Formation Of Nanosuspensions Research Articles

FORMULATION DEVELOPMENT AND CHARACTERIZATION OF LYOPHILIZED FEBUXOSTAT NANOSUSPENSION

Objective: The study aims to prepare and evaluate febuxostat nanosuspension to improve oral bioavailability. Methods: Febuxostat nanosuspension was prepared by the solvent-antisolvent method, followed by a lyophilization technique using PVP K-30 as a stabilizer and sodium lauryl sulfate as a surfactant. Drug content, differential scanning calorimetry, powder x-ray diffraction, Fourier transform infrared spectroscopy, and in vitro dissolution studies were used to characterize the nanosuspension. Results: The results of the characterization studies indicated the formation of nanosuspension. The lyophilized FXT NS particle size is 2170.2 nm, the PDI value is 0.63, the negative zeta potential is 1.6 mV, and the drug content is 19.02%. Functional characterization studies demonstrated that the particle size reduced due to the interaction between the stabilizer and surfactant. Conclusion: It can be concluded that the prepared febuxostat nanosuspension enhances the aqueous solubility of FXT and improves its oral bioavailability.

Formation of nanosuspensions in bottom-up approach: theories and optimization.

Nanosuspensions, liquid dispersions with nanometer size distribution, are becoming trendy in pharmaceutical practice to formulate poorly water-soluble drugs and to enhance their bioavailability. Generally, nanosuspensions are produced in two main approaches; top-down or bottom-up. The former is based on size-reduction of large particles via milling or high pressure homogenization. The latter is focused on the mechanisms of nucleation and particle growth. In this review, the critical factors influencing the kinetics or dynamics of nucleation and growth are discussed. Subsequently, the mechanisms of nanosuspension instability as well as strategies for stabilization are elaborated. Furthermore, the effects of stabilizers on key parameters of instability as well as the process of choosing an appropriate stabilizer is discussed. Steric and electrostatic stabilizations or combination of them is essential for nanosuspensions formulation to prevent coagulation. Accordingly, some characteristics of stabilizers play critical role on stability and optimization of nanosuspensions; i.e., HLB and concentration. Nevertheless, after reviewing various articles, it is ascertained that each formulation requires individual selection of surfactants according to the parameters of the particle surface and the medium. Based on the results, application of excipients such as stabilizers requires proper optimization of type and concentration. This implies that each formulation requires its own optimization process. Graphical Abstract ᅟ.

A study of the impact of polymer–surfactant in drug nanoparticle coated pharmatose composites on dissolution performance

Without a proper stabilizer formulation, drug nanoparticles can aggregate during the formation of nanosuspensions and their drying into composite powders, which in turn can cause inadequate bioavailability enhancement from nanoparticles and ensuing lack of therapeutic efficacy. In this study, formulations with various polymer concentrations–molecular weights in the presence/absence of a surfactant were explored to assess their impact on redispersibility and drug dissolution from the composites. Suspensions of griseofulvin (GF), a poorly water-soluble drug, were prepared by wet stirred media milling and subsequently dried via fluidized bed drying–coating onto Pharmatose® carrier particles. Hydroxypropyl cellulose (HPC), with various molecular weights, sodium dodecyl sulfate (SDS), and their combinations were used as stabilizers during the milling. The dried composites were redispersed in water and SDS solution to recover the GF nanoparticles. Particle sizing via laser diffraction, SEM imaging, and dissolution testing were performed to investigate the redispersion and dissolution performance. Results show that good physical stability of the milled suspension is necessary, but not sufficient to guarantee fast redispersion–drug dissolution. For best performance, presence of SDS is critical; a minimum concentration of the polymer, as a film former, is also required to prevent the formation of hard aggregates during drying.

Investigation of preparation parameters to improve the dissolution of poorly water-soluble meloxicam

The rate of dissolution of drugs remains one of the most challenging aspects in formulation development of poorly water-soluble drugs. The meloxicam, a low molecular analgetic for oral administration, exhibits a slow dissolution. To improve the dissolution rate, the drug was formulated in a nanosuspension by using an emulsion–diffusion method, high-pressure homogenization or sonication. Optimization of the technological parameters (organic solvents, stabilizers, homogenization procedure and recovery of particles) allowed the formation of nanosuspensions with a particle size of 200–900 nm. SEM imaging confirmed the nanosized drug particles. Use of an SMCR method on the XRPD patterns of the nanosuspensions revealed the crystalline form of the drug and the strong interaction between meloxicam and the stabilizer. The rate of dissolution of the dried meloxicam nanosuspension was enhanced (90% in 5 min), relative to that of raw meloxicam (15% in 5 min), mainly due to the formation of nanosized particles. These results indicate the suitability of formulation procedure for preparation of nanosized poorly water-soluble drug with significantly improved in vitro dissolution rate, and thus possibly enhance fast onset of therapeutic drug effect.

System Investigation of the Formation of Beta-Cypermethrin Nanosuspension: Influence of the Formulation Variables

The effects of formulation variables on the formation of beta-cypermethrin nanosuspension prepared from the dilution of microemulsion have been investigated systematically. The formation of nanosuspension depends on several parameters. Surfactants and co-surfactants are the crucial parameters determine the formation of nanosuspension. The size of nanoparticles could be influenced by the species of surfactants (nonionic surfactant, ionic surfactant, high molecular weight surfactant), and the combination of stabilizers might provide additional long-term stabilization. The size and ripening rate of nanosuspension decrease with the increase of polarity of solvent. When the concentration of beta-cypermethrin in oil over 37.5 wt%, microparticles formation process was monitored. Furthermore, the electrolyte in diluted media showed little influence on size when dilution-fold over 40.

Preparation and evaluation of nanosuspensions for enhancing the dissolution of poorly soluble drugs

Poorly water-soluble compounds are difficult to develop as drug products using conventional formulation techniques and are frequently abandoned early in discovery. In the present study, the melt emulsification method traditionally used to prepare solid lipid nanoparticles was adapted to produce drug nanosuspensions. The method was evaluated in comparison with the well known solvent diffusion process for ibuprofen as a model drug. Control of the preparation variables (stabilizers, drug content, homogenization procedure and cooling conditions) allowed formation of nanosuspensions with diameters less than 100 nm. The major advantage of the melt emulsification method over the solvent diffusion method is the avoidance of organic solvents during production, although the mean particle size is slightly greater. The combination of Tween 80 and PVP K25 as stabilizers yields nanosuspensions with the smallest average particle size. The formulation of ibuprofen as a nanosuspension, either in the form of lyophilized powder or granules, was very successful in enhancing dissolution rate, more than 65% of the drug being dissolved in the first 10 min compared to less than 15% of the micronized drug. The increase in in vitro dissolution rate may favourably affect bioavailability and improve safety for the patient by decreasing gastric irritancy.