Solid Form Research Articles

Interaction between peptide and solid lignin suggest mechanisms of abiotic covalent bond formation

The mechanisms behind the formation of soil organic matter (SOM) and associated nitrogen immobilization remain partially elusive, while ongoing research continues to shed light on carbon and nitrogen sequestration in the environment. Studies show that quinone-like structures within alkali-soluble humic extracts of SOM can bond covalently with nitrogen-containing molecules derived from proteinaceous organic matter. However, direct molecular evidence for this chemical bonding with lignin in the solid form and non-solvent-extracted SOM is lacking. Using gel-state 1H-15N heteronuclear single quantum coherence (HSQC) high-resolution magic angle spinning (HRMAS) nuclear magnetic resonance (NMR) spectroscopy, we demonstrate that a 15N-labeled peptide (glycine-glycine-glycine-arginine, GGGR), can covalently bind to solid, untreated, brown rotted wood as well as 1,2-naphthoquinone, a quinone-model molecule typically found in degraded lignin. The new peaks in both reactions represent a change in the environment surrounding the N-functional groups. Interaction of the 15N-labeled peptide with the model quinone produced NMR cross peaks that are similar to those of the solid lignin. This suggests that the quinone-like structures are the most likely functional groups to form covalent bonds with peptides in the degraded lignin. Both Michael addition and Schiff base formation is proposed when the peptide GGGR interacts with white oak lignin and 1,2-naphthoquinone. These processes are of considerable importance to N incorporation into SOM and offer insights into how proteinaceous molecules could potentially be preserved and sequestered through covalent bond formation.

High-performance thermoplastic nanocomposites for aerospace applications: A review of synthesis, production, and analysis

Thermoset polymers are cured under natural or synthetic created conditions and retain their solid form when exposed to heat. Unlike thermosets, thermoplastics melt when exposed to heat after production. Thermoplastics are preferred as raw materials because they can be easily shaped after production, have a high shelf life and are recyclable. In this regard, the prominence of high-performance engineering polymers in recent years has led to the preference of alternative polymers to thermosets. High-performance engineering thermoplastics include thermoplastics such as polyphenylene-sulfide (PPS), polyether-ether-ketone (PEEK), polyether-ketone-ketone (PEKK), polyphenylene-ether, polysulfone,polyoxadiazole, polyimide, polyether-amide, polyether-amide-imide, polynaphthalene, and polyamide-imide. These polymers exhibit application potential in aerospace, defense, automotive, marine, energy, and medical sectors. In challenging conditions such as high pressure, temperature, and corrosive environments, they possess high service temperatures, enhanced mechanical and physical properties, preferable chemical resistance as well as out-of-autoclave and rapid processing properties. In this review article, nanomaterial production methods (bottom-up and top-bottom) are mentioned. In the following sections, PPS, PEEK, and PEKK thermoplastics are explained, and carbon- and boron-based nano additives used in constructing nanocomposites are investigated. In the last section, PPS, PEKK, and PEEK polymer nanocomposites are investigated.

A Method for the Colorimetric Quantification of Sodium Lauryl Sulphate in Tablets: A Proof of Concept.

The deformulation stage of original drug products, which includes the quantification of critical excipients, is crucial for the successful development of generic drug products of solid dosage form. Sodium lauryl sulphate (SLS) belongs to the group of critical excipients due to its influence on the bioavailability of drugs, such as metformin. The purpose of this work is to carry out a feasibility study in order to develop a simple, economical, and robust analytical method for the quantification of SLS in metformin-containing tablets after their dissolution in water. Firstly, SLS is extracted with chloroform in acidic conditions, followed by the addition of methylene blue (MB) in order to form a SLS-MB ion pair, which is then measured photometrically at a wavelength of 651 nm. Additionally, interference from matrix components (excipients and APIs) was assessed, and it was found that metformin also forms a blue complex; therefore, this specific extraction method was developed. Other matrix components did not interfere with SLS determination. This method shows a well-estimated precision of 3.3% and accuracy of 5%, a calibration linearity of R2 = 0.99990, and a working range of 0.38 µg/mL to 10 µg/mL of SLS in water. The midpoint of the calibration graph corresponds to the concentration of SLS obtained by dissolving a single tablet in 1 L of water. This method seems appropriate for total SLS determination in tablets and can be applicable for deformulation.

