Continuous Monitoring of Pseudopolymorphic Transition in Ezetimibe Using T Relaxation with Time-Domain NMR.

The purpose of this study was to continuously monitor the pseudopolymorphic transition from anhydrate to monohydrate by measuring the NMR relaxation using time-domain NMR (TD-NMR). Taking advantage of the simplicity of the low-field NMR instrument configuration, which is an advantage of TD-NMR, the NMR instrument was connected to a humidity controller to monitor the pseudopolymorphic transition. First, ezetimibe (EZT) monohydrate was prepared from its anhydrate using a saturated salt solution method, and T relaxation of EZT monohydrate and anhydrate was measured without a humidity controller.

TGA and NMR relaxation measurement of nonmesoporous silica to investigate the amount of hydrolysis product in acetylsalicylic acid adsorbed on silica.

This study investigated a crucial surface property of silica that contributes to the chemical stability of acetylsalicylic acid (ASA) physically adsorbed on silica. Hydrophilic nonmesoporous types of silica were selected, and the number of hydroxyl groups on silica (N) was evaluated using thermogravimetric analysis (TGA). The ASA-containing silica was stored at 40 °C in drying conditions, and the amount of ASA degradation was quantified based on salicylic acid.

Determination of the Solid Content of Active Pharmaceutical Ingredient Powders in Suspension-Type Pharmaceutical Oral Jelly Using Time-Domain NMR.

This study determined the content of solid active pharmaceutical ingredient (API) powders dispersed in suspension-type pharmaceutical oral jellies using a low-field time-domain NMR (TD-NMR). The suspended jellies containing a designated API content were prepared and tested. Acetaminophen (APAP), indomethacin (IMC) and L-valine were used as test APIs.

Use of Time-Domain NMR for H T Relaxation Measurement and Fitting Analysis in Homogeneity Evaluation of Amorphous Solid Dispersion.

This study examined the usefulness of H T relaxation measurements for evaluating the homogeneity of amorphous solid dispersion (ASD). Indomethacin and polyvinylpyrrolidone were used to prepare two kinds of ASDs. One was inhomogeneous ASD (ASD) prepared by a melt-quenching method, and the other was homogeneous ASD (ASD) prepared by a solvent evaporation method.

Continuous Monitoring of the Agglomeration and Sedimentation of Indomethacin Nanosuspensions Using T Relaxation Time with Time-Domain NMR.

The time-domain NMR technique was utilized to monitor precisely the physicochemical stability of indomethacin (IMC) nanosuspensions using T relaxation time (T). We investigated whether T values can distinguish between agglomeration and sedimentation. Nanosuspensions of IMC were prepared using aqueous wet bead milling with polyvinylpyrrolidone as a stabilizer.

Continuous Monitoring of the Hydration Behavior of Hydrophilic Matrix Tablets Using Time-Domain NMR.

Time-domain NMR (TD-NMR) was used for continuous monitoring of the hydration behavior of hydrophilic matrix tablets. The model matrix tablets comprised high molecular weight polyethylene oxide (PEO), hydroxypropyl methylcellulose (HPMC), and polyethylene glycol (PEG). The model tablets were immersed in water.

A Data-Driven Approach to Predicting Tablet Properties after Accelerated Test Using Raw Material Property Database and Machine Learning.

The purpose of this study was to develop a model for predicting tablet properties after an accelerated test and to determine whether molecular descriptors affect tablet properties. Tablets were prepared using 81 types of active pharmaceutical ingredients, with the same formulation and three different levels of compression pressure. The tablet properties measured were the tensile strength and disintegration time of tablets after two weeks of accelerated test.

Application of unsupervised and supervised learning to a material attribute database of tablets produced at two different granulation scales.

