Vıdya SABALE, Shweta KALE, Vandana ROHİT, Prafulla SABALE

Development and statistical optimization of carvedilol floating beads for chronotherapeutic drug delivery

Background and Aims: The aim of the present research work was to develop and optimize statistically carvedilol floating beads for chronotherapeutic drug delivery. Methods: Multiple unit floating pulsatile beads of carvedilol were prepared by simple ionotropic gelation method intended for chronotherapy of hypertension. Pectin and sodium alginates were used as matrix forming, polymer and sodium bicarbonate was used as floating agent. A 23 full factorial design was applied to investigate the combined effect of three independent formulation variables namely amount of sodium alginate, sodium bicarbonate and calcium chloride on the dependent variables as % entrapment efficiency, floating lag time and drug release percentage. Results: The formulation was optimized and tested based on its drug release pattern which presented minimum drug release in 0.1 N HCl and after 6 h lag time period and showed maximum drug release in 6.8 pH phosphate buffer by burst release within 45 mins. Surface response plots were presented graphically to represent the effect of independent variables on floating lag time, entrapment efficiency and drug release in 0.1 N HCl. The generated mathematical model for each response was validated and checked by formulating three extra-design checkpoint batches. There were no significant changes in drug content, floating lag time, entrapment efficiency and drug release of the formulation following its stability studies at 40 0 C and 75% relative humidity. Conclusion: It was concluded that the floating beads were successfully formulated for chronotherapy of hypertension giving site- and time specific release of drug.

Keywords:

