Quantification of Amlodipine Maleate Content in Amorphous Solid Dispersions Produced by Fluidized Bed Granulation Using Process Analytical Technology Tools.

Active pharmaceutical ingredient (API) content is a critical quality attribute (CQA) of amorphous solid dispersions (ASDs) prepared by spraying a solution of APIs and polymers onto the excipients in fluid bed granulator. This study presents four methods for quantifying API content during ASD preparation. Raman and three near-infrared (NIR) process analysers were utilized to develop methods for API quantification.

Comparative Fitting of Mathematical Models to Carvedilol Release Profiles Obtained from Hypromellose Matrix Tablets.

The mathematical models available in DDSolver were applied to experimental dissolution data obtained by analysing carvedilol release from hypromellose (HPMC)-based matrix tablets. Different carvedilol release profiles were generated by varying a comprehensive selection of fillers and carvedilol release modifiers in the formulation. Model fitting was conducted for the entire relevant dissolution data, as determined by using a paired -test, and independently for dissolution data up to approximately 60% of carvedilol released.

Optimization of radial extrusion and pellet coating processes using PAT approaches.

FDA's initiative Pharmaceutical CGMPs for the 21st century opened the door for introduction of several risk based approaches in pharmaceutical industry. One significant advancement that has emerged is the implementation of process analytical technology (PAT), which has opened doors for understanding and controlling complex technological processes. Two such processes, radial extrusion and pellet coating, offer a solid foundation for the application of PAT tools due to their numerous critical process parameters.

Comparative Study of Selected Excipients' Influence on Carvedilol Release from Hypromellose Matrix Tablets.

Solid dosage forms based on hypromellose (HPMC) with prolonged/extended drug release are very important from the research and industrial viewpoint. In the present research, the influence of selected excipients on carvedilol release performance from HPMC-based matrix tablets was studied. A comprehensive group of selected excipients was used within the same experimental setup, including different grades of excipients.

Characterization of the spray droplets and spray pattern by means of innovative optical microscopy measurement method with the high-speed camera.

Liquid atomization plays an important role in the manufacturing of the pharmaceutical products. It is used in all production steps where liquid is applied. In some productions steps precise control over spraying parameters is essential.

Influence of Formulation Factors, Process Parameters, and Selected Quality Attributes on Carvedilol Release from Roller-Compacted Hypromellose-Based Matrix Tablets.

The importance of roller compaction is recently increasing. This study evaluates the combined effects of formulation factors, process parameters, and selected quality attributes on drug release from roller-compacted hypromellose-based matrix tablets containing carvedilol as a model drug. The influence of selected factors was statistically assessed and good predictive models were developed for various time points of the release profile.

Implementation of spatial filtering technique in monitoring roller compaction process.

This study investigates the use of the spatial filtering technique (SFT) to monitor the particle size distribution (PSD) of granules obtained by roller compaction. In the first part of the study, the influence of the selected process and formulation parameters on the PSD of granules is monitored at-line using SFT. The correlation between the PSD obtained by SFT, sieve analysis, laser diffraction, and dynamic image analysis was satisfactory.

Evaluation of solid carvedilol-loaded SMEDDS produced by the spray drying method and a study of related substances.

In this study, various formulations of solidified carvedilol-loaded SMEDDS with high SMEDDS loading (up to 67% w/w) were produced with the spray drying process using various porous silica-based carriers. The process yield was improved with higher atomization gas flow rate during the spray drying process and with prolonged mixing time of dispersion of liquid SMEDDS and solid porous carriers prior to the spray drying process. Depending on the choice of the carrier and the SMEDDS:carrier ratio in solid SMEDDS, different drug loading, self-microemulsifying properties, drug release rates, and released drug fractions were obtained.

Applicability of Raman and near-infrared spectroscopy in the monitoring of freeze-drying injectable ibuprofen.

The freeze-drying process is an expensive, time-consuming and rather complex process. Therefore, process analytical technology (PAT) tools have been introduced to develop an optimized process and control critical process parameters, which affect the final product quality. The aim of the present work was to study the applicability of at-line near-infrared (NIR) and Raman spectroscopy approach in the monitoring of the freeze-drying process.