The purpose of this study is to demonstrate the usefulness of machine learning (ML) for analyzing a material attribute database from tablets produced at different granulation scales. High shear wet granulators (scale 30 g and 1000 g) were used and data were collected according to the design of experiments at different scales. In total, 38 different tablets were prepared, and the tensile strength (TS) and dissolution rate after 10 min (DS10) were measured.

Quality Evaluation of Humidified Magnesium Oxide Tablet Formulations with Respect to Disintegration Time Prolongation.

In the present study, we conducted a detailed evaluation of the effects of humidification on the quality of five types of commercial magnesium oxide (MgO) tablet formulations. When near-IR spectroscopy was performed, a peak derived from the first overtone of the stretching vibration of the hydroxyl group was observed at approximately 7200 cm in a humidified MgO tablet formulation. To visually evaluate the effect of this humidification, a mapping image was created using microscopic IR spectroscopy.

Usefulness of Applying Partial Least Squares Regression to T Relaxation Curves for Predicting the Solid form Content in Binary Physical Mixtures.

This study applied partial least squares (PLS) regression to nuclear magnetic resonance (NMR) relaxation curves to quantify the free base of an active pharmaceutical ingredient powder. We measured the T relaxation of intact and moisture-absorbed physical mixtures of tetracaine free base (TC) and its hydrochloride salt (TC·HCl). The obtained T relaxation curves were analyzed by two methods, one using a previously reported T relaxation time (T), and the other using PLS regression.

Study of Orally Disintegrating Tablets Using Erythritol as an Excipient Produced by Moisture-Activated Dry Granulation (MADG).

Moisture-activated dry granulation (MADG) is an eco-friendly granulation method that uses a small amount of water and insoluble excipients to absorb moisture. MADG is expected to improve productivity and reduce costs. Erythritol, an excipient used for preparing orally disintegrating tablets (ODTs), has poor tabletability and is difficult to form into tablets by conventional methods, such as high-shear granulation (HSG) and direct compression.

Determination of Hardness of a Pharmaceutical Oral Jelly by Using T Relaxation Behavior Measured by Time-Domain NMR.

Hardness is a critical quality characteristic of pharmaceutical oral jelly. In this study, the hardness was determined by using the T relaxation curves measured by time-domain NMR. For sample preparation, kappa- and iota-carrageenans, and locust bean gum, were used as gel-forming agents.

Low-Field NMR to Characterize the Crystalline State of Ibuprofen Confined in Ordered or Nonordered Mesoporous Silica.

The crystalline state of ibuprofen (IBU) confined in mesoporous silica was characterized using low-field time-domain nuclear magnetic resonance (TD-NMR). IBU was loaded into ordered (Santa Barbara Amorphous-15 [SBA-15]; SBA) or nonordered mesoporous silica (Sylysia 320; SYL) using a well-known incipient wetness impregnation method. The dissolution profile of IBU from the silica was measured.

Characterization of the Salt and Free Base of Active Pharmaceutical Ingredients Based on NMR Relaxometry Measured by Time Domain NMR.

NMR relaxometry measurement by time domain NMR (TD-NMR) is a promising technique for characterizing the properties of active pharmaceutical ingredients (APIs). This study is dedicated to identifying the salt and free base of APIs by NMR relaxometry measured by the TD-NMR technique. Procaine (PC) and tetracaine (TC) were selected as model APIs to be tested.

Application of machine learning to a material library for modeling of relationships between material properties and tablet properties.

This study investigates the usefulness of machine learning for modeling complex relationships in a material library. We tested 81 types of active pharmaceutical ingredients (APIs) and their tablets to construct the library, which included the following variables: 20 types of API material properties, one type of process parameter (three levels of compression pressure), and two types of tablet properties (tensile strength (TS) and disintegration time (DT)). The machine learning algorithms boosted tree (BT) and random forest (RF) were applied to analysis of our material library to model the relationships between input variables (material properties and compression pressure) and output variables (TS and DT).

Effects of Manufacturing Process Variables on the Tablet Weight Variation of Mini-tablets Clarified by a Definitive Screening Design.

