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Self-assembling Organogels Loaded with Tenoxicam for Local Intensive Pain and Inflammation Cure: In Vitro and In Vivo Correlation

  • Research Article
  • Novel Skin Drug Delivery Technology
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Abstract

Due to tenoxicam (TX)’s poor aqueous solubility (0.072 mg/ml), it is poorly absorbable in the GIT, and the long-term oral administration of TX may cause severe GIT disturbances. Topical administration of TX can help in bypassing the GIT adverse effects. Therefore, in the present work, we constructed different pluronic/lecithin organogels (PLOs) for topical delivery of TX. PLO was constructed simply via direct mixing of an aqueous pluronic solution with lecithin solution. The prepared PLO formulations were characterized for their physicochemical properties including pH, drug content, visual inspection, viscosity, and spreadability. Also, the in vitro release and kinetic studies were carried out to investigate the mechanism of drug release. Moreover, the in vivo studies were carried out by investigating the anti-inflammatory and analgesic activities using albino male rats. The results showed that the modified PLOs have good physicochemical properties. The viscosity of the modified gels is a direct proportionality with both lecithin and pluronic concentrations. Also, subsequently, the drug release rate is directly proportional to gel viscosity. Moreover, the in vivo studies showed that the modified PLOs (F19) showed a significant ( < 0.05%) paw edema inhibition and pain analgesia compared with other investigated groups. Also, the results indicated that the increase in dose is accompanied by higher activity and a longer duration of action which extended to 12 h. Hence, the modified PLOs are promising safe candidates or vehicles for effective TX loading with sustained delivery behavior.

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References

  1. Nesseem DI, Eid SF, El-Houseny SS. Development of novel transdermal self-adhesive films for tenoxicam, an anti-inflammatory drug. Life Sciences. 2011;89:430–8. https://doi.org/10.1016/j.lfs.2011.06.026.

    Article  CAS  PubMed  Google Scholar 

  2. Gonzalez JP, Todd PA. Tenoxicam: a preliminary review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy. Drugs. 1987;34:289–310.

    Article  CAS  PubMed  Google Scholar 

  3. Vintiloiu A, Leroux J-C. Organogels and their use in drug delivery - a review. J Control Release. 2008;125:179–92.

    Article  CAS  PubMed  Google Scholar 

  4. Murdan S. Organogels in drug delivery. Expert Opin. 2005;2:29–39.

    Google Scholar 

  5. Garg T, Bilandi A, Kapoor B, Kumar S, Joshi R. Organogels: advanced and novel drug delivery system. Int Res J Pharm. 2011;2:15–21.

    CAS  Google Scholar 

  6. Wade A, Waller D. PJ Handbook of Pharmaceutical Excipients. 2nd ed. Washington DC: American Pharmaceutical Association; 1994.

    Google Scholar 

  7. Szuhaj, BF. Lecithins: Sources, manufacture, and uses. Champaign (Ill.): American Oil Chemists’ Society; 1989. VII, 283 p.: ill. AOCS monographs 12. https://lib.ugent.be/catalog/rug01:000220282.

  8. Raut S, Bhadoriya SS, Uplanchiwar V, Mishra V, Gahane A, Jain SK. Lecithin organogel: a unique micellar system for the delivery of bioactive agents in the treatment of skin aging. Acta Pharm Sin B Elsevier. 2012;2:8–15. https://doi.org/10.1016/j.apsb.2011.12.005.

    Article  CAS  Google Scholar 

  9. Smith J, Hong-Shum, Lily E. Food additives data book. 2nd ed. Food Res Int. 2011. https://doi.org/10.1002/9781444397741.ch8.

  10. Kumar R, Katare OP. Lecithin organogels as a potential phospholipid-structured system for topical drug delivery: A review. AAPS PharmSciTech. 2005;6:298–310.

    Article  Google Scholar 

  11. Motulsky A, Lafleur M, Couffin-Hoarau A-C, Hoarau D, Boury F, Benoit J-P, et al. Characterization and biocompatibility of organogels based on L-alanine for parenteral drug delivery implants. Biomaterials. 2005;26:6242–53.

