IN VIVO PHARMACOKINETICS STUDY OF DICLOFENAC SODIUM LOADED BASELLA ALBA MUCILAGE BASED CARRIER FOR ENHANCEMENT OF ORAL BIOAVAILABILITY

MOUMITA CHOWDHURY; PINTU KUMAR DE

doi:10.22159/ijap.2025v17i4.53926

Authors

MOUMITA CHOWDHURY Guru Nanak Institute of Pharmaceutical Science and Technology, 157/F Nilgunj Road, Panihati, Sodepur, Kolkata-114, West Bengal, India https://orcid.org/0000-0003-0472-8122
PINTU KUMAR DE Department of Pharmaceutical Technology, JIS University 81, Nilgunj Road, Agarpara, Kolkata-700109, West Bengal, India https://orcid.org/0000-0002-9898-7506

DOI:

https://doi.org/10.22159/ijap.2025v17i4.53926

Keywords:

Pharmacokinetics, Diclofenac sodium, Basella alba, Bioavailability, Marketed formulation

Abstract

Objective: The present study aims to evaluate the in vivo bioavailability and pharmacokinetics of diclofenac sodium entrapped in a natural polysaccharide, Basella alba mucilage-based carrier.

Methods: In this study, mucilage from Basella alba was chemically modified to improve its physicochemical properties and evaluated for its extent of modification by elemental analysis. The Diclofenac sodium-loaded sustained-release hydrogel bead developed from tailored Basella alba mucilage was evaluated for particle size, drug entrapment and Scanning electron microscopy. The resulting beads were used to assess the in vivo pharmacokinetics and bioavailability study. The pharmacokinetics of diclofenac sodium and diclofenac sodium loaded formulation were studied and compared with a marketed formulation of Diclofenac sodium (Subsyde^®-CR DRCM capsule) at an equivalent dose in three groups of Wistar albino rats containing six rats in each group. Blood samples were collected via retro-orbital puncture for a period of 24 h. The diclofenac sodium concentration in a plasma sample of rats was detected by HPLC and the pharmacokinetic parameters were analyzed by noncompartmental modeling using PK solver.

Results: The elemental analysis and degree of substitution confirmed the chemical modification of Basella alba mucilage. The Basella alba mucilage-based beads showed uniform surface with drug entrapment efficiency of 71.56%±0.85. The pharmacokinetic parameters of raw drug and test formulation showed significant difference (p<0.01), whereas test and marketed formulation appeared similar without any significant difference. The results showed higher mean residence time, increased t_max, and decreased C_max of drug-loaded beads and marketed formulation than the pure drug. The relative bioavailability of Diclofenac sodium increased from 54.50% to 96.88% by entrapping it in Basella alba mucilage-based bead.

Conclusion: Thus, the present work unfolded the potential of Basella alba mucilage as a bioavailability enhancer, advocating its use in developing novel pharmaceutical formulations.

References

Nurwaini S, Anggraini AF, Sukmawati A, Imanto T, Utami W. Formulation and evaluation of sodium diclofenac slow-release tablet using a combination of mangrove fruit starch (Bruguiera gymnorrhiza) and sodium carboxy methyl cellulose (CMC) as matrix. Int J App Pharm. 2024;16(06):72-7. doi: 10.22159/ijap.2024.v16s6.TY2040.

Gagliardi A, Chiarella E, Voci S, Ambrosio N, Celano M, Cristina Salvatici M. Difucosin: diclofenac sodium salt loaded fucoidan-sericin nanoparticles for the management of chronic inflammatory diseases. Int J Pharm. 2024 Apr 25;655:124034. doi: 10.1016/j.ijpharm.2024.124034, PMID 38531433.

Khadra I, Obeid MA, Dunn C, Watts S, Halbert G, Ford S. Characterisation and optimisation of diclofenac sodium orodispersible thin film formulation. Int J Pharm. 2019;561:43-6. doi: 10.1016/j.ijpharm.2019.01.064, PMID 30772459.

Monika P, Chandraprabha MN, Krishna RH, Maanya V, Likhitha C, Pooja N. Development of targeted nanocapsules using pomegranate peel extract with enhanced bioavailability and anti-inflammatory activity for ulcerative colitis: in vitro studies. Hybrid Adv. 2024;7:100334. doi: 10.1016/j.hybadv.2024.100334.

Zhang Y, Yang D, Shuai B, Ding H, Yang J, Wang J. Diclofenac sodium nanomedicine results in pain-relief and differential expression of the RNA transcriptome in the spinal cord of SNI rats. Int J Pharm. 2024 Jun 25;659:124276. doi: 10.1016/j.ijpharm.2024.124276, PMID 38821436.

