Structure, Martensitic Transformation, and Damping Properties of Functionally Graded NiTi Shape Memory Alloys Fabricated by Laser Powder Bed Fusion.

Besides the unique shape memory effect and superelasticity, NiTi alloys also show excellent damping properties. However, the high damping effect is highly temperature-dependent, and only exists during cooling or heating over the temperature range where martensitic transformation occurs. As a result, expanding the temperature range of martensite transformation is an effective approach to widen the working temperature window with high damping performance. In this work, layer-structured functionally graded NiTi alloys were produced by laser powder bed fusion (L-PBF) alternating two or three sets of process parameters. The transformation behavior shows that austenite transforms gradually into martensite over a wide temperature range during cooling, and multiple transformation peaks are observed. A microstructure composed of alternating layers of B2/B19' phases is obtained at room temperature. The functionally graded sample shows high damping performance over a wide temperature range of up to 70 K, which originates from the gradual formation of the martensite phase during cooling. This work proves the potential of L-PBF to create NiTi alloys with high damping properties over a wide temperature range for damping applications.

A Short Review on the Microstructure, Transformation Behavior and Functional Properties of NiTi Shape Memory Alloys Fabricated by Selective Laser Melting.

Due to unique functional and mechanical properties, NiTi shape memory alloys are one of the most promising metallic functional materials. However, the poor workability limits the extensive utilization of NiTi alloys as components of complex shapes. The emerging additive manufacturing techniques provide high degrees of freedom to fabricate complex structures. A freeform fabrication of complex structures by additive manufacturing combined with the unique functional properties (e.g., shape memory effect and superelasticity) provide great potential for material and structure design, and thus should lead to numerous applications. In this review, the unique microstructure that is generated by selective laser melting (SLM) is discussed first. Afterwards, the previously reported transformation behavior and mechanical properties of NiTi alloys produced under various SLM conditions are summarized.

Microstructure of Pharmaceutical Semicrystalline Dispersions: The Significance of Polymer Conformation.

The microstructure of pharmaceutical semicrystalline solid dispersions has attracted extensive attention due to its complexity that might result in the diversity in physical stability, dissolution behavior, and pharmaceutical performance of the systems. Numerous factors have been reported that dictate the microstructure of semicrystalline dispersions. Nevertheless, the importance of the complicated conformation of the polymer has never been elucidated. In this study, we investigate the microstructure of dispersions of polyethylene glycol and active pharmaceutical ingredients by small-angle X-ray scattering and high performance differential scanning calorimetry. Polyethylene glycol with molecular weight of 2000 g/mol (PEG2000) and 6000 g/mol (PEG6000) exhibited remarkable discrepancy in the lamellar periodicity in dispersions with APIs which was attributed to the differences in their folding behavior. The long period of PEG2000 always decreased upon aging-induced exclusion of APIs from the interlamellar region of extended chain crystals whereas the periodicity of PEG6000 may decrease or increase during storage as a consequence of the competition between the drug segregation and the lamellar thickening from nonintegral-folded into integral-folded chain crystals. These processes were in turn significantly influenced by the crystallization tendency of the pharmaceutical compounds, drug-polymer interactions, as well as the dispersion composition and crystallization temperature. This study highlights the significance of the polymer conformation on the microstructure of semicrystalline systems that is critical for the preparation of solid dispersions with consistent and reproducible quality.

Polymorphism of Indomethacin in Semicrystalline Dispersions: Formation, Transformation, and Segregation.

The crystallization of metastable crystal polymorphs in polymer matrices has been extensively reported in literature as a possible approach to enhance the solubility of poorly water-soluble drug compounds, yet no clarification of the mechanism of the polymorph formation has been proposed. The current work aims to elucidate the polymorphism behavior of the model compound indomethacin as well as the mechanism of polymorph selection of drugs in semicrystalline systems. Indomethacin crystallized as either the α- or τ-form, a new metastable form, or a mixture of the two polymorphs in dispersions containing different drug loadings in polyethylene glycol, poloxamer, or Gelucire as the result of the variation in the mobility of drug molecules. As a general rule, low molecular mobility of the amorphous drug favors the crystallization into thermodynamically stable forms whereas metastable crystalline polymorphs are preferred when the molecular mobility of the drug is sufficiently high. This rule provides insight into the polymorph selection of numerous active pharmaceutical ingredients in semicrystalline dispersions and can be used as a guide for polymorphic screening from melt crystallization by tuning the mobility of drug molecules. In addition, the drug crystallized faster while the polymer crystallized slower as the drug-loading increased with the maxima of drug crystallization rate in 70% indomethacin dispersion. Increasing the drug content in solid dispersions reduced the τ to α polymorphic transition rate, except for when the more stable form was initially dominant. The segregation of τ and α polymorphs as well as the polymorphic transformation during storage led to the inherent inhomogeneity of the semicrystalline dispersions. This study highlights and expands our understanding about the complex crystallization behavior of semicrystalline systems and is crucial for preparation of solid dispersions with reproducible and consistent physicochemical properties and pharmaceutical performance.