    Article  CAS  PubMed  Google Scholar 

  12. Scartazzini R, Luisi PL. Organogels from lecithins. J Phys Chem. 1988;92:829–33.

    Article  CAS  Google Scholar 

  13. Esposito E, Ravani L, Mariani P, Huang N, Boldrini P, Drechsler M, et al. Effect of nanostructured lipid vehicles on percutaneous absorption of curcumin. Eur J Pharm Biopharm. 2014;86:121–32. https://doi.org/10.1016/j.ejpb.2013.12.011. (Elsevier B.V.).

    Article  CAS  PubMed  Google Scholar 

  14. Mandal S, Snigdha SM, Krutika KS. Lecithin stabilized organogel: design and development for topical application of clobetasol propionate. Int J ChemTech Res. 2010;2:1214–9.

    CAS  Google Scholar 

  15. Shaikh IM, Jadhav SL, Jadhav KR, Kadam VJ, Pisal SS. Aceclofenac organogels: in vitro and in vivo characterization. Curr Drug Deliv. 2009;6:1–7.

    Article  CAS  PubMed  Google Scholar 

  16. Shaikh IM, Jadhav KR, Gide PS, Kadam VJ, Pisal SS. Topical delivery of aceclofenac from lecithin organogels: Preformulation study. Curr Drug Deliv. 2006;3:417–27.

    Article  CAS  PubMed  Google Scholar 

  17. García-Couce J, Tomás M, Fuentes G, Que I, Almirall A, Cruz LJ. Chitosan/Pluronic F127 thermosensitive hydrogel as an injectable dexamethasone delivery carrier. Gels. 2022;8:44. https://doi.org/10.3390/gels8010044.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Abdellatif AAH, Mohammed AM, Saleem I, Alsharidah M, Al Rugaie O, Ahmed F, et al. Smart injectable chitosan hydrogels loaded with 5-fluorouracil for the treatment of breast cancer. Pharmaceutics. 2022;14: 661. https://doi.org/10.3390/pharmaceutics14030661

  19. Batrakova EV, Kabanov AV. Pluronic block copolymers: evolution of drug delivery concept from inert nanocarriers to biological response modifiers. J Control Release. 2008;130:98–106. https://doi.org/10.1016/j.jconrel.2008.04.013. (Elsevier B.V.).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Alsaab H, Bonam SP, Bahl D, Chowdhury P, Alexander K, Boddu SHS. Organogels in drug delivery: a special emphasis on pluronic lecithin organogels. J Pharm Pharm Sci. 2016;19:252–73.

    Article  CAS  PubMed  Google Scholar 

  21. Kabanov AV, Batrakova EV, Alakhov VY. Pluronic® block copolymers as novel polymer therapeutics for drug and gene delivery. J Control Release. 2002;82:189–212.

    Article  CAS  PubMed  Google Scholar 

  22. Gu Z, Wang M, Fang Q, Zheng H, Wu F, Lin D, et al. Preparation and in vitro characterization of pluronic-attached polyamidoamine dendrimers for drug delivery. Drug Dev Ind Pharm. 2015;41:812–8.

    Article  CAS  PubMed  Google Scholar 

  23. Kabanov A, Zhu J, Alakhov V. Pluronic block copolymers for gene delivery. Adv Genet. 2005;53:231–61.

    Article  CAS  PubMed  Google Scholar 

  24. Crandall WT, inventor. Topical moisturizing composition and method. USA Patent 6 316 428. November 13, 2001.

  25. Belgamwar VS, Pandey MS, Chauk DS, Surana SJ. Pluronic lecithin organogel. Asian J Pharm. 2008;2:134–8.

    Article  Google Scholar 

  26. Sahoo S, Kumar N, Bhattacharya C, Sagiri SS, Jain K, Pal K, et al. Organogels: properties and applications in drug delivery. Des Monomers Polym. 2011;14:95–108.

    Article  CAS  Google Scholar 

  27. Padilla M, Clark GT, Merrill RL. Topical medications for orofacial neuropathic pain: a review. J Am Dent Assoc. 2000;131:184–95. https://doi.org/10.14219/jada.archive.2000.0146. (American Dental Association).

    Article  CAS  PubMed  Google Scholar 

  28. Burnham R, Gregg R, Healy P, Steadward R. The effectiveness of topical diclofenac for lateral epicondylitis. Clin J Sport Med. 1998;8:78–81.

