Formulation and evaluation of sumatriptan succinate oral disintegrating tablets using super disintegrants
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This document describes the formulation and evaluation of oral disintegrating tablets of sumatriptan succinate using superdisintegrants. Sumatriptan succinate tablets were prepared using different concentrations of Croscarmellose sodium and treated agar as superdisintegrants. The tablets were evaluated for various physical properties and drug release. Treated agar at 7.5% concentration showed the fastest disintegration time and wetting time compared to other formulations. The results indicate that treated agar provided better superdisintegrant properties than Croscarmellose sodium for formulating oral disintegrating tablets of sumatriptan succinate.
![IUPAC Name:
1-[3-[2-(dimethylamino)ethyl]-1H-indol-5-yl]-N-
methylmethanesulfonamide
Bio availability: Approximately 60%
Absorption: Mean absolute oral bioavailability is approximately 40%.
Food has no affect on the rate and extent of absorption.
Volume of distribution: 8.4±3.3 L/kg
Protein binding: 25%
Half life: The mean elimination half-life of Sumatriptan and of the active
N-desmethyl metabolite is 3 hours.
Mechanism of action:
Sumatriptan binds with high affinity to human 5-HT1B and 5-HT1D receptors leading to
cranial blood vessel constriction. The therapeutic activity of Sumatriptan for the
treatment of migraine headache can most likely be attributed to the agonist effects at the
5HT1B/1D receptors on intracranial blood vessels (including the arterio-venous
anastomoses) and sensory nerves of the trigeminal system which result in cranial vessel
constriction and inhibition of pro-inflammatory neuropeptide release.
Dose: 2.5mg, 10mg](https://image.slidesharecdn.com/formulationandevaluationofsumatriptansuccinateoraldisintegratingtabletsusingsuperdisintegrants-190922111819/85/Formulation-and-evaluation-of-sumatriptan-succinate-oral-disintegrating-tablets-using-super-disintegrants-6-320.jpg)
Formulation and evaluation of sumatriptan succinate oral disintegrating tablets using super disintegrants
- 1. Formulation and Evaluation of Sumatriptan Succinate Oral Disintegrating Tablets Using Super Disintegrants In the partial fulfillment of the requirements for the award of the degree of BACHELOR OF PHARMACY By P.V.SIVA KRISHNA (Y15PH2056) Under The Guidance of Lakshmana Rao P M.Pharm(Ph.D) Department of Pharmaceutics
- 2. CONTENTS Introduction Aim and Objectives Drug and excipient Profiles Methodology Results and Discussion Conclusion Bibliography
- 3. INTRODUCTION The oral route of administration continue to be the most preferred route due to its manifold advantages including ease of ingestion, pain avoidance, versatility and most importantly patient compliance. The most popular dosage forms are tablets and capsules, however geriatric patients may have difficulty in swallowing and/or chewing resulting in non compliance and ineffective therapy. To overcome these problems, oral disintegrating tablets (ODT) are a good alternative since they disintegrate and dissolve rapidly in saliva without need for drinking water. . Although the primary benefit of ODT is to improve patient compliance, yet other benefits such as accuracy of dosage, rapid onset of action and increase in bioavailability may be accomplished.
- 4. AIM AND OBJECTIVES In the present study an attempt will be made to design oral disintegrating tablets of Sumatriptan succinate (anti migraine) by using treated agar and Croscarmellose sodium as a superdisintigrants with a view to provide a convenient means of administration to those patients suffering from difficulties in swallowing such as pediatric and geriatric patients and uncooperative mentally ill patients. The objectives of the research work undertaken are as follows: To formulate oral disintegrating tablets of Sumatriptan succinate using treated agar and Croscarmellose sodium as a superdisintegrants in different ratios by direct compression technique. To study the physical characteristics of the individual drug by FTIR spectroscopy and the optimized formulations by FTIR spectroscopy. To evaluate various pre-compressional parameters of tablet blend To evaluate various characteristics of the resulting tablets. To evaluate the drug content and to perform in-vitro drug release study.
