Influence of Polymer Combınatıon Concentratıon on The Characterıstıcs, In Vıtro Release And In Vıvo Lung Deposıtıon of Algınate-Carrageenan Mıcrospheres Encapsulatıng Cıprofloxacın HCl
Keywords:
Respiratory disease, Lung Deposition, Alginate, Carrageenan, Microspheres
Abstract
Inhalation Ciprofloxacin HCl microspheres were formulated with combination of alginate and kappa carrageenan with a total of 1% (F1), 1.5% (F2), and 2% (F3). Aim of this research is to examine effect of polymer concentration on characteristics, release, and lung deposition of microspheres. Microspheres were characterized including loading, efficiency, yield, size, moisture content, mucoadhesivity, and release. Deposition was studied by fluorescence microscopy. Results showed spherical and smooth with size ofless than 2 µm. Loading showed about 18.55% to 29.65%. Entrapment efficiency was 52.86-76.29%. Yield was 49.83-70.72%. Swelling index was less than 10. For moisture content, all formulas demonstrated less than 6.5%. For mucoadhesivity, F1, F2, and F3 showed 0.0090 kg, 0.0217 kg, and 0.0329 kg respectively. It was found that increasing polymer concentration did not affect size, loading, efficiency, and yield of microspheres. Cumulative release at F1, F2, and F3 was 72.64%, 59.25%, and 47.66% respectively in 10 minutes at PBS pH 7.4 with burst release profile. In vivo showed that all formulas were able to deposit on rat lungs and it was found that the intensity were decreased at the 4th hour due to increase of polymer. Remaining intensity indicated that microspheres were able to maintain the drugs loaded.
References
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Musumeci, T., Vicari, L., Ventura, C.A., Gulisano, M., Pignatello, R., dan Puglisi, G., (2006). Lyoprotected Nanosphere Formulations for Paclitaxel Controlled Delivery. Journal of Nanoscience and Nanotechnology, 6; 1–8.
Nokhodchi, A., Jelvhgari, M., Siahi, M. R., Moafari, M. R. (2007). Factors affecting the morphology of benzoyl peroxide microsphonges. Micron, 38; 834-840.
Patil, S.B dan Sawant, K.K., (2009). Development, optimization and in vitro evaluation of alginate mucoadhesive microspheres of carvedilol for nasal delivery. Journal of Microencapsulation, 26(5), 432–443.
Patil, Poonam., Chavanke, Daksha., Wagh, Milind., (2012). A Review of Ionotropic Gelation Method : Novel Approach for Gastroretentive Gelispheres. International Journal of Pharmacy and Pharmaceutical Science, 4; 27 – 32.
Peltola, H., Ukkonen, P., Saxen, H., dan Stab, H., (1998). Single-dose and Steady-state Pharmacokinetics of a New Oral Suspension of Ciprofloxacin in Children. Pediatrics, 658-662.
Purwanti, T., Soeratri, W., dan Zainudin, M., (2018). Characterization of Nisin Microspheres with Combination Matrix Sodium alginate – Gelatin. International Journal of Pharma Research and Health Sciences, 6(6), 2838-2843.
Roh, Y.H., dan Shing, C.S., (2006). Preparation and Characterization of Alginate–Carrageenan Complex Films. Journal of Applied Polymer Science, 99, 3483–3490.
Saravia, P.A dan Riley, C., (2018). Case Study: Cystic Fibrosis in the Newborn. Neonatal Network, 37(3), 164-168.
Setti, C., Suarato, G., Perotto, G., Athanassiou, A., dan Bayer, I.S., (2018). Investigation of in vitro Hydrophilic and Hydrophobic Dual Drug Release from Polymeric Films Produced by Sodium alginat-MaterBi ® Drying Emulsions. European Journal of Pharmaceutics and Biopharmaceutics, 1-32.
Siegel, RA., Rathbone, MJ. (2012). Overview of controlled release mechanisms Fundamentals and applications of controlled release drug delivery, 19-43.
Song, K.H dan Eddington, N.D., (2012). The Influence of Stabilizer and Bioadhesive Polymer on the PermeationEnhancing Effect of AT1002 in the Nasal Delivery of a Paracellular Marker. Archives of Pharmacal Research, 35(2), 359-366.
Tell, Lisa A; Stephens, Kimberly; Teague, Stephen V; Pinkerton, Kent E; Raabe, Otto G. (2015). Study of nebulization delivery of aerosolized fluorescent microspheres to the avian respiratory tract. HHS Public Access, 56(2), 381–386.
Voo, W.P., Ravindra, P., Tey, B.T., Chan, E.S., (2011). Comparison of alginat and pectin based beads for production of poultry probiotic cells. Journal of Bioscience and Bioengineering, 111(3), 294-299.
Yeo, Y., Baek, N., dan Park, K., (2001). Microencapsulation Methods for Delivery of Protein Drugs. Biotechnol. Bioprocess Eng, 6; 213-230.
Zafar, A., Bhattacharyya, A., Bajpai, M., Yasir, M., dan Asif, M., (2013). Formulation and In vitro Characterization of Floating Gel Beads of Metformin Hydrochloride. International Journal of Pharmaceutical Science and Nanotechnology, 7(1), 2356-2362.
