Open Access Open Access  Restricted Access Subscription Access
Open Access Open Access Open Access  Restricted Access Restricted Access Subscription Access

Solubility and Dissolution Improvement of Carbamazepine by Various Methods


Affiliations
1 Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India
     

   Subscribe/Renew Journal


This work was aimed to improve solubility and dissolution rate of carbamazepine (CBZ), an antiepileptic, BCS class II drug by using different solubility enhancement techniques. Self-nanoemulsifying drug delivery system (SNEDDS) and solid dispersions of CBZ was attempted by spontaneous emulsification method and fusion method, respectively. The solubility studies of pure CBZ was performed in different oils, surfactants and co-surfactants. Very small amount of CBZ (20 mg) could be incorporated in SNEDDS, however the solid dispersion of CBZ using Soluplus® was successfully prepared with the required dose. The solid dispersion was characterized and evaluated for saturation solubility, in vitro dissolution studies, solid state characterization such as fourier transform infrared spectroscopy (FTIR) and powder X-ray diffraction studies (XRD). Based on the results, it can be concluded that the due to increased solubility and the dissolution, the bioavailability of CBZ could be improved by preparing solid dispersion.

Keywords

Carbamazepine, Self-Nanoemulsifying Drug Delivery System, Solid Dispersion, Spontaneous Emulsification Method, Fusion Method.
Subscription Login to verify subscription
User
Notifications
Font Size


  • Sander JW. The Natural History of Epilepsy in the Era of New Antiepileptic Drugs and Surgical Treatment. Epilepsia. 2003, 44(s1): 17–20.
  • Mills A. Global comparative assessments in the health sector: Disease burden, expenditures and intervention packages. Vol. 89, Transactions of the Royal Society of Tropical Medicine and Hygiene. Oxford University Press, 1995 [cited 2018 Nov 8]. p. 578.
  • Zybina A, Anshakova A, Malinovskaya J, Melnikov P, Baklaushev V, Chekhonin V, et al. Nanoparticle-based delivery of carbamazepine: A promising approach for the treatment of refractory epilepsy. International Journal of Pharmaceutics. 2018, 547(1–2): 10–23.
  • Acharya SP, Pundarikakshudu K, Panchal A, Lalwani A. Preparation and evaluation of transnasal microemulsion of carbamazepine. Asian Journal of Pharmaceutical Sciences. 2013, 8(1): 64–70.
  • Kou W, Cai C, Xu S, Wang H, Liu J, Yang D, et al. In vitro and in vivo evaluation of novel immediate release carbamazepine tablets: Complexation with hydroxypropyl-β-cyclodextrin in the presence of HPMC. International Journal of Pharmaceutics. 2011, 409(1–2): 75–80.
  • Kalepu S, Nekkanti V. Insoluble drug delivery strategies: review of recent advances and business prospects. Acta Pharmaceutica Sinica B. 2015, 5(5): 442–453.
  • Wang L, Dong J, Chen J, Eastoe J, Li X. Design and optimization of a new self-nanoemulsifying drug delivery system. Journal of Colloid and Interface Science. 2009, 330(2): 443–448.
  • Park M-J, Ren S, Lee B-J. In vitro andin vivo comparative study of itraconazole bioavailability when formulated in highly soluble self-emulsifying system and in solid dispersion. Biopharmaceutics & Drug Disposition. 2007, 28(4): 199–207.
  • Jeevana Jyothi B, Sreelakshmi K. Design and Evaluation of Self-Nanoemulsifying Drug Delivery System of Flutamide.Journal of Young Pharmacists. 2011, 3(1): 4–8.
  • Pouton CW. Lipid formulations for oral administration of drugs: non-emulsifying, self-emulsifying and “self-microemulsifying” drug delivery systems. European Journal of Pharmaceutical Sciences. 2000, 11 Suppl 2: S93-98.
  • Fatouros DG, Karpf DM, Nielsen FS, Mullertz A. Clinical studies with oral lipid based formulations of poorly soluble compounds. Therapeutics and Clinical Risk Management. 2007, 3(4): 591–604.
  • Chakraborty S, Shukla D, Mishra B, Singh S. Lipid – An emerging platform for oral delivery of drugs with poor bioavailability. European Journal of Pharmaceutics and Biopharmaceutics. 2009, 73(1): 1–15.
  • Maulvi FA, Dalwadi SJ, Thakkar VT, Soni TG, Gohel MC, Gandhi TR. Improvement of dissolution rate of aceclofenac by solid dispersion technique. Powder Technology. 2011, 207(1–3): 47–54.
  • Shamsuddin, Fazil M, Ansari SH, Ali J. Development and evaluation of solid dispersion of spironolactone using fusion method. International Journal of Pharmaceutical Investigation. 2016, 6(1): 63–68.
  • Nan Z, Lijun G, Tao W, Dongqin Q. Evaluation of Carbamazepine (CBZ) Supersaturatable Self-Microemulsifying (S-SMEDDS) Formulation In-vitro and In-vivo. Iranian Journal of Pharmaceutical Research. 2012, 11(1): 257–264.
  • Sethia S, Squillante E. Physicochemical Characterization of Solid Dispersions of Carbamazepine Formulated by Supercritical Carbon Dioxide and Conventional Solvent Evaporation Method. Journal of Pharmaceutical Sciences. 2002, 91(9): 1948–1957.
  • Milović M, Djuriš J, Djekić L, Vasiljević D, Ibrić S. Characterization and evaluation of solid self-microemulsifying drug delivery systems with porous carriers as systems for improved carbamazepine release. International Journal of Pharmaceutics. 2012, 436(1–2): 58–65.
  • Biswas M, Akogyeram CO, Scott KR, Potti GK, Gallelli JF, Habib MJ. Development of carbamazepine: phospholipid solid dispersion formulations. Journal of Controlled Release. 1993, 23(3): 239–245.
  • Djuris J, Nikolakakis I, Ibric S, Djuric Z, Kachrimanis K. Preparation of carbamazepine–Soluplus® solid dispersions by hot-melt extrusion, and prediction of drug–polymer miscibility by thermodynamic model fitting. European Journal of Pharmaceutics and Biopharmaceutics. 2013, 84(1): 228–237.
  • Lee J-Y, Kang W-S, Piao J, Yoon I-S, Kim D-D, Cho H-J. Soluplus®/TPGS-based solid dispersions prepared by hot-melt extrusion equipped with twin-screw systems for enhancing oral bioavailability of valsartan. Drug Design, Development and Therapy. 2015, 9: 2745–2756.
  • Balakumar K, Raghavan CV, selvan NT, prasad RH, Abdu S. Self nanoemulsifying drug delivery system (SNEDDS) of Rosuvastatin calcium: Design, formulation, bioavailability and pharmacokinetic evaluation. Colloids Surfaces B: Biointerfaces. 2013; 112: 337–343.
  • Medarević DP, Kachrimanis K, Mitrić M, Djuriš J, Djurić Z, Ibrić S. Dissolution rate enhancement and physicochemical characterization of carbamazepine-poloxamer solid dispersions. Pharmaceutical Development and Technology. 2016, 21(3): 268–276.