- 5. DRUG PROFILE SUMATRIPTAN Description: Sumatriptan is a white to almost white powder that is readily soluble in water. Molecular formula: C14H21N3O2S Molecular weight: 295.401 g/mol Class: Anti migraine Structure: Fig.No.5.1: structure of sumatriptan
- 6. IUPAC Name: 1-[3-[2-(dimethylamino)ethyl]-1H-indol-5-yl]-N- methylmethanesulfonamide Bio availability: Approximately 60% Absorption: Mean absolute oral bioavailability is approximately 40%. Food has no affect on the rate and extent of absorption. Volume of distribution: 8.4±3.3 L/kg Protein binding: 25% Half life: The mean elimination half-life of Sumatriptan and of the active N-desmethyl metabolite is 3 hours. Mechanism of action: Sumatriptan binds with high affinity to human 5-HT1B and 5-HT1D receptors leading to cranial blood vessel constriction. The therapeutic activity of Sumatriptan for the treatment of migraine headache can most likely be attributed to the agonist effects at the 5HT1B/1D receptors on intracranial blood vessels (including the arterio-venous anastomoses) and sensory nerves of the trigeminal system which result in cranial vessel constriction and inhibition of pro-inflammatory neuropeptide release. Dose: 2.5mg, 10mg
- 7. Uses of Sumatriptan • Vascular headaches • Acute treatment of migraine attacks with or without aura. • Not recommended for management of hemiplegic or basilar migraine or for prophylaxis of migraine. EXCIPIENT PROFLE CELLULOSE, MICROCRYSTALLINE Microcrystalline cellulose JP: Microcrystalline cellulose PhEur: Cellulosum microcristallinum USPNF: Microcrystalline cellulose LACTOSE, ANHYDROUS BP: Anhydrous lactose JP: Anhydrous lactose PhEur: Lactosum anhydricum USPNF: Anhydrous lactose
- 8. MATERIALS AND METHODS Sumatriptan succinate was obtained as a gift sample from Pharmatrai, Hyderabad. Agar was obtained from Merck specialties Pvt. Ltd, Mumbai. Croscaramellose sodium, anhydrous Lactose and other excipients were obtained as a gift sample from Kawarlal Exicipients limited, Chennai. All other materials used were of pharmacopoeial grade. Methods Preparation of Standard Graph: Accurately weighed 100mg of drug was dissolved in small amount of 6.8 pH phosphate buffer and volume was made up to the mark with phosphate buffer to get a concentration of 1000 μg/ml (stock-I). The stock-I solution was further diluted to get a solution of concentration 20 µg/ml (stock-II).From the stock-II, a series of dilutions containing 2, 4, 6, 8& 10 µg/ml of drug. The absorbance of the above dilutions was measured using a UV spectrophotometer at 226 nm using phosphate buffer as blank. The method obeyed Beer,s Lamberts law in the concentration range of 0-10 µg/ml. No interference by the excipients used in the study was observed.
- 9. Preparation of Sumatriptan succinate Tablets: Sumatriptan Succinatetablets were prepared by direct compression method as per the formula given in Table 2. The required quantities of drug, Croscarmellose Sodium and Treated Agar as per the formula in each case were blended thoroughly in a closed polyethene bag. Aerosil and magnesium stearate were then added by passing through mesh no.80 and blended. The blend of ingredients was then compressed directly into tablets using CADMACH 16 station tablet punching machine, equipped with round and flat punches of 8 mm diameter. Table 1: Calibration Curve of Sumatriptan succinate in 6.8 pH Phosphate Buffer Concentration(µg/ ml) Absorbance 0 0 2 0.206 4 0.398 6 0.656 8 0.842 10 9.891
- 10. Table 2: Fomulae of Sumatriptan Succinate Tablets Prepared employing Croscarmellose Sodium and Treated Agar as Superdisintegrants Ingredients CCS1 CCS2 CCS3 TA1 TA2 TA3 Sumatriptan Succinate 5 5 5 5 5 5 Lactose Anhydrous 86.5 84 81.5 86.5 84 81.5 Croscarmellose Sodium 2.5 5 7.5 --- --- --- Treated Agar --- --- --- 2.5 5 7.5 Sodium Sacharin 1.5 1.5 1.5 1.5 1.5 1.5 Aerosil 3 3 3 3 3 3 Magnesium Stearate 1.5 1.5 1.5 1.5 1.5 1.5 Total Weight 100 100 100 100 100 100
