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Combining anticancer drugs and phytomolecules with anticancer activity has opened up new avenues for cancer treatment and could be a potent alternative to conventional cancer therapy. Quercetin (QUR) and Erlotinib (ERB) exhibit potential anticancer properties. However, both drugs manifest low oral bioavailability due to low aqueous solubility, and interestingly, there is not a single validated UHPLC-PDA method for quantifying QUR and ERB simultaneously. Thus, the current study aims to address pharmaceutical challenges by encapsulating the two drugs in liquid crystalline nanoparticles (LCNPs) and to develop and validate a sensitive, accurate analytical, and bioanalytical method, as per guidelines, to quantify QUR and ERB simultaneously in LCNPs. Effective chromatographic elution of QUR and ERB has been achieved using a C8 reversed-phase column with an isocratic mobile phase at a flow rate of 1 mL/min, and both drugs were detected at 252 nm wavelength. The retention time was 5.3 and 7.7 min for QUR and ERB, respectively, while LOQ was less than 0.5 µg/mL for both drugs, appropriate for monitoring therapeutic drugs in preclinical and clinical research settings. The validated method was successfully applied to estimate the %drug entrapment efficiency, %drug loading, and %drug release for the simultaneous analysis of QUR and ERB in the LCNPs. The technique investigated both drugs’ pharmacokinetic characteristics in Sprague–Dawley rats. The results were deemed reliable, and the validated method was found to be precise and accurate as per guidelines for the simultaneous estimation of QUR and ERB, which have applications in formulation development and bioanalytical studies.

BackgroundFavipiravir is administered orally, even against airborne RNA viruses, in a loading-dose/maintenance dose regimen. We investigated whether—(a) pulmonary delivery of favipiravir would generate high concentrations in the luminal side of the respiratory tract; and (b) avoiding first-pass metabolism by the liver by inhaled drug would generate comparable pharmacokinetics (PK) with doses significantly smaller than the oral maintenance dose.MethodsA dry powder inhalation (DPI) of favipiravir formulated by mixing with Inhalac 400® was prepared and characterized. Inhalations of ~ 120 µg dose strength, with or without a prior oral loading dose were administered to mice. Comparator mice received human-equivalent oral doses (3 mg). Three mice per sampling time point were sacrificed and favipiravir concentrations in the blood plasma, bronchio-alveolar lavage fluid (BALF) and lung tissue homogenate determined by HPLC.ResultsOne-compartment PK modeling of concentration–time data indicated that the area under the curve (AUC0-24 h) generated in the BALF recovered from mice receiving inhalations of ~ 1/25th of the oral dose subsequent to an oral loading dose was 86.72 ± 4.48 µg⋅mL−1⋅h. This was consistently higher than the AUC observed in the BALF of orally-dosed mice (56.71 ± 53.89 µg mL−1⋅h). In blood serum, the respective values of AUC were 321.55 ± 124.91 and 354.71 ± 99.60 µg⋅mL−1⋅h.ConclusionPulmonary delivery of significantly smaller doses of favipiravir generates meaningful drug disposition and pharmacokinetics at the site of respiratory viral infections. We provide the rationale for designing a self-administered, non-invasive, low-cost, targeted drug delivery system against airborne RNA virus infection.

Vemurafenib (VMF) is a practically insoluble (< 0.1 μg/mL) and least bioavailable (1%) drug. To enhance its oral bioavailability and solubility, we formulated a reliable self-nano emulsifying drug delivery system (SNEDDS). A Quality by Design (QbD) approach was used to optimize the ratio of Capryol 90, Tween 80, and Transcutol HP. VMF-loaded SNEDDS was characterized for its size, polydispersity index (PDI), zeta potential, drug content, and transmittance. The in vitro release profile of the drug loaded in SNEDDS was compared to the free drug in two media, pH 6.8 and 1.2, and the data obtained were analyzed with different mathematical models. A reverse-phase ultra-pressure liquid chromatography (UPLC) technique with high sensitivity and selectivity was developed and validated for the quantification of VMF in analytical and bioanalytical samples. Dissolution efficiency for SNEDDS was estimated using different models, which proved that the developed novel SNEDDS formulation had a better in vitro dissolution profile than the free drug. A 2.13-fold enhanced oral bioavailability of VMF-loaded SNEDDS compared to the free drug demonstrates the superiority of the developed formulation. This work thus presents an overview of VMF-loaded SNEDDS as a promising alternative to improve the oral bioavailability of the drug. Graphical Abstract