FORMULATION AND EVALUATION OF DOLUTEGRAVIR SODIUM SOLID DISPERSIONS AND FAST DISSOLVING TABLETS USING POLOXAMER-188 AND JACK FRUIT SEED STARCH AS EXCIPIENTS
Objective: The current work mainly focuses on solubility enhancement of dolutegravir which is a biopharmaceutical classification system Class-II drug using jack fruit seed starch (JFS2) as excipient which improves the drug release.
Materials and Methods: Starches were extracted using aqueous and alkali methods (sodium hydroxide at 0.1%, 0.25%, and 0.5% concentrations) from jack fruit seed powder. These starches were evaluated for phytochemical and physicochemical parameters. Fast dissolving tablets were prepared using dolutegravir sodium solid dispersion, JFS2, and croscarmellose sodium (CCS) in various concentrations using wet granulation technique. Various pre- and post-compression parameters were evaluated along with in vitro drug release studies; characterization studies such as Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), scanning electron microscopy, X-ray diffraction (XRD), and stability studies.
Results: Phytochemical tests revealed the presence of only starch in all extracts. Starch prepared from 0.1% sodium hydroxide (JFS2) showed best physicochemical properties. From in vitro dissolution studies, it was observed that solid dispersion formulation DF3 containing dolutegravir sodium and poloxamer-188 in 1:1.5 ratios showed a better dissolution rate. From in vitro dissolution studies, tablet formulations DFT6 and DFT9 containing 12.5% w/w of JFS2 and 12.5% w/w of CCS showed enhanced dissolution rate compared with other formulations. FTIR and DSC studies revealed that there were no major interactions between drug and excipients. XRD studies revealed the nature of formulations. Accelerated stability studies showed that all tablets were stable.
Conclusion: The tablets prepared using jack fruit starch seed starch revealed the superdisintegrant property of starch.
2. Dhirendra K, Lewis S, Udupa N, Atin K. Solid dispersions: A review. Pak J Pharm Sci 2009;22:234-46.
3. Clotet B, Feinberg J, van Lunzen J, Khuong-Josses MA, Antinori A, Dumitru I, et al. Once-daily dolutegravir versus darunavir plus ritonavir in antiretroviral-naive adults with HIV-1 infection (FLAMINGO): 48 week results from the randomised open-label phase 3b study. Lancet 2014;383:2222-31.
4. Elzi L, Erb S, Furrer H, Cavassini M, Calmy A, Vernazza P, et al. Adverse events of raltegravir and dolutegravir. AIDS 2017;31:1853-8.
5. Raffi F, Rachlis A, Stellbrink HJ, Hardy WD, Torti C, Orkin C, et al. Once-daily dolutegravir versus raltegravir in antiretroviral-naive adults with HIV-1 infection: 48 week results from the randomised, double-blind, non-inferiority SPRING-2 study. Lancet 2013;381:735-43.
6. Chauhan V, Kumar K, Teotia D. Fast dissolving tablets: A promising approach for drug delivery. Univ J Pharm Res 2017;2:58-4.
7. Fateatun N, Jiaur RM, Sultan MM, Sorifa A, Aminul IT, Ahmed M. Physicochemical properties of flour and extraction of starch from Jack Fruit seed. Int J Nut Food Sci 2014;3:347-54.
8. Menaka T, Nagaraja G, Yogesh DB, Sunil Kumar US, Prakash L. Physicochemical properties of flour and isolated starch from Jackfruit seeds (Artocarpus Heterophyllus). Res J Pharm Sci 2011;1:14-8.
9. Vidyadhara S, Sasidhar RL, Lakshmi HD, Vijetha P, Vijetha K. Studies on jack fruit seed starch as a novel natural superdisintegrant for the design and evaluation of Irbesartan fast dissolving tablets. Int Med Res 2017;6:280-91.
10. Okunlola A, Odeku OA. Comparative evaluation of starches obtained from Dioscorea species as intragranular tablet disintegrants. J Drug Del Sci Technol 2008;18:445-7.
11. Sharda S, Bishambar S, Kirtika M, Monalisha N, Neha K, Shalini M. Solid dispersions: A tool for improving the solubility and dissolution of metronidazole. Int J Drug Del 2013;5:94-8.
12. Appa RB, Shivalingam M, Kishore RY, Somesekhara R, Rajesh K, Sunitha N. Formulation and evaluation of aceclofenac solid dispersions for dissolution rate enhancement. Int J Pharm Sci Drug Res 2010;2:146 50.
13. Sreenivas SA, Gadad A, Patil M. Formulation and evaluation of Ondansetron hydrochloride directly compressed mouth dissolving tablets. Indian Drugs 2006;4:35-7.
14. Bhavar GB, Pekamwar SS, Aher KB, Thorat RS, Chaudhari SR. High-performance liquid chromatographic and high-performance thin-layer chromatographic method for the quantitative estimation of dolutegravir sodium in bulk drug and pharmaceutical dosage form. Sci Pharm 2016;84:305-20.
15. Dharna A, Neelam S, Sukhbir S, Sandeep A. Solid dispersions: A review on drug delivery system and solubility enhancement. Int J Pharm Sci Res 2013;4:2094-105.
16. Shashikumar Y, Veena M, Srinivas M. Solid dispersion technique to enhance the solubility and dissolution rate of Aripiprazole by fusion method. Int J Pharm Pharm Sci 2016;8:187-92.
17. Pratik SD, Sushma V, Puja S. Fast dissolving tablet using solid dispersion technique: A review. Int J Curr Pharm Res 2017;9:1-4.
18. Sharma A, Jain CP. Preparation and characterization of solid dispersions of carvedilol with PVP K30. Res Pharm Sci 2010;5:49-56.
19. Shukla D, Subhashis C, Sanjay S, Brahmeshwar M. Mouth dissolving tablets II: An overview of evaluation techniques. Sci Pharm 2009;77:327-41.
20. Venkatarao M, Vidyadhara S, Sandeep D. Formulation and evaluation of Telmisartan solid dispersions using Entada scandens seed starch and Poloxamer-188 as superdisintegrants. Asian J Pharm Clin Res 2018;11:474-81.
21. Rubendra K, Dinesh KM, Dinesh KJ. Solid dispersion: A novel means of solubility enhancement. J Crit Rev 2016;3:1-8.
22. Emmanuel OO, Musiliu OA, Ekaete IA. Evaluation of callinectes chitosan as a superdisintegrant in metronidazole tablet. Int J Pharm Pharm Sci 2017;9:111-8.
This work is licensed under a Creative Commons Attribution 4.0 International License.
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.