title: Formulation of zolmitriptan sublingual tablets prepared by direct compression with different polymers: in vitro and in vivo evaluation.
abstract: First-pass metabolism can be overcome by sublingual drug delivery, and quick drug entry into the systemic circulation can be obtained. In certain diseases such as migraine therapy, taking fast pharmacological response is an important criteria. In this study, zolmitriptan sublingual tablets were prepared by direct compression method using different mucoadhesive polymers such as hydroxypropyl methyl cellulose, chitosan and sodium carboxy methyl cellulose at a concentration range of 0.5-5% to reduce flushing action of saliva and provide enough time for drug to be absorbed. Tablets were evaluated for the physical properties, and optimum formulations were chosen for in vivo studies to carry on sheep model. The tablets disintegrated rapidly, and dissolution tests revealed that zolmitriptan was dissolved from the formulation within the compendial limits. This especially showed us that the concentration range of polymers is in acceptable limit. It was also concluded that microcrystalline cellulose, spray-dried lactose and sodium starch glycolate are the appropriate excipient and formulated in good proportions. In vivo studies indicated that formulation containing 5% chitosan has the maximum C(max) and AUC and minimum t(max) values (p<0.05). As a result, sublingual tablet administration of zolmitriptan formulated with appropriate excipients and especially with chitosan seems promising alternative to traditional routes.
authors.affiliation: Gulhane Military Medical Academy, Department of Pharmaceutical Sciences, Ankara, Turkey.
authors.forename: Ziya
authors.initials: Z
authors.lastname: Bayrak
authors.forename: Cetin
authors.initials: C
authors.lastname: Tas
authors.forename: Umut
authors.initials: U
authors.lastname: Tasdemir
authors.forename: Halil
authors.initials: H
authors.lastname: Erol
authors.forename: Cansel Kose
authors.initials: CK
authors.lastname: Ozkan
authors.forename: Ayhan
authors.initials: A
authors.lastname: Savaser
authors.forename: Yalcin
authors.initials: Y
authors.lastname: Ozkan
mesh_terms: D000286:Administration, Sublingual; D000818:Animals; D055598:Chemical Phenomena; D019245:Compressive Strength; D004339:Drug Compounding / Q000379:methods*; D016503:Drug Delivery Systems; D005079:Excipients / Q000737:chemistry*; D005260:Female; D007785:Lactose / Q000737:chemistry; D023303:Oxazolidinones / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics; D010539:Permeability; D011108:Polymers / Q000737:chemistry; D058825:Serotonin 5-HT1 Receptor Agonists / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics; D012756:Sheep; D012995:Solubility; D013607:Tablets; D014363:Tryptamines / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: D005079:Excipients; D023303:Oxazolidinones; D011108:Polymers; D058825:Serotonin 5-HT1 Receptor Agonists; D013607:Tablets; D014363:Tryptamines; C089750:zolmitriptan; D007785:Lactose