Current Pharmaceutical Design - Volume 24, Issue 21, 2018

Background: Nowadays, nanoparticles are of great interest for the industry due to their numerous possible applications in several fields. Research on this topic seeks to develop many procedures to produce nanoparticles, mostly at lab scale, batch-wise and with low yield. These procedures generally do not suit industrial needs of continuous, high capacity production. Moreover, the product characteristics require targeting narrow particle size distributions and high quality, which is difficult to achieve by traditional equipment. Methods: Process intensification techniques aim to minimize plant size of continuous, high yield equipment capable to produce specific sized, high quality nanoparticles, combined with an increase in energy efficiency, safety and cost reduction. Discussion: This paper reviews some adopted Process Intensification (PI) techniques for nanoparticles synthesis processes employed in the food and pharmaceutical sector. Conclusion: By reducing the technology transfer gap, nanotechnologies may become convenient and feasible, allowing both industries to achieve the production of higher quality products with particular characteristics without sensibly increasing additional costs. This will represent in the next future a strategic key feature of industries in the global market.

Background: The development of solid drug dosage form and food ingredients is constrained by their low solubility, low dissolution, low bioavailability and poor physicochemical properties. Formation of cocrystal is a novel and promising method to enhance and improve the properties of materials without breaking the covalent bonds. Methods: The goal of this review is to summarize the cocrystals and their applications in the field of Active Pharmaceutical Ingredients (APIs) and food ingredients (AFIs), mainly on the effective improvements of APIs' and AFIs' pharmacokinetic, physicochemical and mechanical properties by the formation of cocrystals. Results: After years of research and development on cocrystals in the area of pharmaceutical and food industries, significant progress has been made. Formation of cocrystal is an efficient method for improving the solubility, dissolution rate, permeability and in vivo bioavailability of APIs and AFIs, as well as for enhancing stability and mechanical properties. Conclusion: Cocrystals exhibit complex structures which can conspicuously affect the physical and chemical properties of original substance, with good clinical performance and outstanding stability during processing and storage.

Background and Objective: Bio-soft material, a class of derivatives of the natural or synthetic material, is getting more and more prevalent in biomedical researches and applications due to the advantages such as in-vivo biodegradation, good water solubility and designable targeting ability. With the presence of bio-soft materials, the drug nanocrystal can be easily generated and aggregated in a feasible process. Given the promising application of the bio-soft material in biological and chemical research, it is valuable to discuss the crucial step in designing bio-soft materials and analyze the emerging properties of bio-soft materials. Methods: A comprehensive literature survey in the field of bio-soft material development and analysis has been conducted. The collected data and figures were meticulously analyzed and interpreted. Results: In this review, the details of bio-soft materials based nanocrystal were demonstrated in three sections with respect to different materials. In each section, the pros and cons for each bio-soft material and its derivatives were elaborately listed and discussed. Conclusion: The review enables an insightful discussion about the properties and the applications of existing biosoft material. It may contribute to the further researches about bio-soft material development and analysis.

Background: Nanocrystallization technologies have been widely studied in recent years, as the formulation of drug nanocrystals solves problems of poor drug solubility and bioavailability. However, drug nanocrystals in the size range of 1–1000 nm usually need to be accompanied by stabilizers, such as polymers or surfactants, to enhance their stability. Despite their simplicity, improved dissolution rate, and enhanced bioavailability, the limited stability of nanocrystal formulations has prevented further development. Objective: The most effective way to handle this instability is to use stabilizers. This paper reviews various factors to consider for the production of stable drug nanocrystals and provides suggestions to overcome the problems associated with instability, such as aggregation and Ostwald ripening. Through various examples of stabilizers acting via electrostatic and steric stabilization, this review highlights the scope of enhancing the stability of drug nanocrystals. Conclusion: Studies on stabilizers used in the production of drug nanocrystals are ongoing; various factors, such as the effect of zeta potential on the stability of drug nanosuspensions, have already been revealed. However, it is necessary to determine the most appropriate stabilizer experimentally based on the various mechanisms and factors have been reviewed since the possible interactions between each drug and stabilizer are diverse.

