Controlling the size and morphology of griseofulvin nanoparticles using polymeric stabilizers by evaporation-assisted solvent–antisolvent interaction method

Abstract

Griseofulvin (GF) is a potential drug for cancer therapy. However, its application is limited by its poor water solubility. Ultrafine GF nanoparticles were prepared through evaporation-assisted solventantisolvent interaction method for improving its solubility. Acetone was used as the solvent and water was used as the antisolvent. It was observed that particle size could be controlled by varying the concentration of GF in acetone. Average particle size was very low, 16 ± 4 and 28 ± 8 nm, when the concentration of GF was 5 and 25 mM, respectively, in acetone. However, the particle size increased drastically to more than 3 lm, when the concentration was increased to 50 mM. Interestingly, the presence of optimized concentration of polyvinylpyrrolidone (PVP) and hydroxypropyl methylcellulose (HPMC) as stabilizers in the antisolvent resulted in significant reduction of particle size. Particle size decreased to less than 40 nm in the presence of the polymeric stabilizers, even when the concentration was 50 mM.Field emission scanning electron microscopy, transmission electron microscopy, and atomic force microscopy imaging revealed that the polymeric stabilizers encapsulated very small GF particles and thus stabilized them. The solubility of GF-HPMC, GF-PVP, and the bare GF particles that were prepared from 50 mM solution (micro-GF) was nearly 24, 19, and 11 times, respectively, higher than that of raw-GF. In vitro dissolution studies revealed that almost 100 % of the drug was released in 60 min from GF-PVP and GF-HPMC. Fourier transform infrared spectroscopy did not detect any strong interaction between GF and the stabilizers. X-ray diffraction showed that the prepared GF nanoparticles and the micro-GF were in polymorphic form I. Differential scanning calorimetric studies showed that the crystallinity of the nanoformulated GF was only slightly lower than that of raw-GF. Thus, particle size reduction and the presence of stabilizers led to significant enhancement in solubility and dissolution rate.

Unusual anti-leukemia activity of nanoformulated naproxen and other non-steroidal anti-inflammatory drugs

“…The nature of the polymer and its concentration can affect the particle size [54]. The z-average particle sizes that were measured using DLS, when different polymers were used at varying concentrations to stabilize the particle sizes are given in Table 2.…”

“…Stabilizers control the particle size by getting adsorbed on the particle surfaces and by preventing aggregation. There may not be enough polymer molecules available to form at least a monolayer over the particles at lower concentrations [54]. This lack of availability of sufficient amount of stabilizers to control the growth of the particles resulted in larger particles [54].…”

“…There may not be enough polymer molecules available to form at least a monolayer over the particles at lower concentrations [54]. This lack of availability of sufficient amount of stabilizers to control the growth of the particles resulted in larger particles [54]. At higher than optimum concentrations of the polymers, increase in osmotic pressure leads to increased attraction among colloidal particles leading to agglomeration [55].…”

Preparation and characterization of polyvinyl alcohol stabilized griseofulvin nanoparticles

“…The same method can be used to produce polymer stabilized drug nanoparticles when the polymer is present in the antisolvent. Here, we report the preparation of GF-PVA nanoparticles with particles size below 30 nm and spherical morphology using EASAI method [15,16].…”

“…[20,22] GF is a highly hydrophobic drug having low solubility and hence, low bioavailability and it exhibits incomplete absorption through the gastrointestinal tract [23]. We have recently shown that solubility of drugs such as CBZ and GF can be enhanced manifold by nanoformulating it with polymeric stabilizers [15,16].…”