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Related Concept Videos

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: 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: Physicochemical Parameters01:22

Factors Influencing Drug Absorption: Physicochemical Parameters

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.
Enhanced drug absorption can be achieved by reducing particle sizes and increasing surface areas, thereby facilitating...
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...
In Vitro Drug Dissolution: Compendial Testing Models I01:13

In Vitro Drug Dissolution: Compendial Testing Models I

Compendial dissolution methods are standardized procedures defined by pharmacopeias to evaluate the rate at which a drug dissolves in a specific medium. These methods ensure batch-to-batch consistency, enable quality control, and support the prediction of drug bioavailability. They are critical for both immediate and modified-release drug products.The apparatuses used for dissolution testing differ in their design and mechanical function, but all aim to simulate the physiological environment of...
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...

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A Package of Established Analytical Tools to Investigate the Solid-State Alteration of Lipid-Based Excipients
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Characterization, dissolution and in vivo evaluation of solid acetazolamide complexes.

María J Mora1, Luis I Tártara, Renée Onnainty

  • 1Departamento de Farmacia, UNITEFA, CONICET, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, X5000HUA, Argentina.

Carbohydrate Polymers
|August 31, 2013
PubMed
Summary

Freeze-drying acetazolamide (ACZ) with hydroxypropyl-β-cyclodextrin (HP-β-CD) and triethanolamine (TEA) created amorphous complexes. These systems enhanced ACZ dissolution and improved intraocular pressure (IOP)-lowering effects in rabbits.

Keywords:
AcetazolamideFreeze-dryingHydroxypropyl-β-cyclodextrinPolymorphismTriethanolamine

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Area of Science:

  • Pharmaceutical Sciences
  • Materials Science
  • Ophthalmology

Background:

  • Acetazolamide (ACZ) is a carbonic anhydrase inhibitor used to manage intraocular pressure (IOP).
  • Improving ACZ solubility and dissolution is crucial for enhancing its therapeutic efficacy.
  • Cyclodextrins, like hydroxypropyl-β-cyclodextrin (HP-β-CD), are known excipients for drug complexation.

Purpose of the Study:

  • To investigate the impact of binary (ACZ/HP-β-CD) and ternary (ACZ/HP-β-CD/TEA) systems on ACZ's crystalline properties, dissolution, and IOP-lowering effects.
  • To evaluate the role of freeze-drying (lyophilization) in modifying ACZ's physical state and performance.
  • To compare the efficacy of binary and ternary systems in vivo.

Main Methods:

  • Preparation of binary and ternary systems using freeze-drying.
  • Characterization of solid-state properties using Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), X-ray Powder Diffraction (XRPD), Scanning Electron Microscopy (SEM), and Fourier-Transform Infrared Spectroscopy (FT-IR).
  • In vitro dissolution studies and in vivo IOP-lowering studies in normotensive rabbits.

Main Results:

  • Freeze-drying converted crystalline ACZ to an amorphous state and formed inclusion complexes with HP-β-CD (alone or with TEA).
  • Both binary and ternary systems exhibited significantly enhanced ACZ dissolution rates compared to native ACZ.
  • The ternary system showed a prolonged IOP-lowering effect peak, consistent with its dissolution profile.

Conclusions:

  • Freeze-drying is an effective method to enhance ACZ dissolution and its IOP-lowering potential through complexation and amorphization.
  • The ternary system (ACZ/HP-β-CD/TEA) demonstrated superior performance in terms of prolonged IOP reduction compared to the binary system.
  • These findings highlight the potential of cyclodextrin-based systems for improving the delivery and efficacy of ACZ in glaucoma management.