This study investigated the effect of manufacturing process variables of mini-tablets, in particular, the effect of process variables concerning fluidized bed granulation on tablet weight variation. Test granules were produced with different granulation conditions according to a definitive screening design (DSD). The five evaluated factors assigned to DSD were: the grinding speed of the sample mill at the grinding process of the active pharmaceutical ingredient (X1), microcrystalline cellulose content in granules (X2), inlet air temperature (X3), binder concentration (X4) and the spray speed of the binder solution (X5) at the granulation process.

Nondestructive Investigation of the Agglomeration Process for Nanosuspensions via NMR Relaxation of Water Molecules.

This study investigated an agglomeration of nanoparticles in a suspension using nuclear magnetic resonance (NMR) relaxation. The nanosuspension was prepared by wet bead milling using indomethacin and polyvinylpyrrolidone as an active pharmaceutical ingredient (API) and stabilizer, respectively. Transmission profiles using a dispersion analyzer based on multilight scattering technology confirmed that agglomeration occurred at 25 °C immediately after wet bead milling.

Time-domain NMR analysis for the determination of water content in pharmaceutical ingredients and wet granules.

The application of time-domain NMR (TD-NMR) analysis to quantify water content in pharmaceutical ingredients is demonstrated. The initial phase of the study employed a range of disintegrants with defined amounts of added water (0-30% of the total weight) as samples; the disintegrants included croscarmellose sodium, corn starch, low-substituted hydroxypropyl cellulose, and crospovidone. After acquisition of the T relaxation curves of the samples by TD-NMR measurements, these curves were analyzed by partial least squares (PLS) regression.

Incompatibility of remimazolam besylate with Ringer's acetate infusion resulting in total occlusion of an intravenous catheter.

Remimazolam besylate is an ultra-short-acting benzodiazepine derivative recently approved in Japan for general anaesthesia. However, less attention has been paid to the compatibility of remimazolam with infusion solutions, and the mechanism underlying the incompatibility remains unknown. The patient was a 65-year-old man who underwent a high tibial osteotomy.

Effect of Disintegrants on Prolongation of Tablet Disintegration Induced by Immersion in Xanthan Gum-Containing Thickening Solution: Contribution of Disintegrant Interactions with Disintegration Fluids.

In clinical practice, a thickening solution is frequently used to allow easy swallowing of tablets by patients suffering from dysphagia. This study investigated the effect of the thickening solution on tablet disintegration. Model tablets containing different disintegrants were prepared and their disintegration times (DTs) measured using standard methods.

Effect of Different Direct Compaction Grades of Mannitol on the Storage Stability of Tablet Properties Investigated Using a Kohonen Self-Organizing Map and Elastic Net Regression Model.

This study tested 15 direct compaction grades to identify the contribution of different grades of mannitol to the storage stability of the resulting tablets. After preparing the model tablets with different values of hardness, they were stored at 25 °C, 75% relative humidity for 1 week. Then, measurement of the tablet properties was conducted on both pre- and post-storage tablets.

Effect of the molecular mobility of water adsorbed by disintegrants on storage-induced hydrolytic degradation of acetylsalicylic acid incorporated into tablets under humid conditions.

The purpose of this study was to investigate the effect of molecular mobility of water adsorbed by disintegrants on the hydrolytic degradation of active pharmaceutical ingredients (APIs). Fourteen different disintegrants were tested. First, powdered disintegrants were stored at conditions of 40 °C/75% relative humidity ("humid conditions") and their T relaxation times were measured by time-domain nuclear magnetic resonance for examination of the molecular mobility of water adsorbed by the disintegrant.

A Precise Prediction Method for the Properties of API-Containing Tablets Based on Data from Placebo Tablets.

We previously reported a novel method for the precise prediction of tablet properties (e.g., tensile strength (TS)) using a small number of experimental data.