Formulation of zolmitriptan sublingual tablets prepared by direct compression with different polymers: In vitro and in vivo evaluation

• Published in: European journal of pharmaceutics and biopharmaceutics 2011-08, Vol.78 (3), p.499-505
• Main Authors: Bayrak, Ziya, Tas, Cetin, Tasdemir, Umut, Erol, Halil, Ozkan, Cansel Kose, Savaser, Ayhan, Ozkan, Yalcin
• Format: Article
• Language: English
• Subjects: Administration, Sublingual; Animals; Biological and medical sciences; Chemical Phenomena; Chitosan; Compressive Strength; Drug Compounding - methods; Drug Delivery Systems; Excipients - chemistry; Female; General pharmacology; Hydroxylpropylmethyl cellulose; Lactose - chemistry; Medical sciences; Neuropharmacology; Oxazolidinones - administration & dosage; Oxazolidinones - blood; Oxazolidinones - chemistry; Oxazolidinones - pharmacokinetics; Permeability; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Polymers - chemistry; Serotonin 5-HT1 Receptor Agonists - administration & dosage; Serotonin 5-HT1 Receptor Agonists - blood; Serotonin 5-HT1 Receptor Agonists - chemistry; Serotonin 5-HT1 Receptor Agonists - pharmacokinetics; Sheep; Sodium carboxy methyl cellulose; Solubility; Sublingual delivery; Tablets; Tryptamines - administration & dosage; Tryptamines - blood; Tryptamines - chemistry; Tryptamines - pharmacokinetics; Zolmitriptan
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2011.02.014

Sublingual administration of zolmitriptan formulated with appropriate excipients and polymers seems promising alternative to traditional routes. 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.