ABSTRACT
Lipids serve as excellent excipients for drug products. Solid lipid microparticles (SLMs) are relatively underexplored in drug delivery; these particles are conventionally prepared using processes yielding polydisperse size distributions, such as spray congealing or emulsification. In this paper, we demonstrate a microfluidics-enabled process for particle engineering of monodisperse solid lipid microparticles with size and content uniformity. To overcome low solubility, we use a volatile solvent to increase drug loading, making the drug-lipid solution a single phase, enabling identical drug loading across particles. We use microfluidic flow extrusion of the solution to generate uniform drug-loaded SLMs, substantially enhancing monodispersity. This method generalises across three drugs-ibuprofen, 5-methyl-2-[(2-nitrophenyl)amino]-3-thiophenecarbonitrile (ROY), and naproxen, and two lipids-beeswax and hard fat (Suppocire NAI 25A), forming particles of various solid states: amorphous naproxen in crystalline lipids, crystalline ROY in crystalline lipids, and a eutectic mixture of ibuprofen-hard fat. In vitro dissolution studies on the ibuprofen-hard fat SLMs reveal gradual release, fitting the Higuchi model with 50-65% drug released over 72 h. This work expands the drug particle engineering toolbox to enable the formulation of SLMs with high precision in particle size and drug loading. Moreover, the diverse solid-state outcomes enabled by our method makes it applicable to various drugs having different formulation requirements (crystalline/amorphous).
Subject(s)
Lipids , Microfluidics , Delayed-Action Preparations , Drug Carriers , Drug Compounding , Particle Size , SolubilityABSTRACT
Electrospun nanofibrous membranes (ENM) which have a porous structure have a huge potential for various liquid filtration applications. In this paper, we explore the viability of using plasma-induced graft copolymerization to reduce the pore sizes of ENMs. Poly(vinylidene) fluoride (PVDF) was electrospun to produce a nonwoven membrane, comprised of nanofibers with diameters in the range of 200-600 nm. The surface of the ENM was exposed to argon plasma and subsequently graft-copolymerized with methacrylic acid. The effect of plasma exposure time on grafting was studied for both the ENM and a commercial hydrophobic PVDF (HVHP) membrane. The grafting density was quantitatively measured with toluidine blue-O. The degree of grafting increased steeply with an increase in plasma exposure time for the ENM, attaining a maximum of 180 nmol/mg after 120 s of plasma treatment. However, the increase in the grafting density on the surface of the HVHP membrane was not as drastic, reaching a plateau of 65 nmol/mg after 60 s. The liquid entry permeation of water dropped extensively for both membranes, indicating a change in surface properties. Field emission scanning electron microscopy micrographs revealed an alteration in the surface pore structure for both membranes after grafting. Bubble point measurements of the ENM reduced from 3.6 to 0.9 um after grafting. The pore-size distribution obtained using the capillary flow porometer for the grafted ENM revealed that it had a similar profile to that of a commercial hydrophilic commercial PVDF (HVLP) membrane. More significantly, water filtration studies revealed that the grafted ENM had a better flux throughput than the HVLP membrane. This suggests that ENMs can be successfully engineered through surface modification to achieve smaller pores while retaining their high flux performance.
