Material-Sparing Approach to Predict Tablet Capping Under Processing Compression Conditions Based on Mechanical and Molecular Properties Derived from Compaction Simulation and Crystal Structural Analysis.

Present study evaluates the usability of compaction simulation-based mechanical models as a material-sparing approach to predict tablet capping under processing compression conditions using Acetaminophen (APAP) and Ibuprofen (IBU). Measured mechanical properties were evaluated using principal component analysis (PCA) and principal component regression (PCR) models. PCR models were then utilized to predict the capping score (CS) from compression pressure (CP).

Design of Experiments-Driven Optimization of Spray Drying for Amorphous Clotrimazole Nanosuspension.

This study employed a Quality by Design (QbD) approach to spray dry amorphousclotrimazole nanosuspension (CLT-NS) consisting of Soluplus and microcrystallinecellulose. Using the Box-Behnken Design, a systematic evaluation was conducted toanalyze the impact of inlet temperature, % aspiration, and feed rate on the criticalquality attributes (CQAs) of the clotrimazole spray-dried nanosuspension (CLT-SDNS). In this study, regression analysis and ANOVA were employed to detect significantfactors and interactions, enabling the development of a predictive model for the spraydrying process.

Strategizing Spray Drying Process Optimization for the Manufacture of Redispersible Indomethacin Nanoparticles Using Quality-by-Design Principles.

The present study adopted a Quality by Design (QbD) approach to spray dry indomethacin nanosuspension (IMC-NS) consisting of HPC-SL, poloxamer 407, and lactose monohydrate. The Box-Behnken Design was used to systematically evaluate the effects of inlet temperature, aspiration rate, and feed rate on the critical quality attributes (CQAs) [redispersibility index (RDI; minimize), % yield (maximize), and % release at 15 min (maximize)] of the indomethacin spray dried nanosuspension (IMC-SD-NS). To identify significant main and quadratic effects, two-way interactions, and create a predictive model for the spray drying process, regression analysis and ANOVA were utilized.

Developing a Formulation Strategy Coupled with PBPK Modeling and Simulation for the Weakly Basic Drug Albendazole.

Albendazole (ABZ) is a weakly basic drug that undergoes extensive presystemic metabolism after oral administration and converts to its active form albendazole sulfoxide (ABZ_SO). The absorption of albendazole is limited by poor aqueous solubility, and dissolution is the rate-limiting step in the overall exposure of ABZ_SO. In this study, PBPK modeling was used to identify formulation-specific parameters that impact the oral bioavailability of ABZ_SO.

Evaluating the effect of glidants on tablet sticking propensity of ketoprofen using powder rheology.

Punch sticking has been a leading drawback that has challenged successful tablet manufacturing since its initial conception. Due to the capricious nature of the complication, this can arise during any phase of the development process. Even now, identifying such a problem is a prerequisite during the initial stage of development.

Modeling of Adhesion in Tablet Compression at the Molecular Level Using Thermal Analysis and Molecular Simulations.

The molecular basis of adhesion leading to sticking was investigated by exploring the correlation between thermal analysis and molecular simulations. It is hypothesized that intermolecular interactions between a drug molecule and a punch face are the first step in the adhesion process and the rank order of adhesion during tablet compression should correspond to the rank order of the energies of these interactions. In the present study, the sticking propensity was investigated using ibuprofen, flurbiprofen, and ketoprofen as model substances.

Understanding the Impact of Multi-factorial Composition on Efficient Loading of the Stable Ketoprofen Nanoparticles on Orodispersible Films Using Box-Behnken Design.

The purpose of the present study was to prepare Orodispersible films (ODFs) loaded with ketoprofen nanoparticles (KT-NP). The Box-Behnken design was constructed in developing and optimizing the KTF-NP-ODFs. The effect of independent variables: Soluplus® concentration (X, stabilizer), Tween 80 concentration (X, surfactant), and KTF concentration (X, drug) were studied on the dependent variables: particle size (PS, Y), zeta potential (ZP, Y), and the polydispersity index (PDI, Y) of the NPs, as well as on the tensile strength (TS, Y) and permeability coefficient (PC, Y) of the KTF-NP-ODFs.

Predicting lubricants effect on tablet sticking using ketoprofen as model drug and evaluating sticking propensity using different metals and powder rheology.