Zhang, Y dan Zhang, Y. (2012). Preparation of kappa-carrageenan-chitosan polyelectrolyte gel beads. Zhongguo Zhong Yao Za Zhi, 37(4), 466-47.
Atalla, SMM., Gamal, NGE., Awad HM., (2020). Chitinase of Marine Penicillium chrysogenum MH745129: Isolation, Identification, Production and Characterization as Controller for Citrus Fruits Postharvest Pathogens, Jordan Journal of Biological Sciences, 13(1), 19-28.
Abdelghany, S., Alkhawaldeh, M., & AlKhatib, H. S. (2017). Carrageenan-stabilized chitosan alginate nanoparticles loaded with ethionamide for the treatment of tuberculosis. Journal of Drug Delivery Science and Technology, 39, 442–449.
Badan Pengawas Obat dan Makanan. 2014. Peraturan Kepala Badan Pengawas Obat Dan Makanan Republik Indonesia Nomor 7 Tahun (2014) Tentang Pedoman Uji Toksisitas Nonklinik Secara In Vivo. Jakarta: BPOM
Dashora, K., Saraf, S., Saraf, S. (2007). Effect of processing variables and in-vitro study of microparticulate system of nimesulide, Rev. Bras. Cienc. Farm. 43(4), 555-562.
Dastidar, DG. (2018). Porous microspheres: synthesis, characterization and applications in pharmaceutical & medical fields. International Journal of Pharmaceutics. 548(1), 34-48.
Geller, David E. (2009). Aerosol Antibiotics in Cystic Fibrosis. Respiratory Care, 54(5), 658-670.
Hariyadi, D. M., Hendradi, E., Purwanti, T., Fadil, F. D., Ramadani, C. N. (2013). Effect of Cross Linking Agent and Polymer on the Characteristics of Ovalbumin Loaded Alginate Microspheres. International Journal of Pharmacy and Pharmaceutical Sciences, 6(4), 369-479.
Hariyadi, D.M., Hendradi, E., Irawan MB, (2016). Preparation and Characterization of Ba-Alginate Microspheres Containing Ovalbumin. Jurnal Farmasi Indonesia, 8(1), 303–309.
Hariyadi, D.M., Ma, Y., Wang, Y., Bostrom, T., Malouf, J., Turner, M.S., Bhandari, B., dan Coombes, A.G.A., (2014). The potential for production of freeze-dried oral vaccines using alginat hidrogel microspheres as protein carriers. Journal of Drug Delivery Science Technology, 24(2), 178-184.
Hariyadi, D.M., Purwanti, T., dan Wardani, D., (2016). Stability of Freeze-Dried Ovalbumin-Alginat Microspheres with Different Lyoprotectants. Research Journal. Pharm. and Tech, 9(1), 20-26.
Hariyadi, DM., Hendradi, E., Kusumawati, I., Azzahra, F. (2017). Histopathology Study of Alginate Microspheres Containing Ovalbumin on Liver and Kidney Following Oral Administration and Evaluation of Uptake by Peyer’s Plaque. Turkish Journal of Pharmaceutical Sciences, 14(3), 243-250.
Hariyadi, DM., Purwanti, T., Maulydia, D., Estherline, CA., Hendradi, E., Rahmadi, M. (2021). Performance and drug deposition of kappa‑carrageenan microspheres encapsulating ciprofloxacin HCl: Effect of polymer concentration. Journal of Advanced Pharmaceutical Technology and Research, 12(3), 242-249.
Hidayah, Izzatul., (2016). Pengaruh Konsentrasi Alginat dan Penyambung Silang CaCl2 Terhadap Pelepasan Metformin HCl Dari Mikrosfer Alginat. SKRIPSI. Surabaya: Fakultas Farmasi Universitas Airlangga.
Jain, K., Wainwright, C., dan Smyth, A.R., (2012). Bronchoscopy-guided antimicrobial therapy for cystic fibrosis. Cochrane Database of Systematic Reviews, 12; 1-9.
Jantarathin, S., Borompichaichartkul, C., dan Sanguandeekul, D., (2017). Microencapsulation of probiotic and prebiotic in alginat-chitosan capsules and its effect on viability under heat process in shrimp feeding. Materials Today: Proceedings 4; 6166–6172.
Jin, M., Zheng, Y., dan Hu, Q., (2009). Preparation and characterization of bovine serum albumin alginat/chitosan microspheres for oral administration. Asian Journal of Pharmaceutical Sciences, 4(4), 215-220.
Kaur, J. (2008). A hand-held apparatus for “ nose-only ” exposure of mice to inhalable microparticles as a dry powder inhalation targeting lung and airway macrophages. European journal of pharmaceutical sciences, 34; 56–65
Kolesnyk, I., Konovalova, V., dan Burban, A., (2015). Alginat/Κ-Carrageenan Microspheres and Their Application for Protein Drugs Controlled Release. Chemistry & Chemical Technology, 9(4), 485-492.
