International Journal of Drug Delivery Technology
Volume 14, Issue 3

Formulation and Evaluation of Haemocoagulase Gel for Dental Pulp- an In-vitro study

Swati Karkare1*, Nilima. Thosar1, Milind Wagh2, Nikita Wagh2

1Dept of Pedodontics and Preventive Dentistry, SPDC, Datta Meghe Institute of Higher Education and Research. (DMIHER) Wardha.

2Dept of Pharmaceutics, NDMVP Samaj’s College of Pharmacy, Nashik, Maharashtra.

Received: 24th January, 2024; Revised: 24th April, 2024; Accepted: 16th May, 2024; Available Online: 25th September, 2024

ABSTRACT

This study aims to develop a novel hemostatic gel of hemocoagulase, a snake venom-derived serine protease enzyme, by incorporating it into the matrix of bioadhesive polymers to prevent damage due to hemorrhage. Haemocoagulase was combined with polymers Carbopol 940 and HPMC K 100, and these formulations were evaluated for physical properties, efficacy, safety and stability. Batches F3 and F6 were selected for further studies on animal models, which were found to be safe without any skin irritation effect and effective as hemostats with blood clotting times of 1.24 ± 0.007 min and 1.36 ± 0.014 min, respectively, in a rat liver incision model. From this study, it can be suggested that the combination of hemocoagulase with bioadhesive polymer can provide a novel hemostatic tool for controlling bleeding.

Keywords: Hemostatic gel, Hemocoagulase, Botroclot, Physical barrier, Blood coagulation. International Journal of Drug Delivery Technology (2024); DOI: 10.25258/ijddt.14.3.01

How to cite this article: Karkare S, Thosar N, Wagh M, Wagh N. Formulation and Evaluation of Haemocoagulase Gel for Dental Pulp- an In-vitro study. International Journal of Drug Delivery Technology. 2024;14(3):1248-1256.

