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Related Concept Videos

Factors Influencing Drug Absorption: Pharmaceutical Parameters01:28

Factors Influencing Drug Absorption: Pharmaceutical Parameters

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...
Factors Affecting Dissolution: Polymorphism, Amorphism and Pseudopolymorphism01:21

Factors Affecting Dissolution: Polymorphism, Amorphism and Pseudopolymorphism

Polymorphism refers to the existence of a drug substance in multiple crystalline forms, known as polymorphs. Recently, this term has been expanded to include solvates (forms containing a solvent), amorphous forms (non-crystalline forms), and desolvated solvates (forms from which the solvent has been removed).
Some polymorphic crystals possess lower aqueous solubility than their amorphous counterparts, leading to incomplete absorption. For instance, the oral suspension of Chloramphenicol, which...
Factors Influencing Drug Absorption: Drug Dissolution01:27

Factors Influencing Drug Absorption: Drug Dissolution

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

Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry

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

Factors Affecting Dissolution: Drug pKa, Lipophilicity and GI pH

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.
A drug's pKa and the pH of the gastrointestinal (GI) tract play crucial roles in drug...
In Vitro Drug Dissolution: Alternative Methods01:17

In Vitro Drug Dissolution: Alternative Methods

Alternative drug dissolution methods include the rotating bottle, intrinsic dissolution test, peristalsis, and the Franz diffusion cell method. The rotating bottle method involves meticulously rotating tightly capped controlled-release beads in a temperature-controlled bath. Periodic decanting of samples allows for residue assay, followed by refilling with fresh medium and testing at various pH levels to emulate the gastrointestinal tract conditions.In contrast, the intrinsic dissolution test...

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A Package of Established Analytical Tools to Investigate the Solid-State Alteration of Lipid-Based Excipients
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Solid-state characterization and in vitro dissolution behavior of lorazepam: Hydroxypropyl-β-cyclodextrin inclusion

R Patel1, M Patel

  • 1Department of Pharmaceutics, S. K. Patel College of Pharmaceutical Education and Research, Ganpat University, Kherva, Gujarat, India.

Drug Discoveries & Therapeutics
|April 12, 2012
PubMed
Summary

Hydroxypropyl-β-cyclodextrin forms inclusion complexes with lorazepam, significantly enhancing its dissolution rate. Lyophilization proved most effective, improving lorazepam solubility and tablet performance.

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Area of Science:

  • Pharmaceutical Sciences
  • Drug Delivery Systems
  • Physical Chemistry

Background:

  • Lorazepam is a water-insoluble drug with poor dissolution rates.
  • Cyclodextrins are known excipients for improving drug solubility and bioavailability.
  • Hydroxypropyl-β-cyclodextrin (HP-β-CD) is a common cyclodextrin derivative used in pharmaceutical formulations.

Purpose of the Study:

  • To prepare and characterize lorazepam-HP-β-CD inclusion complexes.
  • To evaluate the impact of complexation on lorazepam's dissolution rate.
  • To assess the performance of lorazepam-HP-β-CD complexes in tablet formulations.

Main Methods:

  • Phase solubility studies to determine stoichiometry and spontaneity of complex formation.
  • Preparation of inclusion complexes using physical mixing, kneading, spray-drying, and lyophilization.
  • Characterization using DSC, FTIR, SEM, and XRD.
  • In vitro dissolution testing of lorazepam, physical mixtures, and formulated tablets.

Main Results:

  • An AP-type phase solubility profile indicated 2:1 stoichiometric lorazepam-HP-β-CD complexes.
  • Lyophilization yielded complexes with successful lorazepam inclusion into the HP-β-CD cavity.
  • Complexation significantly improved lorazepam solubility, wettability, and in vitro dissolution rate.
  • Tablets containing lorazepam-HP-β-CD complexes showed enhanced drug release compared to plain lorazepam tablets.

Conclusions:

  • Hydroxypropyl-β-cyclodextrin effectively forms inclusion complexes with lorazepam.
  • Lyophilization is a superior method for preparing lorazepam-HP-β-CD complexes with enhanced dissolution.
  • Complexation with HP-β-CD offers a promising strategy to improve the oral bioavailability of lorazepam.