Solid-state Characterization Techniques Research Articles

Application of Casein Micelles for Targeting Huntington's Disease in Experimental Zebrafish Model.

Huntington's disease (HD) is an incorrigible neuropsychiatric disorder with reduced cognition and motor abnormalities. Piperine (PIP) is an alkaloid with antioxidant, anti-inflammatory, and neuroprotective activities; however, poor therapeutic efficacy limits its further use. The current study focuses on the enhanced therapeutic potential of PIP@CM against an experimental zebrafish model of HD. PIP@CM was fabricated using spray drying technology, followed by solid-state investigations. We performed in vitro release and in vitro antioxidant activity (DPPH assay) of PIP and PIP@CMs. In addition, in vivo studies were conducted on zebrafish using 3-nitropropionic acid (3-NPA) (60mg/kg) as a neurotoxin and treated with PIP (5mg/kg) and PIP@CM (25mg/kg equivalent to 5mg/kg PIP). After dosing, various in vivo studies (behavioral, biochemical, and histological) were conducted. The solid-state characterization techniques revealed the loss of crystallinity after micelles formation. In vitro release and antioxidant assays showed higher release and enhanced activity of PIP@CM. In vivo studies revealed that 3-NPA administration causes HD, as evidenced by the results of open field test (OFT) and novel tank diving test (NTD) tests. Moreover, 3-NPA causes an increase in oxidative stress, as confirmed by biochemical and histopathological studies. PIP@CM treatment significantly improved behavioral performance in OFT and NTD tests and reduced oxidative stress markers as compared to pure PIP and untreated HD model.

Design, development and characterization of the Apremilast and Indomethacin coamorphous system

Our main aim in the present investigation, preparation of a drug-drug coamorphous system (CAM) of Apremilast (APR) and Indomethacin (INDO) to improve physiochemical properties, solubility and stability. Various solid-state characterization techniques were used to characterize the prepared APR-INDO CAM system. Single Tg in DSC, hallow pattern in PXRD, and absence of birefringence in PLM indicate the formation of the CAM system between APR and INDO. The molecular level interaction in the CAM system was studied using ATR-FTIR and 1H NMR. The molecular modeling-based analysis was performed to understand intermolecular interactions in the CAM system. Solubility and dissolution studies were carried out to investigate the benefits of the CAM system over its crystalline and amorphous forms of APR and INDO. The CAM system was stable for five months under 40 ± 2 °C and 75 ± 5 % RH. In the permeation study, CAM system had an 8.19-fold higher flux for APR and a 5.83-fold higher flux for INDO compared to crystalline APR and INDO, respectively. The APR-INDO CAM system showed anti-psoriatic and anti-melanogenic activity from the molecular docking results. As a result, we determined that the developed CAM-based supersaturated system has improved physicochemical properties and physical stability.

Cocrystals Enhance Biopharmaceutical and Antimicrobial Properties of Norfloxacin.

A solvate cocrystal of the antimicrobial norfloxacin (NFX) was formed by using isonicotinamide (INA) as a coformer with the solvent evaporation technique. The cocrystal formation was confirmed by performing solid-state characterization techniques. We evaluated the dissolution under supersaturated conditions and also the solubility at the vertex of triphasic domain of cocrystal and NFX in both water and Fasted-State Simulated Intestinal Fluid (FaSSIF). The antimicrobial activity was evaluated using the microdilution technique. The cocrystal showed 1.8 times higher dissolution than NFX in water at 60 min and 1.3 times higher in FaSSIF at 180 min in the kinetic study. The cocrystal also had an increase in solubility of 8.38 times in water and 6.41 times in FaSSIF. The biopharmaceutical properties of NFX with cocrystallization improved antimicrobial action, as shown in the results of minimum inhibitory concentration (MIC) and inhibitory concentrations of 50% (IC50%) and 90% (IC90%). This paper presents, for the first time, a more in-depth analysis of the cocrystal of NFX-INA concerning its dissolution, solubility, and antimicrobial activity. In all these criteria, the cocrystal obtained better results compared to the pure drug.

