International Journal of Drug Delivery Technology
Volume 14, Issue 3

Development and Optimization of Gellan Gum-Based Gastro-Retentive Microbeads for Enhanced Controlled Release of Acyclovir

Ranjan Kumar Sethi1, Sunit Kumar Sahoo1*, Pravat Ranjan Guru2

1University Department of Pharmaceutical Sciences, Utkal University, Vani Vihar, Bhubaneswar, Odisha, India.

2Dadhichi College of Pharmacy, Vidya-Vihar, Sundargram, Cuttack, Odisha, India. 

Received: 15th March, 2024; Revised: 23rd May, 2024; Accepted: 13th August, 2024; Available Online: 25th September, 2024 

ABSTRACT

Modified release systems offer enhanced spatial and temporal control over drug delivery, leading to better blood plasma profiles, targeted therapy, reduced side effects, and improved patient compliance. Recent advancements focus on using biocompatible polymers to achieve sustained or controlled drug release, particularly for gastroretentive systems that enhance oral bioavailability and minimize dose-dependent toxicity. This study explores the formulation of floating microbeads of acyclovir (ACV) using various hydrophilic polymers. The prototype oral formulations demonstrated superior micrometric properties, including bulk density, tapped density, Carr’s index, Hausner’s ratio, angle of repose, average particle size, yield, and drug content. In-vitro dissolution studies revealed controlled release characteristics, with optimal floating time and entrapment efficiency achieved using specific concentrations of olive oil and polymers. Drug release trailed the Korsmeyer-Peppas model, indicating a diffusion- controlled mechanism. The formulations exhibited good storage stability, in-vivo floating ability, and higher bioavailability in rabbits compared to ACV solutions. The results suggest that hydrophilic polymers are effective for formulating floating microbeads with controlled release and reproducible profiles.

Keywords: Acyclovir, Microbeads, Polymer, Drug delivery.International Journal of Drug Delivery Technology (2024); DOI: 10.25258/ijddt.14.3.21

How to cite this article: Sethi RK, Sahoo SK, Guru PR. Development and Optimization of Gellan Gum-Based Gastro-Retentive Microbeads for Enhanced Controlled Release ofAcyclovir. International Journal of Drug Delivery Technology. 2024;14(3):1396-1403.