REFERENCES

  1. Sembulingam K, Sembulingam P. Essentials of Medical Physiology. 5th Jaypee Brothers Medical Publishers (P) Ltd; 2010. 56–58 p.
  2. Adhana R, Chaurasiya R, Verma A. Comparison of bleeding time and clotting time between males and Natl J Physiol Pharm Pharmacol. 2018;8(10):1388–90.Available at: doi: 10.5455/ ijmsph.2018.06201417062018
  3. Andrew Current understanding of Haemostasis. Toxicol Pathol. 2011;39(1):273–80.Available at: doi: 10.1177/0192623310389474
  4. Palta S, Saroa R, Palta Overview of the coagulation system. Indian J Anaesth. 2014;58(5):515–23. Available at: doi: 10.4103/0019-5049.144643.
  5. Stokes ME, Ye X, Shah M, Mercaldi K, Reynolds MW, Rupnow MFT, et al. Impact of bleeding-related complications and/or blood product transfusions on hospital costs in inpatient surgical BMC Health Serv Res. 2011;11(1):135. Available at: doi: 10.1186/1472-6963-11-135.
  6. Rossaint R, Bouillon B, Cerny V, Coats TJ, Duranteau J, Fernández-mondéjar E, et Management of bleeding following major trauma : an updated European guideline. Crit Care. 2010;14:1–29. Available at: doi: 10.1186/cc8943. Epub 2010 Apr 6.
  7. Eikelboom JW, Hirsh Bleeding and management of bleeding. Eur Hear J Suppl. 2006;8:38–45. Available at: doi:10.1093/ eurheartj/sul054
  8. Ruangchainicom N, Mahardawi B, Sakdejayont W. Topical hemostatic agents from an oral-surgery perspective. J Oral Maxillofac Surgery, Med Pathol. 2021;33:249–55.Available at: org/10.1016/j.ajoms.2020.11.007
  9. Wright JD, Ananth C V., Lewin SN, Burke WM, Siddiq Z, Neugut AI, et Patterns of Use of Hemostatic Agents in Patients Undergoing Major Surgery. J Surg Res. 2014;186(1):458.Available at: doi: 10.1016/j.jss.2013.07.042
  10. Budko E , Chernikova DA, Yampolsky LM, Yatsyuk VY. Local hemostatic agents and ways of their improvement. IP Pavlov Russ Med Biol Her. 2019;27(2):274–85.Avialable at: doi.org/10.23888/ PAVLOVJ2019272274-285
  11. Kumar Mp S. Local Hemostatic Agents in The Management of Bleeding in Oral Asian J Pharm Clin Res. 2016;9(3):35–41.A vailable at: https://journals.innovareacademics.in/index. php/ajpcr/article/view/11744
  12. Zhong Y, Hu H, Min N, Wei Y, Li X, Li X. Application and outlook of topical hemostatic materials: a narrative review. Ann Transl 2021;9(7):577–577. Available at:doi: 10.21037/ atm-20-7160.
  13. Pereira BM, Bortoto JB, Fraga Topical hemostatic agents in surgery: Review and prospects. Rev Col Bras Cir. 2018;45(5):1–Available at:doi: 10.1590/0100-6991e-20181900.
  14. CP M, P DN, TU VN. Effect of topical hemocoagulase therapy in wound Int J Surg Sci. 2019;3(4):151–6.Available at: doi.org/10.33545/surgery.2019.v3.i4c.234
  15. Choi SK, Kim CW, Kim JT, Seomun Y, Park MS, Kim CO. Coagulant Effect and Tolerability of Yeast-Produced Recombinant Batroxobin in Healthy Adult Subjects. Clin Drug Investig. 2018;38(9):829–35. Available at:doi: 1007/s40261- 018-0673-x
  16. Guo Y, Wang Y, Zhao X, Li X, Wang Q, Zhong W, et Snake extract-laden hemostatic bioadhesive gel cross-linked by visible light. Vol. 7, Sci. Adv. 2021.Available at: doi: 10.1126/sciadv. abf9635
  17. Kumar VA, Wickremasinghe NC, Shi S, Hartgerink Nanofibrous Snake Venom Hemostat. ACS Biomater Sci Eng. 2015 Dec 14;1(12):1300–5. Available at:doi: 10.1021/ acsbiomaterials.5b00356
  18. Safitri FI, Nawangsari D, Febrina D. Overview: Application of Carbopol 940 in Gel. Adv Heal Sci Reasearch. 2021;34:80–4. Available at:doi.org/10.2991/ahsr.k.210127.018
  19. Tamasree Majumder, Gopa Roy Biswas, Sutapa Biswas Majee. Hydroxy Propyl Methyl Cellulose: Different Aspects in Drug Delivery. J Pharm Pharmacol. 2016 Aug 10;4(8). Available at: DOI:10.17265/2328-2150/2016.08.003
  20. Chakraborti CK, Sahoo S, Behera PK. Role of different biodegradable polymers on the permeability of J Adv Pharm Technol Res. 2014;5(3):140–6. Available at: doi. org/10.4103%2F2231-4040.137434
  21. kumar Voleti V, Kumar Voleti V, Banu Shaik S, Konduru C, Peyam S, Kumar Yaramsetti C, et al. Formulation and development of dental gel containing clove oil for the treatment of human periodontal Vol. 3, Compr Phar. 2016;3(1):1-7
  22. Aslani A, Malekpour Design, formulation, and physicochemical evaluation of periodontal propolis mucoadhesive gel. Dent Res J. 2016;13(6):484–93. Available at: doi: 10.4103/1735-3327.197037.
  23. Upadhye K, Charde K, Dixit G, Bakhle S. Formulation and evaluation of herbal gel for management of mouth ulcers. Indian J Pharm 2021;8(3):226–30. Available at:doi. org/10.18231/j.ijpp.2021.039
  24. Chandira R., Pradeep, Pasupathi A, Bhowmilk D, Chiranjib, Jayakar B, et al. Design, Development and Formulation of Antiacne Dermatological Gel. J Chem Pharm Res. 2010;2(1):401– 14.
  25. Parhi R, Goutam SVS, Mondal Formulation and evaluation of transdermal gel of ibuprofen: Use of penetration enhancer and microneedle. Iran J Pharm Sci. 2020;16(3):11–32. Available at: doi.org/10.22037/ijps.v16.40382
  26. Khullar R, Kumar D, Seth N, Saini Formulation and evaluation of mefenamic acid emulgel for topical delivery. Saudi Pharm2012;20(1):63–7.Available at: doi: 10.1016/j.jsps.2011.08.001. Epub 2011 Aug 22
  27. Garala K, Joshi P, Patel J, Ramkishan A, Shah M. Formulation and evaluation of periodontal in situ gel. Int J Pharm Investig. 2013;3(1):29–41. Available at:doi: 4103/2230-973X.108961
  28. Nugraha SE, Suwarso E. In-vitro hemostatic activity of ethanol extracts of Beetroot (Beta vulgaris L .) in blood male albino J Innov Innov Pharmacutical Biol Sci. 2018;5(1):34–6.
  29. Ayodele OO, Onajobi FD, Osoniyi O. In-vitro anticoagulant effect of Crassocephalum crepidioides leaf methanol extract and fractions on human blood. J Exp Pharmacol. 2019;11:99–107. Available at: doi: 10.2147/JEP.S218261. eCollection 2019.
  30. Wedasingha S, Isbister G, Silva A. Bedside Coagulation Tests in Diagnosing Venom-Induced Consumption Coagulopathy in Snakebite. Toxins (Basel). 2020;12(9):1–15.Available at: doi: 3390/toxins12090583
  31. OECD 404. Guidelines for the Testing of Chemicals. Acute Dermal Irritation/Corrosion. OECD Guidel Test Chem Sect 4 Heal 2015;(July 28th):1–8. 2074-5788 (online) Available at: DOI: 10.1787/20745788
  32. Gebrehiwot M, Asres K, Bisrat D, Mazumder A, Lindemann P, Bucar F. Evaluation of the wound healing property of Commiphora guidottii Chiov. ex. Guid. BMC Complement Altern Med. 2015;15(1):1–11.Available at: doi: 10.1186/s12906- 015-0813-2
  33. Joshua JM, Anilkumar A, Verjina CU, Vasudevan DT, Surendran Formulation and evaluation of antiaging phytosomal gel. Asian J Pharm Clin Res. 2018 Mar 1;11(3):409–22.Available at: doi.org/10.22159/ajpcr.2018.v11i3.24257
  34. Partha N, Snigdha P, Laxmidhar Formulation DevelopmentAnd In-Vitro Evaluation Of Dental Gel Containing Ethanol Extract Of Tephrosia Purpurea LINN. Int J Pharm Pharm Sci. 2016;8(8):132–41.
  35. CROWELL JW, HOUSTON B. Effect of acidity on blood coagulation. Am J Physiol. 2019;379–82.
  36. Pourshahrestani S, Zeimaran E, Kadri NA, Mutlu N, Boccaccini AR. Polymeric Hydrogel Systems as Emerging Biomaterial Platforms to Enable Hemostasis and Wound Healing. Vol. 9, Advanced Healthcare 2020. p. 1–52. Available from: doi: 10.1002/adhm.202000905. Epub 2020 Sep 16.