| Dexibuprofen is the enantiomer of ibuprofen, whose name is 2-(4- isobutyl-phenyl)- propionic acid (C13H18O2). Comparing to ibuprofen, it has a stronger pharmacological activity, and also can avoid the adverse reactions and drug side effects caused by L-ibuprofen. At present, Dexibuprofen formulations include tablets and suppositories,which are widely used for clinical practice to cure rheumatoid arthritis, headache, fever and so on. Up to now, there isn't any formulations for external use in the market. Dexibuprofen gel is one kind of the transdermal delivery systems, which not only can maintain a stable plasma concentration with concentration range of effective treatment and increase the predictability of drugs in the body, but also can avoid first-pass effect of the oral drugs and make the drug go directly into the blood.Objective: The dexibuprofen gels with different pH values was prepared for prescription screening and preparation technology research of the gels. by comparing their rate of percutaneous absorption and the result of stability research, the best prescriptions and preparation technologies were determined. Also the impacts of dexibuprofen stability were clarified to solve the problems of gel stability. Then, the quality evaluation and stability research were finished. BTW, theoretical guidance and experimental evidence for other dexibuprofen formulations R & D were provided.Methods: For the first time, the compatibility tests and degradation research showed that pH value made an important role of dexibuprofen stability. Based on that, the orthogonal experiments were used to determine the prescription and preparation process of different dexibuprofen gels with pH values of 5.0±0.5, 6.0±0.5, 7.0±0.5. Then dexibuprofen gel with pH values of 4.72 ,5.62, 6.16, 6.86, 7.19 were prepared with the best prescriptions to study the percutaneous absorption action of gels, then the percutaneous absorption curves were drawn to determine the most suitable range of gel pH value. Three batches gels were prepared, whose traits, identification, inspection(pH, viscosity, particle size, specific rotation, the material, L-isomer, microbial limit, quantity), assay and stability test were evaluated.Results: (1) the result of prescription and process screening: The optimal gel ibuprofen prescription with pH values of 5.0±0.5, 6.0±0.5, 7.0±0.5 were determined based on the screening of the prescription and preparation process; Percutaneous absorption test results showed that the gel rate of percutaneous absorption and pH value of gel had a certain correlation, that is, with the increasing of pH value, gel dexibuprofen percutaneous absorption rate was also increasing too. As the pH value of the dexibuprofen gel was within 6.0 ~ 6.5, the permeability of drug was highest. pH value range of 6.0~7.0 were determined as the stable range through degradation tests and stability tests. Thus dexibuprofen gel optimum pH value range of agents were determined as 6.0~6.5. (2) The result of the evaluation of quality: the method was feasible, the quality of gel was stable and controllable.Conclusion: The research made up the deficiencies in the research field of diastereoisomers formulations. The degradation tests were used for first time to clarify the reasons of dexibuprofen gel stability, and the pharmaceutic methods were used to solve the problems of stability. (2) Percutaneous absorption test was finished to clarify the relevance of the percutaneous absorption rate and pH values of gels, which provide t new ideas and methods for other gels, this technology is now under patent-pending protection application. (3) Theoretical guidance for evaluation of the dexibuprofen gel quality was provided through the research of quality standards, also the experiment basis for the registration of new drugs was provided.
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