Abstract Views: 386

PDF Views: 0




  • Solubility and Dissolution Improvement of Carbamazepine by Various Methods

Abstract Views: 386  |  PDF Views: 0

Authors

Shreya
Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India
Ayesha Heena
Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India
Ranjitha
Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India
Amrutha A. Shetty
Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India
Chetan H. Mehta
Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India
Usha Y. Nayak
Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India
Srinivas Mutalik
Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India
K. Girish Pai
Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India

Abstract


This work was aimed to improve solubility and dissolution rate of carbamazepine (CBZ), an antiepileptic, BCS class II drug by using different solubility enhancement techniques. Self-nanoemulsifying drug delivery system (SNEDDS) and solid dispersions of CBZ was attempted by spontaneous emulsification method and fusion method, respectively. The solubility studies of pure CBZ was performed in different oils, surfactants and co-surfactants. Very small amount of CBZ (20 mg) could be incorporated in SNEDDS, however the solid dispersion of CBZ using Soluplus® was successfully prepared with the required dose. The solid dispersion was characterized and evaluated for saturation solubility, in vitro dissolution studies, solid state characterization such as fourier transform infrared spectroscopy (FTIR) and powder X-ray diffraction studies (XRD). Based on the results, it can be concluded that the due to increased solubility and the dissolution, the bioavailability of CBZ could be improved by preparing solid dispersion.

Keywords


Carbamazepine, Self-Nanoemulsifying Drug Delivery System, Solid Dispersion, Spontaneous Emulsification Method, Fusion Method.

References