REFERENCES

  1. Singh BN, Kim Floating drug delivery systems: an approach to oral controlled drug delivery via gastric retention. Journal of Controlled Release. 2000;63(3):235-259. https://doi.org/10.1016/ S0168-3659(99)00204-7
  2. Deshpande AA, Rhodes CT, Shah NH, Malick Controlled- release drug delivery systems for prolonged gastric residence: an overview. Drug development and industrial pharmacy. 1996;22(6):531-539. https://doi.org/10.3109/03639049609108355
  3. Hwang SJ, Park H, Park K. Gastric retentive drug-delivery Critical Reviews™ in Therapeutic Drug Carrier Systems. 1998;15(3):243–284. DOI: 10.1615/CritRevTherDrugCarrierSyst. v15.i3.20
  4. Hemalatha K, Lathaeswari R, Suganeswari M, Kumar SV, Shering AM. Formulation and evaluation of metoclopramide hydrochloride microbeads by ionotropic gelation method. International Journal of Pharmaceutical and Biological 2011;2:921-925.
  5. Patil JS, Kamalapur MV, Marapur SC, Kadam DV. Ionotropic gelation and polyelectrolyte complexation: the novel techniques to design hydrogel particulate sustained, modulated drug delivery system: a review. Digest Journal of Nanomaterials and Biostructures. 2010;5(1):241-248.
  6. Al-Kassas RS, Al-Gohary OM, Al-Faadhel MM. Controlling of systemic absorption of gliclazide through incorporation into alginate beads. International journal of pharmaceutics. 2007;341(1- 2):230-237. https://doi.org/10.1016/j.ijpharm.2007.03.047
  7. Takka S, Ocak O, and Acartu, F. Formulation and investigation of nicardipine HCl–alginate gel beads with factorial design-based European Journal of Pharmaceutical Sciences. 1998; 6: 241–246. https://doi.org/10.1016/S0928-0987(97)10005-7
  8. Silva CM, Ribeiro AJ, Figueiredo IV, Gonçalves AR, Veiga
  9. Alginate microspheres prepared by internal gelation: Development and effect on insulin stability. International journal of pharmaceutics. 2006;311(1-2):1-10. https://doi.org/10.1016/j. ijpharm.2005.10.050
  10. Santucci E, Alhaique F, Carafa M, Coviello T, Murtas E, Riccieri FM. Gellan for the formulation of sustained delivery beads. Journal of controlled release. 1996;42(2):157-164. https://doi. org/10.1016/0168-3659(96)01373-9
  11. Ross-Murphy SB. Rheological characterization of polymer gels and Polymer Gels and Networks. 1994;2(3-4):229-237. https://doi.org/10.1016/0966-7822(94)90007-8
  12. Kanapczyk J, Karnicki Z, Brzeski M, Bykowski P, Woytasz-Pajak
  13. Some aspects of chitosan hydrogel ointment base formulation. Chitin World, Karnicki, ZS; Brzeski, MM; Bykowski, PJ. 1994:512-519.
  14. Yang JS, Xie YJ, He W. Research progress on chemical modification of alginate: A review. Carbohydrate polymers. 2011;84(1):33-39. https://doi.org/10.1016/j.carbpol.2010.11.048
  15. Coradin T, Bah S, Livage Gelatine/silicate interactions: from nanoparticles to composite gels. Colloids and surfaces B: Biointerfaces. 2004;35(1):53-58. https://doi.org/10.1016/j. colsurf b.2004.02.008
  16. Tao Y, Lu Y, Sun Y, Gu B, Lu W, Pan J. Development of mucoadhesive microspheres of acyclovir with enhanced International journal of pharmaceutics. 2009;378(1- 2):30-36. https://doi.org/10.1016/j.ijpharm.2009.05.025
  17. Stithit S, Chen W, Price Development and characterization of buoyant theophylline microspheres with near zero order release kinetics. Journal of microencapsulation. 1998;15(6):725-737. https://doi.org/10.3109/02652049809008255
  18. Pongjanyakul T, Puttipipatkhachorn S. Xanthan–alginate composite gel beads: molecular interaction and in-vitro International Journal of Pharmaceutics. 2007;331(1):61-71. https://doi.org/10.1016/j.ijpharm.2006.09.011
  19. Hadjiioannou TP, Christian GD and Koupparis Quantitative Calculations in Pharmaceutical Practice and Research. New York, VCH Publishers Inc. 1993; 343-348.
  20. Korsmeyer RW, Gurny R, Doelker E, Buri P, Peppas NA. Mechanisms of solute release from porous hydrophilic International journal of pharmaceutics. 1983;15(1):25-35. https:// doi.org/10.1016/0378-5173(83)90064-9
  21. Malakar J, Nayak AK, Pal D. Development of cloxacillin loaded multiple-unit alginate-based f loating system by emulsion–gelation method. International journal of biological macromolecules. 2012;50(1):138-147. https://doi.org/10.1016/j. 2011.10.001
  22. Daihom BA, Bendas ER, Mohamed MI, Badawi Development and in-vitro evaluation of domperidone/Dowex resinate embedded gastro-floatable emulgel and effervescent alginate beads. Journal of Drug Delivery Science and Technology. 2020;59:101941. https://doi.org/10.1016/j.jddst.2020.101941
  23. Hua S, Ma H, Li X, Yang H, Wang A. pH-sensitive sodium alginate/poly (vinyl alcohol) hydrogel beads prepared by combined Ca2+ cross-linking and freeze-thawing cycles for controlled release of diclofenac sodium. International journal of biological macromolecules. 2010;46(5):517-23. https://doi. org/10.1016/j.ijbiomac.2010.03.004
  24. ICH guide lines Q1A(R2) ‘guidelines for industry,stability testing of new drug substance and product’ (Available on: http://www. org)
  25. Talukdar MM, Van den Mooter G, Augustijns P, Tjandra- Maga T, Verbeke N, Kinget In-vivo evaluation of xanthan gum as a potential excipient for oral controlled- release matrix tablet formulation. International journal of pharmaceutics. 1998;169(1):105-113. https://doi.org/10.1016/ S0378-5173(98)00112-4
  26. Boxenbaum Pharmacokinetic determinants in the design and evaluation of sustained-release dosage forms. Pharmaceutical research. 1984;1: 82- 88. DOIhttps://doi. org/10.1023/A:1016355431740