    Article  CAS  PubMed  Google Scholar 

  29. Richards H, Thomas CP, Bowen JL, Heard CM. In-vitro transcutaneous delivery of ketoprofen and polyunsaturated fatty acids from a pluronic lecithin organogel vehicle containing fish oil. J Pharm Pharmacol. 2006;58:903–8.

    Article  CAS  PubMed  Google Scholar 

  30. Stationwala R, Patidar A, Main P, Choukse AS, Agrawal S. Transdermal delivery of lornoxicam from pluronic lecithin organogel. Int J Chem Pharm Sci. 2011;2:32–7.

    CAS  Google Scholar 

  31. Mohammed AM, Faisal W, Saleh KI, Osman SK. Self-assembling organogels based on pluronic and lecithin for sustained release of etodolac: In vitro and in vivo correlation. Curr Drug Deliv. 2017;14:926–34.

    Article  CAS  PubMed  Google Scholar 

  32. Yassin TM, Saleh KI, Sarhan H, Osman SK. Formulation and evaluation of sorbitanmonostearate organogel as a topical delivery system for tenoxicam. Int J Innov Drug R&D. 2019;2:1–7.

    Google Scholar 

  33. Goindi S, Narula M, Kalra A. Microemulsion-based topical hydrogels of tenoxicam for treatment of arthritis. AAPS PharmSciTech. 2016;17:597–606. https://doi.org/10.1208/s12249-015-0383-0. (AAPS PharmSciTech).

    Article  CAS  PubMed  Google Scholar 

  34. Nandini D, Chauhan N, Chandra A, Pathak K. Effect of permeation enhancers on the release and permeation kinetics of oxytetracycline hydrochloride organogel formulations. J Young Pharm. 2009;1:285–9.

    Article  CAS  Google Scholar 

  35. Osman SK, Yassin TM, Mohammed AM, Alfayomy AM, Abdellatif AA, Mahdi WA, et al. A novel approach for the availability and ocular delivery of tenoxicam potassium: Synthesis, characterization, and in vivo application. AAPS PharmSciTech. 2023;24:44. https://doi.org/10.1208/s12249-022-02487-3. (Springer International Publishing).

    Article  CAS  PubMed  Google Scholar 

  36. Costa P, Sousa Lobo JM. Evaluation of mathematical models describing drug release from estradiol transdermal systems. Drug Dev Ind Pharm. 2003;29:89–97.

    Article  CAS  PubMed  Google Scholar 

  37. Costa P, Lobo JMS. Modeling and comparison of dissolution profiles. Eur J Pharm Sci. 2001;13:123–33.

    Article  CAS  PubMed  Google Scholar 

  38. Ritger PL, Peppas NA. A simple equation for description of solute release II. Fickian and anomalous release from swellable devices. J Control Release. 1987;5:37–42.

    Article  CAS  Google Scholar 

  39. Burnham KP, Anderson DR. Model selection and inference: a practical information-theoretic approach 2. J. Wildl. Manage. 2004.

  40. Singhvi G, Singh M. Review: In vitro drug release characterization models. Int J Pharm Stud Res [Internet]. 2011;2:77–84. Available from: https://www.researchgate.net/publication/285447890_Review_In_vitro_Drug_Release_Characterization_Models

  41. Kumar L, Verma R. In vitro evaluation of topical gel prepared using natural polymer. Int J Drug Deliv. 2010;2:58–63.

    Article  CAS  Google Scholar 

  42. Lehman PA, Raney SG, Franz TJ. Percutaneous absorption in man: in vitro-in vivo correlation. Skin Pharmacol Physiol. 2011;24:224–30.

    Article  CAS  PubMed  Google Scholar 

  43. Peppas NA. Analysis of Fickian and non-Fickian drug release from polymers. Pharm Acta Helv. 1985;60:110–1.

    CAS  PubMed  Google Scholar 

  44. Varelas CG, Dixon DG, Steiner CA. Zero-order release from biphasic polymer hydrogels. J Control Release. 1995;34:185–92.

    Article  CAS  Google Scholar 

  45. 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.

    Article  CAS  PubMed  Google Scholar 

  46. Gibaldi M, Feldman S. Establishment of sink conditions in dissolution rate determinations—theoretical considerations and application to nondisintegrating dosage forms. J Pharm Sci. 1960;23:247–52.