On the Effect of Hydrogen on the Low-Temperature Elastic and Anelastic Properties of Ni-Ti-Based Alloys.

Linear and non-linear internal friction and the effective Young's modulus of a Ni50.8Ti49.2 alloy have been studied after different heat treatments, affecting hydrogen content, over wide ranges of temperatures (13-300 K) and strain amplitudes (10-7-10-4) at frequencies near 90 kHz. It has been shown that the contamination of the alloy by hydrogen strongly affects the internal friction and Young's modulus of the martensitic phase. Presence of hydrogen gives rise to a non-relaxation internal friction maximum due to a competition of two different temperature-dependent processes. The temperature position and height of the maximum depend strongly on the hydrogen content. We conclude that many of the internal friction peaks, reported earlier for differently treated Ni-Ti-based alloys, had the same origin as the present maximum.

Spectroscopic Investigation of the Formation and Disruption of Hydrogen Bonds in Pharmaceutical Semicrystalline Dispersions.

We recently found that indomethacin (IMC) can effectively act as a powerful crystallization inhibitor for polyethylene glycol 6000 (PEG) despite the fact that the absence of interactions between the drug and the carrier in the solid state was reported in the literature. However, in the present study, we investigate the possibility of drug-carrier interactions in the liquid state to explain the polymer crystallization inhibition effect of IMC. We also aim to discover other potential PEG crystallization inhibitors. Drug-carrier interactions in both liquid and solid state are characterized by variable temperature Fourier transform infrared spectroscopy (FTIR) and cross-polarization magic angle spinning 13C nuclear magnetic resonance spectroscopy (CP/MAS NMR). In the liquid state, FTIR data show evidence of the breaking of hydrogen bonding between IMC molecules to form interactions of the IMC monomer with PEG. The drug-carrier interactions are disrupted upon storage and polymer crystallization, resulting in segregation of IMC from PEG crystals that can be observed under polarized light microscopy. This process is further confirmed by 13C NMR since in the liquid state, when the IMC/PEG monomer units ratio is below 2:1, IMC signals are undetectable because of the loss of cross-polarization efficiency in the mobile IMC molecules upon attachment to PEG chains via hydrogen bonding. This suggests that each ether oxygen of the PEG unit can form hydrogen bonds with two IMC molecules. The NMR spectrum of IMC shows no change in solid dispersions with PEG upon storage, indicating the absence of interactions in the solid state, hence confirming previous studies. The drug-carrier interactions in the liquid state elucidate the crystallization inhibition effect of IMC on PEG as well as other semicrystalline polymers such as poloxamer and Gelucire. However, hydrogen bonding is a necessary but apparently not a sufficient condition for the polymer crystallization inhibition. Screening of crystallization inhibitors of semicrystalline polymers discovers numerous candidates that exhibit the same behavior as IMC, demonstrating a general pattern of polymer crystallization inhibition rather than a particular case. Furthermore, the crystallization inhibition effect of drugs on PEG is independent of the carrier molecular weight. These mechanistic findings on the formation and disruption of hydrogen bonds in semicrystalline dispersions can be extended to amorphous dispersions and are of significant importance for preparation of solid dispersions with consistent and reproducible physicochemical properties.

Effect of Compression on the Molecular Arrangement of Itraconazole-Soluplus Solid Dispersions: Induction of Liquid Crystals or Exacerbation of Phase Separation?

