Enhancing the dissolution of phenylbutazone using Syloid® based mesoporous silicas for oral equine applications

Three mesoporous silica excipients (Syloid® silicas AL-1 FP, XDP 3050 and XDP 3150) were formulated with a model drug known for its poor aqueous solubility, namely phenylbutazone, in an attempt to enhance the extent and rate of drug dissolution. Although other forms of mesoporous silica have been investigated in previous studies, the effect of inclusion with these specific Syloid® silica based excipients and more interestingly, with phenylbutazone, is unknown. This work reports a significant enhancement for both the extent, and rate, of drug release for all three forms of Syloid® silica at a 1:1 drug:silica ratio over a period of 30 minutes. An explanation for this increase was determined to be conversion to the amorphous form and an enhanced drug loading ability within the pores. Differences between the release profiles of the three silicas was concluded to be a consequence of the physicochemical differences between the three forms. Overall, this study confirms that Syloid® silica based excipients can be used to enhance dissolution, and potentially therefore bioavailability, for compounds with poor aqueous solubility, such as phenylbutazone. In addition, it has been confirmed that drug release can be carefully tailored based on the choice of Syloid® silica and desired release profile

Computationally Assisted (Solid-State Density Functional Theory) Structural (X-ray) and Vibrational Spectroscopy (FT-IR, FT-RS, TDs-THz) Characterization of the Cardiovascular Drug Lacidipine

The structural properties of a second-generation dihydropyridine calcium antagonist, lacidipine, were explored by combining low-temperature X-ray diffraction with optical vibrational spectroscopy and periodic density functional theory (PBC DFT) calculations. Crystallographic analysis cannot discriminate between two possible molecular symmetries in crystals made of pure lacipidine: the space group <i>Ama</i>2, where the lacipidine molecule lies on mirror symmetry, or a <i>Cc</i> space group with distorted lacipidine molecules. Intermolecular interactions analysis reveals an infinite net of moderate-strength N–H···O hydrogen-bonds, which link the molecular units toward the crystallographic <i>b</i>-axis. Weak interactions were identified, revealing their role in stabilization of the crystal structure. The vibrational dynamics of lacidipine was thoroughly explored by combining infrared and Raman spectroscopy in the middle- and low-wavenumber range. The given interpretation was fully supported by state-of-the-art solid-state density functional theory calculations (plane-wave DFT), giving deep insight into the vibrational response and providing a complex assignment of spectral features. The vibrational analysis was extended onto the lattice-phonon range by employing time-domain terahertz spectroscopy. Analysis of the anisotropic displacement parameters suggests noticeable dynamics of the terminal (<i>tert</i>-butoxycarbonyl)­vinyl moiety. The terahertz study provides direct experimental evidence of “crankshaft” type motions in the terminal chain. By combining low-wavenumber vibrational spectroscopy with the first-principles calculations, we were able to prove that the quoted thermodynamically stable phase corresponds to the monoclinic <i>Cc</i> space group