Study Of Transdermal Patch Of Asenapin Maleate

Objectives: To prepare transdermal patch containing asenapin maleate and evaluateits in vitro penetration study, pharmaceutical properties, quality and pharmacokineticcharacteristics, to achieve the purpose of sustain drug release.Methods:(1) An HPLC method was established for determination of asenapinmaleate. The physico-chemical property including solubility in different solvent andoil/water partition coefficient was studied. In vitro penetration ability of asenapin maleatewas evaluated by Vertical Franz diffusion cell.(2) The patch was prepared using solventevaporation method. The optimal formulation was achieved through evaluating the effectof cross-linking agent and plasticizer on patch and the main evaluation indicators includingadhesion, release and permeation amount. In addition, the hardening time was investigated.(3) The quality standards of patch including the adhesion, release, permeation amount andcontent uniformity was studied.(4) Rats were used to investigate pharmacokineticproperties of the patch.Results:(1) The determination method of asenapin maleate was stable and reliable.The solubility of asenapin maleate is6.42±0.48mg/mL in pure water and17.90±1.72mg/mL in methanol, therefore methanol was added as the film’s solvent. The solubility ofasenapine maleate shows pH dependent. The determination of oil-water partitioncoefficient is-0.95. The result of in vitro penetration test showed that the permeation rateof asenapin maleate was increased as the the initial concentration increasing. When theconcentration reached5mg/mL, the permeability coefficient reached49.55μg/cm2h andthe cumulative permeation amount of drug achieved61.69%.(2) The optimal formulationwas showed as follow: patch loading capacity was15%,9.5%TEC and0.5%succinicacid were added as the plasticizer and crosslinking agent respectively, the hardening timewas1h. By fitting different equation, the higuchi equation meet with the drug release frompatch, the release mechanism was in the dual role of diffusion and erosion.(3) The qualityevaluation of three batch patch show that, the tack and the cohesion of patch was morethan14and75h respectively; the cumulative permeation amount of drug was more than350μg/cm2, release percentage was greater than14%; permeability was larger than 280μ g/cm2, penetration was greater than11%; patch content uniformity met with theprovisions of Appendix IV of2010edition of 《pharmacopoeia of people’s republic ofchina》.(4) The result of preliminary pharmacokinetic in rats showed that the patchprepared has significant sustained-release effect.Conclusion: Successfully prepared a sustained-release of transdermal patchcontaining asenapin maleate, and the formulation did not seen in any relevant literature andpatent reports. The study has provided potential bases for transdermal absorptionformulations in future research and development.