Personalization of lipid-based oral dosage forms via filament-based 3D-printing

While filament-based 3D-printing (3DP) is the most utilized 3DP technology in the pharmaceutical field, it has not been demonstrated for processing of drug-loaded lipid-based formulations. This work exploits hexa-glycerol ester of palmitic acid (Pg6-C16-P) as an advanced lipid material, loaded with felodipine as a poorly soluble model drug, for fabricating novel oral solid dosage forms (OSDFs) via filament-based 3D-printing. After material melt-blending, the formulation was extruded using the liquid feeding approach to obtain a mechanically manageable, and hence 3D-printable, drug-loaded lipid filament. The fabrication of geometries with variable infill densities was demonstrated. The extent of infill density was found to significantly impact the optimal printing parameters required to achieve the desired shape. The solid-state analysis confirmed the amorphous state of felodipine after 3DP. The release rate of the drug was studied via in vitro dissolution test and showed to be tunable based on the tablet geometry. It was also possible to tailor the design of the dosage form to perform similarly to a commercial product. The formulation was evidenced as safe via in vitro toxicity studies with improved felodipine solubility. This study establishes filament-based 3DP as an alternative platform viable for fabricating advanced lipid-based OSDFs, and concurrently, promotes Pg6-C16-P as a promising and high performing 3DP lipid material for drug delivery.

Flow-Xl: a new facility for the analysis of crystallization in flow systems.

Characterization of crystallization processes in situ is of great importance to furthering knowledge of how nucleation and growth processes direct the assembly of organic and inorganic materials in solution and, critically, understanding the influence that these processes have on the final physico-chemical properties of the resulting solid form. With careful specification and design, as demonstrated here, it is now possible to bring combined X-ray diffraction and Raman spectroscopy, coupled to a range of fully integrated segmented and continuous flow platforms, to the laboratory environment for in situ data acquisition for timescales of the order of seconds. The facility used here (Flow-Xl) houses a diffractometer with a micro-focus Cu Kα rotating anode X-ray source and a 2D hybrid photon-counting detector, together with a Raman spectrometer with 532 and 785 nm lasers. An overview of the diffractometer and spectrometer setup is given, and current sample environments for flow crystallization are described. Commissioning experiments highlight the sensitivity of the two instruments for time-resolved in situ data collection of samples in flow. Finally, an example case study to monitor the batch crystallization of sodium sulfate from aqueous solution, by tracking both the solute and solution phase species as a function of time, highlights the applicability of such measurements in determining the kinetics associated with crystallization processes. This work illustrates that the Flow-Xl facility provides high-resolution time-resolved in situ structural phase information through diffraction data together with molecular-scale solution data through spectroscopy, which allows crystallization mechanisms and their associated kinetics to be analysed in a laboratory setting.

Biowaiver monograph for immediate-release solid oral dosage forms: Raltegravir potassium

The present monograph discusses the possibility of BCS-based biowaivers for immediate release pharmaceutical products containing raltegravir potassium, which is used to treat human immunodeficiency virus (HIV) infections. Raltegravir potassium can be assigned to BCS class II or IV since this compound has low solubility and uncertain permeability. Therefore, according to the ICH M9 guideline, it is not recommended to apply BCS-based biowaiver to approval of immediate release solid dosage forms of raltegravir potassium, either for new generic versions or when moderate to major changes in composition and/or the manufacturing method of the product are made.

