Studies On Flurbiprofen Orally Disintegrating Tablets

BackgroundNew drug development has focused on the solid fast-release oral formulations in recent years, and some new drug delivery systems (DDS) have been developed, e.g. orally disintegrating tablet (ODT). ODT has obvious conveniences, for example, it is taken with little or without water, and it can disintegrate rapidly in mouth without chewing with the resulting rapid onset of action. Recent reports indicated that ODT has a potential international market benefit of more than 30 billion dollars, which has driven many research institutions and pharmaceutical companies to its development. The SFDA of China has regarded ODT as a new dosage form and a variety of drugs in ODT have been registered.ODT is a new administration method, which brings convenience to the special population such as the aged, infants, patients with swallowing difficulties and other special cases. Moreover, it provides a new choice of drug administration to the ordinary patients. ODT has some advantages like quick absorption, high bioavailability, taking convenience, less residual in intestine. Furthermore, it can also avoid the first-pass effect of liver.Flurbiprofen acid is a non-steroidal anti-inflammatory drug(NSAID), with analgesic, antipyretic and anti-inflammatory effects, mainly by inhibiting prostaglandin synthetase. Many flurbiprofen preparations have been developed even on sale, like ordinary tablet, injection, oral controlled release preparations, et al. The purpose of this study is to prepare the ODT of flurbiprofen, and evaluate its effects in vitro and in vivo.Methods1. Based on the establishment of determination of the disintegration time in vitro, the disintegrating agents were screened with disintegration time as the index of investigation. The correctants were selected out according to the taste of the preparations. By L₉(3⁴) orthogonal experimental design, the amount of the disintegrating agents, microcrystalline cellulose (MCC) and the correctants and the hardness of the tablets were investigated to select the optimal prescription of the ODT.2. The ODT of flurbiprofen were prepared according to the optimized prescription. Moreover, the quality and preliminary stability of flurbiprofen ODT were evaluated.3. The bioequivalence of flurbiprofen ODT and ordinary tablets was studied in healthy rabbits.Results1. The determination method of the disintegration time in vitro was established and PVPP was selected as the correctants according to the disintegration time. Stevioside was used as the correctants because of its good modifying effect on taste. By L₉(3⁴) orthogonal experiment, optimized prescription of the flurbiprofen ODT was as follow: MCC 30%, PVPP 5%, hardness of 2 kg, Stevioside 4%.2. The disintegration time of flurbiprofen ODT in vitro and in the mouth of volunteers were below 30 seconds. It has good taste despite little rough granules. The evaluation method of flurbiprofen ODT in vitro was established. The dissolution of flurbiprofen ODT was above 90 % after 2 minutes in PBS (pH 7.2), which meant flurbiprofen in ODT dissolved faster than in ordinary tablets. After half an hour, the dissolution of flurbiprofen ODT was 100%, same as the ordinary tablets. It is suggested that the flurbiprofen was able to release from ODT in the stomach. It was shown that the flurbiprofen ODT was stable at high temperature and light, but moisture-proof preservation was necessary.3. According to the rabbit pharmacokinetic investigation results, there were no statistical significant differences between the pharmacokinetic parameters of flurbiprofen ODT and ordinary tablets,including AUC_0-24,AUC_0-∞and C_max,which indicated that the two preparations of flurbiprofen are bioequivalent. Moreover,the significant difference of Tmax between the two preparations analyzed by non-parameter test demonstrated that their release performances were significantly different.ConclusionThis study developed flurbiprofen ODT can meet the requirement with good taste in the mouth, short disintegration time and rapid release.