Human lactoferrin-clay mineral nanohybrids as emerging green biomaterials: A physicochemical characterization

Herein montmorillonite and halloysite have been exploited to prepare advanced lactoferrin-loaded nanohybrid biomaterials for potential biomedical applications. Nanohybrids were prepared following two methodologies: a traditional procedure which induces spontaneous drug-clay interactions to take place in aqueous environment and by spray drying, as alternative and preferred industrial technique for protein processing. Structural assembly of the obtained nanohybrids was assessed by solid state characterization techniques and determination of their surface charge properties. Full microscopy studies, including scanning electron microscopy and ultra-high resolution transmission electron microscopy coupled with EDS were also carried out. Cytotoxicity assays were performed to assess biocompatibility of nanohybrids towards human fibroblast cell cultures. Results showed that both intercalation-solution and spray drying procedures led to the effective formation of nanohybrids structures, with greater extent of peptide-clay mineral interactions in those obtained by spray drying. All the samples exhibited cell viability % higher than 80%, with best results for halloysite coupled with spray drying technique.

Reactive plasma sputtering deposition of polycrystalline GaN thin films on silicon substrates at room temperature

We report on the successful growth of polycrystalline GaN thin films on Si (100) substrates at room temperature (without intentional heating) using radiofrequency reactive magnetron sputtering. We use Ar and N2 as the main sputtering and N-atom precursor gas sources, respectively, and a gallium cathode as the Ga-atom source. We focus here on studying the effect of working pressure, as it is found to be the parameter that plays the most influential role on the crystalline quality of the thin films in the investigated range (20–95 mTorr). The morphology, microstructure, and composition profile of the GaN thin films are analyzed using a set of ex situ solid-state characterization techniques. This study reveals that for process pressures below 50 mTorr, the resulting films possess an amorphous nature, while for process pressures above that they become polycrystalline. Most of the crystalline films are found to be nanostructured with grain sizes typically ranging from 10 to 30 nm in size. The highest growth rate of ∼ 2.9 Å/s is obtained for the deposition carried out at 50 mTorr. At this pressure, the films exhibit the best crystallinity with a dominant wurtzite hexagonal structure. The elemental distribution of Ga and N throughout the growth profile is uniform with a sharp interface at the substrate, demonstrating one of the interests in working at low temperatures to avoid melt-back etching, a destructive reaction between gallium and silicon, that usually takes place at high temperatures.

Characterization and Molecular Modelling of Non-Antibiotic Nanohybrids for Wound Healing Purposes.

The healing process of chronic wounds continues to be a current clinical challenge, worsened by the risk of microbial infections and bacterial resistance to the most frequent antibiotics. In this work, non-antibiotic nanohybrids based on chlorhexidine dihydrochloride and clay minerals have been developed in order to design advanced therapeutic systems aimed to enhance wound healing in chronic lesions. To prepare the nanohybrids, two methodologies have been compared: the intercalation solution procedure and the spray-drying technique, the latter as a one-step process able to reduce preparation times. Nanohybrids were then fully studied by solid state characterization techniques. Computational calculations were also performed to assess the interactions between the drug and the clays at the molecular level. In vitro human fibroblast biocompatibility and antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa were assessed to check biocompatibility and potential microbicidal effects of the obtained nanomaterials. The results demonstrated the effective organic/inorganic character of the nanohybrids with homogeneous drug distribution into the clayey structures, which had been confirmed by classical mechanics calculations. Good biocompatibility and microbicidal effects were also observed, especially for the spray-dried nanohybrids. It was suggested that it could be due to a greater contact area with target cells and bacterial suspensions.

Introduction to Pharmaceutical Co-amorphous Systems Using a Green Co-milling Technique.

The concept of co-amorphous systems is introduced in an integrated laboratory experiment, designed for advanced chemistry students, using solvent-free, environmentally friendly mechanochemistry. The dual-drug naproxen-cimetidine co-amorphous system (NPX-CIM) is investigated as an example of the emergent field of medicinal mechanochemistry. Students are trained in solid-state characterization techniques including X-ray powder diffraction, Fourier-transform infrared spectroscopy, and thermal analysis by differential scanning calorimetry. This lab experiment also provides an opportunity to discuss the relevance of different solid forms of pharmaceutics, emphasizing particular properties of disordered materials. This experiment can easily fit the curriculum of any Chemistry or Pharmacy master level degree in courses dealing with instrumental analysis, solid state chemistry, or green chemistry, for classes of 6 to 18 students, in a 5-h lab session. Suggestions to adapt it to the use of a single characterization technique are provided.