Performing a physiologically relevant test for cladribine tablets

Introduction. The introduction of devices – analogues of GIS (hereinafter–- Gastro-intestinal simulator) is one of the current ways to develop in-vitro assessment of the quality of solid dosage forms. Testing on a physiologically relevant test device (hereinafter referred to as PRT) makes it possible to predict pharmacokinetic profiles due to more relevant conditions, including the use of biorelevant dissolution media, physiological volumes of the gastrointestinal tract, as well as transit between them.Aim. Conduct a study of cladribine tablets on a physiologically relevant tester in order to predict the behavior of the drug in the human gastrointestinal tract.Materials and methods. The objects of the study are "Mavenclad®, tablets, 10 mg" (series 2200754, expiration date until 04.2025, NERPHARMA, S.r.L., Italy) and "Cladribine, tablets, 10 mg" of domestic production with valid expiration date. During the study, the reagents necessary for the preparation of biorelevant dissolution media and quantitative determination by HPLC. Physiologically relevant test were carried out using an apparatus of our own production, consisting of a DT-6 dissolution tester (ERWEKA GmbH, Germany), a water bath equipped with a Thermomix WB-4 heating element (B. Braun, Germany), and peristaltic pumps (Kamoer, China). The quantitative content of released cladribine was assessed using a highly efficient liquid chromatograph "Khromatek-Kristall HPLC 2014" (ZAO SKB "Khromatek", Russia) using a validated method at a wavelength of 252 nm, analysis time – 7 min, column – Grace HPLC Column Platinum C18-EPS, 250 × 4.6 mm, 5 mm (Grace, USA), temperature – 35 °C, elution mode – isocratic (A : B 80 : 20), mobile phase A – 0.1 % H3PO4 solution, phase B – acetonitrile.Results and discussion. Profiles were obtained to assess the dynamics and degree of release of the studied drugs in various parts of the human gastrointestinal tract. Despite the expected degradation of cladribine in an acidic environment (pH1.2), under physiologically relevant conditions, the drug reached the third section (small intestine model) without degradation. Complete release of cladribine from the test and reference dosage forms was observed. Also, in the future, based on the data obtained, it is possible to predict pharmacokinetic profiles using physiologically based pharmacokinetic modeling approaches.Conclusion. A PSF study was conducted for the drugs "Mavenclad®, tablets, 10 mg" and "Cladribine, tablets, 10 mg". Quantitative determination was carried out by HPLC-UV method. The test results showed complete release of both drugs and reaching the intestinal tract, indicating the absence of degradation of cladribine in the region simulating the stomach.

An interaction-based mixing model for predicting porosity and tensile strength of directly compressed ternary blends of pharmaceutical powders

Predicting the mechanical properties of powder mixtures without extensive experimentation is important for model driven design in solid dosage form manufacture. Here, a new binary interaction-based model is proposed for predicting the compressibility and compactability of directly compressed pharmaceutical powder mixtures based on the mixture composition. The model is validated using blends of MCC, lactose and paracetamol or ibuprofen. Both compressibility and compactability profiles are predicted well for a variety of blend compositions of ternary mixtures for the two formulations. The model performs well over a wide range of compositions for both blends and better than either an ideal mixing model or a ternary interaction model. A design of experiments which reduces the amount of API required for fitting the model parameters for a new formulation is proposed to reduce amount of API required. The design requires only three blends containing API. The model gives similar performance to the well-known Reynolds et al. model (2017) when trained using the same data sets. The binary interaction model approach is generalizable to other powder mixture properties. The model presented in this work is limited to curve-fitting of empirical compaction models for mixtures of common pharmaceutical powders and is not intended to provide guidance on the practical operating space (or design space) limits.

Risperidone Pellets, Pycnogenol®, and Glucomannan Gummy Formulation for Managing Weight Gain and ADHD in Autistic Children.

