Cogrinding as a Tool to Produce Sustained Release Behavior for Theophylline Particles Containing Magnesium Stearate

Abstract

Abstract. The aim of the present study was to explore the cogrinding technique as a tool to slow down the drug release from capsule formulations. To this end, the physical mixtures of theophyllinemagnesium stearate were prepared and subjected to different milling times (1, 15, 30, 120 min). In order to investigate the effect of magnesium stearate concentration on drug release, various concentrations of magnesium stearate (1%, 3%, 5%, and 10%, w/w) were used. The dissolution rate of the drug from coground samples and physical mixtures were determined at pH 6.5 according to USP. The results showed that all coground formulations showed slower release rates than their physical mixture counterparts. The effect of cogrinding time on the drug release was complex. Cogrinding time had no significant effect on drug release when the amount of magnesium stearate was 1% (w/w). When the amount of magnesium stearate was increased from 1% to 3% and cogrinding time increased from 1 to 5 min, there was a significant reduction in drug release. Beyond 5-min cogrinding, the drug release increased again. For coground samples containing 5% or 10% (w/w) magnesium stearate, generally, the highest drug release was obtained at higher cogrinding time. This was due to a significant increase in surface area of particles available for dissolution as proven by scanning electron microscopy results. Fourier transform infrared and differential scanning calorimetry results ruled out any significant interaction between theophylline and magnesium stearate in solid state.

Influence of coating material on the flowability and dissolution of dry-coated fine ibuprofen powders

“…This contradicts previous reports, that co-grinding drug powders with the hydrophobic MgSt retards the dissolution of the drug in powder mixtures by preventing wetting and water penetration (Javadzadeh et al, 2012;Nokhodchi et al, 2009). In this study, we believe the increased dissolution rate from the MgSt-mechanofused powder is due to the enhanced powder de-agglomeration.…”

“…However, there is an extensive historical concern that the hydrophobic properties of some dry coating agents such as magnesium stearate will retard drug dissolution in the powder mixture when over-blended or co-ground (Javadzadeh et al, 2012;Nokhodchi et al, 2009) . Over blending of magnesium stearate is also known to have a negative effect on tableting behaviour (Shah and Mlodozeniec, 1977;Strickland Jr et al, 1956;Wang et al, 2010).…”

Nanosized rods agglomerates as a new approach for formulation of a dry powder inhaler

“…For example, Mg stearate has Mg +2 as a cationic root, so it can interfere with the agglomeration process. 55,56 Stearic acid exists in a solid state at room temperature, which is thought to help in the formation of a thin layer surrounding the drug nanodispersion. 57 The amphiphilic nature of stearic acid makes it perform as a boundary between theophylline nanoparticles and the hydrophilic medium in the lungs.…”

Development of pH-sensitive Insulin Nanoparticles using Eudragit L100-55 and Chitosan with Different Molecular Weights

“…From Table I it could be concluded that the release profile of nanoparticles prepared with high MW chitosan is similar to that of nanoparticles prepared with medium MW chitosan, but different with that of nanoparticles prepared with low MW chitosan. Dissolution efficiency (DE) was calculated from the area under the dissolution curve at time and expressed as percentage of the area of the rectangle described by 100% dissolution in the same time (24)(25)(26)(27). Insulin nanoparticles prepared with chitosan of high MW showed higher dissolution efficiency (Table I).…”