Synthesis, physicochemical characterization of ZnO and α-MoO3/ZnO heterostructures and their photocatalytic activity for the methylene blue (MB) dye degradation

This research fabricated a hybrid of α-MoO3/ZnO heterostructures via ultrasonic-assisted hydrothermal synthesis and evaluated its photocatalytic activity by degradation of Methylene Blue dye (MB) under visible light irradiations. The physicochemical properties of the heterostructure were characterized using several solid-state characterization techniques. Which indicated that with the addition of α-MoO3, there is a change in morphology from ZnO hexagonal to anorthic nanorods, then gradual to a rod like shape. The α-MoO3/ZnO in the ratio of 2:1 (MZ-21) exhibited a faster MB degradation rate of 0.411 min−1, which is three times faster than that of the ZnO nanoparticle. Various parameters, such as catalyst dosage, initial MB concentration, and pH, were varied to determine the optimum condition for the MB degradation. The photodegradation percentage for α-MoO3/ZnO (MZ21) of 99% is higher than that of ZnO (53%), suggesting that the addition of MoO3 to the hybrids enhanced the degradation efficiency. The photodegradation process follows pseudo-first-order kinetics. The radical scavenger's influence on MB degradation provides insights into the MB degradation mechanism. The dominant species that contributed the highest effect toward MB degradation were the OH radical, followed by .O2− radical species, signifying that they are the species largely responsible for the attack of MB dye molecules. The reusability studies revealed that the hybrid photocatalyst could be repeatedly used up to four times without severe deactivation, indicating the excellent reliability of the hybrid.

Physicochemical aspects and comparative analysis of Voxelotor and its salt and cocrystal

Voxelotor (VOX) is a BCS (Biopharmaceutical classification system) Class II drug (poor solubility and high permeability) and is issued for the treatment of sickle cell disease. The VOX free base, VOX-HCl salt and succinic acid (VOX-SC) cocrystals were crystallized and their crystal structures were determined by the Single Crystal X-ray diffraction technique (SCXRD). Further, solid-state characterization techniques such as Nuclear magnetic resonance (NMR) and Fourier transform Infra-red spectroscopy(FT-IR) were carried out. In all three structures, the VOX molecules exhibit an intramolecular S(6)-motif formed by O-H⋅⋅⋅O hydrogen bond. In VOX free base, only weak C-H⋅⋅⋅O, C-H⋅⋅⋅π and π⋅⋅⋅π interactions were observed, which lead to the formation of two-dimensional hydrogen-bonded sheets. In VOX-HCl salt, N-H⋅⋅⋅Cl hydrogen bond along with the C-H⋅⋅⋅π and π⋅⋅⋅π interactions form a discrete dimeric unit. In VOX-SC cocrystal, the VOX and SC molecules were connected through N-H⋅⋅⋅O, O-H⋅⋅⋅O and C-H⋅⋅⋅O interactions and generate a two-dimensional hydrogen-bonded network. Thermal analysis of VOX-SC cocrystal resulted in melting points intermediate to that of API and coformer, while VOX-HCl salt yielded a higher melting point than the parent VOX. Both VOX-HCl and VOX-SC cocrystal showed better solubility compared to VOX free base. The stress analysis revealed that in VOX-SC cocrystal, no physical transformations of solid-phase was observed. Enhancement in solubility and stability was observed in the obtained VOX-SC cocrystal in comparison to the free base.