Background: Nowadays, the polymorphism of solid materials plays important roles in pharmaceutical field, food industry, fine chemicals and so on. Due to the differences in crystal structure, different polymorphs of a given solid drug show different physicochemical characteristics, which may lead to different drug bioavailability and half-life of the drug. Studies about polymorphism of solid drugs have become an indispensable important component in dosage form design, approval, production and quality control of drugs. Methods: In order to reveal the dissimilarity between polymorphs, the classification approach of polymorphism and the features of each category are outlined and discussed in this paper. The influence of polymorphism on physicochemical characteristics of solid drugs such as powder property, melting point, enthalpy of fusion, dissolution behavior and stability are discussed in detail. Furthermore, a variety of differences in drug bioavailability and curative effect of polymorphs are also summarized and discussed. Results: Due to the differences in internal crystalline structure, different polymorphs of the same solid drugs generally show different physicochemical properties, including powder property, melting point, enthalpy of fusion, dissolution behavior and stability. Furthermore, different polymorphs of solid drugs often exert a diverse curative effect. Conclusion: As one of the significant factors to affect the quality and curative effect of solid drugs, polymorphism of drug substances has been investigated in the pharmaceutical field for over 50 years. Considerable studies indicate that comprehensive understanding of polymorphism is important for development, dosage form design, approval, production, quality control and curative effect of solid drugs.

Polymorphism is a behavior of a substance to crystallize into more than one district crystal structures. Preferential formation of a polymorph depends strongly on the kinetics of the relevant mechanisms. Solutionmediated polymorphic transformation is an important mechanism in crystallization of organic compounds from solution. Knowing its kinetics allows us to understand the process and control the polymorphic formation. In this review, concepts, kinetics, and process modeling of crystallization and solution-mediated polymorphic transformation are examined and summarized.

Background: As the quick development of modern methods and technologies currently, more and more drugs have been invented with a better efficiency. However, the poor water solubility has limited the drugs' pharmaceutical application. Methods: Tremendous research has been put in the design and development of nanocrystals for pharmaceutical applications over the past few decades. The nanocrystals not only have the chance to solve the poor solubility problem, but also could conquer the bioavailability and even the specific delivery problems. The physical properties of drugs can be changed dramatically due to the change of their size in a nanodimension. Therefore, the nanocrystals have great potential to overcome the challenge to design and development of new drugs for pharmaceutical applications. Results: In this review, we provide an overview of the recent trends in nanocrystals for pharmaceutical applications. Conclusion: The current technologies including top-down, bottom-up, and combinative technologies for nanocrystals were fully examined. Most importantly, the emphasis is put on the pharmaceutical applications including their formulation, administration methods, safety, and toxicity. The commercial status, limitations, challenges, and future trends of the nanocrystals for pharmaceutical applications were also discussed.

Background: Discovery and development of BCS class 1 drugs through high throughput screening is one of the biggest challenge faced by formulation scientist. Methods: There are a number of approaches that have been exploited to enhance the solubility and permeability of drugs. Among them, development of nanosuspension has offered several benefits. These techniques may increase effective surface area due to nanonization of drug particles and further increases saturation solubility and dissolution properties for improved bioavailability. Various development methods are patented which are cost effective and easy to scale up. Conclusion: Several unique features of nanosuspension make it a versatile delivery system for different routes of administration including oral, dermal, ocular, parenteral and pulmonary. The present review is focused on preparatory techniques and formulation considerations of nanosuspension. Brief information about evaluation parameters, applications of nanosuspension in drug delivery and patented and marketed products available is also discussed.

Background and Objective: Nanocrystal technology is an effective approach which can increase the dissolution rate of poorly water-soluble drugs by raising their saturation solubility, thus improving the drug bioavailability. With the development of nanocrystals, its preparation approaches have gradually matured, which can be generally divided into Bottom-up, Top-down and Combinative technologies. Methods: A systematic literature review in the field of nanocrystal technology for the cancer treatment was scanned and collected data was detailedly analyzed and summarized. Results: Over the past decade, several anticancer drug nanocrystals have been explored and evaluated in preclinical studies and clinical trials. This review mainly covers the utilizations of the nanocrystal technology in enhancing the saturation solubility of anticancer drugs associated with the increased bioavailability and anticancer efficacy. Preparation methods and characterizations of nanocrystals are also introduced in brief. In addition, one critical step in the formation of drug nanocrystals is selecting suitable stabilizers for the system. Many types of research are heading towards the role of the stabilizers in the final nanocrystals formulation. So we summed up several commonly used stabilizers in order to give a reference to the further study. At last, we discussed some considerations raised by the application of nanocrystal drugs for cancer treatment. Conclusion: This review is likely to enable a detailed insight on nanocrystal technology as a strategy to improve drug bioavailability and antitumor efficacy for the cancer treatment and be of particular interest to pharmaceutical industry.

