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Saba Abdulhadi Jabir , Nawal A. Rajab^*✉

1. Department of Pharmaceutics, College of Pharmacy, University of Baghdad, Baghdad, Iraq.

Abstract

The purpose of this research was to compare the traditional aqueous-LAS-suspension (AQS) with the two successful intranasal formulations that use the recently created antimigraine drug Lasmiditan (LAS) as nanoemulsion-based in situ gel (NEIG a and b), in order to determine its relative bioavailability (F-relative) via using rabbits. In this investigation, 18 male rabbits weighing 2.0 to 2.5 kg were employed. The dose of LAS was determined based on the body surface area (BSA) normalization method, which is equivalent to 216μl~4drops of NEIG a, NEIG b, and AQS, each containing 80 mg of LAS per milliliter given separately to the randomly selected rabbit using a parallel design for the study. Serial blood samples were taken out and subjected to drug analysis using the HPLC method previously developed and validated by L. Santosh Kumar. Primary pharmacokinetics parameters, including maximum drug concentration in plasma (C-max), time to reach C-max (T-max), and area under the concentration-time curve from time zero to affinity (AUCt0-∞) were calculated. The results showed that C-max, T-max, and AUC0- ∞ for NEIG a and NEIG b were 8066±242 ng/ml, 0.75±0.05 h, 19616.86±589 ng. h/ml, and 7975.67±239 ng/ml, 1.0±0.05 h, 17912.36±537 ng. h/ml respectively compared with the traditional AQS which is equal to 4181.09±125 ng/ml, 2±0.2 h, and 8852.27±266 ng. h/ml respectively. It was discovered that NEIG a and b had better Intranasal delivery of LAS and can significantly (p<0.05) affect its pharmacokinetic profile and improve its bioavailability by more than 2.5 folds when compared to oral AQS (as a control), according to the results of the pharmacokinetic investigation. The current investigations confirm the potential of LAS as NEIG a and b to increase F, establishing them as a promising intranasal new formula with a faster onset of action and greater bioavailability than the oral dosage form (AQS)‎.

Keywords: Bioavailability study, Nanoemulsion-based in situ gel (NEIG), Lasmiditan, C-max, T-max

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