FORMULATION OF ATOVAQUONE TABLET USING BIOSURFACTANT IN A TERNARY SOLID DISPERSION SYSTEM: IN VITRO AND IN VIVO EVALUATION
Keywords:Atovaquone, Solid dispersion, Physical mixture, Ternary system, Biosurfactant, Bioavailability
Objective: The goal of the present investigation was to improve the solubility and bioavailability of atovaquone tablet, using in-house biosynthesized biosurfactant in the ternary system of solid dispersion containing hydrophilic polymers with varying concentrations of biosurfactant. Atovaquone is an anti-malarial agent and belongs to biopharmaceutical classification system class IV.
Methods: The solid dispersion of binary and ternary mixture was prepared using hydroxyl propyl methyl cellulose (HPMC) and biosurfactant respectively by a solvent evaporation method. All the atovaquone tablet formulations were prepared by incorporation of physical mixture, binary and ternary solid dispersed products with excipients by direct compression method. Pre-compression and post-compression parameters of atovaquone tablets were evaluated. In vivo bioavailability study was performed using female albino rabbits.
Results: In vitro dissolution profile of binary and ternary system of solid dispersion products showed 8.65% and 34.64% respectively. Precompression and post-compression values of all atovaquone tablets formulations were within the specified limits. In vitro dissolution efficiency of F2 and F5 were 1.44 fold and 6.62 fold respectively, in accordance to the F1. In vivo study revealed that bioavailability of optimized formulation F5 was increased by 2.5 times and time to reach peak concentration was reduced to 1.4 h, in accordance to pure atovaquone suspension.
Conclusion: Potential application of biosurfactant in the solid dosage form of atovaquone tablet was proved for enhanced dissolution rate and bioavailability of atovaquone for malaria treatment.
Araon LB, David RH. Antiparasitic agent atovaquone. Antimicrob Agents Chemother 2002;46:1163-73.
Sek L, Boyd BJ. Examination of the impact of a range of pluronic surfactants on the in vitro solubilization behavior and oral bioavailability of lipidic formulations of atovaquone. J Pharm Pharmacol 2006;58:809-20.
Venkatram, Roger JA. Characteristics of drug-phospholipid coprecipitates I: physical properties and dissolution behavior of griseofulvin-dimyristoyl phosphatidylcholine systems. J Pharm Sci 1984;73:757-61.
Vishal J, Parekh, Patravale VB, Aniruddha B, Pandit. Mango kernel fat: a novel lipid source for the fermentative production of sophorolipid biosurfactant using starmerella bombicola NRRL-Y 17069. Ann Biol Res 2012;3:1798-803.
Karadi RV, Lokesh KN, Channarayappa MV, Venkataranganna, Bindu S, Sivakiran RR. Standardization of biosurfactant enrichment process by factorial design and elucidating its physicochemical and structural characteristics. J Biochem Tech 2012;3:161-6.
Zoeller T, Dressman JB, Klein S. Application of a ternary HP-β-CD-complex approach to improving the dissolution performance of a poorly soluble weak acid under relevant conditions. Int J Pharm 2012;430:176–83.
Patil AN, Shinkar DM, Saudagar RB. Review article: solubility enhancement by solid dispersion. Int J Curr Pharm Res 2017;9:15-8.
Biswas M, Akogyeram CO, Scott KR, Potti GK, Gallelli JF, Habib MJ. Development of carbamazepine: phospholipid solid dispersion formulations. J Controlled Release 1993;23:239-45.
Eraga SO, Arhewoh MI, Okunzuwa JI, Iwuagwu MA. Preliminary investigation of the mucoadhesive properties of thermally modified mucin on metronidazole tablets. Int J Pharm Pharm Sci 2015;7:96-00.
Kishore BA, Ramana MV. Development and in vivo evaluation of gastroretentive floating tablets of antipsychotic drug risperidone. Int J Pharm Pharm Sci 2016;8:43-52.
Wadher KJ, Kakde RB, Umekar MJ. Formulation and evaluation of sustained-release tablets of metformin hydrochloride using hydrophilic synthetic and hydrophobic natural polymers. Indian J Pharm Sci 2011;73:208-15.
Khan KA, Rhodes CT. The concept of dissolution efficiency. J Pharm Pharmacol 1975;27:48-9.
Koh PT, Chuah JN, Talekar M, Gorajana A, Garg S. Formulation development and dissolution rate enhancement of efavirenz by solid dispersion systems. Indian J Pharm Sci 2013;75:291-301.
DeAngelis DV, Long JD, Kanics LL, Woolley JL. High-performance liquid chromatographic assay for the measurement of atovaquone in plasma. J Chromatogr 1994;652:211-9.
Reddy SD, Rao PB. Development and in vitro-in vivo evaluation of controlled release matrix tablets of desvenlafaxine. Pharmacol Pharm 2012;3:15-9.
Sareen S, George M, Josep L. Improvement insolubility of poorly water-soluble by solid dispersion. Int J Pharm Investig 201;2:12-7.
Shaiji J, Bhatia V. Dissolution enhancement of atovaquone through cyclodextrin complexation and phospholipid solid dispersion. Int J Pharm Pharm Sci 2013;5:642-50.
Mohammad FK, Muhammad SBS, Khan RI, Tahiatul SM, Saiful I. Study of the binary and ternary solid dispersion of ibuprofen for the enhancement of oral bioavailability. Appi Pharm Sci 2011;1:103-7.
Borhardev, Patak S, Sharma S, Patravale V. Formulation and characterization of atovaquone nanosuspension for improved oral delivery in the treatment of malaria. Nanomedicine 2014;5:649-66.