Spray dried microparticles for controlled delivery of mupirocin calcium: Process–tailored modulation of drug release

Abstract

Spray dried microparticles containing mupirocin calcium were designed as acrylic matrix carriers with modulated drug release for efficient local drug delivery at minimum daily dose. Particle generation in spray drying and its effect on release performance were assessed by varying drug : polymer ratios with consequently altered initial saturations. Narrow-sized microparticles with mean diameters of 1.7-2.5 µm were obtained. Properties of the generated solid dispersions were examined by X-ray, thermal (thermogravimetric analysis, modulated differential scanning calorimetry) and spectroscopic (Fourier transformed infrared, Fourier transformed Raman) methods and correlated with drug loading and in vitro release. The best control over mupirocin release was achieved for 2 : 1 (w/w) drug : polymer ratio and found to be strongly process-dependent. For a particular ratio, increased feed concentration (>4%) boosted while increased inlet temperature (≥ 100 °C) reduced drug release. Antimicrobial activity testing confirmed that encapsulated drug preserved its antibacterial effectiveness. Conclusively, spray drying was proven as a suitable method for preparing structured microparticles which can control drug release even at exceptionally high drug loadings.

An Investigation of Nifedipine Miscibility in Solid Dispersions Using Raman Spectroscopy

“…This suggested that the nitro group of nifedipine might form a hydrogen bond with the OH of Soluplus®. The upward shifts of peak positions on decreasing the drug loading resulted from a change in the micro-environment of nifedipine and suggested weaker drug-polymer interactions compared to drug-drug interactions (12,23,37). There was no significant change in nifedipine peak position over the spectral region of aromatic hydrocarbon between 775 and 850 cm −1 (data not shown).…”

“…The presence of a single peak indicates a molecular dispersion of the drug and suggests the presence of a drug-polymer interaction. A shift in a drug related peak position to lower wavenumber indicates stronger drugpolymer interaction than drug-drug interaction and vice versa (23). The stronger drug-polymer interaction results in a weakening of drug-drug interactions, causing a shift to lower frequency.…”

“…The strength of drug-polymer hydrogen bonding has also been studied by XPS (14) and ss-NMR (16) based on the shift in peak position. Recently, Raman spectroscopy has been widely utilized to reveal the occurrence of specific interaction (5,15,19,21,23). As with IR, changes in the chemical environment of the drug will affect the Raman spectral pattern in terms of peak position (15,(19)(20)(21)(22)(23)(24), peak shape (22) or new peaks (5,24).…”

“…The strength of intermolecular interaction is a key factor governing the physical stabilization of solid dispersions and it may be related to the miscibility of the drug in the polymer matrix (7). To date, there have been several attempts to apply analytical methods to characterize drug-polymer miscibility, e.g., differential scanning calorimetry (DSC) (3,(8)(9)(10)(11)(12)(13)(14)(15)(16), infrared spectroscopy (IR) (8)(9)(10)(11)(12)(13)(17)(18)(19), solid state-nuclear magnetic resonance (ss-NMR) (14,16), Xray powder diffractometry (XRD) (10), X-ray photoelectron spectroscopy (XPS) (14) and Raman spectroscopy (15,(19)(20)(21)(22)(23). The strength of intermolecular hydrogen bonding between drug and polymer in a solid dispersion has been investigated by IR based on the peak position (12,13,18) and peak height ratio (13,17).…”

Development and validation of an in vitro release method for topical particulate delivery systems

“…Topical particulate delivery systems are an advanced form of topical powders. Various release methods have been reported for this type of delivery system: for example methods with paddle or basket apparatus or other similar setups where the sample is added into a container with medium (Alhalaweh et al, 2009;Dürrigl et al, 2011a;Scalia and Mezzena, 2009), flow through cell methods (Salama et al, 2008), dialysis bag methods (Moebus et al, 2012) and methods with Franz cell (vertical diffusion cell) or its modifications (Martinac et al, 2005;Moebus et al, 2012;Salama et al, 2008).…”