• O. SREEKANTH REDDY Department of Chemistry, Sri Krishnadevaraya University, Ananthapuramu 515003, India
  • M. C. S. SUBHA Department of Chemistry, Sri Krishnadevaraya University, Ananthapuramu 515003, India
  • T. JITHENDRA Department of Chemistry, Sri Krishnadevaraya University, Ananthapuramu 515003, India
  • C. MADHAVI Department of Polymer Science and Technology, Sri Krishnadevaraya University, Ananthapuramu 515003, India
  • K. CHOWDOJI RAO Department of Polymer Science and Technology, Sri Krishnadevaraya University, Ananthapuramu 515003, India
  • B. MALLIKARJUNA Department of Chemistry, Government College (A), AKN University, Rajahmundry, India


Objective: The aim of the present study was to fabricate and evaluate the drug release studies using Sodium Alginate (SA) and Gelatin (GE) microbeads intercalated with Kaolin (KA) nanoclay for sustained release of D-Penicillamine (D-PA).

Methods: Sodium alginate/gelatin/Kaolin blend microbeads were prepared by an extrusion method by using glutaraldehyde (GA) as a crosslinker. The obtained microbeads were characterized by Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM) and X–ray diffraction (XRD). Drug release kinetics of the microbeads was investigated in simulated intestinal fluid (pH 7.4) at 37 °C.

Results: Microbeads formation was confirmed by FTIR spectroscopy. X-RD reveals that the KA should be intercalated with the drug and also it confirms the molecular level dispersion of D-Penicillamine into microbeads. Scanning Electron Microscopy (SEM) studies reveal that the beads were in spherical shape with some wrinkled depressions on the surface. The in vitro release study indicates the D-Penicillamine released in a controlled manner. The in vitro release kinetics was assessed by Korsmeyer-Peppas equation and the ‘n’ value lies in between 0.557-0.693 indicates Non-Fickian diffusion process.

Conclusion: The results suggest that the developed KA intercalated microbeads are good potential drug carrier for the controlled release of D-PA.

Keywords: Sodium alginate (SA), Gelatin (GE),, Kaolin (KA), Drug delivery, D-Penicillamine (D-PA)