Tablet sticking occurrence is a persistent, costly, and time-consuming problem that needs to be resolved. Predicting the sticking tendency of a new formulation has been very difficult during the development batches because of short runs and limited data. A model formulation comprising ketoprofen and microcrystalline cellulose was used to predict the effect of magnesium stearate and sodium stearyl fumarate on the occurrence of tablet sticking relative to different punch metals.

Molecular Insights into Warfarin Sodium 2-Propanol Solvate Solid Form Changes and Disproportionation Using a Low Volume Two-Stage Dissolution Approach.

The current research work focuses on understanding the reported discrepancies and our observations in the dissolution profiles of warfarin sodium tablets and potential patient-based failure modes during oral warfarin therapy. It was hypothesized that freely soluble crystalline warfarin sodium (WAR) at first transforms into noncrystalline warfarin sodium (WAR) under stress conditions. The WAR → WAR conversion facilitates the rapid formation of the poorly soluble unionized form, which could lead to dissolution failures and potential poor in vivo performance.

Protocol development, validation, and troubleshooting of in-situ fiber optic bathless dissolution system (FODS) for a pharmaceutical drug testing.

Currently, there is no systematic approach available for the validation, quantitative assessment, and troubleshooting for the in-situ fiber optic/bathless dissolution system (FODS). In this report, a dissolution protocol was developed and validated for a model product, chlorpheniramine maleate (CPM) 4 mg IR tablets. Dissolution runs were conducted at 37 ± 0.

Contribution of Crystal Lattice Energy on the Dissolution Behavior of Eutectic Solid Dispersions.

In the literature, it is reported that eutectics lead to the enhanced dissolution of a poorly soluble compound. However, the solubility theory suggests that since crystal structures of two components are unchanged that all else being equal, the dissolution rates of a fused mixture (FM) should be the same as a physical mixture (PM). The influence of crystal lattice energy on dissolution profiles was investigated using the PM and FM.

Systematic implementation of quality-by-design (QbD) to develop NSAID-loaded nanostructured lipid carriers for ocular application: preformulation screening studies and statistical hybrid-design for optimization of variables.

The objective of the present project was to develop and optimize the Ibuprofen (IBU)-loaded nanostructured lipid carrier (IBU-NLCs) for sustained-release ocular drug delivery using a quality-by-design (QbD) approach. The BCS class II drug IBU was selected as the model drug for the preparation of IBU-NLCs by melt-emulsification and ultrasonication technique. Extensive preformulation screening of the components of NLC dispersion (i.

Effects of compaction pressure, speed and punch head profile on the ultrasonically-extracted physical properties of pharmaceutical compacts.

Despite a well-established manufacturing-process understanding, tablet quality issues are frequently encountered during various stages of drug-product development. Compact breaking force (tensile strength), capping and friability are among the commonly observed characteristics that determine the integrity, quality and manufacturability of tablets. In current study, a design space of the compaction pressure, compaction speed and head flat types is introduced for solid dosage compacts prepared from pure silicified microcrystalline cellulose, a popular tableting excipient.

Stability of Insulin Detemir Injection in Different Primary Packaging Systems at Room Temperature.

Purpose: To assess the stability of insulin detemir at controlled room temperature (RT) at 25°C in different packaging systems over 7 days.

Methods: The degradation characteristics of insulin detemir were determined based on the assay results in different packaging systems (pinhole glass vial, closed glass vial, glass syringe, and plastic syringe) at RT using a reverse-phase high-performance liquid chromatography (HPLC) assay method for insulin injection. Each packaging system was compared to insulin detemir stored in the original packaged closed glass vial at 2°C to 8°C.

Tablet capping predictions of model materials using multivariate approach.

The present study demonstrated the prediction of predominant root causes of capping behavior as a function of the powder rheological and the mechanical behavior of Acetaminophen (APAP) and Ibuprofen (IBU). The authors analyzed powder rheological properties for powder blend permeability, pressure drop, and cohesion. The measured deformation properties were compact porosity, internal air pressure, Brinell hardness, and tensile strength.

Investigate the effect of solvents on wet granulation of microcrystalline cellulose using hydroxypropyl methylcellulose as a binder and evaluation of rheological and thermal characteristics of granules.

Wet granulation is the most commonly used technique in the pharmaceutical industry for delivering oral solid dosage forms. In wet granulation, the binder solvent is one of the critical factors affecting granule properties. In the current study, an attempt was made to investigate the effect of solvents (aqueous and hydro-alcoholic) on thermal and flow properties of Microcrystalline Cellulose (MCC) granules prepared using two different grades of Hydroxypropyl Methylcellulose (HPMC), which served as an effective binder.

