zolmitriptan sublingual tablets
40274100
Formulation of zolmitriptan sublingual tablets prepared by direct compression with different polymers: in vitro and in vivo evaluation.
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.
European journal of pharmaceutics and biopharmaceutics official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
Ziya Bayrak C Tas Umut Tasdemir Halil Kutlu Erol Cansel Kose Ozkan Ayhan Savaser Yalcin Ozkan
50874578
CHAPTER 2 FORMULATION AND EVALUATION OF ZOLMITRIPTAN SUBLINGUAL TABLETS
10mg of zolmitriptan was dissolved in 0.1N hydrochloric acid and volume was made up to 10ml in volumetric flask (1000 mg/ml) From this 1ml was diluted to 10ml to get the stock solution containing 100 mg/ml concentrations. 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7 and 0.8ml of this solution was more diluted to 10ml with 0.1N hydrochloric acid to get 1 mg/ml, 2 mg/ml, 3 mg/ml, 4 mg/ml, 5 mg/ml, 6 mg/ml, 7 mg/ml and 8 mg/ml concentration of zolmitriptan. The absorbance had been measured at 223 nm on a UV VIS spectrophotomer (Schimadzu UV1601) against 0.1N HCl as blank. A graph of concentration versus absorbance was plotted (Figure 2.1)
Zolmitriptan Sublingual Tablets
46590848
Formulation and evaluation of fast disintegrating zolmitriptan sublingual tablets
The drug delivery via sublingual drug route is considered to be a one of promising alternative to oral route and quick entry of drug into the systemic circulation can be possible. A diseases state such as migraine, considering pharmacological response was fast which is an important criteria. In the present study sublingual tablets of a potent anti migraine drug of zolmitriptan 5mg per tablet were prepared. The powdered materials are compressed by direct compression method incorporating various pharmaceutical excipients. The super disintegrates were used are sodium starch glycolate, cross carmellose sodium, cross povidone. The flow properties of powder are important in handling and processing operations. The blend was examined for angle of repose, Carr's compressibility index and Hausner's ratio. The Angle of repose was determined by using conventional fixed funnel method. The Carr's compressibility index and Hausner's ratio were calculated from Bulk and tapped density of the zolmitriptan sublingual powder. The tablets were studied for physiochemical properties and dissolution efficiency. The optimised formulation was used for in vivo studies on rabbit as an animal model. The optimised formulation was disintegrated rapidly and from the dissolution studies, it was within the limits of compendia. This specially reveals that the concentration range of mannitol, cross povidone and avicel 102 are in the appropriate ratios and are formulated in good proportions. From in vivo studies it showed that optimised formulation containing cross povidone has the minimum Tmax and T 1/2 values (P<0.05) and show effective therapeutic Cmax when compared to clinical dose and it's a promising alternate to oral administration route in acute management of migraine.
Haarika Balusu P R Veerareddy
73690772
COMPARATIVE PHARMACOKINETIC STUDIES OF ZOLMITRIPTAN SUBLINGUAL TABLETS
116489790
Bioavailability study of zolmitriptan sublingual tablets on sheep model
Yalcin Ozkan
6334672
FORMULATION AND INVITRO EVALUATION OF ZOLMITRIPTAN SUBLINGUAL TABLETS
Worldwide, migraines affect more than 10% of people. Chronic migraines occur in approximately 1.4 to 2.2% of the population. The mucosa has a rich blood supply and provides rapid absorption for drugs than oral route. The Zolmitriptan is a serotonin (5HT 1B/1D) agonist used for the treatment of migraine with or without aura. The half life of zolmitriptan is 2.5 to 3 hours and it undergoes hepatic metabolism, the absolute oral bioavailability is about 40 to 50% because of hepatic metabolism. So it causes poor bioavailability of zolmitriptan by oral route, so there is a need to increase its bioavailability by formulating it into sublingual dosage form. Hence Zolmitriptan is a suitable drug for buccal dosage forms for fast and better therapeutic profile than oral route. The aim of this study is to increase the bioavailability of zolmitriptan for the potential emergency treatment of migraine pain. An attempts have been made to prepare fast dissolving tablets of zolmitriptan using superdisintegrating agents like crosscarmellose sodium and Crosspovidine. Twelve formulations were developed with two different mucoadhesive polymers (HPMC E 50 and chitosan) They were prepared by direct compression method. Tablet weight variation, hardness, friability, thickness, wetting time, percentage of drug content, disintegrating time and dissolution times were evaluated for each formulation and the results were found satisfactory. By comparing the above twelve formulations F9 (10% chitosan+ 8% cross providence) shows a less disintegration time (6Sec) and more dissolution percentage (98.47+ 0.42) at 10 min. So the formulation F9 is prerequisite for rapid management of migraine.
