Related Experiment Video
Updated: Jun 3, 2025
09:59
Coherent anti-Stokes Raman Scattering CARS Microscopy Visualizes Pharmaceutical Tablets During Dissolution
Published on: July 4, 2014
18.1K
Simultaneously improving tabletability and solubility of diclofenac by cocrystallization with picolinamide
Chenyu Wu1, Zijian Wang2, Xu Han1
1NMPA Key Laboratory for Safety Evaluation of Cosmetics, Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Hygiene Inspection & Quarantine Science, School of Public Health, Southern Medical University, Guangzhou, Guangdong 510515, China.
International Journal of Pharmaceutics
|January 6, 2025
Summary
A new diclofenac-picolinamide cocrystal (DIC-PIC) significantly enhances tabletability and solubility for nonsteroidal anti-inflammatory drug development. This cocrystal formulation overcomes key challenges in creating improved diclofenac tablets.
Area of Science:
- Pharmaceutical Sciences
- Materials Science
- Solid-State Chemistry
Background:
- Diclofenac (DIC), a widely used nonsteroidal anti-inflammatory drug (NSAID), suffers from poor tabletability and low water solubility.
- These limitations hinder the development of effective and stable diclofenac dosage forms, particularly tablets.
- Addressing these challenges is crucial for improving therapeutic outcomes and patient compliance.
Purpose of the Study:
- To develop a novel diclofenac-picolinamide cocrystal (DIC-PIC) to simultaneously enhance tabletability and solubility.
- To characterize the physicochemical properties of the new cocrystal.
- To evaluate the potential of DIC-PIC as an improved formulation for diclofenac.
Main Methods:
- Cocrystal preparation of diclofenac and picolinamide.
- Comprehensive characterization using X-ray diffraction, thermal analysis (DSC/TGA), and spectral methods (FTIR, Raman).
- Evaluation of tabletability through compression testing (yield pressure measurement) and solubility studies in water and buffer solutions.
Main Results:
- The diclofenac-picolinamide cocrystal (DIC-PIC) exhibited significantly improved tabletability compared to pure diclofenac (DIC), evidenced by lower yield pressure (59.5 MPa vs. 86.6 MPa).
- Enhanced plasticity of DIC-PIC, attributed to a slip plane (001) in its crystal structure, facilitates better compaction.
- DIC-PIC demonstrated substantially higher solubility than DIC: 112-fold increase in water and 22-fold increase in pH 6.8 buffer.
Conclusions:
- The developed diclofenac-picolinamide cocrystal (DIC-PIC) successfully addresses the poor tabletability and low solubility of diclofenac.
- The improved physicochemical properties make DIC-PIC a promising candidate for developing advanced diclofenac tablets with enhanced performance.
- This cocrystal strategy offers a viable approach for overcoming formulation challenges with poorly soluble drugs.
Related Concept Videos
01:21Factors Affecting Dissolution: Polymorphism, Amorphism and Pseudopolymorphism
281
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...
Some polymorphic crystals possess lower aqueous solubility than their amorphous counterparts, leading to incomplete absorption. For instance, the oral suspension of Chloramphenicol, which...
281
01:21Factors Affecting Dissolution: Drug pKa, Lipophilicity and GI pH
1.0K
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...
A drug's pKa and the pH of the gastrointestinal (GI) tract play crucial roles...
1.0K
01:28Factors Influencing Drug Absorption: Pharmaceutical Parameters
114
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...
114
01:22Factors Influencing Drug Absorption: Physicochemical Parameters
214
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...
Enhanced drug absorption can be achieved by reducing particle sizes and increasing surface areas, thereby facilitating...
214
01:23Factors Affecting Dissolution: Particle Size and Effective Surface Area
719
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...
719
01:27Factors Influencing Drug Absorption: Drug Dissolution
408
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...
408