Predensification and compression are unit operations imperative to the manufacture of tablets and capsules. Such stress-inducing steps can cause destabilization of solid dispersions which can alter their molecular arrangement and ultimately affect dissolution rate and bioavailability. In this study, itraconazole-Soluplus solid dispersions with 50% (w/w) drug loading prepared by hot-melt extrusion (HME) were investigated. Compression was performed at both pharmaceutically relevant and extreme compression pressures and dwell times. The starting materials, powder, and compressed solid dispersions were analyzed using modulated differential scanning calorimetry (MDSC), X-ray diffraction (XRD), small- and wide-angle X-ray scattering (SWAXS), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), and broadband dielectric spectroscopy (BDS). MDSC analysis revealed that compression promotes phase separation of solid dispersions as indicated by an increase in glass transition width, occurrence of a peak in the nonreversing heat flow signal, and an increase in the net heat of fusion indicating crystallinity in the systems. SWAXS analysis ruled out the presence of mesophases. BDS measurements elucidated an increase in the Soluplus-rich regions of the solid dispersion upon compression. FTIR indicated changes in the spatiotemporal architecture of the solid dispersions mediated via disruption in hydrogen bonding and ultimately altered dynamics. These changes can have significant consequences on the final stability and performance of the solid dispersions.

Compression Effects on the Phase Behaviour of Miconazole-Poly (1-Vinylpyrrolidone-Co-Vinyl Acetate) Solid Dispersions-Role of Pressure, Dwell Time, and Preparation Method.

Compression of miconazole-poly (1-vinylpyrrolidone-co-vinyl acetate) (PVPVA64) solid dispersions prepared by spray drying and hot-melt extrusion was performed to gain insights into effect of compression pressure, dwell time, and preparation method on compression-dependent phase behavior. The solid dispersions prepared by spray drying were initially phase-separated showing two glass transition temperature (Tg), whereas the extruded samples showed one single Tg indicating better mixing. Compression caused mixing of spray-dried solid dispersions at high compression pressures and especially high dwell times. The extruded systems showed no statistically significant differences. However, physical mixtures made up from extruded samples containing 20% and 40% of active pharmaceutical ingredient underwent mixing upon compression. Coincidence Doppler measurements were performed to quantify the free volume of PVPVA64 which is a major contributor to the free volume in the solid dispersion matrix. A small but significant difference was found between the open free volume of the pure polymer subjected to varied manufacturing processes. Compression-induced plastic deformation and plastic flow enhances molecular mobility leading to mixing of different domains in solid dispersions. Different manufacturing methods may result in products with similar free volume, thereby showing similar molecular mobility.

Crystallization Kinetics of Indomethacin/Polyethylene Glycol Dispersions Containing High Drug Loadings.

The reproducibility and consistency of physicochemical properties and pharmaceutical performance are major concerns during preparation of solid dispersions. The crystallization kinetics of drug/polyethylene glycol solid dispersions, an important factor that is governed by the properties of both drug and polymer has not been adequately explored, especially in systems containing high drug loadings. In this paper, by using standard and modulated differential scanning calorimetry and X-ray powder diffraction, we describe the influence of drug loading on crystallization behavior of dispersions made up of indomethacin and polyethylene glycol 6000. Higher drug loading increases the amorphicity of the polymer and inhibits the crystallization of PEG. At 52% drug loading, polyethylene glycol was completely transformed to the amorphous state. To the best of our knowledge, this is the first detailed investigation of the solubilization effect of a low molecular weight drug on a semicrystalline polymer in their dispersions. In mixtures containing up to 55% indomethacin, the dispersions exhibited distinct glass transition events resulting from amorphous-amorphous phase separation which generates polymer-rich and drug-rich domains upon the solidification of supercooled polyethylene glycol, whereas samples containing at least 60% drug showed a single amorphous phase during the period in which crystallization normally occurs. The current study demonstrates a wide range in physicochemical properties of drug/polyethylene glycol solid dispersions as a result of the complex nature in crystallization of this system, which should be taken into account during preparation and storage.

Revival of pure titanium for dynamically loaded porous implants using additive manufacturing.

Additive manufacturing techniques are getting more and more established as reliable methods for producing porous metal implants thanks to the almost full geometrical and mechanical control of the designed porous biomaterial. Today, Ti6Al4V ELI is still the most widely used material for porous implants, and none or little interest goes to pure titanium for use in orthopedic or load-bearing implants. Given the special mechanical behavior of cellular structures and the material properties inherent to the additive manufacturing of metals, the aim of this study is to investigate the properties of selective laser melted pure unalloyed titanium porous structures. Therefore, the static and dynamic compressive properties of pure titanium structures are determined and compared to previously reported results for identical structures made from Ti6Al4V ELI and tantalum. The results show that porous Ti6Al4V ELI still remains the strongest material for statically loaded applications, whereas pure titanium has a mechanical behavior similar to tantalum and is the material of choice for cyclically loaded porous implants. These findings are considered to be important for future implant developments since it announces a potential revival of the use of pure titanium for additively manufactured porous implants.

