The present investigation concerns the experimental design in preparing a solid dispersion of ionized carvedilol with hydroxypropyl-β-cyclodextrin (HPβCD), tartaric acid (TA) by adopting ‘kneading technique’. Simplex lattice design has been chosen to develop model equations that correlate the process variables such as HPβCD (mg), TA (mg), and kneading time (min) with the response variables, such as solubility (mg/mL) and drug release (%) from the solid dispersion. Software-generated ANOVA results confirmed the sufficiency of model equations. Results predicted by model equations are in good agreement with that of experimental results. Optimized formulation with variables ‘CV: HPβCD: TA-kneading time’ (200mg: 689.6mg: 227.6mg-45 min) showed complete drug release (~99%) within 15 min and enhanced solubility of 1.89mg/mL. The instrumental analysis (DSC, XRD& FTIR) of the optimized solid dispersion suggests a transformation of crystallinity of drug to amorphous form, due to its complexation with HPβCD. Hence, this combination of drug and carriers suggests an improvement of carvedilol bioavailability.