Formulation and characterization of nimodipine in situ gels for oral delivery

https://doi.org/10.53730/ijhs.v6nS1.6102

Authors

  • S. K. Madhavi Harika Osmania University, Hyderabad, Telangana
  • M. Sudhakar Malla Reddy college of pharmacy, Hyderabad, Telangana
  • V. V. Basava Rao Osmania University, Hyderabad, Telangana

Keywords:

Oral delivery, Floating in-situ gel, Nimodipine, In vivo Pharmacokinetic study, Sodium Alginate

Abstract

To formulate and evaluate Nimodipine floating in situ gels for oral delivery in order to enhance its residence time and to overcome the inherent drawbacks associated with conventional oral formulations like tablets and capsules. As Nimodipine is a BCS Class II drug, first Nimodipine solid dispersions were made to enhance its solubility. Solvent evaporation method was employed for this. Then in situ gel formulations were prepared using the optimized solid dispersion formulations. Sodium alginate and HPMC K100M were used as gelling agent and viscosifying agent respectively. In vitro characterization like gelling capacity, floating time, drug content, viscosity, % cumulative drug release studies were performed. In vivo pharmacokinetic parameters were studied. Infrared spectroscopy ruled out drug-excipient interactions. The release pattern showed a burst effect in the first 30 minutes followed by a moderate steady release for 12 hours. Stability testing indicated that the formulation remained stable with no significant changes in percent cumulative drug release and viscosity. In vivo pharmacokinetic study results were satisfactory. A promising, stable, sustained release, liquid oral floating in-situ gelling systems of Nimodipine were successfully developed and evaluated. Oral in situ gels could be good alternative for geriatric and pediatric population who have trouble swallowing solid medications.

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References

Ahmed, M.G., Kapoor, C., Adinarayana, S., 2017. Formulation and evaluation of oral sustained in situ gelling system of roxatidine. Indones. J. Pharm. 28, 179–184. https://doi.org/10.14499/indonesianjpharm28iss3pp179 DOI: https://doi.org/10.14499/indonesianjpharm28iss3pp178

Artiga-Artigas, M., Acevedo-Fani, A., Martín-Belloso, O., 2017. Effect of sodium alginate incorporation procedure on the physicochemical properties of nanoemulsions. Food Hydrocoll. 70, 191–200. https://doi.org/10.1016/j.foodhyd.2017.04.006 DOI: https://doi.org/10.1016/j.foodhyd.2017.04.006

Behera, A.L., Sahoo, S.K. and Patil, S.V., 2010. Enhancement of solubility: A pharmaceutical overview. Der Pharm. Lett. 2, 310–318.

Geethalakshmi, A., Karki, R., Sagi, P., Jha, S.K., Venkatesh, D.P., 2013. Temperature triggered in situ gelling system for betaxolol in glaucoma. J. Appl. Pharm. Sci. 3, 153–159. https://doi.org/10.7324/JAPS.2013.30227 DOI: https://doi.org/10.7324/JAPS.2013.30227

Hou, P., Ni, J., Cao, S., Lei, H., Cai, Z., Zhang, T., Yu, F., Tan, Q., 2013. Preparation and evaluation of solid dispersions of a new antitumor compound based on early-stage preparation discovery concept. AAPS PharmSciTech 14, 629–638. https://doi.org/10.1208/s12249-013-9948-y DOI: https://doi.org/10.1208/s12249-013-9948-y

Jaipal, A., Pandey, M.M., Charde, S.Y., Raut, P.P., Prasanth, K. V., Prasad, R.G., 2015. Effect of HPMC and mannitol on drug release and bioadhesion behavior of buccal discs of buspirone hydrochloride: In-vitro and in-vivo pharmacokinetic studies. Saudi Pharm. J. 23, 315–326. https://doi.org/10.1016/j.jsps.2014.11.012 DOI: https://doi.org/10.1016/j.jsps.2014.11.012

Javia, A., Kore, G., Misra, A., 2021. Polymers in Nasal Drug Delivery: An Overview, in: Applications of Polymers in Drug Delivery. pp. 305–332. https://doi.org/10.1016/b978-0-12-819659-5.00011-2 DOI: https://doi.org/10.1016/B978-0-12-819659-5.00011-2

Kanamala, M., Wilson, W.R., Yang, M., Palmer, B.D., Wu, Z., 2016. Mechanisms and biomaterials in pH-responsive tumour targeted drug delivery: A review. Biomaterials 85, 152–167. https://doi.org/10.1016/j.biomaterials.2016.01.061 DOI: https://doi.org/10.1016/j.biomaterials.2016.01.061

Khan, A.D., Bajpai, M., 2010. Floating drug delivery system: An overview. Int. J. PharmTech Res. 2, 2497–2505. https://doi.org/10.52711/2231-5659.2021.00046 DOI: https://doi.org/10.52711/2231-5659.2021.00046

