Development and Evaluation of Micro Emulsion Formulations of Nebivolol for Solubility Enhancement
Nebivolol HCl is a newer drug of β1-adrenergic blocker category, basically used as anti-hypertensive. It is a 3rd generation, antagonist, having NO (nitric oxide) enhancing vasodilator properties. It has 12% oral bioavailability, because of its pre systemic metabolism by the means of cytochrome P450 2D6 enzymes. Its log P value is 4.03 and 5mg is its daily dose. It is highly lipophilic drug and belongs to class BCS II, with slow dissolution. Bioavailability of any drug can be improved by avoiding its first pass metabolism and promoting solubility. Several researchers have worked on the development of ME formulations on different poor water-soluble drugs, to increase their solubility. The purpose of this study is an attempt to enhance the solubility to improve the bioavailability of nebivolol drug by developing a novel delivery system that is microemulsion (ME) .ME formulations were developed using different oil, surfactant and co-surfactants in different ratio and studied on various parameters. Different preformulation tests done on received sample of Nebivolol. FTIR study was performed in order to find out any interactions between the ingredients. Based on the solubility Capmul Pg-12 was finalized oil, Tween 80 as surfactant, propylene glycol as the cosurfactant based on solubility and emulsification efficiency. Five Nebivolol ME formulations were successfully developed by use of oil, water, SA and Co-SA different ratio. Prepared formulations were studied for different properties- transmittance (%), pH, refractive index, viscosity, drug content, and solubility. It was seen that after 4 hours of diffusion, the drug released from the formulation ME5 is faster and more than that of the other i.e., 90.2±0.06%. It was found that ME5 was more stable and Soluble than other prepared formulations. With the better solubilty the bioavailability of Nebivolol will increased and helps in faster absorption and High diffusion in systemic circulation with lower or no risk of degradation. It somehow also reduced frequent intake of drug.
Keywords: Nebivolol, micro emulsion, Ternary phase diagram, surfactant, co-surfactant.
2. Rozec B, Erfanian M, Laurent K, Trochu JN, Gauthier C. "Nebivolol, a vasodilating selective beta (1)-blocker, is a beta (3)-adrenoceptor agonist in the nonfailing transplanted human heart". Journal of the American College of Cardiology.2018, 53 (17):1532-8.https://doi.org/10.1016/j.jacc.2008.11.057
3. Jajere UM, Achadu AE. Fabrication and characterization of ezetimibe solid dispersion for solubility enhancement. Universal Journal of Pharmaceutical Research 2017; 2(1): 11-14. https://doi.org/10.22270/ujpr.v2i1.R3
4. Pravala K, Nagabandi VN, Ajmeera. Enhancement of bioavailability of nebivolol hydrochloride through liquid solid formulations: In VitroandInVivoevaluation. Schol Res Library Pharm Lettre. 2013; 5(6):151-163.
5. Attwood, D., Mallon, C., Taylor, C.J: Phase studies of oil-in water phospholipid microemulsions, Int. J. Pharm. 1992; 84:R5-R8.https://doi.org/10.1016/0378-5173(92)90063-8
6. Ikechukwu UR, John Francis DE, Ambi AA. Development and evaluation of Ritonavir hollow microballoons for floating drug delivery. Universal Journal of Pharmaceutical Research 2017; 2(2): 8-11. https://doi.org/10.22270/ujpr.v2i2.R3
7. Lawrence, M.J: Microemulsions as drug delivery vehicles, Curr.Opin. Colloid Interface Sci. 1996; 1:826-832.https://doi.org/10.1016/S1359-0294(96)80087-2
8. Yadav, V, Jadhav, P, Kumar, K, Bodhe, P. Preparation and evaluation of microemulsion containing antihypertensive drug. International Journal of Applied Pharmaceutics Int J App Pharm. 2018; 10(5):138-146.https://doi.org/10.22159/ijap.2018v10i5.27415
9. Md. Shahidul Islam, Rasheda Akter Lucky. Development and in vitro dissolution study of binary and ternary solid dispersions of aceclofenac. Universal Journal of Pharmaceutical Research 2019; 4(1): 29-34. https://doi.org/10.22270/ujpr.v4i1.240
10. Yusuf FS. Formulation and in-vitro evaluation of floating microballoons of stavudine. Universal Journal of Pharmaceutical Research 2016; 1(1): 8-11. https://doi.org/10.22270/ujpr.v1i1.R3
11. Evelyn, D, Chong wooi, C, Dhanaraj, S.A, Kumar, J.R. Development and evaluation of microemulsion based gel (MBGs) containing econazole nitrate for nail fungal infection. Journal of Pharmacy Research. 2012; 5(4):2385-2390.
12. Shruti G. Shahu, Rita N. Wadetwar, Gouri R. Dixit, Development of Microemulsion for Solubility Enhancement of Poorly Water Soluble Drug Valsartan. Int. J. Pharm. Sci. Rev. Res., 2013; 22(2):246-251.
13. Magdum SS. Liquisolid technique for dissolution and bioavailability enhancement of poorly soluble drugs. Universal Journal of Pharmaceutical Research 2017; 2(5): 42-49. https://doi.org/10.22270/ujpr.v2i5.RW3
14. ALGIN YAPAR E, BESKAN U, KARAVANA SY. A recent overview of locally administered topical otic dosage forms. Universal Journal of Pharmaceutical Research 2019; 4(4): 39-42. https://doi.org/10.22270/ujpr.v4i4.299
15. Fongemie J, Felix-Getzik E. A Review of NebivololPharmacology and Clinical Evidence.Drugs. 2015; 75(12):1349-71.https://doi.org/10.1007/s40265-015-0435-5
16. Kumar A, Kumar K. Solid dispersion-strategy to enhance solubility and dissolution of poorly water soluble drugs. Universal Journal of Pharmaceutical Research 2017; 2(5): 50-55. https://doi.org/10.22270/ujpr.v2i5.RW4
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).