PENGARUH RASIO KITOSAN DAN ATENOLOL TERHADAP KARAKTERITIK FISIK DAN PROFIL PELEPASAN PADA MIKROSFER ATENOLOL
Abstract
Abstrak
Hipertensi banyak dialami oleh geriatri yang cenderung sulit menelan tablet konvensional, sehingga modifikasi bentuk sediaan fast disintegrating tablet (FDT) diharapkan dapat mengatasi masalah tersebut. Taste masking merupakan suatu pertimbangan penting dalam merancang formula FDT. Sehingga dikembangkan teknik taste masking dengan metode enkapsulasi. Penelitian ini bertujuan untuk menganalisa pengaruh rasio kitosan dan atenolol terhadap diameter ukuran, efisiensi penjerapan, dan profil pelepasan mikrosfer atenolol dengan metode emulsifikasi dan mengetahui formula optimum berdasarkan diameter ukuran, efisiensi penjerapan, dan profil pelepasannya. Formula mikrosfer atenolol dibuat dengan rasio kitosan dan atenolol 1 : 0,5 (FI), 1 : 1 (FII), dan 1 : 1,5 (FIII). Karakterisasi mikrosfer yang dilakukan meliputi sifat alir, ukuran dan distribusi ukuran, efisiensi penjerapan, dan profil pelepasan. Berdasarkan hasil penelitian, efisiensi penjerapan tertinggi ditunjukkan pada FI dengan hasil sebesar 68,46 ± 8,95 % yang berbeda signifikan berdasarkan analisis statistika (p < 0,05). Profil pelepasan yang paling tinggi juga ditunjukkan pada FI yaitu 73,162 ± 4.507 % dalam 30 menit yang berbeda signifikan berdasarkan analisis statistic (p<0,05). Kesimpulan penelitian ini adalah variasi rasio kitosan dan atenolol tidak berpengaruh signifikan terhadap sifat alir dan diameter ukuran mikrosfer, jumlah kitosan yang lebih tinggi menghasilkan efisiensi penjerapan dan persen pelepasan yang lebih besar, dan formula mikrofer yang menghasilkan karakteristik fisik dan profl pelepasan yang optimum adalah formula dengan rasio kitosan dan atenolol sebesar 1 : 0,5.
Kata Kunci : Atenolol, Emulsifikasi, Hipertensi, Kitosan, Taste MaskingÂ
References
Guyton AC, Hall JE. 2006. Buku Ajar Fisiologi Kedokteran. Edisi 11. Penerjemah: Irawati, Ramadani D, Indriyani F. Jakarta: Penerbit Buku Kedokteran EGC
Kemenkes RI. 2013. Gambaran Kesehatan Lanjut Usia di Indonesia : Pusat Data dan Informasi Kementerian Kesehatan RI. Kemenkes RI. Jakarta
Stanley, Mickey dan Patricia Gauntlett Beare. 2006. Buku Ajar Keperawatan Gerontik, Edisi2. EGC. Jakarta
Pflieger, Matthew, Bradford T. Winslow, Kyle Mills, Ira M. Dauber. Medical Management of Stable Coronary Artery Disease. American Family Physician, 2011, 83 (7) : 819 – 826
Tripathi KD. Essential of Medical Pharmacology. 5th edn. Jaypee Brothers Medical Publishers Ltd., New Delhi 2003; 129-130.
Koseki, T, H. Onishin, Y. Takahashi, M. Uchida and Y. Machida, Development of novel fast-dis-integrating tablets by direct compression using sucrose stearic acid ester as a disintegration-ac-celerating agent, Chem. Pharm. Bull, 2008, 56 : 1384–1388
Wagh et al. Taste Masking Methods and Techniques in Oral Pharmaceuticals: Current Perspectives. Journal of Pharmacy Research, 2009, 2(6) : 1049-1054
Pokharkar, Versha B.Taste Masking Of Pharmaceuticals. Indian J Pharm Sci. April 2005.
Kumar T.M. Pramod, Manjanna, KM., Shivakumar B. Microencapsulation: An Acclaimed Novel Drug - Delivery System for NSAIDs in Arthritis. Critical Reviews™ in Therapeutic Drug Carrier Systems, 2010, 27(6) : 501–532
Mitra, Analava and Baishakhi Dey. Chitosan Microspheres in Novel Drug Delivery Systems. Indian J Pharm Sci, 2011, 73(4) : 355–366.
Zuidam, N.J. and Shimoni, E. 2010. Overview of microencapsulates for use in food products or processes and methods to make them. In Encapsulation Technologiesfor Active Food Ingredients and Food Processing, N.J. Zuidam and V.A. Nedovic, editors. Springer, London, U.S.A., pp. 3-29.
Bhumkar, D.R. dan Pokharkar, V.B., 2006, Studies on Effect of pH on Crosslinking of Chitosan with Sodium Tripolyphosphate: A Technical Note, AAPS Pharm Sci Tech., 7(2), E1-E6
Aleksandra, Amelian, Marta Szekalska, Patrycja Ciosek, Anna Basa, Katarzyna Winnicka. Characterization and taste masking evaluation of microparticles with cetirizine dihydrochloride and methacrylate-based copolymer obtained by spray drying. Acta Pharm, 2016, 67 : 113–124
Bora, D, P Borude, K Bhise. Taste Masking by Spray-Drying Technique. AAPS Pharm, Sci. Tech. 2008. 9(4) : 1159-1164.
