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Dissolution of bicalutamide processed with polyvinylpyrrolidone by either supercritical carbon dioxide or ball milling has been investigated. Various compositions as well as process parameters were used to obtain binary systems of the drug with the carrier. Thermal analysis and powder X-ray diffractometry confirmed amorphization of bicalutamide mechanically activated by ball milling and the decrease in crystallinity of the supercritical carbon dioxide-treated drug. Both methods led to reduction of particles size what was confirmed by scanning electron microscopy and laser diffraction measurements. Moreover, the effect of micronisation was found to depend on the parameters of applied process. Fourier transform infrared spectroscopy revealed the appearance of intermolecular interactions between drug and carrier molecules that play an important role in the stabilization of amorphous form of the active compound. Changes in crystal structure combined with reduced size of particles of bicalutamide dispersed within polymer matrix were found to improve dissolution of bicalutamide by 4 to 10-fold in comparison to untreated drug. It is of particular importance as poor dissolution profiles are considered to be the major limitation in bioavailability of the drug., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Polymeric microparticles encapsulating two model hydrophobic drugs, beclomethasone dipropionate (BDP) and flutamide (FLU) were prepared by using the high pressure homogenization-solvent evaporation method starting from a oil-in-water emulsion. For the preparation of polymeric microparticles a α,β-poly(N-2-hydroxyethyl)-D,L-aspartamide (PHEA) graft copolymer with comb like structure was properly synthesized via grafting from atom transfer radical polymerization (ATRP) technique, by using two subsequent synthetic steps. In the first step a polymeric multifunctional macroinitiator was obtained by the conjugation of a proper number of 2-bromoisobutyryl bromide (BIB) residues to the PHEA side chains, obtaining the PHEA-BIB copolymer. PHEA-BIB copolymer was then used as macroinitiator for the polymerization via ATRP of the hydrophobic monomer such as butyl methacrylate (BMA) to obtain the α,β-poly(N-2-hydroxyethyl)-D,L-aspartamide-co-(N-2-ethylen-isobutyrate)-graft-poly(butyl methacrylate) copolymer (PHEA-IB-p(BMA)). Spherical microparticles with 1-3 microns diameter were prepared. Microparticles loaded with BDP or FLU were also prepared. In vitro mucoadhesion and enzymatic degradation studies evidenced bioadhesive properties and biodegradability of prepared microparticles, while release studies showed a different release profiles for the two loaded drugs: BDP was totally released from nanoparticles until 24h in pulmonary mimicking conditions; differently a slower FLU release rate was observed in gastro-intestinal mimicking conditions. The in vitro cytotoxicity activity was assessed using 16HBE and Caco-2 cell lines. Results showed that exposure of both cell lines to BDP-loaded microparticles do not inhibited the cell growth; on the contrary FLU-loaded microparticles inhibited the cell growth, in particular of the Caco-2 cancer cell line, in a concentration- and time-dependent manner. Finally, uptake studies demonstrated that BDP-loaded microparticles and FLU-loaded microparticles effectively increased uptake of loaded drugs in a time-dependent manner, respectively on 16HBE and Caco-2 cell lines., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Bicalutamide was loaded on hydrophilic excipients to form nanodispersions via a combination of anti-solvent precipitation and spray drying method. The particle size, BET surface area, contact angles and dissolution rate of the nanodispersions were analyzed. The results indicated that lactose was a suitable matrix to prevent the bicalutamide particles growth and aggregation. The lactose loaded particles had a mean size of 330 nm within a narrow distribution. X-ray diffraction (XRD), differential scanning calorimetry (DSC) and Fourier transform infrared (FT-IR) characterization indicated the nanodispersion exhibited unchanged crystalline and chemical structure. Dissolution rate of bicalutamide nanodispersion was significantly faster than that of commercial products. It increased to 94% in 10 min while both commercial formulas Casodex and bicalutamide tablets dissolved 60% and 38% respectively at the same period. It was proposed that the enhanced dissolution rate of bicalutamide nanodispersion contribute to high surface area and well-wetted state of drug particles., (Copyright © 2010 Elsevier B.V. All rights reserved.)

The utility of the novel polycarbonate, poly(propylene carbonate maleate) (PPCM) to encapsulate and control the release of finasteride, via microspheres, was investigated. The PPCM microspheres loaded with finasteride were elaborated by a simple oil-in-water (O/W) emulsion-solvent evaporation method. Various manufacturing parameters, including the concentration of polymer in dichloromethane (DCM) and the polymer:finasteride ratios were altered to optimize process variables during the microspheres production. The effects of these changes on the characteristics of the microspheres were examined. The structure and morphology were characterized by wide-angle X-ray diffraction (WXRD) and scanning electron microscopy (SEM). The results showed that the mean diameter of microspheres was approximately 2mum, and had both smooth and spherical surfaces. Greater encapsulation efficiency was obtained by increasing the ratios of polymer:finasteride and the concentration of PPCM in DCM. In vitro drug release of these microcapsules was performed in a pH 7.4 phosphate-buffered solution. The release profiles of finasteride from PPCM microcapsules were found to be biphasic with a burst release followed by a gradual release phase. A prolonged in vitro drug release profile was observed. After an initial burst, a continuous drug release was observed for up to 5-6 weeks.

Two crystalline forms (forms I and II) and an amorphous phase of bicalutamide were fully characterized through combined results of differential scanning calorimetry, X-ray powder and single crystal diffraction and Raman spectroscopy. Each polymorph crystallizes with one molecule in the asymmetric unit and the molecular conformations are quite different between them. The main difference is provided by C12-C11-S8-C5 torsion angle, which assumes a value of -88.3(4) degrees (-Syn-Clinal) and 72.5(4) degrees (+Syn-Clinal) in forms I and II, respectively. Consequently, molecules in form I show an open folding and molecules in form II a closed one. The relative stability between forms I and II is presented in an energy versus temperature diagram, where forms I and II are considered as a monotropic system, being form I the more stable one. The amorphous phase was observed very metastable and it converts to form II spontaneously at RT in around a week.