QUALITY-BY-DESIGN APPROACH FOR DEVELOPMENT AND OPTIMIZATION OF NEFOPAM HYDROCHLORIDE LOADED POLY-(ε-CAPROLACTONE) AND POLY-3-HYDROXYBUTYRATE MICROSPHERESAbstract
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® 126.96.36.199 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.
N. Sharma*, S. Singh, S. Arora and J. Madan
Chitkara College of Pharmacy, Chitkara University, Patiala, Punjab, India.
03 April, 2017
17 June, 2017
29 June, 2017
01 December, 2017