Pectin microparticles for peptide delivery: Optimization of spray drying processing

Spray-dried pectin microparticles can potentially improve the oral bioavailability of peptides by virtue of their mucoadhesion. However, developing such formulations with desirable quality attributes is challenging due to the sensitivity of microparticle critical quality attributes towards changes in spray drying processing parameters. In this study, a central composite design approach was applied to investigate the influence of input temperature, aspirator rate, feed flow rate, polymer concentration and polymer feed weight on the yield and particle size of pectin microparticles prepared via spray drying. A mathematical model for the prediction of yield was statistically significant with good predictability. A maximum yield of 72.2% was achieved through optimizing the spray drying conditions. The particle size remained in a relatively narrow range (D50, 2.16-3.67 mu m), and therefore was considered independent of the factors investigated. The model for yield prediction was further validated using octreotide acetate as a representative peptide. The presence of octreotide acetate in the pectin microparticles increased their surface roughness and decreased their melting enthalpy. In addition, it was determined that pectin with a high degree of esterification (72%, AU201) resulted in faster drug release compared to pectin with a lower degree of esterification (62%, CU401). Interestingly, the degree of esterification did not impact microparticle particle size, morphology or thermal properties. This study demonstrates the importance of DoE in optimization of the spray drying process for the development of pectin-based peptide microparticles. This is the first report using spray-dried pectin-based microparticles for octreotide delivery. The yield prediction model achieved using a central composite design may also be helpful for formulation development of similar drug products.

Automated summary

This study utilized a central composite design approach to investigate the sensitivity of yield and particle size of spray-dried pectin microparticles towards different input parameters. By optimizing the spray drying conditions, a maximum yield was achieved with relatively consistent particle size range. The yield prediction model was validated using octreotide acetate as a representative peptide, showing changes in surface roughness and melting enthalpy of pectin microparticles.