Design, Development and Characterization of Fast Dissolving Sublingual Film of Ticagrelor

Priyanga, J (2021) Design, Development and Characterization of Fast Dissolving Sublingual Film of Ticagrelor. Masters thesis, College of Pharmacy, Madurai Medical College, Madurai.

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The primary objective of the work was to formulate and evaluate fast dissolving sublingual film of Ticagrelor for the acute coronary syndrome. ACS encompasses a spectrum of unstable coronary artery disease(CAD), involving an abrupt reduction in coronary blood flow leading to myocardial ischemia and/ or myocardial infarction with or without ST-segment elevation. Ticagrelor is an antiplatelet drug, treating people who have had a myocardial infarction or ACS, blockage of blood flow. Ticagrelor oral bioavailability is 36% and BCS class IV drug. To enhance the bioavailability of the drug, avoid first-pass metabolism, rapid onset of action and better patient compliance ticagrelor formulated as a fast-dissolving sublingual film. Because the drug directly reaches systemic circulation through the ventral surface of the tongue, that is the film placed below the tongue, the film is rapidly wet by saliva. Then it disintegrates in a matter of seconds, dissolve to release the medication in systemic circulation and enhance bioavailability due to the large surface area of the film. so, for the above reason, ticagrelor was developed as a sublingual film. ❖ Preformulation studies were carried out for estimation of Ticagrelor and FTIR study for API & physical mixtures. ❖ Estimation of Ticagrelor (λ max) by using UV spectroscopy using pH 6.8 phosphate buffer concentration at 10μg/ml. The spectrum was obtained at 299nm. ❖ Standard calibration curves of ticagrelor were carried out and the correlation coefficient was found to be 0.9996 at 299nm. It indicates ticagrelor obeys beer’s law within the concentration range of 2-10μg/ml. ❖ A compatibility study was performed with infrared spectroscopy to confirm the compatibility between the drug and polymers used for the preparation of fast dissolving sublingual film & identifying any possible interaction. IR study performed for ticagrelor, PVA, HPMC E15, Pectin and physical mixture of Ticagrelor +PVA, ticagrelor + HPMC E15, ticagrelor +pectin. The peak obtained in the spectrum indicates that there was no interaction between drug and polymer in the formulation. ❖ The fast-dissolving sublingual film was successfully prepared by solvent casting method using various polymers such as PVA, HPMC E15, pectin with different concentrations and cast films were cut into 2x2 cm2. ❖ Formulated sublingual film of ticagrelor was involved for characterization studies such as morphological and organoleptic control, weight variation, thickness, folding endurance, percentage elongation, surface pH, drug content, in-vitro disintegration test and in-vitro dissolution study. ❖ Color, homogeneity, transparency, smell and texture of all formulated films F1-F12 was examined and all formulations were a good appearance. ❖ The average weight of 2x2 cm2 of the F1-F12 formulations was ranges found to be 204 ± 0.45 mg to 248 ± 0.54 mg. From the results obtained all the films were uniform in weight and there was no significant difference in the weight of the individual formulations. ❖ The thickness of the F1-F12 formulations was ranges found to be 0.141 ± 0.002 mm to 0.268 ± 0.002 mm. The difference in the film thickness was observed with the increased concentration of the polymers. The results show no remarkable changes in the thickness of the film and there is a uniform distribution of API and excipients throughout the surface of the films. ❖ Folding endurance was used to determine the ability of the films to withstand rupture and the mechanical strength of the films. The folding endurance of all prepared F1- F12 formulations was found to be 177 to 292( no of folds). All the medicated films had satisfactory folding endurance > 90 indicating that they were strong and flexible enough during handling and application. So, the results show passes the folding endurance test. ❖ The percentage elongation of F1-F12 formulations was performed and results show between 2.5 to 30%. The values show, increasing concentration of polymers in the formulations leads to increase percentage elongation of films. ❖ Surface pH of the F1-F12 formulations was performed and shows ranges between 6.3 to 6.7pH. As per obtained results shows that the pH of all films are near to neutral which indicates that there will be not any kind of irritation or side effects to the mucosal lining of the oral cavity after administration of the formulated films. Surface pH values comply with the acceptable limits. ❖ A drug content test was performed to ensure uniform distribution of the drugs and results shows of F1-F12 formulations was 92.61 to 100.49%. The results indicated satisfactory and good uniformity in the drug content test. ❖ Disintegration time is described as the time(seconds) that a film disperses when it comes into contact with saliva or water. Disintegration time is when the thin film begins to disintegrate. Invitro disintegration study of F1-F12 formulations was performed and values ranged from 30 to 48 seconds. Disintegration time was increased with the increased concentration of polymers used in the formulations. The weight and thickness of the film play a significant role in determining the physical properties of water-soluble films. ❖ Invitro dissolution study were carried out for F1-F12 formulations and results was obtained within 10 minutes 57.56%, 52.32%, 52.45%, 53.37%, 95.77%, 92.82%, 93.34%, 90.20%, 90.46%, 89.46%, 89.13%, 86.03 % respectively from F1- F12 formulations. ❖ PVA based F1-F4 based formulations shows slow drug release within 10 minutes and 30 minutes shows 72 to 77 % of the drug has been released. ❖ HPMC E15 based formulations show rapid drug release that is almost above 90% of drug within 10 minutes and 30 minutes 91.24 to 95.28% drug has been released. ❖ Pectin based formulations show moderate to fast drug release also, within 10 minutes drug release nearly 89% was reached and 30 minutes 91.24 to 95.28 % drug has been released. ❖ Overall characterization studies were carried out for all F1-F12 formulations and results are observed. ❖ Based on all characterization studies of the films, F5 formulations consider as best formulation among all of the F1-F12 formulations and their evaluated study values are following table 13. ❖ Invitro drug release kinetics were performed for F1-F12 formulations and the results was drug release follows first order rate kinetics and drug release mechanism was Korsmeyer peppas plot model (Fickian diffusion). CONCLUSION: Fast Dissolving Sublingual Film of Ticagrelor was successfully prepared by solvent casting method using HPMC E15, pectin, PVA as film forming polymers. These F1-F12 films was developed and characterized as various physical and mechanical properties. From the overall characterization studies showed F5 formulation as best formulation of all other formulation. F5 formulation showed disintegration time was 30 seconds and drug release 95.77 % within 10 minutes. HPMC E15 used formulation give good results compare to other film forming polymers used formulations. HPMC E15 > PECTIN > PVA. Overall of this work can be improving the rapid onset of action, bioavailability and patient compliance.

Item Type: Thesis (Masters)
Additional Information: 261911305
Uncontrolled Keywords: Design, Development, Characterization, Fast Dissolving Sublingual Film, Ticagrelor.
Subjects: PHARMACY > Pharmaceutics
Depositing User: Ramakrishnan J
Date Deposited: 15 Aug 2022 06:28
Last Modified: 18 Aug 2022 02:47

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