Development of Pharmaceutical Additives-Evaluation of Protein and Polysaccharide Hydrolysates as Carrier to Enhance Absorption Rate of Drug

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Protein and polysaccharides such as water-soluble gelatin, egg albumin, casein hydrolysate, low molecular chitosan and alginate are the preferred carriers of drugs in various pharmaceutical formulations. However, improvents of the dissolution and absorption of drugs using natural polymers have been not fully studied. Thus, the present study was undertaken to investigate the possible use of natural polymers such as casein hydrolysate, egg albumin as solubilizing agents to improve the absorption of poorly water soluble drugs. The results obtained here are summarized as follows :1)Two types of fragmented keratin (FKs) were prepared from buffalo horn and hoof using savinase and Na_2S,and their physicochemical and biopharmaceutical properties were examined in mice. The systematic acute toxicity of FKs was significantly lower than that of superoxide dismutase. In plasma, enzymatically fragmented keratin was hydrolyzed slowly, but in liver and kidney homogenates it showed slightly faster hydr … More olysis. In contrast, fragmented gelatin was not hydrolyzed in any of the media used here.2)The solubility of dl-a-tocopherol (VE) was increased by 300-fold in the presence of egg albumin. The apparent dissolution rate of VE from solid dispersion with egg albumin was markedly enhanced in comparison with VE alone. The mean serum levels of VE following oral administration of egg albumin solid dispersions, especially egg albumin solid dispersion containing myristic acid, were significantly higher than those of the drug alone.3)Two types of casein hydrolysates, casein A (mean peptide length 3.3) and casein B (mean peptide length 17.4) were prepared by the enzymatic hydrolysis of casein, and their effects on in vitro dissolution rates and oral bioavailability of drugs were evaluated. The in vitro dissolution behavior of the kneaded mixture of three drugs (diclofenac acid, diazepam, and prednisolone) with caseins A and B were significantly improved compared to the drugs alone. The plasma concentration-time profile showed that prednisolone was completely and rapidly absorbed from the casein A kneaded mixture as well as the prednisolone solution. In addition, prednisolone in the kneaded mixture with casein B was more difficult to absorb up to 1 hr after administration in comparison to prednisolone powder. Less