Drug-loaded casein beads: influence of different metal-types as cross-linkers and oleic acid as a plasticizer on some properties of the beads

The influence of metal cross-linking and plasticization on some properties of drug-loaded casein (CS) beads was evaluated. Different metals (Ca+ 2, Zn+ 2 and Fe+ 3) as cross-linkers, oleic acid (OA) as a plasticizer, and paracetamol (PC) as a model drug for encapsulation were used. Three different mixtures, having the same concentrations of PC and CS (2 CS:1 PC w/w ratio) and different OA concentrations at OA: CS w/w ratios of 0,15, and 33%, were prepared. Each mixture was dropped into three different aqueous media (1 M HCl) having 5% of CaCl2, ZnCl2 or FeCl3. The dried formed beads were characterized for size, drug-loading and surface morphology. In addition, drug-release from the beads in 0.1 M HCl (pH 1.2) followed by in phosphate buffer (pH 6.8) was studied. No significant effect for metal-type or OA concentration on bead size or drug-loading was found. However, apparent effects for metal-type and OA concentration on surface morphology were observed. In the absence of OA, the beads showed cracking and surface drug-crystallization, both were metal-type dependent. Inclusion of OA in the beads was found to reduce both bead cracking and surface drug-crystallization. Sustained drug-release pattern in 0.1 M HCl was obtained from the different cross-linked beads, with no significant effect for the type of metal or OA concentration. However, upon acidic soaking, all CS-Ca+ 2 and CS-Zn+ 2 beads showed rapid drug-release in the buffer medium. In contrast, CS-Fe+ 3 beads, particularly those plasticized with OA, maintained the slow drug-release in the same medium.