Development of lipid-based microsuspensions for improved ophthalmic delivery of gentamicin sulphate
Abstract
Aim: Anterior eye segment disorders are treated with eye drops and ointments, which have low ocular bioavailability necessitating the need for improved alternatives. Lipid microsuspension of gentamicin sulphate was developed for the treatment of susceptible eye diseases. Materials & methods: Lipid microsuspensions encapsulating gentamicin sulphate were produced by hot homogenization and evaluated. Ex vivo permeation and ocular irritancy tests were also conducted. Results & conclusion: Stable microsuspensions with high entrapment efficiency and satisfactory osmolarities were obtained. Release studies achieved 49–88% in vitro release at 12 h with sustained permeability of gentamicin compared with conventional gentamicin eye drop (Evril®). No irritation was observed following Draize’s test. The microsuspensions have great potential as ocular delivery system of gentamicin sulphate.
Papers of special note have been highlighted as: • of interest; •• of considerable interest
References
- 1. . Basics of ocular drug delivery systems. Int. J. Res. Pharm. Biomed. Sci. 2(4), 1541–1552 (2011).
- 2. . Formulation of an ophthalmic lipid emulsion containing an anti–inflammatory steroidal drug, difuprednate. Int. J. Pharm. 301(1–2), 121–128 (2005).
- 3. . Ocular drug delivery: present innovations and future challenges. J. Pharmacol. Exp. Ther. 370(3), 602–624 (2019).
- 4. . Ophthalmic delivery of cyclosporine A from Brij-97 microemulsion and surfactant laden p–HEMA hydrogels. Int. J. Pharm. 361(1–2), 222–229 (2008).
- 5. . An insight to ophthalmic drug delivery system. Int. J. Pharm. Sci. Res. 3(2), 9–13 (2012).
- 6. . Perspective in ocular drug delivery. Pharm. Res. 26(5), 1197–1216 (2009). •• Presents new insight into ocular drug delivery.
- 7. Novel NSAIDs ophthalmic formulation: flurbiprofen axetil emulsion with low irritancy and improved anti-inflammation effect. Int. J. Pharm. 412(1–2), 115–122 (2011).
- 8. . Drug release and permeation studies of nanosuspensions based on solidified reverse micellar solution (SRMS). Int. J. Pharm. 305, 167–175 (2005).
- 9. . Physicochemical characterization of a reverse micellar solution after loading with different drugs. Pharmazie 55, 755–758 (2000).
- 10. . Solidified reverse micellar solution (SRMS): a novel approach for controlling drug release from various lipid-based drug delivery systems. Afr. J. Biotechnol. 12(52), 7138–7146 (2013).
- 11. Evaluation of gentamicin-entrapped solid lipid microparticles formulated with a biodegradable homolipid from Capra hircus. Trop. J. Pharm. Res. 13(18), 1999–1205 (2014). • Presents an earlier work on gentamicin microparticles.
- 12. . Pharmacokinetics and biodistribution of zidovudine loaded in a solidified reverse micellar delivery system. Int. J. Drug Del. 5, 73–80 (2013).
- 13. . Development and evaluation of chloroquine phosphate microparticles using solid lipid as a delivery carrier. J. Drug Discov. Dev. Deliv. 2(1), 1011 (2015).
- 14. . Formulation, in vitro and in vivo evaluation of halofantrine-loaded solid lipid microparticles. Pharm. Dev. Technol. 20(8), 941–948 (2015).
- 15. Formulation design, in vitro and anti-malarial investigations of artemether and lumenfantrine-entrapped solid lipid microparticles. Drug Dev. Ind. Pharm. 42(10), 1708–1721 (2016).
- 16. Solid lipid nanoparticles encapsulating a fluorescent marker (coumarin 6) and antimalarials – artemether and lumefantrine: evaluation of cellular uptake and antimalarial activity. Eur. J. Nanomed. 8(3), 129–138 (2016).
- 17. The safety evaluation of long-acting ocular delivery systems. Drug Discov. Today 24, 1539–1550 (2019). •• Discussed important safety issues associated with ocular delivery systems.
- 18. Biotherapeutics and immunogenicity: ophthalmic perspective. Eye 33, 1359–1361 (2019).
- 19. . Selected aspects of ocular toxicity studies with a focus on high quality pathology reports: a pathology/toxicology consultant's perspective. Toxicol. Pathol. 49(3), 673–699 (2021).
- 20. Immunogenicity testing of therapeutic antibodies in ocular fluids after intravitreal injection. Bioanalysis 10, 803–814 (2018).
- 21. Advancements in understanding immunogenicity of biotherapeutics in the intraocular space. AAPS J. 19, 1656–1668 (2017).
- 22. Endophthalmitis following intravitreal injections. Graefes. Arch. Clin. Exp. Ophthalmol. 250, 499–505 (2012).
- 23. . Preparation of novel solid lipid microparticles loaded with gentamicin and its evaluation in vitro and in vivo. J. Microencapsul. 29(3), 296–307 (2012). • Highlights incorporation of gentamicin into lipid microparticles.
- 24. . Investigation of solidified reverse micellar systems as novel carriers for oral delivery of gentamicin. J. Pharm. Res. 5(9), 4914–4920 (2012).
- 25. United States Pharmacopoeial Convention. The United States Pharmacopeia (USP) 35. 945, MD, USA, 339–342 (2015).
- 26. . Methods for the study of irritation and toxicity of substances applied topically to the skin or mucous membranes. J. Pharmacol. Exp. Ther. 82, 377–390 (1944).
- 27. . Diclofenac sodium delivery to the eye: in vitro evaluation of novel solid lipid nanoparticles formulation using human cornea construct. Int. J. Pharm. 355, 307–313 (2008). •• Presents a new idea on drug delivery to the eye.
- 28. . Ophthalmic drug delivery. In: Drug Delivery and Targeting. Hillery AMLloyd AWSwarbrick J (Eds). Taylor & Francis, NY, USA, 329–354 (2001).
- 29. . Contact lens for drug delivery. Achieving sustained release with novel systems. Am. J. Drug Deliv. 4(3), 131–151 (2006).
- 30. United States Pharmacopeial Convention. The United States Pharmacopeia, Test Solutions (2015). http://www.pharmacopeia.cn/v29240/usp29nf24s0_m34850.html. Accessed on 23/07/2021
- 31. Advanced formulation approaches for ocular drug delivery: state-of-the-art and recent patents. Pharmaceutics 11, 460–488 (2019). •• Presents new insight into ocular drug delivery.
- 32. Pharmaceutical Society of Great Britain. The Pharmaceutical Codex Incorporating the British Pharmacopoiea (11th Edition). The Pharmaceutical Press, London, UK, 387 (1979).
- 33. Remington. The Science and Practice of Pharmacy (22nd Edition). Allen LV Jr (Ed.). The Pharmaceutical Press, London, UK, 3056 (2012).
- 34. . Safety evaluation of ocular drug delivery formulations: Techniques and practical considerations. Toxicol. Pathol. 36, 49–62 (2008).