Santhosh Duddelli Ajay Kumar Zuheb ur rahman T Ashwin Kumar
23929274
Preparation and evaluation of sublingual tablets of zolmitriptan
Aim: Zolmitriptan is a 5 HT receptor agonist (1B/1D) It is used in the acute treatment of migraine having low bioavailability about 40% orally due to hepatic first pass metabolism. The purpose of the present research was to formulate fast acting sublingual tablets of zolmitriptan. Materials and Methods: Sublingual tablets were prepared using ispaghula husk powder, gellan gum, sodium alginate as super disintegrating polymers and citric acid, tartaric acid and camphor as permeation enhancers by direct compressible technique and evaluated for weight variation, thickness, friability, content uniformity, hardness, disintegration time, wetting time, in vitro drug release, in vitro and ex vivo permeation study. Stability study of optimized formulation was performed as per ICH (International Conference on Harmonisation) guideline. Results: The in vitro disintegration time of the optimized formulation (D5) was 9 2 s and all formulations showed 100% of dissolution within 6 2 min. Formulation containing 4% of gellan gum (D5) showed highest disintegration and 2% of citric acid formulation (P3) showed highest permeation 88% within 30 min and ex vivo permeation was 52% within 30 min. Optimized formulation was stable for 1 month during stability study as per ICH guideline. Conclusion: The sublingual tablet formulation gives better results using natural super disintegrant for fast onset of action.
International journal of pharmaceutical investigation
Shailesh T Prajapati Manoj V Patel C N Patel
46193099
Fast relief from migraine attacks using fast disintegrating sublingual zolmitriptan tablets
Zolmitriptan is a potent molecule for treatment of migraine. Its current oral therapies present drawbacks such as slow onset of action, low bioavailability and large inter subject variability. Fast disintegrating sublingual zolmitriptan tablet (FDST) using freeze drying technique has been developed to enhance tablet disintegration and dissolution with the intention of speeding drug absorption and onset of effect, hence mitigating the effects on the gastrointestinal dysmotility that typically accompanies the migraine attack. The FDSTs were prepared using different concentrations of gelatin as binder and mannitol or L alanine as matrix supporting/disintegration enhancing agents. The effect of formulation variables on the physicochemical and solid state properties, as well as the dissolution behaviour of the tablets, was studied. The formulated FDSTs disintegrated within 30 s and showed significantly faster dissolution rate of zolmitriptan compared to the zolmitriptan oral tablet. Tablet containing 2% gelatin and mannitol showed acceptable weight variation, drug content and friability values. Furthermore, it had a low in vitro and in vivo disintegration time (11 s) and it reached 100% of drug release within 30 s. This sublingual formulation gave faster and higher zolmitriptan plasma concentration in rabbits compared to the oral zolmetriptan market product. Zolmitriptan FDST may therefore constitute an advance in the management of acute migraine attacks.
Drug development and industrial pharmacy
Azza A Mahmoud Salwa Salah
137224278
METHOD DEVELOPMENT AND VALIDATION FOR THE QUANTITATIVE ESTIMATION OF ZOLMITRIPTAN IN BULK AND FORMULATED FAST DISINTEGRATING SUBLINGUAL TABLETS BY RP HPLC
Balusu Haarika Selina Sravanthi Veerareddy Prabhakar Reddy
43992389
Effect of Different Meltable Binders on the Disintegration and Dissolution Behavior of Zolmitriptan Oromucosal Fast Melt Tablets
Objective Fast melt tablets and sublingual route have been widely used for providing quick onset of action with the avoidance of first pass metabolism. The objective of this work was to compare the effect of different meltable binders namely; polyethylene glycol (PEG) 4000, pluronic F127 and pluronic F68 on the performance of fast release tablets of the model drug zolmitriptan prepared using the melt granulation technique regarding disintegration time (DT) and dissolution rate (DR) as criteria for rapid absorption and hence quick onset of action. Zolmitriptan is a potent antimigraine drug. Current oral zolmitriptan tablets suffer from slow onset of action, poor bioavailability and large inter subject variability. Methods 3 3 factorial design was adopted. The effect of binder type, binder concentration and croscarmellose sodium (disintegrant) concentration were studied on DT and DR. Results The three factors were found to significantly affect the DR and the inverse square root of DT and significant interactions were elucidated. Conclusion Although satisfactory results were obtained regarding DR, modifications using different excipients and or preparation methods should be considered to comply with pharmacopoeia requirement for DT.
Doaa Ahmed El-Setouhy Emad B Basalious Nevine Shawky Abdelmalak