Floating beads drug release, chronotherapy, ionotropic gelation, hypertension,

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Abbas, A. K., & Alhamdany, A.T. (2020). Foating microspheres of enalapril maleate as a developed controlled release dosage form: Investigation of the effect of an ionotropic gelation technique. Turkish Journal of Pharmaceutical Sciences, 17(2), 159-171.http:// dx.doi.org/10.4274/tjps.galenos.2018.15046 google scholar
Abduljabbar, H.N., Badr-Eldin, S.M., & Aldawsari, H.M. (2015). Gas-troretentiveranitidine hydrochloride tablets with combined float-ing and bioadhesive properties: Factorial design analysis, in vitro evaluation and in vivo abdominal x-ray imaging. Current Drug Delivery, 12(5), 578-590. http://dx.doi.org/10.2174/15672018126 66150608101720 google scholar
Ammanage, A., Rodriques, P., Kempwade, A., & Hiremath, R. (2020).Formulation and evaluation of buccal films of piroxicam co-crystals. Future Journal of Pharmaceutical Sciences, 6(16), 1-11. https://doi.org/10.1186/s43094-020-00033-1 google scholar
Aulton, M.E. (2002). Pharmaceutics: The science of dosage form de-sign (2nd ed.). Edinburgh, NY: Churchill Livingstone. google scholar
Dhoranwala, K.A, Shah, P., &Shah, S. (2015). Formulation optimiza-tion of rosuvastatin calcium-loaded solid lipid nanoparticles by 32 full-factorial design. NanoWorld Journal,1(4), 112-121. google scholar
EMA. (2003). Note for guidance on stability testing: Stability test-ing of new drug substances and products. Retrieved from https:// www.ema.europa.eu/en/documents/scientific-guideline/ich-q-1-r2-stability-testing-new-drug-substances-products-step-5_ en.pdf. google scholar
Gupta, R., & Pathak, K. (2008). Optimization studies on floating multiparticulategastroretentive drug delivery system of famoti-dine. Drug Development and Industrial Pharmacy, 34(11), 12011208. https://doi.org/10.1080/03639040802005016 google scholar
Khonsari, F., Zakeri-Milani, P., & Jelvehgarid, M. (2014). Formulation and evaluation of in-vitro characterization of gastic-mucoadhe-sive microparticles/discs containing Metformin hydrochloride. Iranian Journal of Pharmaceutical Research, 13(1): 67-80. google scholar
Lachman, L., Lieberman, H.A., & Kanig, J.L. (1991). The theory and practice of Industrial pharmacy (3rd ed). Bombay:Varghese Pub House. google scholar
Menini, N., Furalanetto, S.,Maestrelli, F.,Pinzauti, S.,& Mura, P. (2008). Response surface methodology in the optimization of chitosan calcium pectinate bead formulation. European Journal of Phar-maceutical Sciences, 35(4), 318-325. https://doi.org/10.1016/j. ejps.2008.07.011 google scholar
Patel, J.K., Dalvadi, H.P., &Shah, D.P. (2011). Time and/or sitespecific drug delivery of floating pulsatile release delivery system. System-atic Reviews in Pharmacy, 2(1), 59-65. google scholar
Patil, C., Indikar, K., &Umarji, B. (2015). Formulation and evaluation of gastroretentive floating beads of cefuroxime axetil. Research Journal of Pharmacy and Technology, 8(1), 13-19. https://doi. org/10.5958/0974-360X.2015.00003.7 google scholar
Patrick, J. S. (2006). Martin’s Physical Pharmacy and Pharmaceu-tical Sciences (5th ed). Philadelphia: Lippincott Williams and Wilkins, pp. 245-2466. google scholar
Pongjanyakul, T., &Puttipipatkhachorn, S. (2007). Xanthan alginate composite gel beads: molecular interaction and in vitro charac-terization. International Journal of Pharmaceutics, 331, 61-71. https://doi.org/10.1016/j.ijpharm.2006.09.011 google scholar
Reddy, A. B., & Reddy, N.D. (2017). Development of multiple-unit floating drug delivery system of clarithromycin: formulation, in vitro dissolution by modified dissolution apparatus, in vivo radio-graphic studies in human volunteers. Drug Research (Stuttgart) 67(7), 412-418.https://doi.org/10.1055/s-0043-102952 google scholar
Sajan, J., Cinu, T.A., Chacko, A.J., Litty, J., &Jaseeda, T. (2009). Chro-notherapeutics and chronoththerapeutical drug delivery system. Tropical Journal of Pharmaceutical Research, 8(5), 467-475.https:// doi.org/10.4314/tjpr.v8i5.48091 google scholar
Shan, Y., & Kawashima, Y. (2012). Current status and approaches to developing press coated chrono delivery drug system. Journal of Controlled Release,157, 331-353.https://doi.org/10.1016/j.jcon-rel.2011.09.065 google scholar
Siepmann, J., Peppas, N.A. (2001). Modeling of drug release from delivery systems based on hydroxypropyl methylcellulose (HPMC), Advanced Drug Delivery Reviews, 48 (2-3) 139-157. google scholar
Singhai, S.K., Chopra, V., Nagar, M., Gautam, N., &Trivedi, P. (2010). Chronotherapy: A novel concept in drug delivery.Der Pharmacia Lettre, 2(3), 136-153. google scholar
Smolensky, M.H., & Peppas, N.A. (2007). Chronobiology, drug de-livery, and chronotherapeutics. Advanced Drug Delivery Reviews, 59,828-851.https://doi.org/10.1016/j.addr.2007.07.001 google scholar
Tanwar, Y., Chauhan, C., & Sharma, A. (2007). Development and evaluation of carvedilol transdermal patches. Acta Pharmaceu-tica, 57(2), 151-159.https://doi.org/10.2478/v10007-007-0012-x google scholar
Torre, M.L., Giunchedi, P., Maggi, L., Stefli, R., Machiste, E.O., &Conte, U. (1998). Formulation and characterization of cal-cium alginate beads containing ampicillin. Pharmaceuti-cal Development and Technology, 3(2), 193-198.https://doi. org/10.3109/10837459809028495 google scholar
Tripathi, K.D. (2002). Essential of Medical Pharmacology (5th ed). New Delhi: Jaypee Brothers Medical Publishers Pvt. Ltd. google scholar
Verma, A., Sharma, M., Verma, N., & Pandit J.K. (2013). Floating algi-nate beads: Studies on formulation factors for improved drug en-trapment efficiency and in vitro release. Farmacia, 61(1), 143-161. google scholar
Zhang, Y., Zhang, Z., & Wu, F. (2003). A novel pulsed-release sys-tem based on swelling and osmotic pumping mechanism, Jour-nal of Controlled Release, 89, 47-55. google scholar