Preparation of finasteride capsules-loaded drug nanoparticles: formulation, optimization, in vitro, and pharmacokinetic evaluation

Abstract

In this study, optimized freeze-dried finasteride nanoparticles (NPs) were prepared from drug nanosuspension formulation that was developed using the bottom–up technique. The effects of four formulation and processing variables that affect the particle size and solubility enhancement of the NPs were explored using the response surface optimization design. The optimized formulation was morphologically characterized using transmission electron microscopy (TEM). Physicochemical interaction among the studied components was investigated. Crystalline change was investigated using X-ray powder diffraction (XRPD). Crystal growth of the freeze-dried NPs was compared to the corresponding aqueous drug nanosuspension. Freeze-dried NPs formulation was subsequently loaded into hard gelatin capsules that were examined for in vitro dissolution and pharmacokinetic behavior. Results revealed that in most of the studied variables, some of the quadratic and interaction effects had a significant effect on the studied responses. TEM image illustrated homogeneity and shape of the prepared NPs. No interaction among components was noticed. XRPD confirmed crystalline state change in the optimized NPs. An enhancement in the dissolution rate of more than 2.5 times from capsules filled with optimum drug NPs, when compared to capsules filled with pure drug, was obtained. Crystal growth, due to Ostwald ripening phenomenon and positive Gibbs free energy, was reduced following lyophilization of the nanosuspension formulation. Pharmacokinetic parameters from drug NPs were superior to that of pure drug and drug microparticles. In conclusion, freeze-dried NPs based on drug nanosuspension formulation is a successful technique in enhancing stability, solubility, and in vitro dissolution of poorly water-soluble drugs with possible impact on the drug bioavailability.

A potential in situ gel formulation loaded with novel fabricated poly(lactide-co-glycolide) nanoparticles for enhancing and sustaining the ophthalmic delivery of ketoconazole

“…[23][24][25] PVA was added to the aqueous phase as a stabilizer to produce small size and stable NPs. 26,27 The possible formulation parameters affecting the preparation of the NPs were optimized to achieve the optimum concentration of PLGA in the organic solvent, organic to aqueous phase ratio and PVA concentration in the aqueous phase. Central composite experimental design was used as a tool used to investigate the effects of the independent variables (X1-X3) on the dependent variables (Y1-Y2).…”

“…Above this critical micelle concentration, there is a less surfactant surface adsorption since the micelle molecules begin to compete for the adsorption at the solid particles; this effect results in destabilization of the prepared NPs and therefore contributed to increase in the particle size. [26][27][28][29] Second, increase in the concentration of PVA leads to increase in the viscosity of the aqueous phase, which in turn decreases the rate of PLGA solidification and so formation of large size particles. Results also revealed that, as the concentration of PLGA was increased, the particle size of the prepared NPs was increased.…”

Lymph cancer chemotherapy: delivery of doxorubicin-gemcitabine prodrug and vincristine by nanostructured lipid carriers

“…The later sustained release indicated that drugs might be stably retained in the lipid matrix before slow release by drug diffusion. 49 Retardation of drug release in NLCs may be ascribed to the distribution of drugs in the lipid matrix.…”

Development of Capsules Filled with Phenytoin and Berberine Loaded Nanoparticles- A New Approach to Improve Anticonvulsant Efficacy

“…In vitro dissolution analyses were carried out for Nanoparticles filled capsules 26 in dissolution test apparatus (Labinda, Disso) using 900mL of dissolution media, 0.1N HCl of pH value 1.2 for 2h and phosphate buffer of pH value 6.8 for 24 h at 37±0.5°C. Samples were introverted in pre-determined intervals up to 24h.…”