Gummy formulations are defined as gradually or slowly released solid oral dosage forms. Risperidone is an atypical antipsychotic medication used to treat schizophrenia and autism-related irritability. This study presents the development of visually appealing, patient-tailored medicated gummies that act as a novel pharmaceutical form of Risperidone for pediatrics. In this study, two gummy bases were used, one containing Glucomannan and the other containing Gelatin as a gelling agent, where these gummy bases were loaded with coated Risperidone pellets with a controlled release layer. The final products were evaluated for their pH, viscosity, content uniformity, drug content, and dissolution profile. Both formulas showed proper rheology and met content and weight uniformity standards. The release rates for F1 and F2 in the acidic media were 25% and 11%, respectively, after 2 h. At the same time, a full-release profile for Risperidone was noticed in both formulae at pH 6.8 where the release lasts for 24 h. It can be concluded that the chewable semi-solid dosages (gummies) filled with coated pellets are suitable for pediatric patients since pediatrics have drug-related problems which can be solved using high gastro-resistance coated pellets, which also shows a proper release profile for the drug.

The potential of phosphorus-solubilizing purple nonsulfur bacteria in agriculture: Present and future perspectives

Abstract Phosphorus (P) is one of the essential macronutrients for crops. It is present in soil in two forms: soluble and insoluble. However, plants cannot absorb the insoluble forms, including Al-P, Fe-P, and Ca-P; thus, the phosphorus use efficiency is reduced. Therefore, the biological approaches should focus more on sustainable agriculture to overcome this constraint. This article cites publications relating to the biological P solubilizer group of bacteria, which have a highly potential adaptation to many conditions in soils. Among the biological approaches, purple nonsulfur bacteria (PNSB) are a potent group of bacteria according to their adaptability in acidic, saline, and toxic conditions based on their mechanisms in producing exopolymeric substances and siderophores under such adverse environments like acid-sulfate and saline soils. PNSB can solubilize P in soil to have more P availability for soil microbes and plants. This particular group of bacteria has been widely applied in liquid and solid forms from agricultural waste to promote plant growth under submerged conditions. Moreover, this article summarized the P-solubilizing mechanisms of P-solubilizing bacteria and introduced future research perspectives on patterns of PNSB in aspects of nutrient-providing potency, plant growth-promoting capability, and biological control capacity. However, the specific mechanisms of P solubilization by PNSB have not been well documented since the P-solubilizing mechanisms have been investigated on general P-solubilizing bacteria. Thus, specific pathways and metabolites relating to the P-solubilizing PNSB should be investigated, and attention should be addressed to them soon.

Development of Orodispersible Tablets with Solid Dispersions of Fenofibrate and Co-Processed Mesoporous Silica for Improved Dissolution.

Poor water solubility is an important challenge in the development of oral patient-friendly solid dosage forms. This study aimed to prepare orodispersible tablets with solid dispersions of a poorly water-soluble drug fenofibrate and a co-processed excipient consisting of mesoporous silica and isomalt. This co-processed excipient, developed in a previous study, exhibited improved flow and compression properties compared to pure silica while maintaining a high specific surface area for drug adsorption. Rotary evaporation was used to formulate solid dispersions with different amounts of fenofibrate, which were evaluated for solid state properties and drug release. The solid dispersion with 30% fenofibrate showed no signs of crystallinity and had a significantly improved dissolution rate, making it the optimal sample for formulation or orodispersible tablets. The aim was to produce tablets with minimal amounts of additional excipients while achieving a drug release profile similar to the uncompressed solid dispersion. The compressed formulations met the requirements for orodispersible tablets in terms of disintegration time, and the drug release from best formulation approximated the profile of uncompressed solid dispersion. Future research should focus on reducing the disintegration time and tablet size to enhance patient acceptability further.

