Development, characterization and pharmacokinetic study of solid dispersion formulation of telmisartan /
The drugs that belong to class II of Biopharmaceutical Classification System face several challenges in their dissolution and bioavailability due to their poor water solubility. Solid dispersion is an effective method to enhance the solubility of poorly water-soluble drug. Telmisartan is an antihype...
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| Main Author: | |
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| Format: | Thesis |
| Language: | English |
| Published: |
Kuantan, Pahang :
Kulliyyah of Pharmacy, International Islamic University Malaysia,
2019
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| Subjects: | |
| Online Access: | Click here to view 1st 24 pages of the thesis. Members can view fulltext at the specified PCs in the library. |
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| Summary: | The drugs that belong to class II of Biopharmaceutical Classification System face several challenges in their dissolution and bioavailability due to their poor water solubility. Solid dispersion is an effective method to enhance the solubility of poorly water-soluble drug. Telmisartan is an antihypertensive drug with poor dissolution and poor bioavailability because of its low aqueous solubility. To enhance the solubility of telmisartan solid dispersion using freeze-drying method was carried out to formulate telmisartan with PVP K30 as carrier and Na2CO3 as alkalinizer, and complete characterization using in vitro dissolution in different pH dissolution medium, FTIR, DSC, XRD and SEM was performed. Short term stability study in accelerated and ambient conditions on solid-dispersed telmisartan powders was carried out for two months. In vivo study in a rat model was performed to determine the bioavailability of solid-dispersed formulations compared to raw drug and marketed telmisartan tablet. From the results, it was found that the solid dispersion formulations presented higher in vitro drug release rate in different pH media (pH 1.2, 6.8 & 7.5) compared to raw and marketed telmisartan tablet. Solid-dispersed formulations containing drug: PVP K30: Na2CO3 at a weight ratio of 1:1:2, 1:2:2 and 1:3:2 were selected as the most suitable formulations based on the higher dissolution and low amount of excipients. Based on the results of FTIR, there was no physical incompatibility between telmisartan and excipients in the dry state. The DSC and SEM results described the absence or reduction of telmisartan crystallinity. The XRD results confirmed that the crystallinity of telmisartan was significantly reduced and it was changed to amorphous form after solid dispersion. There was no change in in vitro drug release rate and physical nature of dry powder of the selected solid-dispersed formulations after two months of stability study. The pharmacokinetic studies in the rat model were performed after oral administration of selected solid-dispersed formulations (drug: PVP K30: Na2CO3 at a weight ratio of 1:1:2 and 1:2:2), raw drug and marketed telmisartan tablet. The highest Cmax and AUC0-inf recorded for the two tested solid-dispersed formulations (drug: PVP K30: Na2CO3 at a weight ratio of 1:1:2, 1:2:2) were 0.611 ± 0.303, 1.363 ± 0.229 µg/ml and 4.876 ± 0.556, 5.564 ± 0.63 µg h/ml respectively. In addition, Kel and T1/2 of two solid-dispersed formulations 1:1:2, 1:2:2 were 0.198 ± 0.11, 0.241 ± 0.031 h-1 and 4.802 ± 3.619, 2.91 ± 0.39 h respectively, and there was no significant difference (p > 0.05) in Kel and T1/2 between two solid-dispersed formulations and marketed telmisartan tablet. Moreover, the relative bioavailability of the above mentioned solid dispersion formulations were 246.15 ± 28.04 and 280.88 ± 31.80%, respectively with respect to marketed telmisartan tablet. The overall results indicate that reduction of telmisartan crystallinity and the presence of alkalinizer promote higher in vitro dissolution in all mediums in case of solid dispersion formulations of telmisartan. The in vivo relative bioavailability study also indicates better systemic absorption of telmisartan from freeze-dried solid dispersion formulations. It can be concluded that freeze-dried solid dispersion formulations of telmisartan containing PVP K30 as carrier and Na2CO3 as alkalinizer have the potential of overcoming poor solubility and bioavailability issues of telmisartan. |
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| Physical Description: | xviii, 144 leaves : colour illustrations ; 30cm. |
| Bibliography: | Includes bibliographical references (leaves 109-121). |