Electrospun MnCo2O4/carbon-nanofibers as oxygen electrode for alkaline zinc-air batteries

A MnCo2O4 catalyst supported on nitrogen-doped carbon nanofibers (CNF) obtained in a single-step electrospinning process is presented. MnCo2O4/CNF is investigated as bifunctional electrode for the electrocatalysis of oxygen in metal-air batteries. Crystallographic structure, morphology, and surface properties are analyzed using solid-state characterization techniques that reveal the presence of a 20 nm-particle-sized spinel and a large amount of oxidized metal species (Mn4+ and Co3+). These features are correlated with the electrochemical behavior for the oxygen reduction (ORR) and oxygen evolution (OER), showing good performances in particular for the OER compared with IrO2, benchmark catalyst for this reaction. Results revealed a synergistic effect of the catalytically active nitrogen-doped carbon nanofiber and the manganese and cobalt active species from the spinel, being responsible for the remarkable reversibility of this catalyst (ΔE = 799 mV), outperforming most of the previous works in the literature on this type of manganese/cobalt-based spinel materials. A preliminary test of an alkaline Zn-air battery equipped with this catalyst at the oxygen (positive) electrode confirms proper activity and stability during cycling operations typical of these rechargeable devices. Besides, the spinel-nanofiber-based catalyst has been produced by an easily-scalable electrospinning process, representing an advance of the current technology on positive electrodes for metal-air batteries. The curated synthesis of our MnCo-N-CNF spinel is fundamental to obtaining a catalyst with a high intrinsic catalytic activity (determined by rotating disk electrode) and an appropriate performance in a relevant environment (both gas diffusion electrode and Zn-air battery).

Complementarity of mDSC, DMA, and DRS Techniques in the Study of Tg and Sub-Tg Transitions in Amorphous Solids: PVPVA, Indomethacin, and Amorphous Solid Dispersions Based on Indomethacin/PVPVA.

Recently, glasses, a subset of amorphous solids, have gained attention in various fields, such as polymer chemistry, optical fibers, and pharmaceuticals. One of their characteristic features, the glass transition temperature (Tg) which is absent in 100% crystalline materials, influences several material properties, such as free volume, enthalpy, viscosity, thermodynamic transitions, molecular motions, physical stability, mechanical properties, etc. In addition to Tg, there may be several other temperature-dependent transitions known as sub-Tg transitions (or β-, γ-, and δ-relaxations) which are identified by specific analytical techniques. The study of Tg and sub-Tg transitions occurring in amorphous solids has gained much attention because of its importance in understanding molecular kinetics, and it requires the combination of conventional and novel characterization techniques. In the present study, three different analytical techniques [modulated differential scanning calorimetry (mDSC), dynamic mechanical analysis (DMA), and dielectric relaxation spectroscopy (DRS)] were used to perform comprehensive qualitative/quantitative characterization of molecular relaxations, miscibility, and molecular interactions present in an amorphous polymer (PVPVA), a model drug (indomethacin, IND), and IND/PVPVA-based amorphous solid dispersions (ASDs). This is the first ever reported DMA study on PVPVA in its powder form, which avoids the contribution of solvent to the mechanical properties when a self-standing polymer film is used. A good correlation between the techniques in determining the Tg value of PVPVA, IND, and IND/PVPVA-based ASDs is established, and the negligible difference (within 10 °C) is attributed to the different material properties assessed in each technique. However, the overall Tg behavior, the decrease in Tg with increase in drug loading in ASDs, is universally observed in all the above-mentioned techniques, which reveals their complementarity. DMA and DRS techniques are used to study the different sub-Tg transitions present in PVPVA, amorphous IND, and IND/PVPVA-based ASDs because these transitions are normally too weak or too broad for mDSC to detect. For IND/PVPVA-based ASDs, both techniques show a shift of sub-Tg transitions (or secondary relaxation peaks) toward the high-temperature region from -140 to -45 °C. Thus, this paper outlines the usage of different solid-state characterization techniques in understanding the different molecular dynamics present in the polymer, drug, and their interactions in ASDs with the integrated information obtained from individual techniques.

