Melt pelletization of alginate: Effects of air pressurization on consolidation and drug release property of pellets – Abstract
Microstructure consolidation of pellets is envisaged to enable a reduction of drug release in early dissolution phase. This study examines the effects of processing air pressure on drug release property of pellets and their mechanistic modifications on the matrices. The pellets were prepared using a high shear mixer at the jacket temperatures of 55 °C and 75 °C denoting thermoplastic and melt agglomeration, respectively with alginate, polyethylene glycol, calcium acetate and chlorpheniramine maleate as hydrophilic matrix polymer, meltable binder, crosslinker and water-soluble model drug.
Highlights
• Alginate pellets are prepared by air-pressurized melt pelletization technique.
• Melt pelletization is conducted in a high shear mixer.
• Air-pressurized melt pellets exhibit slow drug release characteristics.
• Pellet consolidation within short processing time sustains drug release.
• Prolonged air bubbling induces porous core that fails to sustain drug release.
The formed pellets were subjected to size, shape, morphology, drug content, drug release, calcium content, and molecular pharmaceutics analysis in their fresh state or after undergoing dissolution process. Low jacket temperature agglomeration was characterized by prolonged massing, extensive non-meltable solid particle rearrangement, core-to-surface binder migration and ease of pellet fragmentation at early dissolution phase due to improved matrix wetting by water-soluble surface binder. Air-pressurized agglomeration similarly promoted core-to-surface binder migration and ease of pellet fragmentation. At 75 °C instead of 55 °C, matrix pressurization by air was accompanied by core consolidation. It led to fast pellet breakup into dense fragments that exhibited a sustained drug release behavior. At 55 °C, matrix pressurization by air failed to consolidate the pellets due to air bubbling of core with prolonged massing, and no significant drug release retardation was observed. The processing air pressure can aid to consolidate pellets prepared by melt instead of thermoplastic agglomeration technique and reduce their drug release propensity.
N. Hanafi, T.W. Wong, Melt pelletization of alginate: Effects of air pressurization on consolidation and drug release property of pellets, Chemical Engineering Research and Design, Volume 104, 2015, Pages 479-487, ISSN 0263-8762, https://doi.org/10.1016/j.cherd.2015.09.009.