- 期刊
The Effects of the Finite Dissolution Rate on the Drug Release of Spherical Particles Loaded with Uniformly Dispersed Drugs
負載均勻分散藥物之球狀顆粒之有限溶解速率藥物釋放效應分析
摘要
傳統上用於描述非澎潤性、非基質侵蝕性藥物負載微粒著名的Higuchi藥物釋放模型，忽略藥物有限溶解速率之效應，假設微粒內之藥物以耗盡層由外而內推移之型態釋放，後續雖有諸多釋放理論提出以修正Higuchi模型之不中，惟這些理論同樣多未考慮藥物在微粒中有限溶解速率可能造成的影響。本研究針對此提出， 一考慮了藥物有限溶解速率因素，應用較為廣泛的藥物釋放理論模型。本模型數值解之正確之正確性可經由短時間之解析解驗證。理論分析結果顯示在耗盡層移動與殘留藥量隨時間之變化情形，兩者皆呈現似正弦函數下降之關係。Higuchi模型受限於即溶之假設，僅在系統於擴散／溶解速率比值(B)低之情況下較適用。研究亦發現，盡管Higuchi模型作假穩態之近似橫批，然而即使藥物負載／溶解度(K)值低到1，其所預測之藥物釋放曲線仍與本模型之結果相近，此顯示當K值大時，Higuchi模型與本模型之差異主要來自藥物有限溶解速率之影響。
關鍵字
無資料並列摘要
Higuchi’s well known model, which has traditionally been applied to describe the release of non-swellable and non-erodible drug-loaded microspheres, neglects the effects of the finite drug dissolution rate and assumes that a depletion layer extending inward leaches drugs. Although many release models have amended Higuchi’s model, the effects of the finite dissolution rate are generally still ignored. This study takes the effects of the finite dissolution rate into account and proposes a more generalized drug release model. The numerical solution of the present generalized model was validated by its agreement with a short time analytical solution. The solution reveals that the dynamic curves showing the moving boundary of the depletion layer and the remaining drugs exhibit a sinusoidal shape of decrease with time. Results also indicate that due to the assumption of instantaneous dissolution, Higuchi’s model can be applied only when the ratio of diffusion rate/dissolution rate B is small. It is also found that in spite of the pseudo-steady state approximation, drug release curves predicted by Higuchi’s model for a drug loading ratio K as low as 1 are still close to the present results. This suggests that the significant difference between the present solution and Higuchi’s solution for a large K is mainly due to the effects of the finite dissolution rate.