Preparation of isosorbide dinitrate tablets and in vitro and in vivo evaluation

WANG Nan; LI Zheng-zhao; JIA Jun-wei; FENG Zhong

doi:10.20251/j.cnki.1003-3734.2025.08.012

Abstract：Objective:To prepare isosorbide dinitrate tablets and determine its dissolution curve in vitro,optimize the formulation,conduct evaluate in vitro and in vivo,and investigate its pharmacokinetics in rats.Methods:The dissolution of isosorbide dinitrate tablets was determined by Box-Behnken method to optimize the proportions of the main excipients,magnesium distearate cellulose PH 102 and polyvidone K30 in isosorbide dinitrate tablets,and the dry granulation process was used.The effects of the proportion of raw materials,the pore size of the whole sieve,the pressure of the press roller,and the rotating speed of the screw feed on the dissolution in vitro were investigated.Results:The optimized formulation was as follows:carboxymethyl starch sodium 9.23％,magnesium distearate 1.02％,and cross-linked povidone 4.74％,and the cumulative release rate within 10 min was 91.13％.The optimized process was as follows:the proportion of raw material was isosorbide dinitrate lactose 4∶6,the size of the whole sieve mesh was 1.0 mm,the oil pressure of the roller was 130 bar,and the rotational speed of the screw feed was 50 r·min-1.The permeation rates of the self-developed tablets and the original preparation were 0.020 6 and 0.019 5 μg·mL-1·min-1,respectively.The membrane permeation rates were 2.23 × 10-4 and 2.09 × 10-4 cm·s-1,respectively.The confidence interval of the self-developed tablets was 99.58％～109.29％.The pharmacokinetic parameters of the two preparations had no statistical difference(P＞0.05),the relative bioavailability of homemade preparations 2-ISDN was 106.16％,that of 5-ISDN was 102.62％,while that of ISDN was 110.58％,all equivalent to the reference preparation.Conclusion:The preparation process of isosorbide dinitrate tablets established in this paper is feasible and stable,and the products are bioequivalent to the reference preparation.