  27. Srikanth MV, Janaki Ram B, Sunil SA, Sreenivasa Rao N. and Ramana Murthy KV. Gastro retentive drug delivery systems: Novel approaches and its evaluation a review. International Journal of Pharmaceutical Sciences Review and 2011; 10(1): 203-216.
  28. Timmermans J, Moës AJ. Factors controlling the buoyancy and gastric retention capabilities of floating matrix capsules: new data for reconsidering the controversy. Journal of pharmaceutical sciences. 1994; 83: 18-24. https://doi.org/10.1002/jps.2600830106
  29. Bahrami GH, Mirzaeei SH, Kiani A. Determination of acyclovir in human serum by high-performance liquid chromatography using liquid–liquid extraction and its application in pharmacokinetic studies. Journal of Chromatography B. 2005; 816: 327–331. https://doi.org/10.1016/j.jchromb.2004.11.038
  30. Emami J, Bazargan N, Ajami A. HPLC determination of acyclovir in human serum and its application in bioavailability studies. Research in Pharmaceutical 2009; 4(1): 47-54.
  31. Nayak AK, Pal Development of pH-sensitive tamarindseed polysaccharide–alginate composite beads for controlled diclofenac sodium delivery using response surface methodology. International journal of biological macromolecules.2011; 49:784- 793. https://doi.org/10.1016/j.ijbiomac.2011.07.013
  32. Nayak AK, Das B, Maji R. Calcium alginate/gum Arabic beads containing glibenclamide: development and in-vitro International journal of biological macromolecules. 2012;51: 1070-1078. https://doi.org/10.1016/j. ijbiomac.2012.08.021
  33. González-Rodrıguez ML, Holgado MA, Sánchez-Lafuente C, Rabasco AM, Fini A. Alginate/chitosan particulate systems for sodium diclofenac International Journal of Pharmaceutics. 2002; 232:225-234. https://doi.org/10.1016/ S0378-5173(01)00915-2
  34. Malakar J, Nayak AK, Pal D. Development of cloxacillin loaded multiple-unit alginate-based f loating system by emulsion–gelation method. International journal of biological macromolecules. 2012;50 :140-148. https://doi.org/10.1016/j. 2011.10.001
  35. Kagan L, Hoffman A. Selection of drug candidates for gastroretentive dosage forms: pharmacokinetics following continuous intragastric mode of administration in a rat model. European journal of pharmaceutics and biopharmaceutics. 2008;69: 238–246.
  36. Devhare LD, and Gokhale Antioxidant and Antiulcer Property of Different Solvent Extracts of Cassia Tora Linn. Research Journal of Pharmacy and Technology. 2022;15(3);1109-1113. DOI: 10.52711/0974-360X.2022.00185
  37. Tiwari R, Mishra J, Devhare LD and Tiwari An updated review on recent developments and applications of fish collagen. Pharma Times. 2023;55(6):28-36.
  38. Adimulapu AK, Devhare LD, Anasuya Patil A, Chachda NO,Dharmamoorthy. Design and Development of Novel Mini Tablet Cap Technology for the Treatment of Cardiovascular Diseases. International Journal of Drug Delivery Technology. 2023;13(3):801-806. DOI: 10.25258/ijddt.13.3.04
  39. Chawla A, Devhare LD, Dharmamoorthy G, Ritika, Tyagi S. Synthesis and In-vivo Anticancer Evaluation of N-(4-oxo-2- (4-((5-aryl-1,3,4 thiadiazole-2yl) amino) Phenyl thiazolidine-3-yl) Benzamide derivative. International Journal of Pharmaceutical Quality Assurance. 2023;14(3):470-474.
  40. Gnana RPM, Devhare LD, Dharmamoorthy G, Khairnar MV, Prasidha R. Synthesis, Characterisation, Molecular Docking Studies and Biological Evaluation of Novel Benzothiazole Derivatives as EGFR Inhibitors for Anti-breast Cancer Agents. International Journal of Pharmaceutical Quality Assurance. 2023;14(3):475-480. DOI:10.25258/ijpqa.14.3.03
  41. Sonule M, Devhare LD, Babu MN, Gunjal SD, Varalaxmi S. Microemulgel-based Hydrogel of Diclofenac Sodium using Lipidium sativum as a Gelling Agent. International Journal of Drug Delivery 2023;13(4):1235-1239. DOI:10.25258/ ijddt.13.4.19
  42. Shriram BK, Devhare LD, Mehrotra A, Deokar SS, Singh SP. Formulation and Evaluation of Mosquito Repellent International Journal of Drug Delivery Technology. 2023;13(4):1283-1286. DOI:10.25258/ijddt.13.4.26
  43. Choudhary RK, Beeraka S, Sarkar BK, Dharmamoorthy G, Devhare L. Optimizing Verapamil Hydrochloride In-situ Delivery: A Strategic Formulation Approach using Box- Behnken Design for Enhanced Performance and Comprehensive Evaluation of Formulation Parameters. International Journal of Drug Delivery Technology. 2024;14(1):61-70. DOI: 10.25258/ 14.1.11
  44. Kumar KK, Kiran V, Choudhary RK, Devhare LD, Gunjal SD. Design Development and Characterization of Nicardipine Solid Lipid Nano-Particulars. International Journal of Drug Delivery Technology. 2024;14(1):71-78. DOI: 25258/ijddt.14.1.12
  45. Priya MGR, Prasanth LML, Devhare LD, Yazdan SK, Gunjal S. Synthesis, DNA Binding, Molecular Docking and Anticancer Studies of Copper (II), Nickel (II), and Zinc (II) Complexes of Primaquine-based Ligand. International Journal of Pharmaceutical Quality Assurance. 2024;15(1):69-75. DOI: 25258/ijpqa.15.1.10
  46. Uplanchiwar VP, Raut SY, Devhare LD, et Pharmacological Assessment of Antiulcer Activity of Gloriosa Superba Linn Tubers In Experimentally Induced Gastric Ulcers. Journal of Medical Pharmaceutical and Allied Science. 2021;10(3);2852- 2856.
  47. Tiwari G, Gupta M, Devhare LD, & Tiwari Therapeutic and Phytochemical Properties of Thymoquinone Derived from Nigella Sativa. Current Drug Research Reviews. 2024;16(2):145-DOI: https://doi.org/10.2174/2589977515666230811092410