Factors influencing the elastic moduli, reversible strains and hysteresis loops in martensitic Ti-Nb alloys.

While the current research focus in the search for biocompatible low-modulus alloys is set on ß-type Ti-based materials, the potential of fully martensitic Ti-based alloys remains largely unexplored. In this work, the influence of composition and pre-straining on the elastic properties of martensitic binary Ti-Nb alloys was studied. Additionally, the phase formation was compared in the as-cast versus the quenched state. The elastic moduli and hardness of the studied martensitic alloys are at a minimum of 16wt.% Nb and peak between 23.5 and 28.5wt.% Nb. The uniaxial deformation behavior of the alloys used is characterized by the absence of distinct yield points. Monotonic and cyclic (hysteretic) loading-unloading experiments were used to study the influence of Nb-content and pre-straining on the elastic moduli. Such experiments were also utilized to assess the recoverable elastic and anelastic deformations as well as hysteretic energy losses. Particular attention has been paid to the separation of non-linear elastic from anelastic strains, which govern the stress and strain limits to which a material can be loaded without deforming it plastically. It is shown that slight pre-straining of martensitic Ti-Nb alloys can lead to considerable reductions in their elastic moduli as well as increases in their total reversible strains.

Additively manufactured porous tantalum implants.

The medical device industry's interest in open porous, metallic biomaterials has increased in response to additive manufacturing techniques enabling the production of complex shapes that cannot be produced with conventional techniques. Tantalum is an important metal for medical devices because of its good biocompatibility. In this study selective laser melting technology was used for the first time to manufacture highly porous pure tantalum implants with fully interconnected open pores. The architecture of the porous structure in combination with the material properties of tantalum result in mechanical properties close to those of human bone and allow for bone ingrowth. The bone regeneration performance of the porous tantalum was evaluated in vivo using an orthotopic load-bearing bone defect model in the rat femur. After 12 weeks, substantial bone ingrowth, good quality of the regenerated bone and a strong, functional implant-bone interface connection were observed. Compared to identical porous Ti-6Al-4V structures, laser-melted tantalum shows excellent osteoconductive properties, has a higher normalized fatigue strength and allows for more plastic deformation due to its high ductility. It is therefore concluded that this is a first step towards a new generation of open porous tantalum implants manufactured using selective laser melting.

A new twist in the old story-can compression induce mixing of phase separated solid dispersions? A case study of spray-dried miconazole-PVP VA64 solid dispersions.

PURPOSE: The phase response of Miconazole-PVP VA64 solid dispersions upon compression was investigated. This would allow understanding the phase behavior of these solid dispersions upon application of a different kind of stress (other than humidity and temperature) and ultimately lead to mechanistic perception of the phase changes taking place. METHODS: Miconazole and PVP VA64 were chosen as a model drug and polymer, respectively and solid dispersions were prepared by spray drying. Dried solid dispersions were compressed using different compression pressure but constant dwell time. MDSC and XRPD were used to characterize and study the effect of compression on the system. RESULTS: The solid dispersions showed a single Tg till 20% drug loading after which two Tg's were observed. Application of compression to the phase separated 30 and 40% compositions induced mixing resulting in only a single Tg. This reduction in number of Tg's upon compression is a result of mixing which can be attributed to polymer flow resulting in reduction of the domain size of different phases in the solid dispersions. CONCLUSIONS: Application of compression can influence the phase behavior of Miconazole-PVP VA64 solid dispersions. This observation may have drastic impact on the formulation development approach for solid dispersions to be administered as tablets.

Preventing release in the acidic environment of the stomach via occlusion in ordered mesoporous silica enhances the absorption of poorly soluble weakly acidic drugs.

