| Objective To study the preparation, quality control and to evaluat the physicaland chemical stability of compound vitamin A acid cream so as to provide the basis ofapplying a new preparation with better stability and effect for dermatology department.Methods Compound vitamin A acid cream was consisted of three kinds ofeffective components, vitamin A acid, allantoin and vitamin E. The cream was preparedby using the method of emulsion process according to the requirments of O/W typecream preparing standard. The three components were qualitatively identified by usingUV scanning spectrum, thin-layer chromatography (TLC) and chemical coloration ways.Reverse phase HPLC method was used to determine three components in cream.Moreover, the major component vitamin A acid and its degradation product iso-vitaminA acid were simultaneously analyzed quantitatively by the external standard method.The assaying was conducted on a ODS syncronis C18chromatographic column at35℃under a gradient elution progress containing methanol and0.5%glacial acetic acidaqueous solution. As stipulated in the pharmacopoeia, compound vitamin A acid creamwas investigated about the stability under centrifugation, hot and cold condition,especially the chemical stability including wet stability, light stability and thermalstability of accelerated test at constant temperature. In the constant temperatureaccelerated test, data was plotted by C against t, log C against t and1/C against t (C isfor drug content), respectively. The degradation kinetics (order of reaction) could bedetermined by the the correlation coefficient r of the regression equation. At fourdifferent temperatures (40℃,60℃,80℃,100℃) under dark conditions, the sampleswere collected and analyzed at different time. Then the reaction rate constants (K1, K2, K3, K4) at different temperature could be obtained. According to the Arrhenius equation,the activation energy E and t0.9at25℃could be calculated in order to compare thestability among three components of compound vitamin A acid cream. The differentialstability between the compound and simple recipe was compared by using the singlevitamin A acid cream to be as the control, aiming at to determine the validity andpreservation conditions of the compound cream.Results1、The products of this study can satisfy the preparation requirementsabout cream in the Chinese pharmacopoeia2010edition. The appearance of theprepared compound cream is good, and the drug was distributed homogeneously andexquisitely in the matrix. No separation could be seen under the condition of3000RPMcentrifugation, at low temperature of15℃and at hightemperature of55℃.2、 In the uv spectrophotometry scanning of vitamin A acid, the maximum absorptionwavelengths was found to be345nm.VA acid was analyzed in TLC method with silicagel GF254board, and cyclohexane, chloroform, methanol, formic acid (20:9:4:1) wereused as developing agents, the positions and color of the main spots were inconcordance of the reference substance, and the Rf value is0.43, which is valid. HPLCmethod was used to quantitatively determine the major component and its degradationproducts of the compound cream. The maximum absorption wavelengths were226nm,224nm and345nm for allantoin, vitamin A acid and vitamin E, respectively. Theinvestigation of column temperature showed that with the increase of columntemperature, the retention time was gradually shortened. However, at40℃, theseparation ratio between vitamin A acid and iso-vitamin A acid was obviously declined,therefore, we chose35℃as the best column temperature.Methodology verificationshowed that this method can be specifically analyzed the three kinds of main drug,without the interference by cream matrix, and the baseline separation could be procuredbetween vitamin A acid and iso-vitamin A acid. The linear relationship of thecomponent to be measured was good, the intra-and inter-day precisions were all lessthan2%, the recoveries of allantoin, vitamin A acid, iso-vitamin A acid and vitamin E were98.5%,99.2%,98.7%and99.8%, respectively. All the results could meet thestandards requirements of pharmacopoeia of2010edition.3、Centrifugation, heat-resistant and coldness-resistant experiments showed that thecompound cream had a good physical stability. The preparations had no obviousdelamination, discoloration and oil-water separation phenomenon. But after theilluminance under4500lx for5d and10d, the content of vitamin A acid of thecompound cream was significantly decreased by15%and30%, and the degradationpercent of single recipe was20%and37%, respectively. In the determination ofreaction order, r value of the linear regression of logC against t was the biggest, whichmeant that the three kinds of components exhibited first-order kinetics of degradation.According to the constant temperature accelerated test, t0.9of allantoin, vitamin E andvitamin A acid in the compound cream was476d,482d and370d, respectively, whilethe t0.9for single recipe was only253d.Conclusion Compound vitamin A acid O/W cream preparation consistents withthe quality control2th item of cream preparation of "Chinese Pharmacopoeia"2010edition. The physical stability is good. The three component degradation correspondsfirst-order kinetics, in which vitamin A acid is the most unstable. In addition, it is easyto be degradated (isomerization) by light. However, the stability of dimension A acidhas been greatly improved than that of its unilateral one after it participates the composeof compound preparation,... |
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