    Google Scholar 

  47. Wagner JG. Interpretation of percent dissolved-time plots derived from in vitro testing of conventional tablets and capsules. J Pharm Sci. 1969;58:1253–7.

    Article  CAS  PubMed  Google Scholar 

  48. Higuchi T. Rate of release of medicaments from ointment bases containing drugs in suspension. J Pharm Sci. 1961;50:874–5.

    Article  CAS  PubMed  Google Scholar 

  49. Higuchi T. Mechanism of sustained-action medication-theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J Pharm Sci. 1963;52:1145–9.

    Article  CAS  PubMed  Google Scholar 

  50. 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.

    Article  CAS  Google Scholar 

  51. Auda SH, El-Rasoul SA, Ahmed MM, et al. In-vitro release and in-vivo performance of tolmetin from different topical gel formulations. J Pharm Investig. 2015;45:311–7. https://doi.org/10.1007/s40005-015-0174-3.

    Article  CAS  Google Scholar 

  52. Winter CA, Risley EA, Nuss GW. Carrageenin-induced edema in hind paw of the rat as an assay for antiinflammatory drugs. Exp Biol Med. 1962;3:544–7.

    Article  Google Scholar 

  53. Reddy DN, Udupa N. Formulation and evaluation of oral and transdermal preparations of flurbiprofen and piroxicam incorporated with different carriers. Drug Dev Ind Pharm. 1993;19:843–52.

    Article  CAS  Google Scholar 

  54. Shahiwala A, Misra A. Studies in topical application of niosomally entrapped Nimesulide. J Pharm Pharm Sci. 2002;5:220–5.

    CAS  PubMed  Google Scholar 

  55. Habib FS, Hassan MA, Abou El Ela AESF, El Sayeh F, Raheem R. Different topical formulations of ketorolac tromethamine for anti-inflammatory application and clinical efficacy. Dig J Nanomater Biostructures. 2014;9:705–19.

    Google Scholar 

  56. Winter CA, Risley EA, Nuss GW. Anti-inflammatory and antipyretic activities of indomethacin, 1-(p-chlorobenzoyl)-5- methoxy-2-methyl-indole-3-acetic acid. J pharmacol ExperTherapeutics. 1963;141:369–76.

    CAS  Google Scholar 

  57. Koster R. Acetic acid for analgesic screening. Fed proc. 1959;18:412.

    Google Scholar 

  58. Dambisya YM, Lee TL, Sathivulu V, Mat Jais AM. Influence of temperature, pH and naloxone on the antinociceptive activity of Channa striatus (haruan) extracts in mice. J Ethnopharmacol. 1999;66:181–6.

    Article  CAS  PubMed  Google Scholar 

  59. Vogel GH. Drug discovery and evaluation: pharmacological assays. 3rd ed. Germany: Springer Science & Business Media; 2002.

    Book  Google Scholar 

  60. Draize JH, Woodard G, Calvery HO. Methods for the study of irritation and toxicity of substances applied topically to the skin and mucous membranes. J Pharmacol Exp Ther. 1944;82:377–90.

    CAS  Google Scholar 

  61. Boddu SH, Bonam SP, Wei Y, Alexander K. Preparation and in vitro evaluation of a pluronic lecithin organogel containing ricinoleic acid for transdermal delivery. Int J Pharm Compd. 2014;18:256–61.

    CAS  PubMed  Google Scholar 

  62. Shchipunov YA, Shumilina EV. Lecithin bridging by hydrogen bonds in the organogel. Mater Sci Eng C. 1995;3:43–50.

    Article  Google Scholar 

  63. Chawla A, Sharma P, Pawar P. Eudragit S-100 coated sodium alginate microspheres of naproxen sodium: Formulation, optimization and in vitro evaluation. Acta Pharm. 2012;62:529–45.

    Article  CAS  PubMed  Google Scholar 

  64. Purohit B, Gupta N, Jain S. Formulation and evaluation of diclofenac sodium organogel. Res J Pharm Technol. 2013;6:375–8.

    Google Scholar 

  65. Aiyalu R, Govindarjan A, Ramasamy A. Formulation and evaluation of topical herbal gel for the treatment of arthritis in animal model. Brazilian J Pharm Sci. 2016;52:493–507.

