Purpose: Paraffin wax (PW) has not been well investigated for developing specialized drug delivery systems. Being hydrophobic and readily meltable, it is potentially useful for producing spray-congealed drug-loaded microparticles with sustained release and taste masking properties. These desired properties will be hampered if the surface drug particles are not entirely coated by the paraffin wax matrix. Moreover, highly viscous melts are unsuitable for spray-congealing. It is therefore of interest to understand the effects of various formulation parameters to achieve the desired outcome. In this study, drug-loaded paraffin wax microparticles were produced by spray congealing. The effects of three drug particle sizes (large [DL], medium [DM] and small [DS]) and lipid additives, such as stearic acid (SA), cetyl alcohol (CA) and cetyl esters (CE), on the melt viscosity and degree of surface drug coating by paraffin wax were investigated.
Methods: The influence of drug particle size and lipid additives on the melt viscosity of paraffin wax was investigated through continuous ramping rheological tests. Selected formulations were spray-congealed using a laboratory-scale spray congealer with a pneumatic fountain two-fluid nozzle. The microparticles produced were characterized for their size, drug content, degree of surface drug coating and drug release through optical microscopy, UV spectrophotometry, Raman spectroscopy and dissolution studies respectively.
Results: The melt viscosity increased with a smaller drug particle size. In contrast, the lipid additives decreased the melt viscosity in the following order: CA > SA > CE (Figure 1) and they could be employed to modulate the melt viscosity for successful spray-congealing. Polar functional groups of the lipid additives could disrupt the network of drug particles through the formation of hydrogen bonds with the drug particles. The total and useful yields obtained for all spray-congealed formulations were greater than 88 % and 86 % respectively. Theoretical drug content was 15 % for all formulations, while the useful yield obtained had drug contents of 16.0 % to 17.3 %. The size of the spray-congealed microparticles was largely dependent on the melt viscosity, where melts of lower viscosity produced smaller microparticles. Raman spectroscopy showed that addition of lipid additives to paraffin wax enabled better coating of drug particles at the surface of the microparticles, and this can be ranked from highest to lowest as follows: CA > SA > CE (Figure 2). The drug release rate was affected by the type of lipid additive. CA produced microparticles with the slowest overall drug release rate, followed by SA and CE (Figure 3). This trend corresponds to that observed for surface drug coating as seen from Raman spectroscopy, implying slower drug release with higher degree of surface drug coating. Based on the drug release studies, the drug particle size affected the surface drug coating effect of CA, but not of SA and CE. The addition of CA and CE also enhanced the drug release without compromising taste masking.
Conclusion: The drug particle size and lipid additives altered the rheological properties of paraffin wax. The lipid additives reduced the hydrophobicity of the melt and are useful for enhancing the degree of surface drug coating by paraffin wax. Judicious choice of matrix materials and drug particle size is pertinent for the feasibility of spray congealing and production of microparticles with desired characteristics.
Chen Yee Ang– Undergraduate, National University of Singapore
Paul Wan Sia Heng– Associate Professor, National University of Singapore
Lai Wah Chan– Associate Professor, National University of Singapore