This study aimed to assess the pharmaceutical performance of formulations consisting of either indomethacin or glibenclamide and the ordered mesoporous silica material SBA-15. Both compounds were loaded on SBA-15 via solvent impregnation. Adsorption in the SBA-15 mesopores was confirmed using nitrogen physisorption. Differential scanning calorimetry results suggested that both compounds were dispersed monomolecularly onto the SBA-15 surface. In in vitro experiments simulating the gastric-to-intestinal transition, the release of both compounds from SBA-15 remained under 1% in simulated gastric fluid (SGF, pH 1.2), whereas both drugs were completely released within 10 min after transfer to fasted state simulated intestinal fluid (FaSSIF, pH 6.5). As both drugs exhibited very rapid precipitation from the supersaturated state in SGF, the preferential release in FaSSIF--where conditions are more favourable by virtue of either much higher solubility (indomethacin) or more stable supersaturation (glibenclamide)--was considered crucial towards achieving optimal absorption. This hypothesis was confirmed by an in vivo study, where the extent of absorption of a glibenclamide-SBA-15 formulation was found to be more than fourfold higher than that of the commercial glibenclamide product Daonil®.

The conflict between in vitro release studies in human biorelevant media and the in vivo exposure in rats of the lipophilic compound fenofibrate.

The performance of four different lipid-based (Tween 80-Captex 200P, Tween 80-Capmul MCM, Tween 80-Caprol 3GO and Tween 80-soybean oil) and one commercially available micronized formulation (Lipanthyl Micronized(®)) of the lipophilic compound fenofibrate was compared in vitro in various biorelevant media and in vivo in rats. In simulated gastric fluid without pepsin (SGF(sp)) and fasted state simulated intestinal fluid (FaSSIF), only Tween 80-Captex 200P system resulted in a stable fenofibrate concentration, but no supersaturation was obtained. The other three lipid based systems created fenofibrate supersaturation; however they did not maintain it. In fed state simulated intestinal fluid (FeSSIF), all lipid-based formulations resulted in complete dissolution of fenofibrate during the experiment, which represented a supersaturated state for Tween 80-Capmul MCM and Tween 80-Caprol 3GO systems. In both FaSSIF and FeSSIF, all lipid-based formulations yielded a higher fenofibrate concentration than the micronized formulation. Contrary to the in vitro results, no significant difference in the in vivo performance was observed among the four tested lipid-based formulations both in the fasted and the fed states. The in vivo performance of all lipid-based formulations was better than that of Lipanthyl Micronized(®), in the fasted as well as in the fed state. The fact that for the lipid based systems the in vitro differences in pharmaceutical performance were not translated into in vivo differences can be attributed to the continuous excretion of bile in the gastrointestinal tract of rats, causing enhanced solubilizing capacity for lipophilic drugs. This study clearly points to the conflicting situation that might arise during the preclinical phase of the development of lipid based formulations of lipophilic drugs as the performance of such systems is very often evaluated by both in vitro release studies in human biorelevant media as well as in vivo studies in rats. Care must be taken to select a relevant animal model.

Stability of Ni in nitinol oxide surfaces.

The stability of Ni in titanium oxide surface layers on nitinol wires known to release certain amounts of Ni was investigated by first principles density functional theory and transmission electron microscopy. The oxides were identified as a combination of TiO and TiO(2) depending on the thickness of the layer. The calculations indicate that free Ni atoms can exist in TiO at ambient temperature while Ni particles form in TiO(2), which was confirmed by the transmission electron microscopy observations. The results are discussed with respect to surface stability and Ni release due to free Ni atoms and Ni particles.

Enhanced absorption of the poorly soluble drug fenofibrate by tuning its release rate from ordered mesoporous silica.

The aim of the present study was to evaluate the effect of release rate from ordered mesoporous silica materials on the rate and extent of absorption of the poorly soluble drug fenofibrate. Three ordered mesoporous silica materials with different pore diameter (7.3 nm, 4.4 nm and 2.7 nm) were synthesized and loaded with fenofibrate via impregnation. Release experiments were conducted under sink conditions and under supersaturating conditions in biorelevant media, simulating the fasted and the fed state. Subsequently, all silica-based formulations were evaluated in vivo (rat model). The release experiments under sink conditions indicated a clear increase in release rate with increasing pore size. However, under supersaturating conditions (FaSSIF), the, pharmaceutical performance (in terms of both the degree and duration of supersaturation), increased with decreasing pore size. The same trend was observed in vivo (fasted state): the area under the plasma concentration-time profile amounted to 102 ± 34 µMh, 86 ± 19 µMh and 20 ± 13 µMh for the materials with pore diameter of 2.7 nm, 4.4 nm and 7.3 nm, respectively. The results of this, study demonstrate that a decrease in drug release rate - and thus, a decrease of the rate at which supersaturation is created - is beneficial to the absorption of fenofibrate.

Comparison of the complexation between methylprednisolone and different cyclodextrins in solution by 1H-NMR and molecular modeling studies.