1. Isabel Carretero M, Manuel Pozo. Clay and non-clay minerals in the pharmaceutical industry part I. Excipients and medical applications. Appl Clay Sci 2009;46:73–80.
2. Jeffrey G Lundin, Christopher L, McGann, Grant C Daniels, Benjamin C Streifel, James H Wynne. Hemostatic kaolin-polyurethane foam composites for multifunctional wound dressing applications. Materials Sci Eng C 2017;79:702-9.
3. Maide Gokce Bekaroglu, Fuad Nurili, Sevim?sci. Montmorillonite as imaging and drug delivery agent for cancer therapy. Appl Clay Sci 2018;162:469-77.
4. Shilpa Jain, Monika Datta. Montmorillonite-alginate microspheres as a delivery vehicle for oral extended release of venlafaxine hydrochloride. J Drug Delivery Sci Technol 2016;33:149-56.
5. Shuibo Hua, Huixia Yang, Aiqin Wang. A pH-sensitive nanocomposite microsphere based on chitosan and montmorillonite with in vitro reduction of the burst release effect chitosan/montmorillonite nanocomposite microspheres. Drug Development Industrial Pharm 2010;36:1106–14.
6. Janicijevic J, Krajisnik D, Calija B, Vasiljevic BN, Dobricic V, Dakovic A, et al. Modified local diatomite as potential functional drug carrier-a model study for diclofenac sodium. Int J Pharm 2015;496:466-74.
7. Ruggiero I, Terracciano M, Martucci NM, De Stefano L, Migliaccio N, Tate R, et al. Diatomite silica nanoparticles for drug delivery. Nanoscale Res Lett 2014;9:329-35.
8. Janicijevic J, Krajisnik D, Calija B, Dobricic V, Dakovic A, Krstic J, et al. Inorganically modified diatomite as a potential prolonged-release drug carrier. Materials Sci Eng C 2014;42:412-20.
9. Jie Wu, Shijie Ding, Jing Chen, Suqin Zhou, Hongyan Ding. Preparation and drug release properties of chitosan/organomodifiedpalygorskite microspheres. Int J Biol Macromol 2014;68:107–12.
10. Joanna Kurczewska, Micha? Ceg?owski, Beata Messyasz, Grzegorz Schroeder. Dendrimer-functionalized halloysite nanotubes for effective drug delivery. Appl Clay Sci 2018;153:134–43.
11. Yuri Lvov, Wencai Wang, Liqun Zhang, Rawil Fakhrullin. Halloysite clay nanotubes for loading and sustained release of functional compounds. Adv Mater 2016;28:1227–50.
12. Yuri M Lvov, Melgardt M DeVilliers, Rawil F Fakhrullin. The application of halloysite tubule nanoclay in drug delivery. Expert Opinion Drug Delivery 2016;13:977-86.
13. Yi Zhang, Mei Long, Peng Huang, Huaming Yang, Shi Chang, Yuehua Hu, et al. Intercalated 2D nanoclay for emerging drug delivery in cancer therapy. Nano Res 2017;10:2633-43.
14. Yuping Liang, Congcong Xu, Guofeng Li, Tianchi Liu, Jun F Liang, Xing Wang. Graphene-kaolin composite sponge for rapid and riskless hemostasis. Colloids Surf B 2018;169:168–75.
15. Mahmoud E Awad, Alberto Lopez Galindo, Massimo Setti, Mahmoud M El-Rahmany, Cesar Viseras Iborra. Kaolinite in pharmaceutics and biomedicine. Int J Pharma 2017;533:34-48.
16. Omaimah M N Al Gohary. In vitro adsorption of mebeverine hydrochloride onto kaolin and its relationship to pharmacological effects of the drug in vivo. Pharma Acta Helvetiae 1997;72:11-21.
17. Myung Hun Kim, Goeun Choi, Ahmed Elzatahry, Ajayan Vinu, Young Bin Choy, Jin-Ho Choy. Review of clay-drug hybrid materials for biomedical applications: administration routes. Clays Clay Minerals 2016;64:115-30.
18. Lynda B Williams. Geomimicry: harnessing the antibacterial action of clays. Clay Minerals 2017;52:1-24.
19. Ghadiri M, Chrzanowskiab W, Rohanizadeh. Biomedical applications of cationic clay minerals. RSC Adv 2015;5:29467-81.
20. Mallikarjuna Reddy K, Ramesh Babu V, Krishna Rao KSV, Subha MCS, Chowdoji Rao K, Sairam M, et al. Temperature sensitive semi-IPN microspheres from sodium alginate and n-isopropylacrylamide for controlled release of 5-fluorouracil. J Appl Polymer Sci 2008;107:2820–9.
21. Wu T, Huang J, Jiang Y, Hu Y, Ye X, Liu D, et al. Formation of hydrogels based on chitosan/alginate for the delivery of lysozyme and their antibacterial activity. Food Chem 2017;240:361-9.
22. Raghavendra V Kulkarni, Sreedhar V, Srinivas Mutalik, Mallikarjun Setty C, Biswanath Sa. Interpenetrating network hydrogel membranes of sodium alginate and poly(vinyl alcohol) for controlled release of prazosin hydrochloride through skin. Int J Biol Macromolecules 2010;47:520–7.
23. KV Ramana Reddy, MV Nagabhushanam. Process and parameters affecting drug release performance of prepared cross-linked alginate hydrogel beads for ezetimibe. Int J Pharm Pharm Sci 2016;9:254-62.
24. Fabian Martinez Gomez, Juan Guerrero, Betty Matsuhiro, Jorge Pavez. In vitro release of metformin hydrochloride from sodiumalginate/polyvinyl alcohol hydrogels. Carbohydrate Polymers 2017;155:182–91.
25. Madhusudana Rao K, Krishna Rao KSV, Ramanjaneyulu G, Chang Sik Ha. Curcumin encapsulated pH sensitive gelatin based interpenetrating polymeric network nanogels for anti cancer drug delivery. Int J Pharma 2015;478:788–95.
26. M Das, PR Suguna, K Prasad, JV Vijaylakshmi, M Renuka. Extraction and characterization of gelatin: a functional biopolymer. Int J Pharm Pharm Sci 2017;9:239-42.