Detecting Crystallinity Using Terahertz Spectroscopy in 3D Printed Amorphous Solid Dispersions

This study demonstrates the applicability of terahertz time-domain spectroscopy (THz-TDS) in evaluating the solid-state of the drug in selective laser sintering-based 3D printed dosage forms. Selective laser sintering is a powder bed-based 3D printing platform, which has recently demonstrated applicability in manufacturing amorphous solid dispersions (ASDs) through a layer-by-layer fusion process. When formulating ASDs, it is critical to confirm the final solid state of the drug as residual crystallinity can alter the performance of the formulation. Moreover, SLS 3D printing does not involve the mixing of the components during the process, which can lead to partially amorphous systems causing reproducibility and storage stability problems along with possibilities of unwanted polymorphism. In this study, a previously investigated SLS 3D printed ASD was characterized using THz-TDS and compared with traditionally used solid-state characterization techniques, including differential scanning calorimetry (DSC) and powder X-ray diffractometry (pXRD). THz-TDS provided deeper insights into the solid state of the dosage forms and their properties. Moreover, THz-TDS was able to detect residual crystallinity in granules prepared using twin-screw granulation for the 3D printing process, which was undetectable by the DSC and XRD. THz-TDS can prove to be a useful tool in gaining deeper insights into the solid-state properties and further aid in predicting the stability of amorphous solid dispersions.

Photo-Fenton degradation of sulfamethoxazole using MIL-53(Fe) under UVA LED irradiation and natural sunlight

The MOF MIL-53(Fe) was synthesized, activated and evaluated in photo-Fenton reactions assisted by UVA LED irradiation and natural sunlight using the antibiotic sulfamethoxazole (SMX) as a degradation target molecule. A 23 full factorial design of experiments was carried out in order to determine the effects of several parameters' influence on the degradation of SMX. The effect of different operational parameters such as pH, hydrogen peroxide and catalyst concentration was analyzed, and tests of reuse of the catalyst were performed. Likewise, the dissolved organic carbon (DOC), iron leached from the MIL-53(Fe) structure and H2O2 consumption were monitored, and the degradation products of the reaction were identified. The use of MIL-53(Fe) as a heterogeneous photo-Fenton catalyst using natural sunlight as an irradiation source allowed the degradation of 96% of the SMX in solution in just 120 min under near-neutral conditions. Likewise, removal of 30% of the DOC in solution was achieved, being the leached iron concentration less than 0.20 mg L−1, a value within the quality standard of water intended for human consumption imposed by the European Union (Directive 98/83/CE). Efficiency and stability after multiple cycles postulate the MOF MIL-53(Fe) as a potential heterogeneous catalyst to be considered in the development of alternative water purification systems based on the photo-Fenton process. An appropriate combination of solid-state characterization and chemical analysis techniques were applied, including PXRD, DRS, ZP, SEM, FTIR, HPLC-DAD, HPLC-MS/MS, and UV-Vis, which provided the experimental evidence that supports this study.

Understanding the Impact of Protein-Excipient Interactions on Physical Stability of Spray-Dried Protein Solids.

Mannitol, leucine, and trehalose have been widely used in spray-dried formulations, especially for inhalation formulations. The individual contribution of these excipients on protein physical stability in spray-dried solids was studied here using bovine serum albumin (BSA) as a model protein. The spray-dried solids were characterized with scanning electron microscopy, powder X-ray diffraction, and solid-state Fourier-transform infrared spectroscopy to analyze particle morphology, crystallinity, and secondary structure change, respectively. Advanced solid-state characterizations were conducted with solid-state hydrogen-deuterium exchange (ssHDX) and solid-state nuclear magnetic resonance (ssNMR) to explore protein conformation and molecular interactions in the context of the system physical stability. Trehalose remained amorphous after spray-drying and was miscible with BSA, forming hydrogen bonds to maintain protein conformation, whereby this system showed the least monomer loss in the stability study. As indicated by ssNMR, both crystalline and amorphous forms of mannitol existed in the spray-dried BSA-mannitol solids, which explained its partial stabilizing effect on BSA. Leucine showed the strongest crystallization tendency after spray-drying and did not provide a stabilizing effect due to substantial immiscibility and phase separation with BSA as a result of crystal formation. This work showed novel applications of ssNMR in examining protein conformation and protein-excipient interaction in dry formulations. Overall, our results demonstrate the pivotal role of advanced solid-state characterization techniques in understanding the physical stability of spray-dried protein solids.

