QUALITY-BY-DESIGN APPROACH FOR DEVELOPMENT AND OPTIMIZATION OF NEFOPAM HYDROCHLORIDE LOADED POLY-(ε-CAPROLACTONE) AND POLY-3-HYDROXYBUTYRATE MICROSPHERES

The objective of present study was to investigate optimized nefopam hydrochloride loaded microspheres (NPH-MS) by investigating the relationship between independent and dependent variables using response surface methodology. Central composite design with thirty three batches was constructed using drug: polymer (X₁), PHB: PCL (X₂), stirring speed (X₃), stirring time (X₄) and polyvinyl alcohol (PVA) (X₅) level as independent factors. NPH-MS were manufactured using polyhydroxybutyrate (PHB) and poly ε-caprolactone (PCL) by double emulsion solvent evaporation technique. The response variables were % entrapment efficiency (Y₁), mean diameter (Y₂), % drug loading (Y₃), and % yield (Y₄). Second-order polynomial equations for (Y₁-Y₄) were developed by Design-expert® 9.0.5.1 software. Positive and negative signs of regression coefficient indicated synergistic and antagonistic effect on response variables, respectively. Optimized NPH-MS estimated by design-expert software have highest desirability function, D = 0.911 and X₁, X₂, X₃, X₄ and X₅ were 1: 2.86, 1:1.19, 1501 rpm, 2.98 h and 0.54 % w/v, respectively. The model predicted values of Y₁, Y₂, Y₃ and Y₄ for optimized NPH-MS were 83.80%, 100.78μm, 21.50% and 77.99% respectively. Check point batch analysis validated the authenticity of predictive power of designed model as % bias between experimental and model predicted values was < 5%. It was concluded that quality-by-design approach has great utility in formulation optimization.