27. Van Den Bulcke AI, Bogdanov B, De Rooze N, Schacht EH, Cornelissen M, Berghmans H. Structural and rheological properties of methacrylamide modified gelatin hydrogels. Biomacromolecules 2000;1:31–8.
28. Keerti V Phadke, Lata S Manjeshwar, Tejraj M Aminabhavi. Microspheres of gelatin and poly(ethylene glycol) coated with ethyl cellulose for controlled release of metronidazole. Indian Eng Chem Res 2014;53:6575?84.
29. Ajit P Rokhade, Sunil A Agnihotri, Sangamesh A Patil, Nadagouda N Mallikarjuna, Padmakar V Kulkarni, Tejraj M Aminabhavi. Semi-interpenetrating polymer network microspheres of gelatin and sodium carboxymethyl cellulose for controlled release of ketorolac tromethamine. Carbohydrate Polymers 2006;65:243–52.
30. Pal A, Bajpai J, Bajpai AK. Poly (acrylic acid) grafted gelatin nanocarriers as swelling controlled drug delivery system for optimized release of paclitaxel from modified gelatin. J Drug Delivery Sci Technol 2018;45:323-33.
31. Abhinav Agarwal, Surendra Prasad, Radhey M Naik. Inhibitory kinetic spectrophotometric method for the quantitative estimation of D-penicillamine at micro levels. Microchemical J 2016;128:181-6.
32. Taheri M, Ahour F, Keshipour S. Sensitive and selective determination of Cu2þ at D-penicillamine functionalized nano-cellulose modified pencil graphite electrode. J Phys Chem Solids 2018;117:180–7.
33. Prabhakar MN, Sajankumarji Rao U, Kumara Babu P, Subha MCS, Chowdoji Rao K. Interpenetrating polymer network hydrogel membranes of PLA and SA for control release of penicillamine drug. Indian J Adv Chem Sci 2013;1:240-9.
34. Sarika PR, Nirmala Rachel James. Polyelectrolyte complex nanoparticles from cationised gelatin and sodium alginate for curcumin delivery. Carbohydrate Polymers 2016;148:354–61.
35. Sarika PR, Nirmala Rachel James, Anil kumar PR, Deepa K Raj. Preparation, characterization and biological evaluation of curcumin loaded alginate aldehyde–gelatin nanogels. Materials Sci Eng C 2016;68:251–7.
36. Utkarsh Bhutani, Anindita Laha, Kishalay Mitra, Saptarshi Majumdar. Sodium alginate and gelatin hydrogels: viscosity effect on hydrophobic drug release. Materials Lett 2016;164:76-9.
37. Madhumathi K, Jeevana Rekha L, Sampath Kumar TS. Tailoring antibiotic release for the treatment of periodontal infrabony defects using bioactive gelatin-alginate/apatite nanocomposite films. J Drug Delivery Sci Technol 2018;43:57-64.
38. Madhusudana Rao K, Mallikarjuna B, Krishna Rao KSV, Prabhakar MN, Chowdoji Rao K, Subha MCS. Preparation and characterization of pH sensitive poly(vinyl alcohol)/sodium carboxymethyl cellulose IPN microspheres for in vitro release studies of an anti-cancer drug. Polym Bull 2012;68:1905–19.
39. Ikhuoria M Arhewoh, Augustine O Okhamafe. An overview of site-specific delivery of orally administered proteins/peptides and modelling considerations. J Med Biomed Res 2004;3:7–20.
40. Donbrow M, Samuelov Y. Zero order drug delivery from double-layered porous films: release rate profiles from ethyl cellulose, hydroxypropyl cellulose and polyethylene glycol mixtures. J Pharm Pharmacol 1980;32:463-70.
41. Suvakanta Dash, Padala Narasimha Murthy, Lilakanta Nath, Prasanta Chowdhury. Kinetic modeling on drug release from controlled drug delivery systems. Acta Poloniae Pharm Drug Res 2010;67:217-23.
42. Paulo Costa, Jose Manuel Sousa Lobo. Modeling and comparison of dissolution profiles. Eur J Pharm Sci 2001;13:123–33.
43. Korsmeyer RW, Gurny R, Doelker E, Buri P, Peppas NA. Mechanisms of solute release from porous hydrophilic polymers. Int J Pharm 1983;15:25–35.
44. Aleanizy FS, Alqahtani F, Al Gohary O, El Tahir E, Al Shalabi R. Determination and characterization of metronidazole–kaolin interaction. Saudi Pharma J 2015;23:167-76.
45. Sonia Bouzid Rekik, Sana Gassara, Jamel Bouaziz, Andre Deratani, Semia Baklouti. Development and characterization of porous membranes based onkaolin/chitosan composite. Appl Clay Sci 2017;143:1–9.
46. Madhavi C, Kumara Babu P, Maruthi Y, Parandhama A, Sreekanth Reddy O, Chowdoji Rao K, et al. Sodium alginate–locust bean gum IPN hydrogel beads for the controlled delivery of nimesulide-anti-inflammatory drug. Int J Pharm Pharm Sci 2017;9:245-52.
47. Keerti V Phadke, Lata S Manjeshwar, Tejraj M Aminabhavi, MP Sathisha. Cellulose acetate butyrate bilayer coated microspheres for controlled release of cipro?oxacin. Polymer Bull 2018;75:1329-48.
48. Praveen B Kajjari, Lata S Manjeshwar, Tejraj M Aminabhavi. Semi-interpenetrating polymer network hydrogel blend microspheres of gelatin and hydroxyethyl cellulose for controlled release of theophylline. Indian Eng Chem Res 2011;50:7833–40.
49. Elif Yilmaz, Gulcihan Guzel Kaya, Huseyin Deveci. Preparation and characterization of pH-sensitive semi-interpenetrating network hybrid hydrogels with sodium humate and kaolin. Appl Clay Sci 2018;162:311–6.
111 Views | 68 Downloads
How to Cite
Original Article(s)