Supersaturating drug delivery systems containing fixed-dose combination of two antihypertensive drugs: Formulation, in vitro evaluation and molecular metadynamics simulations

The purpose of this study was to associate the poorly water-soluble antihypertensive drugs candesartan cilexetil (CC) and hydrochlorothiazide (HCTZ) as fixed-dose combination, in the form of ternary Amorphous Solid Dispersions (ASD), using hydroxypropylmethylcellulose acetate succinate (HPMCAS) type M as polymeric carrier. The potential of the system to generate and to maintain supersaturation of both drugs was also evaluated. The ASDs were prepared by ball milling technique and solid-state characterization was performed by differential scanning calorimetry (DSC), Fourier transformed infrared spectroscopy (FTIR) and X-ray powder diffraction (XRPD). Interaction between drugs and polymer in solid-state was evaluated by molecular metadynamics simulations. In vitro supersaturation profiles were determined in biorelevant medium. Physicochemical stability of ASDs was also evaluated under different storage conditions. Amorphization of both drugs was confirmed by solid-state characterization techniques. Molecular metadynamics simulations indicated that CC has stronger interaction with HMPCAS than HCTZ. In vitro supersaturation studies have shown that ternary ASDs could generate and maintain supersaturation of both drugs in biorelevant medium. The polymer reduced the desupersaturation of both drugs. Ternary ASDs also showed physicochemical stability over a period of 90 days, demonstrating the potential of the polymer in reducing the drugs recrystallization over the time. Ternary ASDs of CC, HCTZ and HPMCAS can be considered a promising system to associate the drugs as fixed-dose combinations. Also, these systems generate and maintain supersaturation of both drugs in biorelevant medium, with great storage stability. HPMCAS M was a good carrier for reducing the desupersaturation of associated HCTZ and CC.

Design of Potential Pharmaceutical-Based Metal Complexes Derived from Cromolyn a Mast Cell Stabilizer.

A series of pharmaceutical metal complexes (pMCs) were produced and characterized using the mast cell stabilizer, cromolyn, and bioactive metal ions (Zn+2, Mg+2, and Ca+2). Three novel pMCs, Cromolyn-Zn, Cromolyn-Mg, and Cromolyn-Ca, were formed through reactions under controlled temperature and pH conditions. Additional characterization for these materials was performed employing a number of solid-state characterization techniques, such as thermogravimetric analysis (TGA), powder and single-crystal X-ray diffraction (PXRD and SCXRD), and scanning electron microscopy coupled with energy-dispersive spectroscopy (SEM-EDS). TGA demonstrated that these metal complexes showed an enhanced thermal stability due to the strong coordination with the ligand, cromolyn. PXRD data indicates a high degree of crystallinity as well as a unique packing arrangement for each pMCs. SEM analysis showed materials with well-defined morphologies, while EDS presented elemental evidence for the unique composition of each pMCs. The crystal structure for these materials was elucidated through SCXRD, and a variety of binding modes and packing motifs were found within each respective metal complex. Only two-dimensional (2D) structures were achieved under the conditions studied. These binding modalities might affect the activity and delivery of cromolyn sodium (CS). The stability of the metal complexes was assessed in phosphate-buffered saline (PBS, pH = 7.40) and fasted-state simulated gastric fluids (FaSSGF, pH = 1.60). Dissolution studies show high stability and slow degradation for the metal complexes, while a higher dissolution was observed for the drug compound in PBS. Neither CS nor the pMCs dissolved significantly in FaSSGF at 37 °C.

A novel amorphous solid dispersion based on drug-polymer complexation.

Rafoxanide (RAF) is a poorly water-soluble drug that forms a complex with povidone K25 (PVP) in a cosolvent system containing acetone and an alkaline aqueous medium. This study aims to investigate the impact of RAF-PVP complexation on in vitro and in vivo release of RAF. We prepared two RAF amorphous solid dispersions (ASDs) spray-dried from these two cosolvents. The first is a complexation-based spray-drying using a 70% 0.1N NaOH solution with 30% acetone. The second is a traditional spray-dried formulation containing 80% acetone and 20% ethanol. Evidence from multiple solid-state characterization techniques indicated that ASDs spray-dried using both methods were amorphous. However, RAF ASDs based on drug-polymer complexation in the feed solution demonstrated not only faster drug release during dissolution testing but also higher in vivo absorption in an animal model. The improved RAF release in the complexation-based ASD is due to (1) high energy state of RAF owing to the amorphous form, (2) high pH in the microenvironment due to the ionized state of RAF and residual sodium hydroxide, (3) increased apparent solubility of RAF results from RAF-PVP complexation in dissolution media and biological media, and (4) improved wettability.

