Effect of drug load and lipid-wax blends on drug release and stability from spray-congealed microparticles.

This study was designed to evaluate paraffin wax as a potential controlled release matrix for spray congealing and its impact on drug release and stability of the microparticles. Paraffin wax can form a hydrophobic barrier to moisture and reduce drug degradation besides retarding drug release in the gastrointestinal tract. More hydrophilic lipid-based additives can be incorporated to modulate the drug release through the paraffin wax barrier. This study reports the findings of lipid-wax formulations at preserving the stability of moisture-sensitive drugs in spray-congealed microparticles. Aspirin-loaded microparticles formulated with different drug loads, lipid additives, and lipid:wax ratios were produced by spray congealing. Stearic acid (SA), cetyl alcohol (CA), and cetyl ester (CE) were the lipid additives studied. The microparticles were evaluated for yield, encapsulation efficiency, particle size, drug stability, and release. CE exhibited the greatest effect on increasing drug release, followed by CA and SA. Dissolution profiles showed the best fit to Weibull kinetic model. The degree of drug degradation was low, with CA imparting the least protective effect, followed by SA and CE. Paraffin wax is useful for preserving the stability of moisture-sensitive aspirin and retarding its release from spray-congealed microparticles. The addition of lipid additives modulated drug release without compromising drug stability.

Effects of Drug Particle Size and Lipid Additives on Drug Release from Paraffin Wax Formulations Prepared by Spray Congealing Technique.

Paraffin wax is a hydrophobic meltable material that can be suitably used in spray congealing to develop drug-loaded microparticles for sustained release, taste-masking or stability enhancement of drugs. However, these functional properties may be impaired if the drug particles are not completely embedded. Moreover, highly viscous melts are unsuitable for spray dispersion. In this study, the effects of drug particle size and lipid additives, namely stearic acid (SA), cetyl alcohol (CA) and cetyl esters (CE), on melt viscosity and extent of drug particles embedment were investigated. Spray congealing was conducted on the formulations, and the resultant microparticles were analysed for their size, drug content, extent of drug particles embedment and drug release. The melt viscosity increased with smaller solid inclusions while lipid additives decreased the viscosity to varying extents. The spray-congealed microparticle size was largely dependent on the viscosity. The addition of lipid additives to paraffin wax enabled more complete embedment of the drug particles. CA produced microparticles with the lowest drug release, followed by SA and CE. The addition of CA and CE enhanced the drug release and showed potential for taste-masking. Judicious choice of drug particle size and matrix materials is important for successful spray congealing to produce microparticles with the desired characteristics.

Effect of Lipid Additives and Drug on the Rheological Properties of Molten Paraffin Wax, Degree of Surface Drug Coating, and Drug Release in Spray-Congealed Microparticles.

Paraffin wax is potentially useful for producing spray-congealed drug-loaded microparticles with sustained-release and taste-masking properties. To date, there is little information about the effects of blending lipids with paraffin wax on the melt viscosity. In addition, drug particles may not be entirely coated by the paraffin wax matrix. In this study, drug-loaded paraffin wax microparticles were produced by spray-congealing, and the effects of lipid additives on the microparticle production were investigated. The influence of lipid additives (stearic acid, cetyl alcohol, or cetyl esters) and drug (paracetamol) on the rheological properties of paraffin wax were elucidated. Fourier transform-infrared spectroscopy was conducted to investigate the interactions between the blend constituents. Selected formulations were spray-congealed, and the microparticles produced were characterized for their size, drug content, degree of surface drug coating, and drug release. The viscosity of wax-lipid blends was found to be mostly lower than the weighted viscosity when interactions occurred between the blend constituents. Molten paraffin wax exhibited Newtonian flow, which was transformed to plastic flow by paracetamol and pseudoplastic flow by the lipid additive. The viscosity was decreased with lipid added. Compared to plain wax, wax-lipid blends produced smaller spray-congealed microparticles. Drug content remained high. Degree of surface drug coating and drug release were also higher. The lipid additives altered the rheological properties and hydrophobicity of the melt and are useful for modifying the microparticle properties.