Manipulation of solid dosage forms for oral administration to paediatric patients for drug-resistant tuberculosis in South Africa: an observation study

BackgroundChildren represent a particularly vulnerable demographic in the context of drug-resistant (DR) tuberculosis (TB) due to their increased likelihood of close contact with adults diagnosed with the disease. Approximately 25 000–30 000 children develop DR-TB annually. While treatment success rates for DR-TB in children surpass those in adults, children and adolescents encounter distinct challenges throughout the diagnosis and treatment of DR-TB (including MDR-TB, Pre-XDR TB, and XDR-TB).AimTo identify current practices in drug administration to children diagnosed with DR-TB where appropriate dosage forms are not available in South Africa.MethodAn observational study was carried out at the study site to determine how medication prescribed was manipulated and administered by nursing staff to paediatric patients in the wards.ResultsThe observational study identified 8 drugs used in DR-TB at the study site, where some manipulation to the formulation was necessary to enable administration to paediatric patients. Linezolid and para-aminosalicylic acid are the only drugs available and registered in the South Africa in a formulation that is suitable for administration to paediatric patients. Activities carried out by nursing staff to enable the administration of DR-TB medication included cutting capsules and tablets and dissolving the tablet or capsule contents in distilled water to obtain the required suitable dose.DiscussionLack of availability of suitable dosage forms for paediatrics patients results in several challenges, such as additional time required for drug preparation, increased time duration of medication administration, and unpalatability of drugs. These challenges may subsequently affect compliance and therapeutic outcomes of the treatment of paediatric patients, especially as outpatients.ConclusionResearch needs to focus on the development of appropriate dosage forms for the paediatric population and focus on identifying cases of DR-TB in children. This will assist in building evidence to advocate for registration of child-friendly dosage forms thereby ensuring a sustainable supply of medication.

A rapid chemical method for production of xylitol from D-xylose as a renewable feedstock from spent aromatic waste

Xylitol is occurring naturally as a minor constituent in many fruits and vegetables. Commercially, xylitol is produced by chemical methods from D-xylose for application as an alternative sweetener in food and pharmaceutical products. Although biomass-derived xylose can be used as a potential substrate for xylitol production, its prerequisite purification before a catalytic hydrogenation directly impacts the production cost. In addition, the isolation of xylose falls under a routine pretreatment activity during conversion of biomass to platform chemicals. The resulting hydrolysate often exhibits a low concentration of xylose and other monosaccharides. Concentrating the hydrolysate to a desired level for conversion to xylitol under chemical/biological methods increases the expenditure cost. Many times, concentration by heating may cause the degradation of contained sugars in the hydrolysate. Therefore, this study has been carried out to obtain a mixture of C5/6 sugars, predominantly the D-xylose in a solid dry form (∼10 % yield, >98 % purity) directly from acid hydrolysate of spent aromatic waste. Biomass-derived D-xylose was further transformed to xylitol (100 % conversion) by a fast (10 min), efficient, and solvent-free chemical approach using a modified sodium borohydride (NaBH4) catalyst on a wet silica (SiO2) support at RT. All reagents and solvents used in the process were recovered and recycled, leading to the minimal waste generation.

Graded h-BNC for nanoscale antifouling

Although considerable efforts have been made in various fields for surface cleaning, keeping solid surfaces from nanoscale contamination remains extremely challenging. It is demonstrated here, based on molecular dynamics simulations, that graded hexagonal boron-nitride/graphene (h-BNC) can be an intrinsic and robust antifouling coating material. It is shown that nanoobjects in both solid and liquid forms can move spontaneously on the graded h-BNC toward the direction of decreasing carbon content. The driving mechanism is attributed to the gradient in van der Waals potential induced by the gradient in carbon content. The graded structure of graded h-BNC allows for its use in robust nanoscale surface cleaning and offers new opportunities for the development of antifouling coatings.

