Mechanisms of burst release from pH-responsive polymeric microparticles

• Published in: Journal of pharmacy and pharmacology Vol. 63; no. 9; pp. 1141 - 1155
• Main Authors: Rizi, Khalida, Green, Rebecca J., Khutoryanskaya, Olga, Donaldson, Michael, Williams, Adrian C.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-09-2011
• Subjects: burst release; Crystallization; Delayed-Action Preparations - chemistry; Desiccation - methods; Drug Administration Schedule; Drug Carriers - chemistry; Drug Compounding - methods; Emulsions; Eudragit L100; hydrocortisone; Hydrocortisone - administration & dosage; Hydrogen-Ion Concentration; Hydrophobic and Hydrophilic Interactions; microencapsulation; Microspheres; Oils; Polymers - chemistry; Polymethacrylic Acids - chemistry; Porosity; Solutions; Solvents - chemistry; spray drying
• ISSN: 0022-3573; 2042-7158
• DOI: 10.1111/j.2042-7158.2011.01322.x

Objectives  Microencapsulation of drugs into preformed polymers is commonly achieved through solvent evaporation techniques or spray drying. We compared these encapsulation methods in terms of controlled drug release properties of prepared microparticles and investigated the underlying mechanisms responsible for the ‘burst release’ effect.
Methods  Using two different pH‐responsive polymers with a dissolution threshold of pH 6 (Eudragit L100 and AQOAT AS‐MG), hydrocortisone, a model hydrophobic drug, was incorporated into microparticles below and above its solubility within the polymer matrix.
Key findings  Although, spray drying was an attractive approach due to rapid particle production and relatively low solvent waste, the oil‐in‐oil microencapsulation method was superior in terms of controlled drug release properties from the microparticles. Slow solvent evaporation during the oil‐in‐oil emulsification process allowed adequate time for drug and polymer redistribution in the microparticles and reduced uncontrolled drug burst release. Electron microscopy showed that this slower manufacturing procedure generated nonporous particles whereas thermal analysis and X‐ray diffractometry showed that drug loading above the solubility limit of the drug in the polymer generated excess crystalline drug on the surface of the particles. Raman spectral mapping illustrated that drug was homogeneously distributed as a solid solution in the particles when loaded below saturation in the polymer with consequently minimal burst release.
Conclusions  Both the manufacturing method (which influenced particle porosity and density) and drug:polymer compatibility and loading (which affected drug form and distribution) were responsible for burst release seen from our particles