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Development of Solid Self-Microemulsifying System of Tizanidine Hydrochloride for Oral Bioavailability Enhancement: In Vitro and In Vivo Evaluation

Abstract

The aim of the present investigation was to formulate self-microemulsifying drug delivery system (SMEDDS) tablets to enhance the oral bioavailability of tizanidine hydrochloride. SMEDDS was prepared by using Capmul G as the oil phase, Tween 20 as the surfactant, and propylene glycol as the co-surfactant. The optimized formulation was characterized by dilution test, % transmittance, thermodynamic stability, dye solubility, assay, globule size, zeta potential, and TEM. A dye solubility test confirmed the formation of o/w microemulsion. Optimized formulation of SMEDDS had a drug content of 98 ± 0.75% (3.2± 0.3 mg) and droplet size of 96.61 ± 2.3 nm. Dilution and centrifugation tests indicated the physical stability of the formulation. The optimized SMEDDS was mixed with Neusilin as adsorbent, microcrystalline cellulose as diluent, and magnesium stearate as flow promoter, and compressed into tablets. The prepared tablets passed the tests of weight variation, hardness, friability, and assay. In vitro dissolution test indicated sustained release of tizanidine hydrochloride from the SMEDDS tablet for a period of 4 h. In vivo pharmacokinetic studies performed on male New Zealand rabbits showed a 4.61-fold increase in bioavailability compared with the marketed formulation. Thus, the developed SMEDDS tablet proved to be capable of enhancing oral bioavailability of tizanidine hydrochloride.

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Correspondence to Hetal Thakkar.

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Approval of the experimental protocol was obtained from the Institutional Animal Ethics Committee of the Pharmacy department, The M. S. University of Baroda, Vadodara vide protocol no: MSU/IAEC/2016-17/1647. The experiments were conducted as per the requirements of Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA).

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Pramanik, S., Thakkar, H. Development of Solid Self-Microemulsifying System of Tizanidine Hydrochloride for Oral Bioavailability Enhancement: In Vitro and In Vivo Evaluation. AAPS PharmSciTech 21, 182 (2020). https://doi.org/10.1208/s12249-020-01734-9

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  • DOI: https://doi.org/10.1208/s12249-020-01734-9

KEY WORDS

  • tizanidine
  • SMEDDS
  • oral bioavailability