| Summary: | This work was done to investigate succinylated commercial whey protein isolate (S-WPI) as an oral sustained-release delivery carrier for puerarin 5 (PR-5). The succinylation conditions were established for S-WPIs by optimization of single factor study and Box–Beehnken design. The effect of succinylation degree on S-WPIs solubility was evaluated. Physicochemical properties of S-WPIs dried by different three methods on their flow ability, particle size, morphology and in vitro release behavior were studied. After preparing PR-5 sustained release protein tablets with S-WPIs as the carrier by direct powder compression method, the drug release were studied in vitro and the oral pharmacokinetics and bioavailability was evaluated using in vivo dog model. It was observed that concentration of substrate has a significant effect on succinylation. Release behavior in vitro showed spry dried S-WPIs with 100% succinylation rate and 30% drug loading would be applied to the preparation of PR-5 sustained-release protein tablets based on the swelling mechanism (protein loss). Compared with PR-5 conventional tablet with oral administration, Tmax value of PR-5 sustained-release protein tablets was approximately 1.58 fold greater than those of the conventional tablets as further evidenced by the significantly prolonged MRT and T1/2. The findings demonstrated that spray-dried S-WPIs has potential as a promising functional excipient for the design of PR-5 oral sustained-release tablets which can fully improve sustained-release effect and oral bioavailability. Keywords: Whey protein isolate, Succinylation, Puerarin 5, Sustained drug delivery, Pharmacokinetics
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