Dry Gel Containing Optimized Felodipine-Loaded Transferosomes: a Promising Transdermal Delivery System to Enhance Drug Bioavailability
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Felodipine has a very low bioavailability due to first-pass metabolism. The aim of this study was to enhance its bioavailability by transdermal application. Felodipine-loaded transferosomes were prepared by thin-film hydration using different formulation variables. An optimized formula was designed using statistical experimental design. The independent variables were the used edge activator, its molar ratio to phosphatidylcholine, and presence or absence of cholesterol. The responses were entrapment efficiency of transferosomes, their size, polydispersity index, zeta potential, and percent drug released after 8 h. The optimized formula was subjected to differential scanning calorimetry studies and its stability on storage at 4°C for 6 months was estimated. This formula was improved by incorporation of different permeation enhancers where ex vivo drug flux through mice skin was estimated and the best improved formula was formulated in a gel and lyophilized. The prepared gel was subjected to in vivo study using Plendil® tablets as a reference. According to the calculated desirability, the optimized transferosome formula was that containing sodium deoxycholate as edge activator at 5:1 M ratio to phosphatidylcholine and no cholesterol. The thermograms of this formula indicated the incorporation of felodipine inside the prepared vesicles. None of the tested parameters differed significantly on storage. The lyophilized gel of labrasol-containing formula was chosen for in vivo study. The relative bioavailability of felodipine from the designed gel was 1.7. In conclusion, topically applied lyophilized gel containing felodipine-loaded transferosomes is a promising transdermal delivery system to enhance its bioavailability.
KEY WORDSdry gel factorial study felodipine transdermal delivery transferosomes
Compliance with Ethical Standards
The study protocol meets the international requirements for the care and use of laboratory animals and it was approved by The University Protection of Experimental Animals Committee and by the Ethics Committee of Faculty of Pharmacy, Cairo University.
- 6.Abramoweiz M. Felodipine—another calcium channel blocker for hypertension. Med Lett Drugs Ther. 1991;33:115–6.Google Scholar
- 7.Reddy PD, Balanjineyulu R, Swarnalatha D, Badarinath AV, Gopinath C. Design, development and in vitro characterization of felodipine mucoadhesive buccal tablets. J Pharm Res. 2015;9(2):170–6.Google Scholar
- 9.Mishra AD, Khunt DM, Ghayal AH, Patel CN, Shah DR. Formulation and optimization of ethosomes for transdermal delivery of felodipine. Res J Pharm Technol. 2012;5(12):1509–17.Google Scholar
- 12.Cevc G, Gebauer D, Stieber J, Schätzlein A, Blume G. Ultraflexible vesicles, transfersomes, have an extremely low pore penetration resistance and transport therapeutic amounts of insulin across the intact mammalian skin. Biochim Biophys Acta (BBA) Biomembr. 1998;1368(2):201–15.CrossRefGoogle Scholar
- 16.Al-mahallawi AM, Khowessah OM, Shoukri RA. Nano-transfersomal ciprofloxacin loaded vesicles for non-invasive trans-tympanic ototopical delivery: in-vitro optimization, ex-vivo permeation studies, and in-vivo assessment. Int J Pharm. 2014;472(1–2):304–14. https://doi.org/10.1016/j.ijpharm.2014.06.041.CrossRefPubMedGoogle Scholar
- 19.Moore J, Flanner H. Mathematical comparison of curves with an emphasis on in-vitro dissolution profiles. Pharm Technol. 1996;20(6):64–74.Google Scholar
- 21.Setti A, Takhelmayum PD, Reddy YPK, Sarikonda S, Rao JV, Pawar SC. Method development, validation and stability studies of felodipine by RP-HPLC and molecular interaction studies of felodipine and voltage gated L-type calcium channel. Int J Pharm Sci Rev Res. 2013;24(1):15–20.Google Scholar
- 31.Stan CD, Tătărîngă G, Gafiţanu C, Drăgan M, Braha S, Popescu MC, et al. Preparation and characterization of niosomes containing metronidazole. Farmacia. 2013;61(6):1178–85.Google Scholar