Kilicarslan, M., Ilhan, M., Inal, O., Orhan, K., 2018. Preparation and evaluation of clindamycin phosphate loaded chitosan/alginate polyelectrolyte complex film as mucoadhesive drug delivery system for periodontal therapy. Eur. J. Pharm. Sci. 123, 441–451. https://doi.org/10.1016/j.ejps.2018.08.007 DOI: https://doi.org/10.1016/j.ejps.2018.08.007

Kubo, W., Konno, Y., Miyazaki, S., Attwood, D., 2004. In situ gelling pectin formulations for oral sustained delivery of paracetamol. Drug Dev. Ind. Pharm. 30, 593–599. https://doi.org/10.1081/DDC-120037490 DOI: https://doi.org/10.1081/DDC-120037490

Liu, Z., Li, J., Nie, S., Liu, H., Ding, P., Pan, W., 2006. Study of an alginate/HPMC-based in situ gelling ophthalmic delivery system for gatifloxacin. Int. J. Pharm. 315, 12–17. https://doi.org/10.1016/j.ijpharm.2006.01.029 DOI: https://doi.org/10.1016/j.ijpharm.2006.01.029

Maheswaran, A., Padmavathy, J., Nandhini, V., Saravanan, D., Angel, P., 2017. Formulation and evaluation of floating oral in situ gel of diltiazem hydrochloride. Int. J. Appl. Pharm. 9, 50–53. https://doi.org/10.22159/ijap.2017v9i1.15914 DOI: https://doi.org/10.22159/ijap.2017v9i1.15914

Mathews, R., Prakash Rao, B., Konde, A., Sudarshan, S., Taha, N.A., Suresh, C., 2019. Statistical design and development of a liquid oral floating in situ gel of metformin hydrochloride for sustained release: Pharmacodynamic and toxicity (histopathology) studies. Int. J. Appl. Pharm. 11, 96–104. https://doi.org/10.22159/ijap.2019v11i5.30793 DOI: https://doi.org/10.22159/ijap.2019v11i5.30793

Miyazaki, S., Suzuki, S., Kawasaki, N., Endo, K., Takahashi, A., Attwood, D., 2001. In situ gelling xyloglucan formulations for sustained release ocular delivery of pilocarpine hydrochloride. Int. J. Pharm. 229, 29–36. https://doi.org/10.1016/S0378-5173(01)00825-0 DOI: https://doi.org/10.1016/S0378-5173(01)00825-0

Mohammadi, H., Kumar, V.H., 2019. Formulation and Evaluation of Solid Dispersion Incorporated Fast Disintegrating Tablets of Tenoxicam Using Design of Experiment. Int. J. Pharm. Sci. Drug Res. 11. https://doi.org/10.25004/ijpsdr.2019.110106 DOI: https://doi.org/10.25004/IJPSDR.2019.110106

Mooranian, A., Negrulj, R., Mathavan, S., Martinez, J., Sciarretta, J., Chen-Tan, N., Mukkur, T.K., Mikov, M., Lalic-Popovic, M., Stojancěvić, M., Golocorbin-Kon, S., Al-Salami, H., 2014. Stability and release kinetics of an advanced gliclazide-cholic acid formulation: The Use of artificial-cell microencapsulation in slow release targeted oral delivery of antidiabetics. J. Pharm. Innov. 9, 150–157. https://doi.org/10.1007/s12247-014-9182-5 DOI: https://doi.org/10.1007/s12247-014-9182-5

Nassour, L., Hasan, I., El-Hammadi, M., Abboud, H., 2014. Floating in-situ-gelling gellan formulations of metformin hydrochloride. J. Chem. Pharm. Res. 6, 1509–1517.

Pande, S.D., Vaidya, K.P. V., Gulhane, K.P.N., 2013. Floating Drug Delivery System (FDDS): A New Way for Oral drug delivery system. Int. J. Pharm. Clin. Sci. 3, 1–13.

Pandya, K., Aggarwal, P., Dashora, A., Sahu, D., Garg, R., Pareta, L.K., Menaria, M., Joshi, B., 2013. Formulation and Evaluation of Oral Floatable in-Situ Gel of Ranitedine Hydrochloride. J. Drug Deliv. Ther. 3. https://doi.org/10.22270/jddt.v3i3.516 DOI: https://doi.org/10.22270/jddt.v3i3.516

Pashikanti, S., Jyothsna, B., 2019. Formulation and evaluation of floating in situ gel of ciprofloxacin. Int. J. Appl. Pharm. 11, 198–204. https://doi.org/10.22159/ijap.2019v11i1.28603 DOI: https://doi.org/10.22159/ijap.2019v11i1.28603

Patel, D.M., Patel, D.K., Patel, C.N., 2011. Formulation and Evaluation of Floating Oral In Situ Gelling System of Amoxicillin . ISRN Pharm. 2011, 1–8. https://doi.org/10.5402/2011/276250 DOI: https://doi.org/10.5402/2011/276250

