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Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry01:20

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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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Factors Influencing Drug Absorption: Pharmaceutical Parameters01:28

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Solid dosage forms such as tablets and capsules undergo rigorous manufacturing processes to ensure stability and effectiveness. Their dissolution and absorption properties are influenced significantly by the choice of excipients (inactive ingredients that serve various roles in the formulation), and the methodology applied during production. The manufacturing parameters, such as compression force and granulation techniques, significantly affect dissolution rates. Elevated compression forces...
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Factors Influencing Drug Absorption: Physicochemical Parameters01:22

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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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The pharmacokinetic journey of drugs from solid oral dosage forms into systemic circulation is multifaceted. It begins with disintegration, a prerequisite ensuring a solid dosage form's subdivision into minute particles. Dissolution occurs next as these granulated entities solubilize in gastrointestinal fluids. This solubilization is crucial for the succeeding stage, permeation, which describes the traversal of the drug across the intestinal membrane and its subsequent entry into the blood...
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The process of oral drug absorption can be influenced by several factors. Weakly acidic drugs tend to be absorbed more readily from the stomach due to their nonionized state. However, absorption may be less efficient in the upper intestine, where drugs are often ionized. Interestingly, despite the stomach's apparent advantage for drug absorption, its mucous layer can hinder diffusion. Its surface area is also smaller than the intestine's, which can further slow down the absorption rate.
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The enteral drug administration involves three primary routes: oral, sublingual, and buccal. Oral ingestion is the most prevalent, safe, economical, and convenient method for drug administration. However, it has certain drawbacks, including limited absorption due to the drug's low water solubility or poor membrane permeability, possible emesis from GI mucosa irritation, destruction of drugs by digestive enzymes or low gastric pH, and irregular absorption along with food or other drugs.
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Tigecycline Absorption Improved by Selected Excipients.

Hubert Ziółkowski1, Kalina Szteyn1, Dawid Jędrzkiewicz2

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Excipients like HP-β-CD, TPGS, and SDOCH significantly enhanced tigecycline oral bioavailability in chickens. Other tested compounds showed varying degrees of improvement, suggesting potential for better tigecycline absorption.

Keywords:
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Area of Science:

  • Pharmacology
  • Drug Delivery
  • Veterinary Medicine

Background:

  • Tigecycline, a tetracycline antibiotic, exhibits poor oral absorption.
  • Enhancing tigecycline's oral bioavailability is crucial for effective therapeutic applications.
  • Broiler chickens serve as a relevant animal model for gastrointestinal absorption studies.

Purpose of the Study:

  • To evaluate the impact of various excipients on tigecycline's plasma concentration and oral bioavailability.
  • To identify specific excipients that can significantly improve tigecycline absorption in broiler chickens.

Main Methods:

  • Tigecycline was administered intravenously and orally to broiler chickens, with and without excipients.
  • Plasma concentrations of tigecycline were measured using high-performance liquid chromatography coupled with tandem mass spectrometry.
  • Pharmacokinetic analyses (compartmental and non-compartmental) were performed on plasma concentration-time data.

Main Results:

  • HP-β-CD, TPGS, and SDOCH approximately doubled tigecycline's area under the curve and oral bioavailability.
  • DM-β-CD and TMC showed smaller, yet significant, increases in these pharmacokinetic parameters.
  • Sodium caprate did not significantly affect tigecycline bioavailability.

Conclusions:

  • HP-β-CD, TPGS, and SDOCH are effective in substantially enhancing tigecycline's oral bioavailability.
  • DM-β-CD and TMC may also offer significant bioavailability improvements, warranting further investigation.
  • These findings suggest potential strategies for improving oral tigecycline delivery in veterinary medicine.