Investigation of design space for freeze-drying injectable ibuprofen using response surface methodology.

This study explores the use of a statistical model to build a design space for freeze-drying two formulations with ibuprofen. A 2 × 3 factorial experimental design was used to evaluate independent variables (filling volume and annealing time) and responses as residual moisture content, specific surface area and reconstitution time. A statistical model and response surface plots were generated to define the interactions among the selected variables.

Process analytical technology tools for process control of roller compaction in solid pharmaceuticals manufacturing.

This article presents an overview of using process analytical technology in monitoring the roller compaction process. In the past two decades, near-infrared spectroscopy, near-infrared spectroscopy coupled with chemical imaging, microwave resonance technology, thermal effusivity and various particle imaging techniques have been used for developing at-, off-, on- and in-line models for predicting critical quality attributes of ribbons and subsequent granules and tablets. The common goal of all these methods is improved process understanding and process control, and thus improved production of high-quality products.

Solidification of SMEDDS by fluid bed granulation and manufacturing of fast drug release tablets.

Solidification of self-microemulsifying drug delivery systems (SMEDDS) is a rising experimental field with important potential for pharmaceutical industry, however fluid-bed granulation with SMEDDS is yet an unexplored solidification technique. The aim of the study was to solidify carvedilol-loaded SMEDDS utilizing fluid bed granulation process and to investigate how the formulation variables (type of solid carrier, optimization of granulation dispersion) and fluid-bed granulation process variables can be optimized in order to achieve suitable agglomeration process, high drug loading and appropriate product characteristics. Obtained granulates exhibited complete drug release, comparable to liquid SMEDDS and superior to crystalline carvedilol, nevertheless compromise between large SMEDDS loading and appropriate flow properties of the granules has to be made.

Solubilization of ibuprofen for freeze dried parenteral dosage forms.

Ibuprofen, a weakly acidic non-steroidal anti-inflammatory drug having poor aqueous solubility, is a challenging drug for the development of pharmaceutical formulations, resulting in numerous research attempts focusing on improvement of its solubility and consequently bioavailability. Most studies have been done for solid dosage forms, with very little attention paid to parenterals. Hence, the main purpose of the present study was to enhance ibuprofen solubility as a result of formulation composition and the freeze drying process.

Solidification of carvedilol loaded SMEDDS by swirling fluidized bed pellet coating.

Self-(micro)emulsifying drug delivery systems (S(M)EDDS) have emerged as effective vehicles for enhancing bioavailability of poorly water soluble drugs, however solidification of the systems represents a major challenge. Objective of this study was development of carvedilol loaded liquid SMEDDS and transformation into solid pellets employing fluid-bed coating technologies. Carvedilol-loaded formulation of SMEDDS was comprised of Capmul® MCM EP, castor oil, Kolliphor® RH40 and PEG 400.

A study on the applicability of multiple process analysers in the production of coated pellets.

Process analytical technology (PAT) has become an important factor in design, analysis and control of complex technological processes. In the present study, pellet coating process was monitored using four different PAT approaches, i.e.

Does the performance of wet granulation and tablet hardness affect the drug dissolution profile of carvedilol in matrix tablets?

Wet granulation is mostly used process for manufacturing matrix tablets. Compared to the direct compression method, it allows for a better flow and compressibility properties of compression mixtures. Granulation, including process parameters and tableting, can influence critical quality attributes (CQAs) of hydrophilic matrix tablets.

Preparation of poloxamer-based nanofibers for enhanced dissolution of carvedilol.

Polymer nanofibers have become increasingly important for improvement of dissolution and bioavailability of poorly soluble drugs, representing a great challenge in pharmaceutical development. Here, we introduced a new concept of using amphiphilic polymers as fundamental excipients in electrospun nanofibers, which would improve drug solubilization and accelerate its release. Hydrophilic poloxamer-based nanofibers were developed as a novel drug delivery system for carvedilol.

Overview of PAT process analysers applicable in monitoring of film coating unit operations for manufacturing of solid oral dosage forms.

