The Parmaceutical Research Of The Sustained-release Patch Of Phencynonate Hydrochloride

Phencynonate hydrochloride is a kind of new central anticholinergic drugs developed by the institute of pharmacology and toxicology,academy of military medical sciences in China.It can has effectively been shown to relieve the subjective symptoms of nausea and vomiting which caused by motion sickness.It also can achieve strong pharmacological effects and few side reactions.At present,there are phencynonate hydrochloride tablets(trade name:Feisaile)on sale and proved to be available.Because of its biological half-life,short action time and frequent administration,it need to be taken every 4-5h for long-distance travel of patients with motion sickness in order to maintain therapeutic concentration.After administration of gastrointestinal reactions and fluctuations in serum concentration are more common reaction.Compared with the traditional drug delivery system,percutaneous absorption preparation can produce a lasting and controllable blood concentration,thereby reducing adverse reactions,avoiding the liver first-pass effect.Patients can self-medication,remove the drug timely when problem occurs.It is convenient to use.Based on the physicochemical properties of phencynonate hydrochloride and the functional characteristics of sustained-release patch,we have preliminarily designed the formulation of the sustained-release patch of phencynonate hydrochloride.In this study,phencynonate hydrochloride was selected as model drug to prepare the sustained-release patch ofphencynonate hydrochloride with the different types of acrylic pressure sensitive adhesive as matrix.Besides,the formula optimization,quality control and stability of the sustained-release patch were studied.1.The HPLC method was established to determine the release degree and infiltration of the sustained-release patch of phencynonate hydrochloride and to evaluate its in-vitro release and the transdermal permeation behavior.The method is shown to be accurate and sensitive,and it can be used to screen the formulation of the phencynonate hydrochloride transdermal patch.2.The present investigation was focused to ensure that the appropriate preparation process was screened on the processing parameters of drying temperature and time,mixing speed and time,and the thickness of the drug-contained adhesive layer.The technological parameters showed that the mixing speed of drug-contained glue was 120r·min-1 the mixing time was 1h,the drying temperature was 40℃,the drying time was 10min and the thickness of the drug-containing adhesive layer was 0.4mm.3.Cumulative penetration amounts in unit area(Q)and steady penetration rate(Jss)were taken as observed indexes.The three important factors of the prescription composition such as drug dosage(A)azone(B),and acrylic pressure sensitive adhesive(C)on transcutaneous permeation of the self-prepared patches were investigated using single-factor to obtain an optimal formula.Based on this three factors,by the Box-Behnken design-response surface method,the formulation was optimized.The optimal prescriptions were A=263mg,B=165mg,C=1.94g,and the prescription was validated.The result patches had a higher higher penetration amount.The penetration amounts were(119.48 ±2.95)μg/cm2 at 48 h and by prediction showed the deviation was 2.48%.The application of Box-Behnken design-response surface method in the sustained-release patch of phencynonate hydrochloride had good predictability and the optimal formulation was reasonable.4.According to the principles referring testing to the drug stability in the Chinese Pharmacopoeia(Edition 2015),the stress of high temperature(60 ℃),high humidity(RH90± 5%),light(4500lx)and accelerated stability test(40±2 ℃,RH75 ±5%)were carried out.The stability of the sustained-release patch of phencynonate hydrochloride was determined.To assess the factors that impact the characteristics,adhesion force,content,and the accumulated infiltration amount of the patch.The results showed that the characteristics,adhesion force,content,and the accumulated infiltration in unit area amount of the self-prepared patches under the condition of without external packaging were significantly changed when they were exposed to high temperature,high humidity and high light.accelerated stability test conditions at 3 months,the characteristics and adhesion force did not change too much,but the content and accumulated infiltration in unit area changed dramatically.There were indications that the temperature and humidity were the main factor affecting the stability of the patches.