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Drug Particles (drug + particle)
Selected AbstractsAn investigation into the mechanism of dissolution rate enhancement of poorly water-soluble drugs from spray chilled gelucire 50/13 microspheresJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 1 2010Sheng Qi Abstract The production and physicochemical characterisation of spray chilled Gelucire 50/13 microspheres is described with a view to improving the dissolution of a poorly water-soluble drug, piroxicam, and understanding the fundamental mechanisms associated with the improved drug release. Thermorheological testing was developed as a fast screening method for predicting the processability of dispersions for spray chilling preparation. Spray chilled piroxicam loaded microspheres were spherical in shape with a median diameter of circa 150,µm. DSC indicated no interaction between piroxicam and lipid matrix, while HSM studies performed in polarized light mode indicated that the spheres contained distinct drug crystals. Polarising light microscopy and small-angle XRD investigations on the hydration behaviour of the lipid and the spray chilled microspheres revealed the formation of liquid crystalline phases depending on the degree of hydration. The dissolution behaviour of the piroxicam loaded microspheres showed significant improvements compared to drug alone. The particle size, drug loading and aging of the microspheres were all found to have an influence on the release behaviour. It was proposed that Gelucire 50/13 microspheres release the entrapped piroxicam via formation of a lyotropic liquid crystalline phase, which allows dissolution of the drug particles in a finely divided, high surface area and well-wetted state. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:262,274, 2010 [source] Direct drug loading into preformed porous solid dosage units by the controlled particle deposition (CPD), a new concept for improved dissolution using SCF-technologyJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 10 2008Ragna S. Wischumerski Abstract The controlled particle deposition (CPD), a supercritical fluid precipitation process, is used to load porous tablets with ibuprofen to improve drug dissolution. Porous tablets (porosity 44.3,±,5.5%), consisting of microcrystalline cellulose pellets and hydroxyethylcellulose, or sugar cubes (porosity 37.2,±,0.5%), are used as carrier material. Loading experiments are conducted at 313 K and 25 MPa, drug concentrations between 6.25 and 33.3 mg ibuprofen/mL supercritical carbon dioxide and contact times of 15.5 h or 5 min. The resulting products have drug contents of 3,5 g ibuprofen/mL void volume in the carrier. Comparison of a predicted value, calculated from pore volume and loading concentration to the actual drug concentrations yielded by the loading process demonstrates the efficiency and controllability of the process. The mean particle size d50 of deposited ibuprofen is around 25 µm, half the size of the starting material. Drug dissolution from loaded carriers is significantly increased by a rise in the dissolution coefficient from 0.07 min,1 for the starting material to 0.13 or 0.14 min,1 for the CPD products. The CPD method therefore is presented as a feasible and controllable process to load porous solid dosage forms with drug particles in order to improve dissolution. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:4416,4424, 2008 [source] Drug release phenomena within a hydrophobic starch acetate matrix: FTIR mapping of tablets after in vitro dissolution testingJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 8 2008Jari Pajander Abstract The aim of this study was to assess the utility of Fourier transform infrared mapping to study the drug release phenomena within a hydrophobic matrix tablet. Starch acetate with a degree of substitution (2.7) was used as a hydrophobic matrix former. Anhydrous caffeine and riboflavin sodium phosphate were used as water soluble model drugs. The USP (XXVIII) paddle-method was selected as an in vitro dissolution test. Mapping of the diluted tablets' cross-section was performed by attenuated total reflection mode. Fourier transform infrared mapping can distinguish drug particles from the bulk matrix and it can be considered as a valuable method for obtaining both quantitative and qualitative information on drug release processes. The physicochemical properties of the drug compound strongly contribute to its release behavior when the USP paddle in vitro dissolution test is used. Mapping of the riboflavin product revealed a more homogenous matrix distribution due to its smaller particle size. Consequently, its dissolution release profile was more uniform than caffeine which possessed a wider particle size distribution and lower solubility. Mapping showed that caffeine became localized in the lower part of the tablet unlike riboflavin. The hydrodynamic conditions during the in vitro release test might contribute to this differentiation. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97: 3367,3378, 2008 [source] Immediate drug release from solid oral dosage formsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 1 2005Thomas Schreiner Abstract Fast drug release from solid dosage forms requires a very fast contact of the vast majority of the drug particles with the solvent; this, however, is particularly delayed in tablets and granulations. Starch and cellulose substances favor the matrix disintegration during the starting phase and the generation of the effective dissolution surface of the drug substance, thereby. To investigate the very complex interrelation between the functionality of commonly used excipients and the structural effects of the production processes, wettability, porosity, water uptake, and drug release rates of several ketoprofen-excipient preparations (powder blends, granulations, tablets) were measured. Significant linear correlation between these parameters, however, was not achieved; only qualitative tendencies of the effects could be detected. In consequence, a general mathematical model describing the mechanistic steps of drug dissolution from solid dosage forms in a fully correct way was not realized. However, the time-dependent change of the effective dissolution surface follows stochastic models: a new dissolution equation is based on the differential Noyes-Whitney equation combined with a distribution function, e.g. the lognormal distribution, and numerically solved with the software system EASY-FIT by fitting to the observations. This new model coincides with the data to a considerably higher degree of accuracy than the Weibull function alone, particularly during the starting, matrix disintegration, and end phases. In combination with a procedure continuously quantifying the dissolved drug, this mathematical model is suitable for the characterization and optimization of immediate drug release by the choice and modification of excipients and unit operations. The interdependence of some characteristic effects of excipients and production methods is discussed. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 94:120,133, 2005 [source] The influence of relative humidity on the cohesion properties of micronized drugs used in inhalation therapyJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 3 2004Paul M. Young Abstract The influence of relative humidity (RH) on the cohesion properties of three drugs: salbutamol sulphate (SS), triamcinolone acetonide (TAA), and disodium cromoglycate (DSCG) was investigated using the atomic force microscope (AFM) colloidal probe technique. Micronized drug particles were mounted in heat-sensitive epoxy resin for immobilization. Multiple AFM force,distance curves were conducted between each drug probe and the immobilized drug particulates at 15, 45, and 75% RH using Force,Volume imaging. Clear variations in the cohesion profile with respect to RH were observed for all three micronized drugs. The calculated force and energy of cohesion to separate either micronized SS or DSCG increased as humidity was raised from 15 to 75% RH, suggesting capillary forces become a dominating factor at elevated RH. In comparison, the separation force and energy for micronized TAA particles decreased with increased RH. This behavior may be attributed to long-range attractive electrostatic interactions, which were observed in the approach cycle of the AFM force,distance curves. These observations correlated well with previous aerosolization studies of the three micronized drugs. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93: 753,761, 2004 [source] Enhancing the oral bioavailability of the poorly soluble drug dicumarol with a bioadhesive polymerJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 8 2003Chris G. Thanos Abstract This article investigates the effect of particle size and the incorporation of a bioadhesive polymer, poly(fumaric- co -sebacic) anhydride p(FA:SA), on the relative bioavailability of dicumarol. A novel method was used to reduce particle size of the drug, and encapsulated formulations were fabricated using a phase inversion technique to produce nanospheres and microspheres with varying size. Groups of Yorkshire swine were catheterized and gavaged after fasting for 12 h with each formulation in a 50 mg/mL suspension. Blood was collected at different time points, from 0 to 96 h, and pharmacokinetic analysis revealed that formulations incorporating the smaller drug particles showed the highest bioavailability: micronized drug with 7% p(FA:SA) 17:83 polymer had 190% relative bioavailability, and phase inverted p(FA:SA) 17:83 microspheres with 31% (w/w) loading had 198% relative bioavailability to spray dried formulation. Formulations with larger drug particles achieved 71% relative bioavailability. A nonadhesive formulation, fabricated with poly(lactic acid) (PLA), showed 91% relative bioavailability. Both particle size and polymer composition play a role in oral absorption of dicumarol. © 2003 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 92:1677,1689, 2003 [source] Factors affecting the deposition of inhaled porous drug particlesJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 7 2002Cynthia J. Musante Abstract Recent findings indicate that the inhalation of large manufactured porous particles may be particularly effective for drug delivery. In this study, a mathematical model was employed to systematically investigate the effects of particle size, particle density, aerosol polydispersity, and patient ventilatory parameters on deposition patterns of inhaled drugs in healthy human lungs. Aerodynamically similar particles with densities of 0.1, 1.0, and 2.0 g/cm3 were considered. Particle size distributions were defined with mass median aerodynamic diameters (MMADs) ranging from 1 to 3 ,m and geometric standard deviations ranging from 1.5 to 2.5, representing particles in the respirable size range. Breathing rates of 30 and 60 L/min with tidal volumes of 500 to 3000 mL were assumed, simulating shallow to deep breaths from a dry powder inhaler. Particles with a high density and a small geometric diameter had slightly greater deposition fractions than particles that were aerodynamically similar, but had lower density and larger geometric size (typical of manufactured porous particles). This can be explained by the fact that particles with a small geometric diameter deposit primarily by diffusion, which is a function of geometric size but is independent of density. As MMAD increased, the effect of density on deposition was less pronounced because of the decreased efficiency of diffusion for large particles. These data suggest that polydisperse aerosols containing a significant proportion of submicron particles will deposit in the pulmonary airways with greater efficiency than aerodynamically similar aerosols comprised of geometrically larger porous particles. © 2002 Wiley-Liss Inc. and the American Pharmaceutical Association J Pharm Sci 91:1590,1600, 2002 [source] Effect of chirality on PVP/drug interaction within binary physical mixtures of ibuprofen, ketoprofen, and naproxen: A DSC studyCHIRALITY, Issue 8 2009Ivan T. Ivanov Abstract We report on the thermal behavior of freshly prepared binary drug/polymer physical mixtures that contained ibuprofen, ketoprofen, or naproxen as a drug, and polyvinylpyrrolidone (PVP), hydroxyethylcellulose (HEC), or methylcellulose (MC) as excipient. At 6,10°C/min heating rates the DSC detected a sharp, single endotherm that corresponds to the melting of drug. On heating physical mixtures of PVP and racemic ibuprofen or ketoprofen at lower heating rates, another endotherm was registered in front of the original one. To observe the additional endotherm, specific minimal values of the heating rate and of PVP weight fraction were needed; for ibuprofen and ketoprofen they were 1.5 and 2.0°C/min, and 5 and 15% (w/w), respectively. At greater PVP weight fractions the top temperatures, Tmp, of both peaks were reduced almost linearly indicating strong solid-state interfacial reaction between the drug particles and PVP matrix. The additional endotherm was abolished at greater heating rates (2°C/min for ibuprofen, 3°C/min for ketoprofen), by replacing the racemate with respective S(+)-enantiomer and by replacing PVP with HEC and MC. Hence, the possible inclusion of enantioselective component within the PVP/drug interaction, responsible for the amorphization of physical mixture over storage, is assumed. Chirality, 2009. © 2008 Wiley-Liss, Inc. 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