Zafar A, Alruwaili NK, Imam SS, Yasir M, Alsaidan OA, Alquraini A. Development and optimization of nanolipid-based formulation of diclofenac sodium: in vitro characterization and preclinical evaluation. Pharmaceutics. 2022;14(3):507. doi: 10.3390/pharmaceutics14030507, PMID 35335883.

Ngwuluka NC, Ochekpe NA, Aruoma OI. Naturapolyceutics: the science of utilizing natural polymers for drug delivery. Polymers. 2014;6(5):1312-32. doi: 10.3390/polym6051312.

Tan LS, Tan HL, Deekonda K, Wong YY, Muniyandy S, Hashim K. Fabrication of radiation cross-linked diclofenac sodium loaded carboxymethyl sago pulp/chitosan hydrogel for enteric and sustained drug delivery. Carbohydr Polym Technol Appl. 2021;2:100084. doi: 10.1016/j.carpta.2021.100084.

Upadhyay M, Adena SK, Vardhan H, Yadav SK, Mishra B. Locust bean gum and sodium alginate based interpenetrating polymeric network microbeads encapsulating capecitabine: improved pharmacokinetics, cytotoxicity & in vivo antitumor activity. Mater Sci Eng C Mater Biol Appl. 2019 Nov;104:109958. doi: 10.1016/j.msec.2019.109958. PMID 31500043.

Niu B, Jia J, Wang H, Chen S, Cao W, Yan J. In vitro and in vivo release of diclofenac sodium-loaded sodium alginate/carboxymethyl chitosan-ZnO hydrogel beads. Int J Biol Macromol. 2019 Dec 1;141:1191-8. doi: 10.1016/j.ijbiomac.2019.09.059, PMID 31518622.

Chowdhury M, Kumar De P. Tailored Basella Alba mucilage-based bipolymeric hydrogel beads for controlled release of diclofenac sodium. Int J App Pharm. 2023;15(5):106-16. doi: 10.22159/Ijap.2023v15i5.48803.

Fegade TD, Patil VR, Deshmukh TA. Evaluation of Vateria indica Modified Gum as a Release Retardant Matrix in the tablet dosage form. Int J Pharm Pharm Sci. 2023;15(4):28-32. doi: 10.22159/Ijpps.2023v15i4.47329.

Haju SS, Yadav S. Formulation and evaluation of cilnidipine mucoadhesive buccal film by solvent casting technique for the treatment of hypertension. Int J Pharm Pharm Sci. 2021;13(9):34-43. doi: 10.22159/Ijpps.2021v13i9.42641.

Jeevana JB, Ramya K. Development and in vitro evaluation of phytosomes of ellagic acid. Asian J Pharm Clin Res. 2023;16(3):105-9. doi: 10.22159/ajpcr.2023.V16i3.47129.

McLean MK, Khan SA. Toxicology of frequently encountered nonsteroidal anti-inflammatory drugs in dogs and cats: an update. Vet Clin North Am Small Anim Pract, 2018;48(6):969-84. doi: 10.1016/j.cvsm.2018.06.003, PMID 30149968.

Yuan J, Ma H, Cen N, Zhou A, Tao H. A pharmacokinetic study of diclofenac sodium in rats. Biomed Rep. 2017;7(2):179-82. doi: 10.3892/br.2017.942, PMID 28781777.

Zhang Y, Huo M, Zhou J, Xie S. PK Solver: an add-in program for pharmacokinetic and pharmacodynamic data analysis in microsoft excel. Comput Methods Programs Biomed. 2010;99(3):306-14. doi: 10.1016/j.cmpb.2010.01.007, PMID 20176408.

Peris Ribera JE, Torres Molina F, Garcia Carbonell MC, Aristorena JC, Pla Delfina JM. Pharmacokinetics and bioavailability of diclofenac in the rat. J Pharmacokinet Biopharm. 1991;19(6):647-65. doi: 10.1007/BF01080872, PMID 1815046.

Chatchawal C, Nualkaew N, Preeprame S, Porasuphatana S, Priprame A. Physical and biological properties of mucilage from Basella alba L. Stem and Its gel formulation. Isan J Pharm Sci. 2010;6(3):104-12. doi: 10.14456/ijps.2010.26.

Davies NM, Anderson KE. Clinical pharmacokinetics of diclofenac. Therapeutic insights and pitfalls. Clin Pharmacokinet. 1997;33(3):184-213. doi: 10.2165/00003088-199733030-00003, PMID 9314611.

Kohli K, Mujtaba A, Malik R, Amin S, Alam MS, Ali A. Development of natural polysaccharide-based nanoparticles of berberine to enhance oral bioavailability: formulation, optimization, ex vivo, and in vivo assessment. Polymers. 2021;13(21):3833. doi: 10.3390/polym13213833, PMID 34771389.

Uns Q, Asma H, Khawla R. Compartmental and non-compartmental pharmacokinetic analysis of extended-release diclofenac sodium Tablet. 2016;19(1):161-5.