(Invited) Plasma Designing of Hybrid 2D Graphene: A Green Approach for Future Energy Materials

The global research interest in two-dimensional (2D) materials and their derivatives has increased significantly, driven by the requirements of application-oriented materials for different sectors, including energy storage. Among the various classes of material groups, 2D layered materials have emerged as a critical research area due to their high aspect ratio, open edge boundaries, high surface-to-volume ratios, and mechanical and electrical properties. Graphene is a widely researched 2D class material with an atomically thin structure, excellent electronic properties, very high intrinsic mobility and exceptional thermal and electrical conductivity1. Even though the research on the electronic properties of graphene is explored very well and in a matured state, the studies on non-electronic properties are still in the budding phase. One of the significant obstacles to extending the studies of graphene to different fields is the cost-effective and environmentally friendly large-scale synthesis and processing of high-quality graphene. Thus, a cutting-edge approach for probing graphene structures at the atomic scale is required to produce high-quality graphene for next-generation applications. As an alternative progressive technique, plasma-enabled methods have emerged as safe and green approaches to tailor different graphene structures at the nanoscale. During graphene production, plasma assembles the nanostructures from gaseous into a solid form or converts solid precursor to graphitic form 2,3. Besides, plasma techniques open up the possibility of tailoring the properties by crafting heteroatoms to the graphene lattice, which is beneficial for energy storage applications4. Therefore, this paper introduces the advantages of plasma-enabled techniques in designing graphene-based materials with different morphologies and orientations and tailoring them at the nanoscale using heteroatoms. Such plasma-assisted techniques ensure the high structural quality of graphene and controllability in the hybrid morphologies, making them frontrunner energy storage applications. Plasma also offers the production of graphene directly on any substrate surface, gives a new direction to designing binder-free electrodes for energy-related applications, and could be used as a competitive alternative approach to the widely known wet chemical procedures to design advanced graphene electrode materials for next-generation energy storage devices.Reference Geim, A. K. Graphene: Status and prospects. Science (1979) 324, 1530–1534 (2009).Dias, A. et al. N-Graphene-Metal-Oxide(Sulfide) hybrid Nanostructures: Single-step plasma-enabled approach for energy storage applications. Chemical Engineering Journal 430, 133153 (2022).Jagodar, A. et al. Growth of graphene nanowalls in low-temperature plasma: Experimental insight in initial growth and importance of wall conditioning. Appl Surf Sci 643, 158716 (2024).Santhosh, N.M. et al. N-Graphene Nanowalls via Plasma Nitrogen Incorporation and Substitution: The Experimental Evidence. Nanomicro Lett 12, 53 (2020).

Mix-match synthesis of nanosynbiotics from probiotics and prebiotics to counter gut dysbiosis via AI integrated formulation profiling

Antibiotics, improper food, and stress have created a dysbiotic state in the gut and almost 81% of the world’s population has been affected due to the pandemic of COVID-19 and the prevalence of dengue virus in the past few years. The main intent of this study is to synthesize nanosynbiotics as nu traceuticals by combining probiotics, and prebiotics with nanoformulation. The effectiveness of the nanosynbiotics was evaluated using a variety of Nutra-pharmacogenetic assays leading to an AI-integrated formulation profiling was assessed by using machine learning methods. Consequently, Acetobacter oryzoeni as a probiotic and inulin as a prebiotic has been chosen and iron-mediated nanoformulation of symbiotic is achieved. Nanosynbiotics possessed 89.4, 96.7, 93.57, 83.53, 88.53% potential powers of Nutra-pharmacogenetic assays. Artificial intelligent solid dispersion formulation of nanosynbiotics has high dissolution, absorption, distribution, and synergism, in addition, they are non-tox, non-allergen and have a docking score of − 10.83 kcal/mol, implying the best interaction with Pregnane X receptor involved in dysbiosis. The potential of nanosynbiotics to revolutionize treatment strategies through precise targeting and modulation of the gut microbiome for improved health outcomes and disease management is promising. Their transformational influence is projected to be powered by integration with modern technology and customized formulas. Further in-vivo studies are required for the validation of nanosynbiotics as nutraceuticals.

