SOLUBILITY AND DISSOLUTION ENHANCEMENT OF POORLY AQUEOUS SOLUBLE DRUG GEFITINIB BY SELF EMULSIFYING DRUG DELIVERY SYSTEMAbstract
The present research work was aimed at the enhancement of solubility and dissolution rate of Gefitinib by Self Emulsifying Drug Delivery Systems (SEDDS). Gefitinib is a BCS class II drug with poor aqueous solubility (oral bioavailability 60%). The saturated solubility of Gefitinib in different oils, surfactants and co-surfactants were determined. The excipients were screened and selected showing maximum solubility and compatibility for Gefitinib. SEDDS formulations of Gefitinib were developed using selected Oils, Surfactants and Co-Surfactant combinations (4:1 and 3:1). Pseudo ternary phase diagrams were created using Triplot V 4.1.2 software and applying Pseudo ternary phase diagrams, the nano-emulsification region was identified. Formulations were optimized based on Pseudo ternary phase diagrams using various proportions of oil (Peceol), surfactants (Kolliphor HS 15) and co-surfactants (Labrasol). The prepared four formulations were selected among them F1 was optimized and carried out for further evaluations like robustness to dilution (Passed), dispersibility test (Grade A), self emulsification time (29 ± 1.05 sec), percentage transmittance (Clear emulsions), drug loading efficiency (98.735 ± 0.43%), thermodynamic stability study (Passed), emulsion globule size (104.2 d.nm) and zeta potential (-16.2 mV), in-vitro drug release studies. Among the four formulations, F1 (PK154LA1 1:9) was optimized formulation because it gave the optimum results in terms of required in-vitro drug release. The dissolution rate of F1 SEDDS (88.253 ± 0.20 %) was compared with Gefitinib (API) (41.139 ± 0.32 %). The results indicate the solubility and dissolution rate of Gefitinib SEDDS has a significant increase of 2.14 times when compared to a pure drug (API). Accelerated stability studies showed that the optimized formulation F1(PK154LA1 1:9) was found to be stable for 1 month with respect to Drug loading efficiency (97.975 ± 0.25%), globule size (105.0 d.nm), zeta potential (-18.1 mV) and dissolution study (88.171 ± 0.36%). There is no significant change in drug loading efficiency, globule size, PDI, zeta potential and dissolution study. The results of the present studies demonstrate that Gefitinib SEDDS can be used as a potential means for improving the solubility and dissolution rate of Gefitinib.
M. S. Reddy * and B. S. Vahini
Centre for Pharmaceutical Sciences, Institute of Science and Technology, Jawaharlal Nehru Technological University, Kukatpally, Hyderabad, Telangana, India.
14 August 2019
24 November 2019
08 February 2020
01 May 2020