    Article  CAS  Google Scholar 

  66. Asghar A, Aamir MN, Sheikh FA, Ahmad N, Elsherif MA, Bukhari SNA. Co-combination of pregabalin and withania coagulans-extract-loaded topical gel aleviates allodynia and hyperalgesia in the chronic sciatic nerve constriction injury for neuropathic pain in animal model. Molecules. 2022;27:4433.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Plaza-Villegas F, Heir G, Markman S, Khan J, Noma N, Benoliel R, et al. Topical pregabalin and diclofenac for the treatment of neuropathic orofacial pain in rats. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012;114:449–56. https://doi.org/10.1016/j.oooo.2012.05.002. (Elsevier).

    Article  PubMed  Google Scholar 

  68. Jhawat V, Gupta S, Saini V. Formulation and evaluation of novel controlled release of topical pluronic lecithin organogel of mefenamic acid. Drug Deliv. 2016;23:3573–81.

    Article  CAS  PubMed  Google Scholar 

  69. Abu-Elyazid SK, Kassem AA, Samy AM, Gomaa ME. Evaluation of skin permeation and pharmacological effects of tenoxicam nanoemulsión in topical formulations. Asian J Pharm Heal Sci. 2011;1:99–105.

    Google Scholar 

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Acknowledgements

The authors are thankful to the Researchers Supporting Project number (RSP2024R146) at King Saud University, Riyadh, Saudi Arabia. The authors would like to thank the Deanship of Scientific Research at Shaqra University for supporting this work.

Funding

This research was funded by Researchers Supporting Project number (RSP2024R146) at King Saud University, Riyadh, Saudi Arabia.

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Authors and Affiliations

  1. Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Al-Azhar University, Assiut, 71524, Egypt

    Shaaban K. Osman, Ahmed M. Mohammed, Ahmed A. H. Abdellatif & Khalid I. Saleh

  2. Department of Pharmaceutical Technology, Faculty of Pharmacy, Minofia University, Minofia, Egypt

    Taher M. Yassin

  3. General Authority for Health Insurance, Qena, Egypt

    Arafat Abdelzaher

  4. Department of Zoology, Faculty of Science, Sohag University, Sohag, 82524, Egypt

    Fatma Ahmed

  5. Department of Pharmaceutics, College of Pharmacy, Qassim University, 51452, Buraydah, Saudi Arabia

    Ahmed A. H. Abdellatif

  6. Department of Pharmaceutics, College of Pharmacy, King Saud University, 11451, Riyadh, Saudi Arabia

    Wael A. Mahdi & Sultan Alshehri

  7. Department of Pharmaceutical Chemistry, College of Pharmacy, Shaqra University, 11961, Shaqra, Saudi Arabia

    Mohamed A. El Hamd

  8. Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, South Valley University, Qena, 83523, Egypt

    Mohamed A. El Hamd

  9. Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia, Egypt

    Hatem Sarhan

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  1. Shaaban K. Osman
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Contributions

Conceptualization, S.K.O. Data curation, T.M.Y., A.M.M., F.A., and S.K.O. Formal analysis, A.M.M., T.M.Y., F.A., and S.K.O. Investigation, A.A.A. and S.K.O. Methodology, S.K.O., T.M.Y., and A.M.M. Project administration, M.A.E.H., W.A.M., S.A., and S.K.O. Resources, W.A.M., S.A., and S.K.O. Software, A.M.M., W.A.M., and S.A. Validation, M.A.E.H. and F.A. Visualization, T.M.Y. and S.K.O. Writing—original draft, T.M.Y and S.K.O. Writing—review and editing, T.M.Y, F.A., A.A.A., A.A., W.A.M., S.A., and S.K.O.

Corresponding authors

Correspondence to Shaaban K. Osman or Mohamed A. El Hamd.

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The animal study protocol was approved by the Institutional Review Board (or Ethics Committee) of Faculty of Pharmacy, Al-Azhar University, with approval number AZ-AS/PH/3/C/2021, for studies involving animals.

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Communicated by Nisarg Modi, Yousuf Mohammed, and Lakshmi Raghavan

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Osman, S.K., Yassin, T.M., Abdelzaher, A. et al. Self-assembling Organogels Loaded with Tenoxicam for Local Intensive Pain and Inflammation Cure: In Vitro and In Vivo Correlation. AAPS PharmSciTech 25, 18 (2024). https://doi.org/10.1208/s12249-024-02742-9

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