Patel, M., Patel, D., 2006. Fast dissolving valdecoxib tablets containing solid dispersion of valdecoxib. Indian J. Pharm. Sci. 68, 222–226. https://doi.org/10.4103/0250-474X.25719 DOI: https://doi.org/10.4103/0250-474X.25719

Prajapati, V.D., Jani, G.K., Zala, B.S., Khutliwala, T.A., 2013. An insight into the emerging exopolysaccharide gellan gum as a novel polymer. Carbohydr. Polym. 93, 670–678. https://doi.org/10.1016/j.carbpol.2013.01.030 DOI: https://doi.org/10.1016/j.carbpol.2013.01.030

Qiu, Y., Park, K., 2012. Environment-sensitive hydrogels for drug delivery. Adv. Drug Deliv. Rev. 64, 49–60. https://doi.org/10.1016/j.addr.2012.09.024 DOI: https://doi.org/10.1016/j.addr.2012.09.024

Qureshi, D., Nayak, S.K., Maji, S., Anis, A., Kim, D., Pal, K., 2019. Environment sensitive hydrogels for drug delivery applications. Eur. Polym. J. 120. https://doi.org/10.1016/j.eurpolymj.2019.109220 DOI: https://doi.org/10.1016/j.eurpolymj.2019.109220

Rajinikanth, P.S., Balasubramaniam, J., Mishra, B., 2007. Development and evaluation of a novel floating in situ gelling system of amoxicillin for eradication of Helicobacter pylori. Int. J. Pharm. 335, 114–122. https://doi.org/10.1016/j.ijpharm.2006.11.008 DOI: https://doi.org/10.1016/j.ijpharm.2006.11.008

Rao, G.U., 2012. International Journal of Comprehensive Pharmacy Buoyant Sustained Release Drug Delivery Systems Current Potentials Advancements and Role of Polymers : a Review. Pharm. Glob. 03, 1–5. DOI: https://doi.org/10.7897/2230-8407.04601

Rathod, H.J., Mehta, D.P., Yadav, J.S., 2014. A review on stomach specific floating in-situ gel. Int. J. Pharm. Res. 6, 19–30.

Ravi Kumar, M.N., 2000. Nano and microparticles as controlled drug delivery devices. J. Pharm. Pharm. Sci. 3, 234–258.

Shoaeba, S., Sharav, D., Hitesh, J., Asit, S., Meshram, D.B., 2021. Formulation and Evaluation of in Situ Ophthalmic Gel. J. Chem. Pharm. Res. 9, 25–29. DOI: https://doi.org/10.18231/j.joapr.2021.25.29

Srinivas, M., Singh, A., 2021. Enhancement of Solubility and Dissolution Rate of BCS Class-II Fluvoxamine Tablets using Solvent Evaporation Solid Dispersion Technique. J. Pharm. Res. Int. 44–53. https://doi.org/10.9734/jpri/2021/v33i31b31689 DOI: https://doi.org/10.9734/jpri/2021/v33i31B31689

Suresh, S., Bhaskaran, S., 2005. Nasal drug delivery: An overview. Indian J. Pharm. Sci. 67, 19–25.

Swamy, N.G.N., Abbas, Z., 2012. Mucoadhesive in situ gels as nasal drug delivery systems: An overview. Asian J. Pharm. Sci. 7, 168–180.

Thomas, L.M., 2014. Formulation and evaluation of floating oral in-situ gel of metronidazole. Int. J. Pharm. Pharm. Sci. 6, 265–269.

Uchida, T., Yasutake, T., Goto, S., 1992. Utility of Mixture of Commercially Available Polymers as Constituents of Sustained-Release Microcapsules Containing Cefadroxil or Theophylline1e. Chem. Pharm. Bull. 40, 463–466. https://doi.org/10.1248/cpb.40.463 DOI: https://doi.org/10.1248/cpb.40.463

Vipul, V., Basu, B., 2013. Formulation and characterization of novel floating in-situ gelling system for controlled delivery of ramipril. Int. J. Drug Deliv. 5, 43–55.

Xu, H., Shi, M., liu, Y., Jiang, J., Ma, T., 2014. A Novel In Situ Gel Formulation of Ranitidine for Oral Sustained Delivery. Biomol. Ther. (Seoul). 22, 161–165. https://doi.org/10.4062/biomolther.2013.109 DOI: https://doi.org/10.4062/biomolther.2013.109

Published

22-04-2022

How to Cite

Harika, S. K. M., Sudhakar, M., & Rao, V. V. B. (2022). Formulation and characterization of nimodipine in situ gels for oral delivery. International Journal of Health Sciences, 6(S1), 5445–5463. https://doi.org/10.53730/ijhs.v6nS1.6102

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Section

Peer Review Articles