Lieberman HA, Lachman L, Schwartz. 1989. Pharmaceutical Dosage Forms: Tablet Volume 1. Marcel Decker Inc, New York
The United States Pharmacopeial Convention. 2006. USP30-NF25. The United States Pharmacopeial Convention, United States of America
Gaisford, Simon, Mark Saunders. 2013. Essentials of Pharmaceutical Preformulation. John Wiley & Sons Ltd. United Kingdom
Nayak, Usha Y, Gopal V. Shavi, M. Sreenivasa Reddy. A. Karthik, Praful B. Deshpande, A. Ranjith Kumar, N. Udupa. Sustained release optimized formulation of anastrozole-loaded chitosan microspheres: in vitro and in vivo evaluation. J Mater Sci: Mater Med, 2011, 22 : 865–878
Thanoo, B.C., M.C. Sunny and A. Jayakrishnan, 1992. Cross-linked chitosan microspheres: Preparation and evaluation as a matrix for the controlled release of pharmaceuticals. J. Pharm. Pharmacol., 44: 283-286.
L. Lusi, “Cara mengetahui ukuran suatu partikel,†Nanotech Indonesia. 28-Feb-2011.
Bao W, J. Zhou, J. Luo, D. Wu. Journal of Microencapsulation, 2006, 23 : 471–479
Caetano, Liliana A, Antonio J. Almeida, Lidia M.D. Goncalves. Effect of Experimental Parameters on Alginate/Chitosan Microparticles for BCG Encapsulation. Mar. Drugs, 2016, 14 (90) : 1 -30Depkes RI. 1995. Farmakope Indonesia Edisi IV. Jakarta : Ditjen Pengawasan Obat dan Makanan
Depkes RI. 1995. Farmakope Indonesia Edisi IV. Jakarta : Ditjen Pengawasan Obat dan Makanan
Hurtado, FK, Raanello A, Torres BGS, Souto GD, Beck RCR, Rolim CMB. Development of a discriminating in vitro dissolution method for the poorly soluble drug rimonabant : Effect of Formulation Variables on Dosage Form Release Profiles. Dissolution. 2012 : 30 – 36
Júnior, AnÃbal de Freitas Santos, Igor Santos Barbosa 1, Venyson Lima dos Santos, Rangel Leal Silva, Edimar Caetite Junior. Test of dissolution and comparison of in vitro dissolution profiles of coated ranitidine tablets marketed in Bahia, Brazil. Brazilian Journal of Pharmaceutical Sciences, 2014, 50 (1)
Kondi, Vanitha, Ramesh Alluri. Optimization And Evaluation Of Prazosin Hydrochloride Floating Microspheres Using Response Surface Methodology. IOSR Journal of Pharmacy and Biological Sciences, 2015,10 (3) Ver. II : 68 – 68
Jain AK, Jain CP, Buoyant Microspheres of Famotidine: An Approachable Dosage Form for Gastric Treatment, J Young Pharm, 2009, 1 : 20 - 23
Pavanveena, C., K Kavitha, SN Anil Kumar. International Journal of Applied Pharmaceutics, 2010, Vol 2 Issue 2.
Hassan, EE., Parish RC, Gallo JM. 1992. Optimized Formulation of Magnetic Chitosan Microsphere Containing the Anticancer agent, oxantrazole. Pharm Res 9 : 390 – 397
Kiliçarslan M1, Baykara T. The effect of the drug/polymer ratio on the properties of the verapamil HCl loaded microspheres. Int J Pharm. 2003, 252(1-2) : 99-109.
Biswal I. A Dinda, S. Mohanty, M Dhara, D. Das, K.A. Chowdary. Influence of Drug/Polymer Ratio on the Encapsulation Efficiency of Highly Hydrophilic Drug. Asian Journal of Chemistry, 2011, 23 (5) : 1973-1978
Malvern Instruments Limited. 2016. Top tips for avoiding particle sizing failures with your laser diffraction method. Grovewood Road, Malvern, Worcestershire, UK.
Jelvehgari et al. Effect of Formulation and Processing Variables on the Characteristics of Tolmetin Microspheres Prepared by Double Emulsion Solvent Diffusion Method. Indian J Pharm Sci, 2010, 72 (1) : 72-78.
Bodmeier, R.Oh, K.H., Pkamar, Y. 1989. Preparation and evaluation of drug containing chitosan beads. Drug development and industrial pharmacy, 15: 1475-1494.
Gaur, Praveen Kumar, Shikha Mishra, Meenakshi Bajpai. Formulation and evaluation of controlled-release of telmisartan microspheres: In vitro/in vivo study. Journal of Food and Drug Analysis, 2014, 22 (4) : 542-548
Rowe, Raymond C. Paul J. Sheskey, Sian C Owen. 2006. Handbook of Pharmaceutical Excipient. Pharmaceutical Press and American Pharmacist Association, USA
Nishimura, S.I., Kohgo, O., Kurita, K. and Kuzuhara, H. (1991) Chemospecific manipulations of a rigid polysaccharide-syntheses of novel chitosan derivatives with excellent solubility in common organic-solvents by regioselective chemical modifications. Macromolecules, 24(17), 4745-4748.
Varma, Manthena V.S., Aditya M. Kaushal, Alka Garg and Sanjay Garg. Factors Affecting Mechanism and Kinetics of Drug Release from Matrix-Based Oral Controlled Drug Delivery Systems. Am J Drug Deliv .2004. 2(1) : 43 – 57
Sundar, S., Kundu, J., Kundu, SC, Biopolymeric Nanoparticles, Sci. Technol. Adv. Mater, 2010, 11 : 1-13
Muzzarelli, R. V., Baldassare, F. Conti, P. Ferrara, dan G. Biagini. 1988. Biological Activity of Chitosan: Ultrastructural Study Biomaterial. 9:247-252.
Gupta, K. C.,F. H. Jabrail. Effect of molecular weight and degree of deacetylation on controlled release of isoniazid from chitosan microspheres. Polymers for Advanced Technologu, 2008, 19 (5) : 432–441