Nanotechnology Versus other Techniques in Improving Drug Dissolution

Abstract

Many newly discovered drug molecules have low aqueous solubility, which results in low bioavailability. One way to improve their dissolution is to formulate them as nanoparticles, which have high specific surface areas, consequently increasing the dissolution rate and solubility. Nanoparticles can be produced via top-down or bottom-up methods. Top-down techniques such as wet milling and high pressure homogenisation involve reducing large particles to nano-sizes. Some pharmaceutical products made by these processes have been marketed. Bottom-up methods such as precipitation and controlled droplet evaporation form nanoparticles from molecules in solution. To minimise aggregation upon drying and promote redispersion of the nanoparticles upon reconstitution or administration, hydrophilic matrix formers are added to the formulation. However, the nanoparticles will eventually agglomerate together after dispersing in the liquid and hinders dissolution. Currently there is no pharmacopoeial method specified for nanoparticles. Amongst the current dissolution apparatus available for powders, the flow-through cell has been shown to be the most suitable. Regulatory and pharmacopoeial standards should be established in the future to standardise the dissolution testing of nanoparticles. More nanoparticle formulations of new hydrophobic drugs are expected to be developed in the future with the advancement of nanotechnology. However, the agglomeration problem is inherent and difficult to overcome. Thus the benefit of dissolution enhancement often cannot be fully realised. On the other hand, chemical strategies such as modifying the parent drug molecule to form a more soluble salt form, prodrug, or cyclodextrin complexation are well established and have been shown to be effective in enhancing dissolution. Thus the value of nanoformulations needs to be interpreted in the light of their limitations. Chemical approaches should also be considered in new product development.

Resveratrol loaded glycyrrhizic acid-conjugated human serum albumin nanoparticles for tail vein injection II: pharmacokinetics, tissue distribution and bioavailability

“…RES can be used in combination with albumin to significantly enhance its water solubility and bioavailability. Nano-size has obvious advantages over other technologies that achieve these goals (Kwok & Chan, 2014;Jain et al, 2015). Nanoemulsion systems can greatly help to resolve their potential pharmacokinetic limitations and preserve the therapeutic value of drugs (Musthaba et al, 2010;Sengupta & Chatterjee, 2017).…”

Physicochemical Properties, Form, and Formulation Selection Strategy for a Biopharmaceutical Classification System Class II Preclinical Drug Candidate

“…69,70 In the present research, although the mean AUC 0-24 value achieved after dosing 1-Form B nanosuspension (dissolution data not shown) was twofold higher than that of the benchmark (i.e., 1-Form B suspension), the increase was not statistically significant (Table 7), which was attributed to the fact that nanosizing a drug mainly increases dissolution rate, as previously reported. 71 As discussed in this work, compound 1 showed significant solubility-related issues that are better addressed by cocrystal or amorphous solid dispersions-based approaches that were implemented as a mitigation strategy after the discovery of the lower solubility Form B of Compound 1.…”

Preparation, characterization and antifungal activity of pyraclostrobin solid nanodispersion by self‐emulsifying technique

“…Owing to the large surface area, strong penetration and fast dissolution rate of the nanoparticles, the smaller pyraclostrobin nanoparticles could act quickly on the biological target and increase the absorption and accumulation of the active components by fungi. [40][41][42]…”