Local Drug Delivery to Bone Joints with Microspheres

  • Chidambaram Soundrapandian Department of Pharmaceutics, Himalayan Pharmacy Institute, Majhitar – 737136, India
  • Adarsh Pratik Poudyal Department of Pharmaceutics, Himalayan Pharmacy Institute, Majhitar – 737136, India

Abstract

The concept of local drug delivery in the form of microspheres has potential for use as an alternative to conventional therapy strategies in the treatment of pain and inflammatory symptoms in case of certain bone and joint diseases. Commonly preferred treatment options for these symptoms (such as oral NSAIDs, analgesics, opioid pain medications) need to be frequently administered or applied and additionally, these suffer from multiple limitations. A prolonged release formulation of an NSAID i.e. Diclofenac Sodium, might prevent frequent administrations and improve the therapeutic outcome. In the current research, Diclofenac Sodium (DS)-loaded microspheres were prepared using thermal control and ionic cross-linking techniques. Calcium sulfate hemihydrate (CaSO4) was used in specific quantities to enhance the self-hardening property of the microspheres. An encapsulation efficiency and loading capacity of up to 90.24% and 61.41% respectively were achieved from the formulations. FTIR analysis indicated no major interactions between the active ingredient and the excipients used in the formulation process. In-vitro studies on the biodegradability of the microspheres disclosed that the microspheres showed a slow degradation pattern over time. Release study of the prepared microspheres revealed that the release of DS was prolonged achieving release of drug over a period of up to 11 days. The microspheres seem to fulfil the requisite criteria in-vitro. The results obtained suggest that DS-loaded microspheres have the potential for further investigation and development.


Keywords: Local drug delivery, microspheres, bone and joint diseases, NSAIDs

Downloads

Download data is not yet available.

Author Biographies

Chidambaram Soundrapandian, Department of Pharmaceutics, Himalayan Pharmacy Institute, Majhitar – 737136, India

Department of Pharmaceutics, Himalayan Pharmacy Institute, Majhitar – 737136, India

Adarsh Pratik Poudyal, Department of Pharmaceutics, Himalayan Pharmacy Institute, Majhitar – 737136, India

Department of Pharmaceutics, Himalayan Pharmacy Institute, Majhitar – 737136, India

