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 employed to reduce the particle size of drug products.
Micronization, which reduces particle size, improves the oral absorption of drugs such as griseofulvin, nitrofurantoin, and certain steroids. Adding a disintegrant or surfactant can further boost dissolution by promoting tablet disintegration and wetting.
In some cases, nanosizing may be employed when micronization or excipient selection fails to resolve solubility-related bioavailability issues. Nanosizing enhances dissolution, absorption, and therapeutic effectiveness, making it a valuable technique for difficult-to-deliver drugs. This method produces even smaller drug substance particles, potentially suitable for injection drug products, like nano-suspensions, alongside traditional oral dosage forms. However, there's a caveat: nanosized particles may not dissolve easily post-IV administration due to particle aggregation in bloodstream and could be sequestered by the reticuloendothelial system (RES). They eventually dissolve and permeate into the cytoplasm, contributing to systemic drug exposure in a pseudo-extended-release pharmacokinetic profile.
Recall the Noyes-Whitney equation, which suggests a direct correlation between dissolution rate and a drug's surface area.
A solid drug's surface area is inversely related to its particle size.
A drug's smaller particle size increases its effective surface area and enhances drug-solvent interaction, leading to rapid drug dissolution.
Certain drugs, such as griseofulvin, nitrofurantoin, and steroids, such as hydrocortisone exhibit poor oral absorption due to low aqueous solubility.
Such drugs are micronized to reduce particle size. This increases the drug's surface area, enhancing the dissolution rate and elevating oral absorption while decreasing dosing frequency in certain drugs.
Hydrophobic drug micronization can benefit from surfactant addition, like polysorbate 80, which promotes wetting and solubility by lowering the surface tension between the ingredients.
At times, micronization fails to resolve solubility-related bioavailability issues. So, nanosizing an alternate technique, is used to yield drug particles in nanometer size, which can be administered orally or injected intravenously as nanosuspensions.
繁體中文