Nanocrystals: Characterization Overview, Applications in Drug Delivery, and Their Toxicity Concerns

Nanocrystals (NCs) are the class of solid dosage forms which utilizes the concept of nanoscience together with crystal nature of drug to achieve advantages in terms of solubility, dissolution, and physicochemical properties. Comparing with other solid dosage forms, NC often comes with so many challenges in terms of physical stability as well as chemical stability during the manufacturing process and storage. Therefore, physicochemical properties of nanocrystals, toxic effect on the human body, and application in drug delivery through the various routes of administration are critical step formulation of NCs. There are various techniques involved to ensure solid state uniformity in the NCs and its impact on therapeutic performance. This review article emphasizes on various solid-state characterization techniques that are used to evaluate NCs, their toxicity, and pharmaceutical application. Further, NC-based marketed formulation is also discussed in this review.

Novel On-Demand 3-Dimensional (3-D) Printed Tablets Using Fill Density as an Effective Release-Controlling Tool.

This research demonstrates the use of fill density as an effective tool for controlling the drug release without changing the formulation composition. The merger of hot-melt extrusion (HME) with fused deposition modeling (FDM)-based 3-dimensional (3-D) printing processes over the last decade has directed pharmaceutical research towards the possibility of printing personalized medication. One key aspect of printing patient-specific dosage forms is controlling the release dynamics based on the patient’s needs. The purpose of this research was to understand the impact of fill density and interrelate it with the release of a poorly water-soluble, weakly acidic, active pharmaceutical ingredient (API) from a hydroxypropyl methylcellulose acetate succinate (HPMC-AS) matrix, both mathematically and experimentally. Amorphous solid dispersions (ASDs) of ibuprofen with three grades of AquaSolveTM HPMC-AS (HG, MG, and LG) were developed using an HME process and evaluated using solid-state characterization techniques. Differential scanning calorimetry (DSC), powder X-ray diffraction (pXRD), and polarized light microscopy (PLM) confirmed the amorphous state of the drug in both polymeric filaments and 3D printed tablets. The suitability of the manufactured filaments for FDM processes was investigated using texture analysis (TA) which showed robust mechanical properties of the developed filament compositions. Using FDM, tablets with different fill densities (20–80%) and identical dimensions were printed for each polymer. In vitro pH shift dissolution studies revealed that the fill density has a significant impact (F(11, 24) = 15,271.147, p < 0.0001) and a strong negative correlation (r > −0.99; p < 0.0001) with the release performance, where 20% infill demonstrated the fastest and most complete release, whereas 80% infill depicted a more controlled release. The results obtained from this research can be used to develop a robust formulation strategy to control the drug release from 3D printed dosage forms as a function of fill density.

Preparation and Characterization of Fenofibrate-Loaded PVP Electrospun Microfibrous Sheets.

Fenofibrate-loaded electrospun microfibrous sheets were prepared in an attempt to enhance the dissolution of the poorly soluble antihyperlipidemic agent and to improve its bioavailability. Physicochemical changes that appeared during the electrospinning process were monitored using a wide array of solid-state characterization techniques, including attenuated total reflectance Fourier-transformed infrared spectroscopy and positron annihilation lifetime spectroscopy, while fiber morphology was monitored via scanning electron microscopy. Dissolution studies carried out both in 0.025 M sodium dodecyl sulfate and in water revealed an immediate release of the active agent, with an approximately 40-fold release rate enhancement in water when compared to the micronized active agent. The dramatic increase in dissolution was attributed partially to the amorphous form of the originally crystalline active agent and the rapid disintegration of the electrospun microfibrous sheet due to its high surface area and porosity. The obtained results could pave the way for a formulation of the frequently used antihyperlipidemic agent with increased bioavailability.