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Related Concept Videos

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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Factors Influencing Drug Absorption: Drug Dissolution01:27

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

Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry

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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 Affecting Dissolution: Drug pKa, Lipophilicity and GI pH01:21

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Drug absorption within the gastrointestinal (GI) tract is a complex process influenced by several critical factors, including the site pH, the drug's dissociation constant (pKa), and the drug's lipophilicity. The GI tract exhibits a pH gradient, with an acidic environment in the stomach and a more alkaline environment in the small intestine. This pH variation directly affects the ionization state of drugs.
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Factors Influencing Bioavailability: First-Pass Elimination01:23

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When a drug is taken orally, it undergoes a journey starting from the gastrointestinal (GI) tract, passing through the portal vein, reaching the liver, and finally entering the systemic circulation. This process involves the absorption of the drug across the GI tract. The liver is the primary site for metabolizing the drug, with some metabolism also occurring in the gut wall. This journey significantly reduces the quantity of the drug that reaches the systemic circulation, a phenomenon known as...
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Potentiation of Brain Bioavailability Using Thermoreversible Cubosomal Formulation.

Harshvardhan Jain1, Bala Prabhakar1, Pravin K Shende1

  • 1Shobhaben Pratapbhai Patel School of Pharmacy and Technology Management, SVKM'S NMIMS, V. L. Mehta Road, Vile Parle (W), Mumbai 400056, India.

Molecular Pharmaceutics
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Summary

This study developed a fluoxetine-loaded cubosomal in situ gel for intranasal delivery, enhancing brain bioavailability by bypassing the blood-brain barrier (BBB). The novel formulation demonstrated improved drug release and pharmacokinetic profiles in vivo.

Keywords:
brain bioavailabilitybrain targetingcubosomefluoxetinein situ gelmajor depressive disorder

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Area of Science:

  • Pharmaceutical Sciences
  • Drug Delivery Systems
  • Neuroscience

Background:

  • The blood-brain barrier (BBB) poses a significant challenge for delivering therapeutic agents, like fluoxetine, to the brain.
  • Intranasal drug delivery offers a potential non-invasive route to bypass the BBB and target the central nervous system.
  • Cubosomal in situ gels are advanced formulations designed for sustained drug release and enhanced permeation.

Purpose of the Study:

  • To develop and characterize intranasal fluoxetine-loaded cubosomal in situ gel for improved brain targeting.
  • To evaluate the in vitro, ex vivo, and in vivo performance of the developed formulation.
  • To assess the potential of this system to enhance fluoxetine bioavailability and efficacy.

Main Methods:

  • Fluoxetine-loaded cubosomes were prepared using homogenization and cold methods.
  • In situ gel formulation was developed incorporating the fluoxetine-loaded cubosomes.
  • In vitro and ex vivo drug release studies were conducted.
  • In vivo biodistribution and pharmacokinetic studies were performed in male Wistar rats via intranasal administration.

Main Results:

  • Fluoxetine-loaded cubosomes exhibited high encapsulation efficiency (82.60 ± 1.25%).
  • The intranasal cubosomal in situ gel showed sustained in vitro release (93.22 ± 2.47%) and ex vivo release (96.31 ± 2.88% over 24 h).
  • In vivo studies indicated a 2.83-fold increase in bioavailability compared to the drug solution, with enhanced pharmacokinetic parameters (AUC, Cmax, Tmax, t1/2).

Conclusions:

  • Intranasal fluoxetine-loaded cubosomal in situ gel is a promising carrier for effective brain drug delivery.
  • The mucoadhesive nature and sustained release properties enhance drug retention and permeation through the nasal mucosa.
  • This formulation offers a viable strategy to improve brain targeting and therapeutic outcomes for fluoxetine.