Co-Amorphization of Ibuprofen by Paracetamol for Improved Processability, Solubility, and In vitro Dissolution

Co-amorphous (COAM) systems of ibuprofen (IB) and paracetamol (PA), in clinical dose ratios, were prepared by ball milling to enhance solubility and dissolution of IB. Subsequently, COAM were characterized by solubility, processability, XRPD, DSC, ATR-FTIR, SEM, in-vitro dissolution and accelerated stability studies. Maximum increase in aqueous solubility of IB was seen in 500:200 mg dose ratio (COAM 1) with 6.7 fold rise from 78.3 ± 1.1 to 522.6 ± 1.29 ∆g/ml. COAM 1 exhibited 99.80 ± 0.58% dissolution of IB at 20 min in phosphate buffer, significantly high (P < 0.05) compared to plain IB. Thus saturation solubility and dissolution rate of IB was found significantly improved unlike PA. The flowability/ processability of COAM system was remarkably improved compared to pure IB, speculated due to as formation of miniscular forms of PA-IB, having strong adhesive interactions. XRPD and DSC results confirmed amorphization of IB. ATR-FTIR results evidenced hydrogen bonding interactions between both the drugs. In accelerated stability studies, flowability, XRPD, DSC and in-vitro dissolution studies demonstrated insignificant changes, thus confirming successful stabilisation of IB by PA.