| Diphenidol hydrochloride is one of the commonly used drugs for the treatment of vertigo,with weakened vestibular stimulation,inhibition of labyrinthine,inhibition of nausea and vomiting in the medullary chemoreceptive trigger zone,and improve the vertebral arteries blood flow and other pharmacological characteristics.Diphenidol also possesses a weak peripheral antimuscarinic action.It is widely used for antivertigo and antiemetic,mainly used for motion sickness or vertigo associated with middle ear and inner ear disturbance.It’s also applied to the treatment of nausea and vomiting caused by antineoplastic drugs,anesthesia,and radiotherapy.Currently,there are diphenidol hydrochloride tablets on sale and proved to be effective.But because of it’s short biological half-life,about 3-4 hours,they are needed to be taken three times per day in order to maintain therapeutic concentration.The frequent administration not only results in decreased patient’s compliance,but also makes the blood concentration "peak" wave.In this study,diphenidol hydrochloride was selected as a model drug to prepare monolithic osmotic pump tablets(MOPT)and push-pull osmotic pump tablets(PPOP),the preparation process and in-vitro drug release behavior of the two were studied.Besides,the optimization of the prescription and stability of diphenidol hydrochloride push-pull osmotic pump tablets were studied.In this study,sodium chloride(NaCl)and different molecular weight polyethylene oxide(PEO)were selected as the main material of the core sheet while polyethylene glycol(PEG)and cellulose acetate(CA)were used as the coating materials and acetone was served as organic coating solvent to prepare PPOP.The f2 similarity factor method recommended by FDA was used as the evaluation index of release to investigate the influence of different aspects in-vitro release from core formulation,coating formulation and the drug in-vitro release condition.According to the single-factor study,we selected three influential factors which affected the 12h in-vitro cumulative release rate(Y1)and the release curve lineanty(Y2):dosage of PEO(factor A)in push-pull layer and the dosage of NaCl(factor B)in drug layer and the weight of coating film(factor C).We took the above three factors as the dependent variable,the 12h in-vitro cumulative release rate and the release curve lineanty as independent variables,using Box-Behnken Design-Response Surface Methodology(BBD-RSM)with three factors three levels in optimization experiments.After verified,the results show that the measured values and the predicted values were basically same with a small deviation.The optimized prescription of homemade diphenidol hydrochloride osmotic pump tablets meet zero-order model(r=0.9901)with good reproducibility.In addition,the diphenidol hydrochloride monolithic osmotic pump tablets were also investigated.The effects of drug loading,osmotic pressure accelerating agent,coating film thickness on the drug release were studied.At last,the stability of homemade diphenidol hydrochloride osmotic pump tablets was investigated.The results of influencing factor test show that the products were not stable and something like grume effused from the drug hole when exposed on conditions of relative humidity of 92.5%for 10 days,while stable when exposed on conditions of 60 ℃ or 4500Lx illumination for 10days.The results indicated that the samples were sensitive to humidity thus the sealing and moisture proof should be paid attention when choosing the packing materials.The Accelerated testing results showed that:under the condition of 40 ℃,relative humidity of 75%,three batch samples simulated the listed packaging for an accelerated test,the examining indexes showed no obvious changes within 3 months,the follow-up testing is in progress.The Long-term testing results showed that:under the condition of 25℃,relative humidity 60%,three batch samples simulated the listed packaging for a long test,the examining indexes showed no obvious changes within 3 months,the follow-up testing is in progress. |
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