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Drug Delivery: Miscellaneous Routes01:22

Drug Delivery: Miscellaneous Routes

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Drug delivery methods like oral inhalation, nasal sprays, transdermal patches, eye drops, intravitreal injection,  and rectal administration provide localized effects with reduced toxicity.
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Non-oral extravascular routes, which encompass sublingual, buccal, topical, intramuscular, and inhalation methods, primarily utilize passive diffusion to transport drugs into the systemic circulation. The absorption rates and effectiveness of these routes depend on the drug's physicochemical properties, as well as the patient's anatomical and pathophysiological state.
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Orally administered drugs primarily enter the systemic circulation via passive diffusion through the intestinal membranes. The drug's absorption is influenced by drug stability in the gastrointestinal GI tract, membrane permeability, the surface area available for absorption, luminal drug concentration, and residence time in the lumen. Drug permeability can be enhanced by adjusting the lipophilicity, polarity, or molecular size of the drug, promoting its passive transport across intestinal...
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The physicochemical characteristics of drugs play a crucial role in formulating stable and bioavailable drug products. The solubility of a drug, governed by the varying pH along the GI tract and its dissociation constant (pKa), is pivotal in determining its ionization state and absorption rate. Notably, weak acids and bases remain unionized and are absorbed more rapidly.
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Cyclodextrin-enabled nepafenac eye drops with improved absorption open a new therapeutic window.

Anna Vincze1, Réka Facskó1, Mária Budai-Szűcs2

  • 1Department of Chemical and Process Engineering, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem Quay 3, H-1111 Budapest, Hungary.

Carbohydrate Polymers
|March 16, 2023
PubMed
Summary

New nepafenac eye drops improve patient compliance by overcoming the limitations of current suspension formulations. These novel formulations offer enhanced bioavailability and equivalent efficacy with potentially reduced dosage.

Keywords:
CyclodextrinHomogeneous eye drop formulationIn vitro and ex vivo corneal permeabilityNepafenacSodium hyaluronate

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Area of Science:

  • Ophthalmology
  • Pharmaceutics
  • Drug Delivery

Background:

  • Nepafenac is an effective non-steroidal anti-inflammatory drug (NSAID) for postoperative ocular inflammation and pain post-cataract surgery.
  • Current Nevanac® suspension eye drops exhibit poor patient compliance due to irritation, blurred vision, and inconsistent dosing.
  • Hydroxypropyl-β-cyclodextrin and sodium hyaluronate were utilized to improve nepafenac solubility, mucoadhesion, and viscosity.

Purpose of the Study:

  • To develop novel, preservative-free nepafenac eye drop formulations with improved patient compliance.
  • To evaluate the physicochemical properties, in vitro performance, and ex vivo bioavailability of the new formulations compared to Nevanac®.

Main Methods:

  • Eleven nepafenac eye drop formulations were prepared using hydroxypropyl-β-cyclodextrin, sodium hyaluronate, and a carbomer base.
  • In vitro testing included viscosity, mucoadhesion, drug release, and corneal permeability assessments.
  • Ex vivo studies on porcine eyes involved bioavailability assessment and corneal distribution analysis using RAMAN mapping.

Main Results:

  • Two promising formulations were identified from the initial eleven.
  • One formulation demonstrated superior ex vivo bioavailability compared to Nevanac® 0.1% suspension.
  • Another formulation, with 60% of the original nepafenac dose, showed equivalent ex vivo performance to Nevanac®.

Conclusions:

  • Novel nepafenac eye drop formulations can be developed to enhance solubility and mucoadhesion.
  • These new formulations offer potential for improved patient compliance compared to existing suspension products.
  • Further development could lead to more effective and patient-friendly nepafenac ophthalmic treatments.