Liang, L., Shao, Y., dan Mao, S., (2013). Carrageenan and its applications in drug delivery. Carbohydrate Polymers, 103, 1– 11.
Manjanna, K.M., Kumar, T.M.P., Shivakumar, B., (2010). Calcium Alginat Cross-linked Polymeric Microbeads for Oral Sustained Drug Delivery in Arthritis. Drug Discoveries and Therapeutics, 4(2): 109-122.
Mohamadnia, Z., Zohuriaan-Mehr, M.J., Kabiri, K., Jamshidi, A., dan Mobedi, H., (2012). Ionikally cross-linked carrageenan-alginat hidrogel beads. Journal of Biomaterials Science, Polymer Edition, 19; 47-59.
Musumeci, T., Vicari, L., Ventura, C.A., Gulisano, M., Pignatello, R., dan Puglisi, G., (2006). Lyoprotected Nanosphere Formulations for Paclitaxel Controlled Delivery. Journal of Nanoscience and Nanotechnology, 6; 1–8.
Nokhodchi, A., Jelvhgari, M., Siahi, M. R., Moafari, M. R. (2007). Factors affecting the morphology of benzoyl peroxide microsphonges. Micron, 38; 834-840.
Patil, S.B dan Sawant, K.K., (2009). Development, optimization and in vitro evaluation of alginate mucoadhesive microspheres of carvedilol for nasal delivery. Journal of Microencapsulation, 26(5), 432–443.
Patil, Poonam., Chavanke, Daksha., Wagh, Milind., (2012). A Review of Ionotropic Gelation Method : Novel Approach for Gastroretentive Gelispheres. International Journal of Pharmacy and Pharmaceutical Science, 4; 27 – 32.
Peltola, H., Ukkonen, P., Saxen, H., dan Stab, H., (1998). Single-dose and Steady-state Pharmacokinetics of a New Oral Suspension of Ciprofloxacin in Children. Pediatrics, 658-662.
Purwanti, T., Soeratri, W., dan Zainudin, M., (2018). Characterization of Nisin Microspheres with Combination Matrix Sodium alginate – Gelatin. International Journal of Pharma Research and Health Sciences, 6(6), 2838-2843.
Roh, Y.H., dan Shing, C.S., (2006). Preparation and Characterization of Alginate–Carrageenan Complex Films. Journal of Applied Polymer Science, 99, 3483–3490.
Saravia, P.A dan Riley, C., (2018). Case Study: Cystic Fibrosis in the Newborn. Neonatal Network, 37(3), 164-168.
Setti, C., Suarato, G., Perotto, G., Athanassiou, A., dan Bayer, I.S., (2018). Investigation of in vitro Hydrophilic and Hydrophobic Dual Drug Release from Polymeric Films Produced by Sodium alginat-MaterBi ® Drying Emulsions. European Journal of Pharmaceutics and Biopharmaceutics, 1-32.
Siegel, RA., Rathbone, MJ. (2012). Overview of controlled release mechanisms Fundamentals and applications of controlled release drug delivery, 19-43.
Song, K.H dan Eddington, N.D., (2012). The Influence of Stabilizer and Bioadhesive Polymer on the PermeationEnhancing Effect of AT1002 in the Nasal Delivery of a Paracellular Marker. Archives of Pharmacal Research, 35(2), 359-366.
Tell, Lisa A; Stephens, Kimberly; Teague, Stephen V; Pinkerton, Kent E; Raabe, Otto G. (2015). Study of nebulization delivery of aerosolized fluorescent microspheres to the avian respiratory tract. HHS Public Access, 56(2), 381–386.
Voo, W.P., Ravindra, P., Tey, B.T., Chan, E.S., (2011). Comparison of alginat and pectin based beads for production of poultry probiotic cells. Journal of Bioscience and Bioengineering, 111(3), 294-299.
Yeo, Y., Baek, N., dan Park, K., (2001). Microencapsulation Methods for Delivery of Protein Drugs. Biotechnol. Bioprocess Eng, 6; 213-230.
Zafar, A., Bhattacharyya, A., Bajpai, M., Yasir, M., dan Asif, M., (2013). Formulation and In vitro Characterization of Floating Gel Beads of Metformin Hydrochloride. International Journal of Pharmaceutical Science and Nanotechnology, 7(1), 2356-2362.
Zhang, Y dan Zhang, Y. (2012). Preparation of kappa-carrageenan-chitosan polyelectrolyte gel beads. Zhongguo Zhong Yao Za Zhi, 37(4), 466-47.
Published
2023-03-31
How to Cite
Hariyadi, D. M., Erawati, T., Rosita, N., Desanto, G., Firman, A., Azizah, N., Hendradi, E., & Rahmadi, M. (2023). Influence of Polymer Combınatıon Concentratıon on The Characterıstıcs, In Vıtro Release And In Vıvo Lung Deposıtıon of Algınate-Carrageenan Mıcrospheres Encapsulatıng Cıprofloxacın HCl. Indonesian Journal of Pharmacy, 34(1), 162-173. https://doi.org/10.22146/ijp.4162
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Research Article