A layered solid finite element formulation with interlaminar enhanced displacements for the modeling of laminated composite structures

A layered solid finite element formulation with interlaminar enhanced displacements for the modeling of laminated composite structures

Near UV and Visible Light Photodegradation in Solid Formulations: Generation of Carbon Dioxide Radical Anions from Citrate Buffer and Fe(III).

Near UV and visible light photodegradation can target therapeutic proteins during manufacturing and storage. While the underlying photodegradation pathways are frequently not well-understood, one important aspect of consideration is the formulation, specifically the formulation buffer. Citrate is a common buffer for biopharmaceutical formulations, which can complex with transition metals, such as Fe(III). In an aqueous solution, the exposure of such complexes to light leads to the formation of the carbon dioxide radical anion (•CO2-), a powerful reductant. However, few studies have characterized such processes in solid formulations. Here, we show that solid citrate formulations containing Fe(III) lead to the photochemical formation of •CO2-, identified through DMPO spin trapping and HPLC-MS/MS analysis. Factors such as buffers, the availability of oxygen, excipients, and manufacturing processes of solid formulations were evaluated for their effect on the formation of •CO2- and other radicals such as •OH.

Thermal stability, preformulation, and kinetic degradation studies for gestrinone

AbstractGestrinone is an active pharmaceutical ingredient used in the treatment of endometriosis as capsules, with ongoing evaluation for intravaginal administration, while also having been studied for its potential antitumoral effects. The purpose of this study was to determine the compatibility of gestrinone with four excipients used in the development of solid pharmaceutical formulations (α-lactose monohydrate, magnesium stearate, starch, and talc) and to obtain a fully characterized thermoanalytical profile of gestrinone with the help of kinetic analysis. Preformulation studies were carried out on 1:1 mass/mass binary mixtures between gestrinone and each excipient by instrumental screening under ambient conditions using ATR-FTIR spectroscopy investigations, and later by studying the effect of thermal treatment over the samples (TG/DTG/DSC). The obtained results suggest that under ambient conditions, no chemical interactions take place between the active pharmaceutical ingredient and selected excipients, whereas under thermal stress incompatibilities are observed in all systems. The mechanism of decomposition was preliminary evaluated by the ASTM E698 and later completed by the isoconversional methods of Friedman, Kissinger–Akahira–Sunose, and Flynn–Wall–Ozawa, which suggest similar mean activation energies. The mechanism of decomposition was elucidated in the last part of the study, by employing the modified NPK method. This method suggests that gestrinone is thermally degraded by the contribution of two individual processes, both consisting of superimposed physical transformations and chemical degradations.

Terahertz Frequency-Domain Spectroscopy with a Method for Suppressing Water Vapor Absorption Peaks for Analysis of Pharmaceutical Hydrate Samples

Measurements of terahertz absorption spectra of pharmaceutical hydrate samples are achieved under a normal humidity condition by combining terahertz frequency-domain spectroscopy with a newly proposed method for suppressing absorption peaks caused by water vapor. In this method, only simple mathematical operations such as subtraction, thresholding, interpolation, and smoothing are applied to extinction (or absorbance) data obtained by locating samples under a normal humidity condition. By considering the difference in spectral line width between narrow absorption peaks caused by water vapor and the relatively wide absorption peaks caused by active pharmaceutical ingredients (APIs) in solid forms, the absorption peaks caused by water vapor can be effectively suppressed without affecting the absorption peaks of the APIs in the samples. In the present study, levofloxacin hydrates were used as samples to investigate the performance of the proposed method. Spectra were obtained under both dry and normal humidity conditions. The temperature of the samples was raised from 300 to 363 K to dehydrate them and brought back to 313 K to observe hydration under the normal humidity condition. Spectra obtained under the normal humidity condition were processed with the proposed method. The spectra of the hydrates obtained under the dry condition were slightly different from those obtained under the normal humidity condition and processed by our method. Dehydration during the measurements under the dry condition was suggested. Stable and reliable results are expected by measuring spectra under normal humidity conditions and applying the proposed method to suppress absorption peaks by water vapor.