Blend Segregation in Tablets Manufacturing and Its Effect on Drug Content Uniformity—A Review

Content uniformity (CU) of the active pharmaceutical ingredient is a critical quality attribute of tablets as a dosage form, ensuring reproducible drug potency. Failure to meet the accepted uniformity in the final product may be caused either by suboptimal mixing and insufficient initial blend homogeneity, or may result from further particle segregation during storage, transfer or the compression process itself. This review presents the most relevant powder segregation mechanisms in tablet manufacturing and summarizes the currently available, up-to-date research on segregation and uniformity loss at the various stages of production process—the blend transfer from the bulk container to the tablet press, filling and discharge from the feeding hopper, as well as die filling. Formulation and processing factors affecting the occurrence of segregation and tablets’ CU are reviewed and recommendations for minimizing the risk of content uniformity failure in tablets are considered herein, including the perspective of continuous manufacturing.

Analysis of Flow Characteristics and Paracetamol Tablet Hardness Using 2D Double Mixer of Design Drum Type with Rotation and Mixing Time Variations

One of the tablet manufacturing processes using the wet granulation method is the process of mixing the active ingredient granules, fillers, binders and pelicans. The parameters of the mixing process are important to study because they will affect the physical properties of the tablet. This study studied the effect of the variable duration and the size of the mixing cycle on the physical properties of paracetamol tablets using a 2D double mixer. The results of the analysis and testing showed that the variation of mixing time and the size of the rotation had a significant effect on the flow properties of the granules and the hardness of the tablets. In addition, the optimal parameter results to obtain optimal tablet hardness occurred at 15 minutes of mixing process and 50 rpm of rotation.

COPROCESSED EXCIPIENTS-PREPARATION AND FUNCTIONALITIES

With the advancements of tablet manufacturing techniques, the urge to develop and produce high, multifunctional excipients have been increased to meet the set of functionalities. The functionality of the coprocessed excipients enhances the manufacturing process and as well improves quality,performance of tablets.Coprocessed excipients are defined as the mixture of two or more than two excipients that possess specific potential advantages which cannot be produced by simple physical mixing of same combination of excipients.The aim of this review is to focus on advantages, preparation methods of coprocessed excipients. Coprocessing is a technique, where these compendial or non compendial excipients are modified physically in a special way without changing their chemical structure.This review article discusses the need for developing coprocessed excipients, advantages of coprocessed excipients, different methods of preparation of coprocessed excipients and functionalities of coprocessed excipients

Concept for the Urban Production of Pharmaceuticals to Compensate for Local Shortages

Long and complex supply chains are one of the main reasons for drug shortages. The COVID-19 pandemic and abrupt global lockdown have highlighted how precarious the global pharmaceutical market is. This paper presents a concept for pharmaceutical production in greenfield, urban and local areas as a way to mitigate drug shortages around the world. This approach represents a paradigm shift because the production of medicine tablets still happens mostly at big brownfield sites. The concept is based on the VDI 5200 guidelines and procedures used for factory planning at general production plants. The derived methodology takes three phases into account and enables the integration of continuous tablet manufacturing into urban areas to supply the local population with medicine.

Technologies in Bilayer Tablet Manufacturing: A Review

Bilayer tablet is a recent time for the successful development of controlled release formulation along with various quality to provide a way of the successful drug delivery system. Over the past 30 years stated that the cost and complications involved in marketing new drug entities have increased, with consequent recognition of therapeutic advantages of controlled drug delivery, greater attention has been concentration on development of sustained or controlled release drug delivery systems. Bilayer tablet it is used in the different aspect for anti-inflammatory and analgesic. Bilayer tablet incidental release of two drugs in combination, separate two incompatible substance and also for sustained release tablet in which one layer is immediate release as initial dose and second layer is maintenance dose. Bilayer tablet is enhancing beneficial technology to control the shortcoming of the single layered tablet. There is various application used in the bilayer tablets.

The Challenges of Producing Bilayer Tablet: A Review

Bilayer tablets are the advanced form of conventional immediate release tablet system, which consist of either two similar or different drugs combined in a single dose for effective treatment of the disease improving patient compliance. However, the multilayer tablet technology is demanding It also necessitates meticulous selection of excipients and manufacturing conditions for each technological stage. The aim of this review is to provide an outline of state of art of bilayer tablet technology and emphasise the difficulties experienced during Bilayer tablet manufacturing along with its intend solutions for these challenges. Keyword: Bilayer tablet, Conventional release, Challenges encountered, Compliance.

Impact of Critical Material Attributes (CMAs)-Particle Shape on Miniature Pharmaceutical Unit Operations

The U.S. Food and Drug Administration (FDA) emphasizes drug product development by Quality by Design (QbD). Critical material attributes (CMAs) are a QbD element that has an impact on pharmaceutical operations and product quality. Pharmaceutical drugs often crystallize as needle-shaped (a CMA) particles and affect the process due to poor flowability, low bulk density, and high compressibility, and eventually the product performance. In this study, the product obtained from crystallization was needle-shaped Ciprofloxacin HCl (CIPRO), formed lumps during drying, and compacted during processing through feeders. To delump small amounts of materials and break the needles, multiple available devices (mortar-pestle, Krups grinder) and custom-made grinder were assessed before formulation. The processed CIPRO powder was then used to make tablets in the miniature tablet manufacturing unit developed by the team at MIT. The critical quality attributes (CQA) of the tablets, set by the United States Pharmacopeia (USP), were then assessed for the drug powder processed with each of these devices. Powder properties comparable to commercial CIPRO were obtained when the custom MIT-designed grinder was used, leading to tablets that meet the USP criteria, with comparable dissolution profiles of those for marketed CIPRO tablets. This study demonstrates how needle-shaped crystals have an impact on pharmaceutical operations, even if it is on a miniature scale, and how proper shape and subsequent flow properties can be obtained by processing the particles through the MIT team-designed grinder. Graphical Abstract