- 11. RESULTS AND DISCUSSIONS y = 0.105x R² = 0.999 0 0.2 0.4 0.6 0.8 1 1.2 0 2 4 6 8 10 12 Absorbance Conc. (µg/ml) Calibration Curve of Sumatriptan Succinate with 6.8pH Phosphate Buffer Fig.No.1: Calibration Curve of Sumatriptan Succinate with 6.8pH Phosphate Buffer Drug-excipients Compatibility studies
- 12. Formulations* Average Weight* Hardness *Kg/cm2 Friability *(%) Water absorption ratio* CCS1 98±0.12 3.6±0.11 0.481±0.16 39±0.14 CCS2 98±0.21 3.6±0.24 0.56±0.17 28±0.15 CCS3 99.8±1.8 3.5±0.49 0.57±0.17 34±0.24 TAG1 98±0.16 3.2±0.2 0.31±0.16 51±0.13 TAG 2 99±0.87 3.4±0.32 0.30±0.22 54±0.17 TAG 3 99±0.87 3.6±0.32 0.295±0.22 54±0.17 Table 4: Evaluation of ODT for formulations * Data represent mean ±SD (n=3)
- 13. Formulations Cumulative % drug dissolved (mins) 0 2.5 5 10 15 20 CCS1 0 38±0.26 61±0.35 75±0.92 88±0.24 94±0.31 CCS2 0 40±0.12 63±0.95 77±0.7 89±0.24 95±0.71 CCS3 0 52±0.21 72±0.31 80±0.12 90±0.21 96±0.11 Table 7: Dissolution profile of Sumatriptan succinate ODTs with Croscarmellose Sodium * Data represent mean ±SD (n=3)
- 14. Comparative dissolution profile of Sumatriptan succinate ODTs containing different concentrations of Treated Agar as a natural superdisintegrant. 0 20 40 60 80 100 120 0 5 10 15 20 25 %CumulativeDrugRelease Time in mins TAG1 TAG 2 TAG 3
- 15. DISCUSSIONS The main objective of this research work was to formulate and evaluate the oral disintegrating tablets of sumatriptan succinate using superdisintegrants. The FT-IR represents the peaks of the sumatriptan succinate functional groups. These peaks were not affected, they were prominently observed in IR-spectra of sumatriptan succinate along with Croscarmellose Sodium, Treated agar etc.The spectral details of the drug and the excipients shown in (Table.3) and (Figure.2-5). For each formulation blend of drug and excipients were prepared and evaluated for various precompression parameters like angle of repose, bulk density, tapped density, carr’s index and Hausner’s ratio. The powder blend of all the formulations had Hausner’s ratio of 1.12 indicating good flowability. The carr’s index was found to be between 7.6-15.84% indicating fairly good flowability of the blend. The good flowability of blend was also made evident with angle of repose values (31˚-37˚) which is below 40˚ indicating good flowability. Since the powder material was free flowing and used for the direct compression. The tablets were prepared by direct compression technique and evaluated for different post compression parameters. The hardness & Friability of the tablets was found to be 3.2±0.2 to 3.6±0.32 and 0.295±0.22 to 0.57±0.17, all values were found to be within the limits.
- 16. The wetting time of the formulations was found to be 10 ±0.12 to 20±0.13secand the disintegration time was ranging from 12 ±0.55 to 24±0.45 seconds. The wetting time and disintegration time both are less for the formulation containing treated agar (7.5% w/w) as a modified superdisintegrant. The dissolution profile of all the formulations was shown in the table 7.6 and in fig 7.5 & 7.6. The formulation with Treated Agar (TAG3) shows faster disintegration and wetting time than formulation with croscaramellose sodium. The order of enhancement of dissolution rate with various superdisintegrants was found to be Treated Agar˃ croscaramellose sodium.
- 17. CONCLUSION The above results suggest that the formulated oral disintegrating tablets of sumatriptan succinate exhibited good physical parameters and rapidly disintegrating without affecting the release profile and is very effective in case of elderly and pediatric patients. The overall results indicated that formulation with Treated Agar (7.5%) had a higher edge compared to other formulations containing croscaramellose sodium. They satisfied all the criteria for oral disintegrating tablets. This direct compression process is simple, reproducible and robust to prepare orally disintegrating tablets of sumatriptan succinate and other anti-migraine drugs.
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