Feeding liquid, non-ionic surfactant and cyclodextrin affect the properties of insulin-loaded poly(lactide-co-glycolide) microspheres prepared by spray-drying

The potential of spray-drying technique for the encapsulation in poly(lactide-co-glycolide) (PLGA) microspheres of bovine insulin, a poorly stable peptide, has been investigated. Insulin-loaded microspheres were prepared by spray-drying different feeding liquids containing insulin and PLGA, that is a S/O dispersion, a W/O emulsion or an acetic acid solution. In the case of the emulsion, insulin was also co-encapsulated with either non-ionic surfactants such as polysorbate 20 and poloxamer 188, or complexing agents such as HPbetaCD. In the microspheres prepared from the acetic acid solution of insulin and PLGA, HPbetaCD was tested. Microspheres containing surfactants were aggregated, whereas good quality particles displaying a mean diameter in the range 12.1-27.9 mum were produced in the other cases. Insulin was efficiently loaded inside microspheres except for S/O formulation (only 22% of total insulin content was entrapped). The impact of the microencapsulation process on insulin chemical and conformational stability was assessed by HPLC, circular dichroism and turbidimetry studies. Under the adopted manufacture conditions, insulin was encapsulated in the native state and its chemical and conformational stability was preserved along the fabrication process. The formulations containing only insulin displayed low burst effects (6-11%), whereas the addition of surfactants resulted in much higher burst effects (49-54%) and faster release rate. The co-encapsulation of HPbetaCD slowed down the overall release rate and, in the case of microspheres prepared from the emulsion, allowed a constant insulin release up to 45 days. The study of insulin stability along the release phase showed that insulin was released in the intact form and un-released insulin was stable inside all the microsphere formulations. We conclude that insulin can be effectively encapsulated in PLGA microspheres by the spray-drying technique. Additives with complexing properties such as HPbetaCD have demonstrated a potential in optimizing the release rate of insulin when used in microspheres prepared from W/O emulsions. (C) 2002 Elsevier Science B.V. All rights reserved.