Solubility has always been a challenge for the pharmaceutical fraternity owing to the dependency of bioavailability on the same. The objective of the current work was to improve the aqueous solubility of a BCS class II anti-retroviral drug, ritonavir, by using melt technology via the Pastillation technique. EUDRAGIT ® EPO was chosen as representative of amorphous high molecular weight synthetic functional polymers. Ritonavir with EUDRAGIT ® EPO and other plasticization aid was processed using the melt technique to fabricate ritonavir-loaded pastilles by using an in-house Pastillation device. The ratio of the ingredients was studied using the DOE approach where the quantities of drug, polymer, and plasticizer were studied as independent variables, and dissolution time and processability were studied as responses. The optimized pastilles were further subjected to physicochemical analysis, morphological characterization, in-vitro drug release, and in-vivo pharmacokinetic studies in Wistar rats. It was observed that the optimized pastilles had excellent processability, good physical properties, and an improved dissolution rate compared to the marketed tablets. The improved dissolution was supported by the DSC and XRD data which showed the amorphous conversion of the drug, thus improving solubility in the aqueous medium. In-vivo pharmacokinetic evaluation in rats resulted in an improved bioavailability of the drug from the pastilles compared to the marketed tablets. It is believed that a simple and economic technique such as Pastillation can be efficiently used with high molecular weight synthetic functional polymers to improve the drug solubility thereby improving the bioavailability of the drug, which is a major problem in the pharmaceutical industry.