普萘洛尔鼻用制剂的纤毛毒性

CILIOTOXICITY OF PROPRANOLOL PREPARATIONS FOR INTRANASAL ADMINISTRATION

目的：筛选一种合适的剂型以降低鼻用制剂的鼻纤毛毒性。方法：以盐酸普萘洛尔为模型药物，分别制备微球剂、复合乳剂和环糊精包合物。以在体蟾蜍上腭粘膜纤毛为动物模型，评价上述鼻用制剂对盐酸普萘洛尔纤毛毒性的改善作用。结果：微球剂能有效地降低盐酸普萘洛尔的纤毛毒性；复合乳剂因包裹率较低，而环糊精因与药物的结合常数较小，使这２种制剂对纤毛毒性均无明显的改善作用。结论：微球剂是降低药物鼻纤毛毒性的一种较为理想的剂型，机理主要是它的缓释作用。

AIM: To screen a suitable dosage form for reducing ciliotoxicity of intranasal preparations. METHODS: Propranolol hydrochloride (PRO) was selected as a model drug and microspheres, multipleemulsions and cyclodextrin inclusions for intranasal administration were prepared. The effect of the above preparations on ciliary movement was evaluated with in situ toad palate model. RESULTS: The microspheres were shown to be able to reduce the ciliotoxicity of PRO, but multipleemulsions and cyclodextrin inclusions in this research were found to be inefficient because the embedding rate of the multipleemulsions was low and the binding constant between PRO and cyclodextrin was small. CONCLUSION: The microspheres are an ideal dosage form for reducing ciliotoxicity and the involved mechanism is the sustained release effect of the microspheres.