Complexation in solution between methylprednisolone and three different cyclodextrins [2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD), gamma-cyclodextrin (gamma-CD), and 2-hydroxypropyl-gamma-cyclodextrin (HP-gamma-CD)] was studied using phase solubility analysis, one and two-dimensional (1)H-NMR and molecular modeling. Estimates of the complex formation constant (K(1:1)) show that the tendency of methylprednisolone to complex with CDs follows the order: gamma-CD > HP-gamma-CD > HP-beta-CD. The large variation of chemical shifts from protons located around the interior of the hydrophobic cavity (H-3', H-5', and H-6') coupled with minimal variation of shifts from protons located on the outer sphere of gamma-CD (H-1', H-2', and H-4') provided clear evidence of inclusion complexation. The molecular modeling study, indicated inclusion complexation between methylprednisolone and gamma-CD and HP-gamma-CD by entrance of the A and B rings of methylprednisolone into the CD cavity from its bigger rim. For the methylprednisolone: HP-beta-CD complex, the molecular modeling study could not be carried out; hence, two possibilities of complex formation are proposed: (1) methylprednisolone enters HP-beta-CD from the wider rim by its D and C ring, (2) the A and B ring of methylprednisolone enters deeper in to the CD cavity so that a part of the A ring of steroidal structure is outside of the cavity.

Theoretical and experimental investigation on the solid solubility and miscibility of naproxen in poly(vinylpyrrolidone).

The objective of the present study was to determine the solid state solubility and miscibility of naproxen in poly(vinylpyrrolidone) (PVP) and the mutual interaction using the standard thermodynamic models and thermal analysis. Solid dispersions were prepared by spray drying several compositions of naproxen and PVP with different molecular weights, viz., PVP K 12, PVP K 25 and PVP K 90, and analyzed using modulated differential scanning calorimetry (mDSC). The kinetic miscibility limit in terms of a single mixed phase glass transition temperature was found to be relatively similar for the dispersions containing PVP with different chain lengths (>or=50% w/w drug in PVP). But the systems with different PVP followed diverse patterns of composition dependent mixed phase glass transition temperature as well as the degree of plasticization by water. The crystalline solid solubility values of naproxen in PVP estimated by using its solubility data in n-methylpyrrolidone, a low molecular weight analogue of PVP, were 6.42, 5.85 and 5.81% w/w of drug in PVP K 12, PVP K 25 and PVP K 90 respectively. The values estimated for corresponding amorphous solubility showed no marked difference. The remarkable difference between thermodynamic solubility/miscibility and kinetic miscibility implied that naproxen was highly supersaturated in the PVP solid dispersions and only stabilized kinetically. The negative value of the drug-polymer interaction parameter (-0.36) signified the systems to be favorably mixing. The melting point depression data of naproxen in PVP pointed to the composition dependence and chain length effect on the interaction. The moisture sorption by the physical mixtures not only provided the composition dependent interaction parameter but also conferred an estimate of composition dependent miscibility of naproxen in PVP in the presence of water.

Combined use of ordered mesoporous silica and precipitation inhibitors for improved oral absorption of the poorly soluble weak base itraconazole.

The release of poorly soluble drugs from mesoporous silicates is often associated with the generation of supersaturation, which implies the risk of drug precipitation and reduced availability for absorption. The aim of this study was to enhance the in vivo performance of an ordered mesoporous silicate (SBA-15) by combining it with the precipitation inhibitors hydroxypropylmethylcellulose (HPMC) and hydroxypropylmethylcellulose acetate succinate (HPMCAS). The poorly soluble weak base itraconazole was used as a model compound. Formulations were prepared by physically blending itraconazole-loaded SBA-15 with the precipitation inhibitors. In vitro release experiments implementing a transfer from simulated gastric fluid to simulated intestinal fluid were used to evaluate the pharmaceutical performance. Subsequently, the formulations were evaluated in vivo in rats. When high enough amounts of HPMC were co-administered with itraconazole-loaded SBA-15 (itraconazole:SBA-15:HPMC 1:4:6), the extent of absorption was increased by more than 60% when compared to SBA-15 without precipitation inhibitors (AUC 14,937+/-1617 versus 8987+/-2726nMh). HPMCAS was found ineffective in enhancing the in vivo performance of SBA-15 due to its insolubility in the stomach. The results of this study demonstrate that the pharmaceutical performance of SBA-15 is enhanced through addition of an appropriate precipitation inhibitor.