<p>Development Of Saquinavir Mesylate Nanoemulsion-Loaded Transdermal Films: Two-Step Optimization Of Permeation Parameters, Characterization, And Ex Vivo And In Vivo Evaluation</p>

Abstract

BackgroundSaquinavir mesylate (SQR) tablets are widely used against human immunodeficiency virus. SQR has bioavailability issues owing to its poor aqueous solubility, extensive first-pass metabolism, and even low gastrointestinal tract permeability and absorption.ObjectiveAn in-depth optimization process was carried out using factorial design to improve the permeation parameters and thereby the bioavailability of SQR by formulating self-nanoemulsifying drug delivery system (SNEDDS)-loaded polymeric transdermal films.MethodsThe solubility of SQR in different nanoemulsion components was examined. Various combinations of selected components were prepared in an extreme vertices mixture design to identify the useful nanoemulsion zone and to develop SNEDDS with minimum globule size. The optimized SQR-SNEDDS was loaded in polyvinyl alcohol (PVA)-based transdermal films. The Box-Behnken design was used to optimize and evaluate SQR permeability. The prepared films were characterized for thickness, tensile strength, elongation, folding endurance, and accelerated stability studies. The optimized film was examined for ex vivo skin permeation and in vivo pharmacokinetic parameters.ResultsThe optimized SQR-SNEDDS was prepared in proportions of 0.1, 0.55, and 0.35 of clove oil, labrasol, and Transcutol, respectively. The implemented Box-Behnken design indicated the optimized film consisted of 1.0% PVA, 0.25% propylene glycol, and clove oil as the oil phase. The tensile strength, thickness, percent elongation, and folding endurance of the optimized SQR-SNEDDS film were 0.93 ± 0.013 kg/cm2, 0.22 ± 0.006 mm, 43.1 ± 0.022%, and >200 times, respectively. A higher Cmax and double the AUC were observed for SQR-SNEDDS–loaded film in comparison to pure SQR-loaded films.ConclusionImplementation of a two-step design to optimize and control experimental factors in the preparation of SQR-SNEDDS and its loading onto PVA-based transdermal films was achieved. The films indicated improved ex vivo skin permeation, enhanced bioavailability, and overcame the limitations of the oral dosage form.

Exploring LIPIDs for their potential to improves bioavailability of lipophilic drugs candidates: A review

“… Unlikely, On Dispersion loose solvent capacity On dispersion, clear or almost clear dispersion On dispersion, clear or almost clear dispersion Formulation have good solvent capability Disadvantages Poor solvent capability Relatively Coarse O/W dispersion,ingestion probablebut not decisive On dispersion, possibility is loose of solvent capability or ingestion On dispersion, possibility is loose of solvent capability or ingestion On dispersion, possibility is loose of solvent capability Example Etomidate (anesthetic) ( Geng et al, 2021 ) – Cyclosporin (an immunosuppressant), ( Keohane et al, 2015 ) Saquinavir (an antiretroviral). ( Hosny, 2019 ) Amphotericin B (antifungal) ( Faustino, 2020 ), …”

“…In antifungal therapy, LBFs have been employed to improve the solubility and bioavailability of drugs like Amphotericin B ( Faustino, 2020 ). These formulations have also demonstrated promise in antiretroviral drugs like saquinavir ( Hosny, 2019 ) more bioavailable. Additionally, lipid-based systems have been utilized to improve the delivery of immunosuppressants, like cyclosporine ( Keohane et al, 2015 ), for organ transplant patients.…”

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“…In contrast to pure SQR-loaded films, SQR-SNEDDS-loaded films had a higher Cmax and doubled the AUC. The films demonstrated improved ex vivo skin permeation, increased bioavailability, and circumvented the disadvantages of the oral dosage type 13 . The optimized Febuxostat FBX-SNEDDS primed transdermal film to treat gout, and chronic hyperuricemi may be a good way to boost solubility and skin permeability, resulting in increased patient compliance.…”

One‐Pot Synthesis of 2‐(Alkylsulfanyl)quinolines from Aryl Isothiocyanates and Allenes or Alkynes

“…[1,2] Numerous natural and synthetic compounds containing the quinoline ring exhibit immense therapeutic potential, [1h,i,2] including broad spectrum of important biological and biochemical activities such as antiviral, [3] anticancer, [4] antitubercular, [5] anti-HIV, [6] antimalarial, [7] antimicrobial, [8] antiinflammatory, [9] antifungal, [10] antibiotic, [11] antiplasmodial, [12] antitrichomonal, [13] antiplatelet, [14] antioxidant, [15] anticonvulsant, [16] analgesic, [17] antidiabetic, [18] cardiovascular, [19] reproductive, [20] anthelmintic, [21] antiprotozoal, [22] antidepressant, [23] antihypertensive, [24] etc. [25] Such compounds are also extensively used as effective drugs for the treatment of various diseases, particularly malaria (e. g., chloroquine, quinine, amodiaquine, piperaquine, primaquine, mefloquine), [26] cancer (e. g., imiquimod, tasquinimod, requinimex), [27] tuberculosis (e. g., bedaquiline), [28] HIV/AIDS (saquinavir), [29] etc. They also have found application as organocatalysts, [30] dyes, [31] ligands, [32] building blocks for materials science, [33] and in other areas.…”