Development of an amorphous nanosuspension by sonoprecipitation-formulation and process optimization using design of experiment methodology.

A Design of Experiment (DoE) methodology was adopted to investigate and optimize process parameters and formulations variables for preparing an amorphous clotrimazole (CLT) nanosuspension by sonoprecipitation technique. The amorphous nanosuspension can provide a synergistic effect of increase in dissolution velocity and kinetic solubility which can be advantageously used to improve bioavailability of low-solubility drugs. A Box-Behnken design was utilized to study the effect of formulation parameters (drug concentration, polymer concentration, and surfactant concentration) and process parameter (antisolvent: solvent ratio) on particle size, polydispersibility index (PDI), and zeta potential of amorphous CLT nanoparticles.

Evaluation of self-nanoemulsifying drug delivery systems using multivariate methods to optimize permeability of captopril oral films.

The present report demonstrates a quality by design approach to understand and optimize self-nanoemulsifying orodispersible films (SNEODF) of captopril for hypertension. A central composite experimental design was used to study the formulation parameters effects (primary emulsion, aqueous phase, and surfactant) on the film properties (globule size, film burst, adhesion, Young's moduli, disintegration time, tensile strength and dissolution). Principle component analysis (PCA) and principle component regression (PCR) were employed to identify and quantify the effects of formulation variables and physico-mechanical properties of the film on the drug permeability.

A Mechanistic Approach To Model the Compression Cycle of Different Toolings Based on Compression Roller Interactions.

The aim of the current work was to model and understand the mechanical interactions of tooling heads with compression rollers during tableting. Binary direct compression blends of Prosolv® SMCC with 0.5% w/w magnesium stearate and ternary blends with 30% w/w acetaminophen were used.

Investigating a Novel Hot Melt Extrusion-Based Drying Technique to Solidify an Amorphous Nanosuspension Using Design of Experiment Methodology.

The hot melt extrusion (HME) technology was explored and optimized to solidify an amorphous nanosuspension using Quality by Design (QbD) methodology. A design of experiments (DoE) approach was used to perform a set of 15 experiments, varying independent variables (feed rate, input temperature, and screw speed) within a design space. Redispersibility index (RDI), moisture content, and process yield constituted the critical quality attributes (CQAs) of the experimental design.

Influence of punch geometry (head-flat diameter) and tooling type ('B' or 'D') on the physical-mechanical properties of formulation tablets.

The presented study assessed the influence of punch geometry (head-flat [HF] diameter) and tooling type ('B' or 'D') on the physical-mechanical properties of tablets prepared by direct-compression of two guaifenesin (25% or 40% w/w) formulations. Tablets of both formulations were prepared on instrumented, single-layer, rotary tablet press using 10 mm, flat-faced, 'B' or 'D'-type tooling with different HF diameters, and compression forces (CF) ranging from 5 to 25 kN with 5 kN increments. The tablets were evaluated for dimensions, weight variation, tensile strength (TS), friability, and capping index.

A quality-by-design study to develop Nifedipine nanosuspension: examining the relative impact of formulation variables, wet media milling process parameters and excipient variability on drug product quality attributes.

Wet milling is a multifunctional and the most common method to prepare a drug nanosuspension for improving the bioavailability of poorly water soluble drugs. A suitable way of preparing a high drug-loaded nifedipine nanosuspension using wet stirred media milling was investigated in the present study. Nifedipine, a poorly water soluble drug, was selected as a model drug to enhance its dissolution rate and oral bioavailability by preparing an appropriate crystalline nanosuspension.

Polymorphic Transformation of Indomethacin during Hot Melt Extrusion Granulation: Process and Dissolution Control.

Purpose: To study and elucidate the effect of the intensity and duration of processing stresses on the possible solid-state changes during a hot melt extrusion granulation process.

Methods: Blends of α-indomethacin and PEG 3350 (w/w 4:1) were granulated using various screw sizes/designs on the melt extruder under different temperature regimes. Differential Scanning Calorimetry and X-ray Powder Diffraction were employed for characterization.

Influence of processing methods on physico-mechanical properties of Ibuprofen/HPC-SSL formulation.

The objective of the present study was to investigate the influence of processing methods on the physical and mechanical properties of formulations containing Ibuprofen and HPC-SSL. The powder blends, containing Ibuprofen and HPC-SSL in ratio of 9:0.5, were processed using melt granulation (MG) by hot melt extrusion (HME) and wet granulation (WG) by high shear mixer.