| ObjectiveTopical preparation is an important way for drug delivery to therapy skin disease with the prerequisite that drug must permeate skin to reach the action site. But drug transdermal delivery is affected by multiple factors such as skin barriers, drug physical and chemical properties, pharmaceutical preparations, etc. Among these Pharmaceutical preparations is especially important for its directly related with the existing state of drugs, clinical use and compliance.In this article, compound diphenhydramine preparation was chosen as a model to investigate the relationship between two aspects of drug transdermal delivery and pharmacodynamics/ pharmaceutical preparation by in vitro transdermal permeation and pharmacodynamics research on liniment and cream. This could provide consult and guidance for pharmaceutical preparation selection and reformation of compound preparation, moreover, provide experimental basis for formula rationale.Method and Result1. Excised nude mice skin permeation of drug in cream and linimentThe penetrating experiments were performed by using nude mice skins,which were placed in a modified Franz diffusion cell.The acceptor fluid was 20% ethanol solution, Accumulated permeation amount per Unit area (Q) has been adopted as evaluating indicator. Transdermal permeations of 4 kinds of active components in cream(T1)/liminent(T2) were evaluated. Every component permeation acceptor fluid was taken from 0 to 8 h. Diphenhydramine hydrochloride (BH) and Benzocaine(BZ) in receptor solution were determined by HPLC-UV and MT and CP were determined by GC.Accumulated permeation amount per Unit area 8 h for mice skin(Q8h) of 4 various of components in T1 was benificial for drug to permeate than T2(P<0.05) which suggested that cream facilitated drug transdermal permeation. In the limiment, permeation of BZ and CP were mainly focused on the first 2h and Q0.5h and Q1.0h of two components were obviously higher than that in cream. But the diversity decreased gradually after 1h and achieved the same accumulated amount as cream after 2h(Q2h). Permeation of BH and MT were mainly focused on the first 3h, and Q of 2 components in the first 2h were all significantly higher than cream, but the diversity gradually decreased after 2h. Q of liniment hardly increased any more after 3h, and as drug permeation of 4 components in cream increased continuously within 8h that Q8h of every kind was equally as 1.6 times (BH, BZ),1.8 times(MT) and 2.6 times(CP) as liniment respectively. The result suggested that liniment had fast effect but could not last long, and cream played more lasting effecacy than liniment.2. Permeation of BH, BZ affected by MT, CP in creamExperiment and sample determination method was the same as 1, excised piglets skin was selected as a barrier to investigate the permeation of BH and BZ which were affect by MT and CP. The experiment were divided into normal cream group and cream group without MT and CP.Results showed that in normal cream group, Q8h of BZ was lower than that in cream group without MT and CP (P<0.05), lagging time (T1ag) of BZ had been prolonged(P<0.05) which suggested that except for pharmacological activite in pharmaceutical preparation, MT and CP could also modulate the other two other components transdermal permeation but not the meaning formally mentioned. restrain to BZ permeation may facilitate drug exert topo-therapeutic effect and this may be the basis of the compound preparation.3. Pharmacodynamics experimentCompared with normal saline as control group(R group), study the effect of compound diphenhydramine cream or liniment on carrageenan-induce hindpow oedema in rat and pain-induce by heat stimulation in mice, anti-inflammatory and analgesia effect were investigated. preliminarily for compound diphenhydramine cream (T1) and liniment (T2). Results showed that T1 group and T2 group could restrain rat hind paw oedema caused by carrageenan(P<0.01) and significantly prolong reaction time of mice pain threshold by heat stimulation. (P< 0.01).As to restraining rat hind paw oedema caused by carrageenan (inflammation), there was significant difference between T1 group and T2 group, effect of cream restraining carrageenan-induce hind paw oedema in rats (inflammation) was longer than that of linment(P<0.05), and effect of restraining pain reaction by heat stimulation in mice was significantly enhanced than liniment(P<0.05).ConclusionIt was confirmed from transdermal permeation and pharmacodynamic experiment of compound diphenhydramine preparation that in vitro transdermal permeation and pharmacodynamics could be affected by pharmaceutical preparation. Speed and duration time of drug effect in topical preparation is related with the pharmaceutical preparation. MT and CP can restrain to BH and BZ transdermal permeation The method and conclusion of this research in the article provided novel idea for compound of topical preparation, selection of dosage form and evaluation. |
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