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One-Compartment Open Model for Extravascular Administration: Zero-Order Absorption Model01:12

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Extravascular administration, such as oral or intramuscular routes, is a non-invasive drug delivery method, often preferred for ease and patient compliance. A key factor here is absorption, which dictates how quickly and effectively the drug enters the bloodstream from the administration site. Absorption follows either zero-order or first-order kinetics.
Zero-order absorption maintains a steady rate irrespective of the amount of drug left to be absorbed, making it a constant process. In the...
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The one-compartment model is a pharmacokinetic tool that models the body as a single, uniform compartment, facilitating the understanding of drug distribution and elimination. This model is particularly beneficial for intravenous (IV) bolus administration, where the drug rapidly circulates throughout the body.
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The one-compartment open model is a simplified approach used in pharmacokinetics to understand the distribution and elimination of a drug administered through an intravenous bolus. This model assumes rapid drug dispersal throughout the body and elimination using a first-order process. Key pharmacokinetic parameters, such as the elimination rate constant (k), half-life (t1/2), and the apparent volume of distribution (Vd), can be estimated from this model. The elimination rate is calculated...
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One-Compartment Open Model for Extravascular Administration: First-Order Absorption Model01:15

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The first-order absorption model for extravascular administration describes the rate at which a drug is absorbed and eliminated, following the principles of first-order kinetics. This model is vital as it provides a mathematical representation of drug behavior within the body. It also allows for the prediction and interpretation of drug absorption and elimination based on the rate of change in drug concentration over time. This model can be visualized as a plasma concentration-time profile...
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The two-compartment model for intravenous (IV) bolus administration illustrates drug distribution in the body, subdividing it into central and peripheral compartments. This model operates on the concept of two-compartment kinetics. The drug's plasma concentration shows a bi-exponential decline following IV bolus administration, signaling the presence of two disposition processes: distribution and elimination.
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Drugs administered through various routes can lead to nonlinear elimination, resulting in complex pharmacokinetic behaviors crucial to understanding efficacious drug dosing.
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Ocular Therapeutic Delivery and Advanced Tissue Retrieval in Adult Rats
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An ocular insert with zero-order extended delivery: Release kinetics and mathematical models.

M Mariz1, J Murta2, M H Gil1

  • 1University of Coimbra, Chemical Engineering Department, CIEPQPF, 3030-790 Coimbra, Portugal.

European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V
|November 9, 2022
PubMed
Summary

New ocular inserts (InEye®) using PCL-PEG-PCL copolymers offer prolonged drug release for glaucoma treatment. These inserts provide a unique, tailor-made solution for consistent medication delivery, enhancing patient compliance.

Keywords:
Drug deliveryGlaucomaOcular insertRelease kinetics

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Area of Science:

  • Polymer Chemistry
  • Ophthalmology
  • Drug Delivery Systems

Background:

  • Ocular drug delivery faces challenges with frequent administration and poor patient compliance, especially for chronic conditions like glaucoma.
  • Polymeric ocular inserts offer a potential solution for sustained drug release, improving therapeutic outcomes.
  • Poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL) block copolymers are suitable materials for ophthalmic applications due to their tunable properties.

Purpose of the Study:

  • To develop and characterize novel ocular inserts (InEye®) for sustained drug release using PCL-PEG-PCL block copolymers.
  • To investigate the influence of copolymer composition (PEG percentage) and insert characteristics on drug release kinetics.
  • To evaluate the potential of InEye® as a promising formulation for treating chronic ocular diseases.

Main Methods:

  • Synthesis of PCL-PEG-PCL block copolymers via ring-open polymerization of ε-caprolactone.
  • Characterization of polymer properties including molecular weight, PCL/PEG ratio, mass loss, and swelling.
  • Fabrication of ellipsoidal ocular inserts by entrapping moxifloxacin within a PCL-PEG-PCL matrix.
  • In vitro assessment of drug release kinetics, analyzing release profiles and rates.

Main Results:

  • Ocular inserts (InEye®) were successfully prepared using PCL-PEG-PCL copolymers with varying PEG percentages (24% and 33%).
  • Drug release kinetics demonstrated a strong dependence on PEG content, insert size, and immobilized drug amount.
  • All formulations exhibited zero-order release kinetics, achieving 95% drug release at a constant rate over 20 to 200 days, with no initial burst effect.

Conclusions:

  • InEye® ocular inserts represent a unique and promising drug delivery technology for sustained ophthalmic medication.
  • The tunable nature of PCL-PEG-PCL copolymers allows for the creation of tailor-made inserts for prolonged and constant drug release.
  • This formulation technology has significant potential for improving treatment compliance in chronic ocular diseases like glaucoma.