural and release properties of solid lipid microparticles (MPs) of tristearin containing 5 % w/w of four different liquid additives used as crystal modifiers: isopropyl myristate (IM), ethyl oleate (EO), oleic acid (OA) and medium chain triglycerides (MCT). All additives accelerated the conversion of the unstable alpha-form of tristearin, formed after the MPs manufacturing, to the stable beta-polymorph and the transformation was completed within 24 h (for IM and EO) or 48 h (for OA and MCT). The kinetic of polymorphic transition at 25 degrees C was investigated by simultaneous synchrotron SAXS/WAXS and DSC analysis after melting and subsequent cooling of the lipid mixture. After crystallization in the alpha-phase, additives accelerate the solid-solid phase transformation to beta-tristearin. SAXS data showed that two types of structural modifications occurred on MPs during storage: compaction of the crystal packing (slight decrease in lamellar thickness) and crystal growth (increased number of stacked lipid lamellae). The release behavior of a model hydrophilic drug (caffeine) at two different amounts (15 % and 30 %) from MPs was studied in water and biorelevant media simulated the gastric and intestinal environment. It was particularly significant that the introduction of IM, EO and MCT were able to prolong the drug release in water, passing from a diffusion-based Higuchi kinetics to a perfect zero-order kinetic. Moreover, the overall release profiles were higher in biorelevant media, where erosion/digestion of MPs was observed. After 6 months, a moderate but statistically significant change in release profile was observed for the MPs with IM and EO, which can be correlated with the timedependent structural alterations (i.e. larger average crystallite size) of these formulations; while MPs with OA or MCT displayed stable release profiles. These findings help to understand the correlation between release behavior, polymorphism and supramolecular-level structural modification of lipid formulations containing crystal modifiers.
2024
Bertoni S., Simone E., Sangiorgi S., Albertini B., Passerini N. (2024). The use of polymorphic state modifiers in solid lipid microparticles: The role of structural modifications on drug release performance. EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 192, 1-12 [10.1016/j.ejps.2023.106650].
Bertoni S.; Simone E.; Sangiorgi S.; Albertini B.; Passerini N.
File in questo prodotto:
File Dimensione Formato  
1-s2.0-S0928098723002798-mmc1.docx

accesso aperto

Descrizione: supplementary materials
Tipo: File Supplementare
Licenza: Licenza per Accesso Aperto. Creative Commons Attribuzione (CCBY)
Dimensione 391.37 kB
Formato Microsoft Word XML
391.37 kB Microsoft Word XML Visualizza/Apri
pdf editoriale.pdf

accesso aperto

Tipo: Versione (PDF) editoriale
Licenza: Licenza per Accesso Aperto. Creative Commons Attribuzione (CCBY)
Dimensione 914.57 kB
Formato Adobe PDF
914.57 kB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/966237
Citazioni
  • ???jsp.display-item.citation.pmc??? 1
  • Scopus 2
  • ???jsp.display-item.citation.isi??? 2
social impact