Over the last two decades, regulatory agencies have demanded better understanding of pharmaceutical products and processes by implementing new technological approaches, such as process analytical technology (PAT). Process analysers present a key PAT tool, which enables effective process monitoring, and thus improved process control of medicinal product manufacturing. Process analysers applicable in pharmaceutical coating unit operations are comprehensibly described in the present article.

Overview of solidification techniques for self-emulsifying drug delivery systems from industrial perspective.

Self-emulsifying drug delivery systems (SEDDS) are lipid formulations that improve solubility and oral bioavailability of the incorporated drug with poor biopharmaceutical properties. As liquids they are traditionally filled into soft or hard capsules. Transformation of SEDDS into solid dosage form has been extensively investigated in the recent years because solid dosage forms improve stability, handling and patient compliance.

A study of critical functionality-related characteristics of HPMC for sustained-release tablets.

The drug release profile from hydrophilic matrix tablets can be crucially affected by the variability of physicochemical properties of the controlled release agent. This study investigates and seeks to understand the functionality-related characteristics (FRCs) of hydroxypropyl methylcellulose (HPMC) type 2208, K4M grade, that influence the release rate of the model drug carvedilol from hydrophilic matrix tablets during the entire dissolution profile. The following FRCs were examined: particle size distribution, degree of substitution, and viscosity.

The performance of HPMC matrix tablets using various agglomeration manufacturing processes.

Context: The flow and compaction properties of a compaction mixture or powder and the drug-release profile of final tablets are important critical quality attributes (CQAs) that have an impact on the overall performance of hydrophilic matrix tablets. The selection of granulation method can importantly affect these CQAs.

Objective: This study investigates various agglomeration methods of sustained-release formulation using HPMC K4M as a release polymer with various wet- and dry-granulation techniques.

Applicability of near-infrared spectroscopy in the monitoring of film coating and curing process of the prolonged release coated pellets.

Although process analytical technology (PAT) guidance has been introduced to the pharmaceutical industry just a decade ago, this innovative approach has already become an important part of efficient pharmaceutical development, manufacturing, and quality assurance. PAT tools are especially important in technologically complex operations which require strict control of critical process parameters and have significant effect on final product quality. Manufacturing of prolonged release film coated pellets is definitely one of such processes.

Effect of crystal habit on the dissolution behaviour of simvastatin crystals and its relationship to crystallization solvent properties.

Simvastatin crystals, having same crystal structure but different types of habits and hence different intrinsic dissolution rate, were prepared by recrystallization from solvents selected according to their polarity index. Scanning electron microscopy, laser diffraction, image analysis, X-ray powder diffractometry, Fourier transform infrared spectroscopy and differential scanning calorimetry were used to investigate the physicochemical characteristics of the prepared crystals. The isolated crystals exhibited different crystal habits but possessed the same internal crystal structure.

Flow and compaction properties of hypromellose: new directly compressible versus the established grades.

Context: Information about flow and compaction properties of hypromellose (HPMC) polymers is essential for the technologists who are facing challenges regarding poor flow and compaction while developing new controlled release matrix tablets. There is a profound lack of studies in this field and none of the published ones deal with the compaction of the newly introduced HPMC grades specifically designed for direct compression (DC).

Objective: The objective behind this study was the evaluation of flow and compaction properties of six different grades of HPMC substitution type 2208 polymers, including two second generation directly compressible grades from Dow Chemical Company (K100LV, K15M, K4M CR, K4M DC, K100M CR and K100M DC).

Influence of Crystal Habit on the Dissolution of Simvastatin Single Crystals.

In order to achieve better in-vivo performance of the final dosage form comprising a poorly soluble drug the physicochemical properties of the active pharmaceutical ingredient can be altered not only by changing the solid state form but also through the conversion of their crystal habits. To elucidate this approach in the case of simvastatin, the dissolution behaviour of large crystals with the same internal structure but expressing different crystal habits was studied using atomic force microscope. The obtained differences in the dissolution were explained through the determination of crystal morphology its orientation and assignation of the molecular functional groups that were emerging on the surface of the dissolving crystal face.