References

1. Kidd BL, Langford RM, Wodehouse T. Arthritis and pain. Current approaches in the treatment of arthritic pain. Arthritis research & therapy. 2007 Jun; 9(3):214.
2. Conaghan PG, Cook AD, Hamilton JA, Tak PP. Therapeutic options for targeting inflammatory osteoarthritis pain. Nature Reviews Rheumatology. 2019 May 8:1.
3. Walsh DA, McWilliams DF. Mechanisms, impact and management of pain in rheumatoid arthritis. Nature Reviews Rheumatology. 2014 Oct; 10(10):581.
4. Frank RG, Kashani JH, Parker JC, Beck NC, Brownlee-Duffeck MA, Elliott TR, Haut AE, Atwood CA, Smith EL, Kay DR. Antidepressant analgesia in rheumatoid arthritis. j Rheumatol. 1988 Nov 1; 15(11):1632-8.
5. Meng Z, Huang R. Topical treatment of degenerative knee osteoarthritis. The American journal of the medical sciences. 2018 Jan 1; 355(1):6-12.
6. Bisicchia S, Tudisco C. Hyaluronic acid vs corticosteroids in symptomatic knee osteoarthritis: a mini-review of the literature. Clinical Cases in Mineral and Bone Metabolism. 2017 May; 14(2):182.
7. van Laar M, Pergolizzi Jr JV, Mellinghoff HU, Merchante IM, Nalamachu S, O'Brien J, Perrot S, Raffa RB. Pain treatment in arthritis-related pain: beyond NSAIDs. The open rheumatology journal. 2012; 6:320.
8. Larsen C, Østergaard J, Larsen SW, Jensen H, Jacobsen S, Lindegaard C, Andersen PH. Intra‐articular depot formulation principles: Role in the management of postoperative pain and arthritic disorders. Journal of pharmaceutical sciences. 2008 Nov 1; 97(11):4622-54.
9. Evans CH, Kraus VB, Setton LA. Progress in intra-articular therapy. Nature Reviews Rheumatology. 2014 Jan; 10(1):11.
10. Elmowafy M, Elrehaily A, Elharby A, Ali T, Elelian A, Elsemaihy A, Elgabry N. Transdermal Drug Delivery Systems; Review Article.
11. Buchholz HW, Elson RA, Engelbrecht E, Lodenkamper H, Rottger J, Siegel A. Management of deep infection of total hip replacement. The Journal of bone and joint surgery. British volume. 1981 Aug; 63(3):342-53.
12. Lyles KW, Siris ES, Singer FR, Meunier PJ. A clinical approach to diagnosis and management of Paget's disease of bone. Journal of Bone and Mineral Research. 2001 Aug; 16(8):1379-87.
13. Kim KK, Pack DW. Microspheres for drug delivery In BioMEMS and biomedical nanotechnology 2006 (pp. 19-50). Springer, Boston, MA.
14. Shahzad MK, Ubaid M, Raza M, Murtaza G. The formulation of flurbiprofen loaded microspheres using hydroxypropylmethycellulose and ethylcellulose. Advances in clinical and experimental medicine: official organ Wroclaw Medical University. 2013; 22(2):177-83.
15. Kondolot Solak E, Er A. pH-sensitive interpenetrating polymer network microspheres of poly (vinyl alcohol) and carboxymethyl cellulose for controlled release of the nonsteroidal anti-inflammatory drug ketorolac tromethamine. Artificial cells, nanomedicine, and biotechnology. 2016 Apr 2; 44(3):817-24.
16. Kulkarni S, Sharma SB, Agrawal A. PREFORMULATION-A FOUNDATION FOR FORMULATION DEVELOPMENT. International Journal of Pharmaceutical, Chemical & Biological Sciences. 2015 Apr 1; 5(2).
17. Larsson J. Methods for measurement of solubility and dissolution rate of sparingly soluble drugs.
18. http://www.chem.ucalgary.ca/courses/351/laboratory/meltingpoint.pdf (accessed on 17th May, 2019)
19. https://www.flinnsci.com/api/library/Download/46b1e79b05414c7f8e4164d9df5215ff (accessed on 17th May, 2019)
20. Cummings NA, Nordby GL. Measurement of synovial fluid pH in normal and arthritic knees. Arthritis & Rheumatism: Official Journal of the American College of Rheumatology. 1966 Feb;9(1):47-56.
21. Goldie I, Nachemson A. Synovial pH in Rheumatoid Knee-Joints I. The Effect of Synovectomy. Acta orthopaedica Scandinavica. 1969 Jan 1;40(5):634-41.
22. Jalsenjak I, Nicolaidou CF, Nixon JR. The in vitro dissolution of phenobarbitone sodium from ethyl cellulose microcapsules. Journal of Pharmacy and Pharmacology. 1976 Dec; 28(12):912-4.
23. Das MK, Senapati PC. Evaluation of furosemide-loaded alginate microspheres prepared by ionotropic external gelation technique. Acta Pol Pharm. 2007; 64(3):253-62.
24. Gangurde HH, Chavan NV, Mundada AS, Derle DV, Tamizharasi S. Biodegradable chitosan-based ambroxol hydrochloride microspheres: Effect of cross-linking agents. Journal of Young Pharmacists. 2011 Jan 1; 3(1):9-14.
25. Trivedi P, Verma AM, Garud N. Preparation and characterization of aceclofenac microspheres. Asian Journal of Pharmaceutics (AJP): Free full text articles from Asian J Pharm. 2014; 2(2).
26. https://www.sigmaaldrich.com/technical-documents/articles/materials-science/drug-delivery/drug-delivery-questions.html
27. Pandey N, Sah AN, Mahara K. Formulation and evaluation of floating microspheres of nateglinide. International Journal of Pharma Sciences aand Research. 2016; 7(11):453-64.
28. Pi C, Yuan J, Liu H, Zuo Y, Feng T, Zhan C, Wu J, Ye Y, Zhao L, Wei Y. In vitro and in vivo evaluation of curcumin loaded hollow microspheres prepared with ethyl cellulose and citric acid. International journal of biological macromolecules. 2018 Aug 1; 115:1046-54.
29. Rout PK, Nayak BS. Formulation design, preparation of losartan potassium microspheres by solvent evaporation method and it’s in vitro characterization. Archives of Pharmaceutical Sciences and Research. 2009; 1(1):166-70.
30. Jagtap YM, Bhujbal RK, Ranade AN, Ranpise NS. Effect of various polymers concentrations on physicochemical properties of floating microspheres. Indian journal of pharmaceutical sciences. 2012 Nov; 74(6):512.
31. Riley RE, Hausner HH. Effect of particle size distribution on the friction in a powder mass. Int. J. Powder Met. 1970;6.
32. https://particle.dk/methods-analytical-laboratory/bulk-and-tapped-density/ (accessed on 19th May, 2019)
33. Andhariya JV, Burgess DJ. Recent advances in testing of microsphere drug delivery systems. Expert opinion on drug delivery. 2016 Apr 2; 13(4):593-608.
34. Ghosh S, Choudhury D, Roy T, Mamat AB, Masjuki HH, Pingguan-Murphy B. Tribological investigation of diamond-like carbon coated micro-dimpled surface under bovine serum and osteoarthritis oriented synovial fluid. Science and technology of advanced materials. 2015 May 14; 16(3):035002.
35. Saravanan M, Bhaskar K, Maharajan G, Pillai KS. Development of gelatin microspheres loaded with diclofenac sodium for intra-articular administration. Journal of drug targeting. 2011 Feb 1; 19(2):96-103.
Statistics
73 Views | 88 Downloads
How to Cite
Soundrapandian, C., & Poudyal, A. P. (2019). Local Drug Delivery to Bone Joints with Microspheres. Journal of Drug Delivery and Therapeutics, 9(3-s), 430-442. https://doi.org/10.22270/jddt.v9i3-s.3043