Studies On Zolmitriptan Buccal Adhesive Tablets

Backgrand and Objective:Oral mucoadhesive drug delivery system is a common novel drug delivery method, and is the adhesion of the drug through the use of polymers produced with the oral mucosa adhesion to adhesion in the oral mucosa on the release of drug. It can treat oral disease, and drugs can be absorbed through the oral mucosa directly into circulation system to play the role of systemic treatment. Oral mucoadhesive drug delivery system can avoid enzymes metabolism and acid degradation in gastrointestinal tract and first-pass effect in liver.In this study zolmitriptan was chosen as a model drug, which is the first-line drug in the treatment of moderate and severe attrack of migraine. Although the common oral drug formulations and oral disintegrating tablets is convenient to use, having good compliance and tolerance, gastrointestinal disorder is the common symptoms of migraine. The main performance of gastrointestinal disorder is nausea, vomiting, even in the absence of nausea symptoms which may also lead to delayed gastric emptying and reduction of oral drug absorption and bioavailability. So the bioavailalility is not high. We can see the effect of poor oral route of administration. Furthermore, patients need more treatment choices. Therefore, in this study, zolmitriptan will be made into buccal adhesive tablets to make the drug absorption directly enters the circulation systemic through the oral mucosa, avoiding the influence of the gastrointestinal tract and liver first-pass affect and increasing the bioavailalility. At the same time, buccal adhesive tablets may extend the time of the tablet in the oral mucosa to achieve sustained release, which will reduce the number of administration and adverse drug reactions.Methods:A high performance liquid chromatography was established and used to detect the concentration of zolmitriptan. The partition coefficients for the n-octanol-water/buffer solution systems of zolmitriptan were determined by shaking flask method. The porcine oral mucosa in vitro organizations has used the experiment of zolmitriptan oral mucosa infiltration and penetration mechanism. The blank buccal adhesive tablets based on CP 934P and HPMC K4M at different ratios were prepared by direct compression of mixed powders to study its adhesion to the impact of factors. Based on the single tests,four important factors were chosen that affected the drug release rate of zolmitriptan buccal adhesive tablets by the actual and the ideal prescription prescription "Ward" as the indicator and standying adhesion, release rate, permeability and stability of it. Using common tablets as control, the use of single dose randomized crossover study design and statistical 3p87 pharmacokinetic software pharmacokinetic parameters of the processing analysis of adhesion of zolmitriptan buccal adhesive tablets in Beagle dogs preliminary pharmacokinetic nature.Results:In the range of pH 3.6 to pH 9.0, the equilibrium solubility of zolmitriptan was decreased while the apparent oil / water partition coefficient was increased with the increasing of pH values with the pH-distribution theory.Zolmitriptan is transferred by passive diffusion, and access to cells by means of absorption of oral mucosa. Characters such as adhesive force, swelling rate and adhesive time of Carbopol 934(Cp) and HPMC K4M (HPMC) are studied. When the Cp: HPMC is 1:2 to 2:1, it is appropriate rate of swelling, adequate adhesion, and long adhesive time.The single-layer buccal adhesive tablets have two-way trend of drug release. The zolmitriptan buccal adhesive tablets are prepared using double layers structure composed of drug core and adhesive layer. The orthogonal design was used to optimize the formulation. Composition of drug-containing layer was Cp 8mg, lactose 24 mg, while protective layer was Cp 17.5mg, HPMC 17.5mg. Hardness was 5kg. It is in vitro release slowly in 12h according with zero release kinetic. The release of the drug was one-way and it has good adhesion. Its penetration rate is 60.21% in vitro. Selection of 1% sodium dodecyl sulfate as mucosal permeability agent, it can improve penetration rate. The stability test showed that the optimum formulation was instability in the high humidity and light conditions. It should be in the dark and confined department preservation.The Pharmacokinetics parameters of oral mucosal drug delivery and oral administration showed that the relative bioavailability of the latter is (200.87±5.2) % in Beagle dogs.Conclusion:In this paper, the zolmitriptan buccal adhesive tablets have good adhesion and release rate in 12h, and the zolmitriptan bioavailability has been improved in Beagle dogs.