L Phencynonate Hydrochloride Nasal Spray

To prepare a phencynonate hydrochloride nasal spray with high bioavailability, fast onset and low or without toxicity.First, the solubility of phencynonate hydrochloride were determined. Then, the influence of pH on the stability of phencynonate hydrochloride, were studied. Then isolated sheep nasal mucous was employed to evaluate the influence of kinds of cyclodextrin and its devations on the model drug permeation in vitro."toad palate mucoas method"was used to assay the ciliotoxicity of the drug and the effect by adding cyclodextrin or its devations. And mucous membrane irritation test of rats was carry out by studing the structural and specific cellular changes of nasal mucosa after administered the spray. Technique process study was made and a quality specification protocol of phencynonate hydrochloride nasal spray was developed. In the research of formulation stability, the package and storage condition were investigated as well. Finally, in vivo study was carried out with beagle dogs to make pharmacokinetics and bioavailability research on the phencynonate hydrochloride nasal spray.Results: The solubility of phencynonate hydrochloride was above 10mg·mL-1 at acid or neutral condition. The phencynonate hydrochloride nasal spray was stable in a pH range from 4.0 to 5.5. The results of transmucoas absorption test and ex vivo toad palate mucosa study showed that a nice enhanced penetration effect was reached with low ciliotoxicity and protection to nasal mucosa by adding cyclodextrin or its derivate s. The influence of the spray on cilia structural and specific cellular changes of nasal mucosa also showed the ciliotoxicity of the formulation was low and reversible.Cyclodextrin C can also depress the antisepsis efficacy of chlorbutanol above the concentration 2.5%. The established formulation and technique process were confirmed by the quality study of three repeated batches with promising results. Long term storage study under ambient temperature showed that the nasal spray was very stable. The results of pharmacokinetic study indicated that nasal spray fit with two compartment model in vivo with Tmax (12.5±2.74)min, about 5 times higher than that of conventional tablets; Cmax (10.00±3.66)ng·mL-1, around 4 folds than that of conventional tablets; the relative bioavailability was (231±79)% compared with conventional tablets.Conclusion: The phencynonate hydrochloride nasal spray developed in this study was confirmed with coherent formulation, controllable quality, repeatable technique process, good stability, little ciliotoxicity, quick absorption and higher relative bioavailability etc,which basically met the aim and requirements of this study.