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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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Neurokinin 1 (NK1) receptors are distributed across the GI tract, vagal afferents, and key CNS regions including the central vomiting center and chemoreceptor trigger zone (CTZ) Chemotherapy agents stimulate enterochromaffin cells in the gastrointestinal (GI) tract to release large amounts of substance P (SP). SP is a neuropeptide released by specific sensory nerves in response to many different stressors, including those in the GI mucosa affected by chemotherapy.  SP binds and activates...
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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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Compared with pure water, the solubility of an ionic compound is less in aqueous solutions containing a common ion (one also produced by dissolution of the ionic compound). This is an example of a phenomenon known as the common ion effect, which is a consequence of the law of mass action that may be explained using Le Chȃtelier’s principle. Consider the dissolution of silver iodide:
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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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Dissolution kinetics, an essential aspect of oral drug delivery, is significantly influenced by the drug's particle size. According to the Noyes-Whitney dissolution model, the dissolution rate correlates directly with the drug's surface area. The larger the surface area, the higher the drug's solubility in water, leading to a faster drug dissolution rate. Reducing particle size increases the effective surface area, enhancing the dissolution process. Micronization and nanosizing are...
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Updated: Sep 14, 2025

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Aprepitant: Review on Solubility Enhancement.

Lata Kothapalli1, Navdeep Singh1, Abhay Upare2

  • 1Department of Pharmaceutical Chemistry and Quality Assurance, Dr. D.Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune, Maharashtra, India.

Recent Advances in Drug Delivery and Formulation
|July 23, 2025
PubMed
Summary
This summary is machine-generated.

Aprepitant (APT), an NK-1 antagonist, faces solubility challenges for parenteral delivery. Enhancing APT solubility through techniques like nanoformulation is crucial for its potential as an anticancer therapy and for managing CINV.

Keywords:
Anti-emeticAprepitantCINVNK-1 antagonistsolubilitysolubility enhancement.

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Area of Science:

  • Pharmacology
  • Drug Delivery
  • Oncology

Background:

  • Substance P and neurokinin (NK-1) receptors are implicated in various diseases.
  • NK-1 receptor overexpression in cancer presents a therapeutic target.
  • Aprepitant (APT) is an NK-1 antagonist clinically used for chemotherapy-induced nausea and vomiting (CINV).

Purpose of the Study:

  • To review solubility enhancement techniques for Aprepitant (APT).
  • To explore APT's potential as a synergistic agent in cancer treatment.
  • To address challenges in developing parenteral dosage forms of APT.

Main Methods:

  • Literature search for Aprepitant (APT) chemistry and solubility enhancement.
  • Utilized databases: Science Direct, PubMed, Bentham, Google Scholar.
  • Keywords: Aprepitant, solubility, NK1 receptor, parenteral dosage form.

Main Results:

  • Reviewed methods to improve APT solubility, including nanotechnology.
  • Innovative technologies offer pathways to enhance APT bioavailability.
  • Discussed challenges and benefits of various solubility enhancement techniques.

Conclusions:

  • APT faces bioavailability challenges, particularly for parenteral administration due to its BCS Class IV status.
  • Solubility enhancement is key for APT's efficacy in CINV and cancer therapy.
  • Prodrugs (e.g., Fosaprepitant) and nanoformulations with excipients are promising for parenteral APT delivery.