Ohashi-Doi Katsuyo, Kito Hirokazu, Du Weibin, Nakazawa Hiroshi, Ipsen Henrik, Gudmann Pernille, Lund Kaare
Torii Pharmaceutical Co. Ltd., Tokyo, Japan.
Int Arch Allergy Immunol. 2017;174(1):26-34. doi: 10.1159/000479693. Epub 2017 Sep 27.
In sublingual immunotherapy (SLIT), the immune system is addressed by solubilized allergen that interacts with immunocompetent cells of the oral mucosa, the efficiency of which is governed by 2 main factors of SLIT allergen bioavailability: the allergen concentration and the mucosal contact time. Recently, 3 house dust mite (HDM) SLIT tablets were developed that differ with regard to allergen content, nominal strength (maintenance doses: 6 SQ-HDM/10,000 Japanese Allergen Units [JAU], 12 SQ-HDM/ 20,000 JAU, and 300 IR/57,000 JAU), and formulation (freeze-dried/compressed). Here, the importance of the SLIT tablet formulation for HDM major allergen bioavailability is examined.
The HDM major allergen content, tablet disintegration times, and allergen release kinetics were determined. Dissolution kinetics (allergen concentration vs. time) of Der f 1, Der p 1, and Der 2 were measured. Area under the curve (AUC) was used as a surrogate parameter for allergen bioavailability.
The release of HDM major allergens from the freeze-dried tablets was complete after 30 s, while only partial release was achieved with the compressed tablets, even after prolonged dissolution. At 1 min, i.e., the recommended sublingual holding time for the freeze-dried tablets, the allergen bioavailability (AUC) of the compressed 300 IR/57,000 JAU tablet was 4.7-fold (Der f 1), 10.8-fold (Der p 1), and 23.6-fold (Der 2) lower than that of the freeze-dried 12 SQ-HDM/20,000 JAU tablet and similar to (Der f 1) and 5.3-fold (Der p 1) and 12.5-fold (Der 2) lower than that of the freeze-dried 6 SQ-HDM/10,000 JAU tablet.
SLIT tablet allergen bioavailability depends highly on the tablet formulation. Only the fast-dissolving freeze-dried tablets provide maximal delivery of soluble allergens and achieve allergen concentrations that reflect the nominal tablet strengths within the recommended sublingual holding time.
在舌下免疫疗法（SLIT）中，免疫系统通过与口腔黏膜免疫活性细胞相互作用的可溶性变应原得以调节，其疗效受SLIT变应原生物利用度的两个主要因素支配：变应原浓度和黏膜接触时间。最近，研发出了3种屋尘螨（HDM）舌下免疫片，它们在变应原含量、标称强度（维持剂量：6 SQ-HDM/10,000日本变应原单位[JAU]、12 SQ-HDM/20,000 JAU和300 IR/57,000 JAU）及制剂（冻干/压制）方面存在差异。在此，对HDM主要变应原生物利用度的SLIT片制剂的重要性进行了研究。
测定HDM主要变应原含量、片剂崩解时间及变应原释放动力学。测量了Der f 1、Der p 1和Der 2的溶解动力学（变应原浓度与时间关系）。曲线下面积（AUC）用作变应原生物利用度的替代参数。
冻干片在30秒后HDM主要变应原完全释放，而压制片即使经过长时间溶解也仅部分释放。在1分钟时，即冻干片推荐的舌下含服时间，300 IR/57,000 JAU压制片的变应原生物利用度（AUC）比12 SQ-HDM/20,000 JAU冻干片低4.7倍（Der f 1）、10.8倍（Der p 1）和23.6倍（Der 2），与6 SQ-HDM/10,000 JAU冻干片相比，Der f 1相似，Der p 1低5.3倍，Der p 2低12.5倍。
SLIT片变应原生物利用度高度依赖于片剂制剂。只有速溶冻干片能提供可溶性变应原的最大递送量，并在推荐的舌下含服时间内达到反映标称片剂强度地变应原浓度。
