Solubility and Dissolution Enhancement of Poorly Aqueous Soluble Drug Ibrutinib by Self Emulsifying Drug Delivery System

Author(s): M. Sunitha Reddy* and Gavvalapally Swapna

Abstract: The present work mainly emphasized on the enhancement of solubility of Ibrutinib by developing Self-emulsifying lipid formulations. Ibrutinib is a BCS class II drug with poor aqueous solubility (oral bioavailability 3.9%). The saturated solubility of Ibrutinib in various oils, surfactants and co-surfactants was determined using UV-spectroscopy. The excipients were screened and selected based on their maximum solubility and compatibility for Ibrutinib. SEDDS formulations of Ibrutinib were developed using different Oils, Surfactants and Co-Surfactant combinations (4:1 and 3:1). Pseudo ternary phase diagrams were constructed using Triplot V 4.1.2 software and based on Pseudo ternary phase diagrams, nano-emulsification area was evaluated. Formulations were designed based on Pseudo ternary phase diagrams using various proportions of oil (Capmul MCM C8 EP), surfactants (Kolliphor EL) and co-surfactants (Labrasol). The prepared four formulations were selected among them F3 was optimized and carried out for further evaluations like robustness to dilution (Passed), dispersibility test (Grade A), self-emulsification time (28 ±1.08 sec), percentage transmittance (Clear emulsions), drug loading efficiency (96.49 ± 0.48%), thermodynamic stability study (Passed), emulsion globule size (17.6 d.nm) and zeta potential (-10.6 mV), invitro drug release studies. Among the four formulations, F3 (C8KEL3LA1 1:9) was optimized formulation because it gave the best results in terms of required In-vitro drug release. The dissolution rate of F3 SEDDS (84.22 ± 0.20 %) was compared with Ibrutinib (API) (54.98 ± 0.32 %). The results indicated that the solubility and dissolution rate of Ibrutinib SEDDS has significant increase of 1.53 times when compared to pure drug (API). The results of the present studies demonstrate that Ibrutinib SEDDS can be used as a potential means for improving solubility and dissolution rate of Ibrutinib.

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