Copovidone-Based Stable Nebivolol Hydrochloride Formulation: Dissolution and Characterization Studies Stable Nebivolol Hydrochloride Formulation
Iranian Journal of Pharmaceutical Sciences,
Vol. 19 No. 4 (2023),
24 April 2024
,
Page 325-338
https://doi.org/10.22037/ijps.v19i4.42029
Abstract
Copovidone Based Stable Nebivolol Hydrochloride Formulation: Dissolution and Characterization Studies. The study aimed to develop a formulation for the poorly water-soluble drug Nebivolol Hydrochloride. The formulation was carried out in two stages. Stage I attempts to enhance the drug's solubility, while stage II deals with the development of a drug-incorporated tablet formulation. Various strategies with different solid dispersion techniques, like solvent evaporation, melt fusion, and kneading, were used to improve the drug's solubility. Drugs and carriers were mixed with the ratios 1:1, 1:2, 1:3, and 1:4. Apart from the solid dispersion method, the hydrophilic carrier was activated with an acidifier and then mixed with the drug. Preformulation studies were conducted, which included API characterization, solubility measurement over a physiological pH range, and drug-excipients compatibility study. FTIR, DSC, and XRD characterized the developed solid dispersion, which shows the drug exists in the amorphous form in the solid dispersion with no molecular interaction. The dissolution profile revealed a significant improvement in drug solubility with solid dispersion compared to pure drugs. Solid dispersion prepared with Drug, Plasdone, and Tartaric Acid exhibits the most improved solubility and formulated immediate release tablet. Stability studies indicate excellent stability of formulation over six months at accelerated and real-time conditions.
- Acidifier
- BCS class
- Copovidone
- Nebivolol hydrochloride
- Solid dispersion
- Plasdone
How to Cite
References
Sanklecha M. A systematic review on solid dispersion: Enhancing the solubility of poorly soluble
drug. Austin J Nanomed Nanotechnol. (2020) 8(1): 1059.
Dhirendra K, Lewis S, Udupa N, Atin K. Solid Dispersions: a review. Pak J Pharm Sci (2009) 22(2): 234- 236.
ICH Harmonised guideline, Biopharmaceutics classification system-based biowaivers M9 (2019)
-9.
Lipinski C. Avoiding investment in doomed drugs, is poor solubility an industry wide problem. Current Drug Discovery (2001) 4: 17-19.
Niazi S. Handbook of Bioequivalence Testing. CRC Press. (2014) 162.
Drug Bank. http:// www.drugbank.ca.
Khalaf Z, Ardelean S, Draganescu D, Ardelean M, Lupuleasa D. Delivery of Nebivolol Hydrochloride from immediate release tablets. Studia Universitatis “Vasile Goldis”, Seria stiintele Vietii (2015) 25 (1):47-50.
Shah I, Bhatt S, Yadav A. Enhancement of solubility and dissolution of Nebivolol by solid dispersion technique. Int. j. pharm. pharm. sci. (2014) 6(7): 566-571.
Avachat A, Raut V. Solubility and dissolution enhancement of Nebivolol hydrochloride using hydrophilic carriers. Asian J. Pharm. Sci. (2012) 7 (5): 337-345.
Ashland.com. https://www.ashland.com/industries/pharmaceutical/oral-solid-dose/plasdone-s-630-and-s630-ultra.
Raymond. C, Paul. S. Handbook of Pharmaceutical Excipients. Pharmaceutical Press (2009) 6.
Rahman, M., Lester J., Keshtmand, M., El-saleh, F., Farzana, V. and Durig, T. Comparison of amorphous solid dispersion of piroxicam in plasdone S-630 copovidone prepared by spary drying and hot melt extrusion. Ashland Pharmaceutical Technical Report (2013) 93.
Bystolic.2008 Jun. USFDA. https://www.accessdata.fda.gov.
Sun, Y., Rui, Y., Wenliang, Z. and Xing, T. Nimodipine semi-solid capsules containing solid dispersion for improving dissolution. International Journal of Pharmaceutics (2008) 359: 144–149.
Trana T, Trana P, Choib H. Hanc H, Leea B. The roles of acidifiers in solid dispersions and physical mixtures. Int. J. Pharm. (2010) 384: 60–66.
Saygh M. S. Enhanced dissolution rate of tiaprofenic acid using Gelucire44/1. Scientia Pharmaceutica (2002) 70 (3): 295-307.
Roussin, P. and Laforet, J. Investigating semi-solid formulations: Physical characterization and stability study of Gelucire 44/14. Farmacevtski Vestnik (1997) 8 :260-261.
Fernandez, S., Chevrier, S., Ritter, N., Mahler, B., Demarne, F., Carrière, F. and Jannin, V. In Vitro Gastrointestinal Lipolysis of Four Formulations of Piroxicam and Cinnarizine with the Self Emulsifying Excipients Labrasol and Gelucire 44/14. Pharmaceutical Research (2009) 26 (8): 1901–1910.
El-Badry M, Fetih G, Fathy M. Improvement of solubility and dissolution rate of indomethacin by solid dispersions in Gellucire 50/13 and PEG4000. Saudi Pharm J (2009) 17: 217–225.
Sathigari, S. K., Radhakrishnan, V. K., Davis, V. A., Parsons, D. L., and Babu, R. J. Amorphous-state characterization of efavirenz—Polymer hot-melt extrusion systems for dissolution enhancement’, Journal of Pharmaceutical Sciences (2012) 101 (9): 3456–3464.
Mai, N. N. S., Otsuka, Y., Kawano, Y., and Hanawa, T. Preparation and characterization of solid dispersions composed of curcumin, hydroxypropyl cellulose and/or sodium dodecyl sulfate by grinding with vibrational ball milling. Pharmaceuticals (2020) 13 (11): 383.
Munir, R., Hadi, A., Khan, S. D., Asghar, S., Irfan, M., Khan, I. U., Hameed, M., Inam, S., Islam, N., Hassan, S. F., Ishtiaq, M., Akhtar Shah, P., Iqbal, M. S., Khalid Syed, H., Khames, A., and A. S. Abourehab, M. Solubility and Dissolution Enhancement of Dexibuprofen with Hydroxypropylbetacyclodextrin (HPβCD) and Poloxamers (188/407) Inclusion Complexes: Preparation and In Vitro Characterization. Polymers (2022) 14 (3): 579.
- Abstract Viewed: 57 times
- IJPS_Volume19_Issue4_Pages325-338 Downloaded: 55 times