Crystallization is a significant process employed to produce a wide variety of materials in pharmaceutical and food area. The control of crystal dimension, crystallinity, and shape is very important because they will affect the subsequent filtration, drying and grinding performance as well as the physical and chemical properties of the material. This review summarizes the special features of crystallization technology and the preparation methods of nanocrystals, and discusses analytical technology which is used to control crystal quality and performance. The crystallization technology applications in pharmaceutics and foods are also outlined. These illustrated examples further help us to gain a better understanding of the crystallization technology for pharmaceutics and foods.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, leading to the second most likely cause of cancer-related deaths. Medical imaging is crucial in clinic for HCC screening and diagnosis. Due to the relatively high special resolution and excellent sensitivity, magnetic resonance imaging (MRI) by using magnetic nanoparticle-based contrast agents has been used so far in HCC imaging and staging, demonstrating great potential and promising in vivo applications. This review focuses on the use of different magnetic nanoparticles for construction of HCC nanoprobes for MR imaging and theranostic purpose.

Background and objective: Pulmonary drug delivery has transformed over a past few decades from being a platform for local pulmonary disease treatment to systemic drug delivery opportunities. In case of pulmonary delivery systems, particle properties are critical as they affect inhalation efficacy, pulmonary deposition, drug delivery and overall performance. With this in view, particle engineering has emerged as an advanced science that helps in designing of efficacious pulmonary delivery systems. Among various particle engineering branches, crystal engineering is being extensively explored as it provides an opportunity to optimize particles at morphological, physicochemical and molecular levels which are essential to understand the role of crystal engineering in pulmonary drug delivery. Methods: A thorough literature survey in the field of crystal engineering approaches explored for pulmonary drug delivery was conducted and the collected data was meticulously studied and summarized. Results: In the review, pulmonary system is discussed with respect to various sites for drug deposition in respiratory tract, mechanism of drug deposition and clearance. Further, critical crystal parameters are discussed in-depth and various crystal engineering methods are summarized with emphasis on their impact on pulmonary delivery. Also, inhalation devices are overviewed to understand their performance in relation to crystal based pulmonary formulations. Conclusion: The review enabled a detailed insight on crystal engineering approaches for design of pulmonary delivery systems.

Background: Pharmaceutical industry is witnessing increased pressure to introduce innovative and efficient processes for manufacturing Active Pharmaceutical Ingredients (APIs) in order to be competitive as well as to meet the stringent product quality requirements set by regulatory authorities. Crystallization with its ability to engineer the final product to the desired qualities such as purity, polymorphic form, particle size and shape is one of the most important steps involved in the manufacturing of APIs. Therefore, development of crystallization processes with better understanding of process parameters and their impact on quality of APIs and subsequently the drug products assume great significance for the pharmaceutical industry. Methods: This review paper focuses on the application of PAT tools, an integral part of Quality by Design (QbD) approach, for better understanding, control, and design of crystallization processes in the manufacturing of APIs. Results: Firstly, various steps involved in the drug development process are introduced briefly with emphasis on crystallization as one of the most important steps in manufacturing of drug products. Secondly, Critical Quality Attributes (CQAs) of drug products, their dependence on material attributes of APIs and role of crystallization in manipulating material attributes of APIs has been discussed. Finally, application of PAT tools such as advanced process analyzers for continuous monitoring, chemometric methods for multivariate data analysis, and control strategy for APIs crystallization processes has been reviewed along with some examples. Conclusion: Application of PAT in crystallization of APIs facilitates development of robust processes that works within the design space to produce the drug products of consistent quality. Furthermore, it opens up the opportunities for continuous improvement of the process by generating knowledge base of existing processes.

Background: Crystal engineering is dealing with the creation of new structures and new properties in drug molecules through inter-molecular interactions. Researchers of pharmaceutical sciences have used this knowledge to alter the structure of crystalline medications in order to remedy the problems of more than 40% of the new designed drugs which suffer from low solubility and consequently, low bioavailability which have limited their clinical application. Methods: This review covers a broad spectrum of aspects of the application of crystal engineering in pharmaceutics and includes a comprehensive wide range of different techniques used in crystal engineering of active pharmaceutical ingredients (API) to compensate the low water solubility and bioavailability of drugs related specially to class II of biopharmaceutical classification system (BCS). Results: These techniques include; crystalline habit modification, polymorphism, solvates and hydrates, cocrystals, surface modification, crystallization, spherical agglomeration, liquisolid crystals and solid dispersions which are introduced and discussed in this review article. Conclusion: Each of these techniques has advantages and limitations which are emphasized on them.

Background: Nanocrystals technology is a promising method for improving the dissolution rate and enhancing the bioavailability of poorly soluble drugs. In recent years, it has been developing rapidly and applied to drug research and engineering. Nanocrystal drugs can be formulated into various dosage forms. Objective: This review mainly focused on the nanocrystals technology and its application in pharmaceutical science. Firstly, different preparation methods of nanocrystal technology and the characterization of nanocrystal drugs are briefly described. Secondly, the application of nanocrystals technology in pharmaceutical science is mainly discussed followed by the introduction of sustained release formulations. Then, the scaling up process, marketed nanocrystal drug products and regulatory aspects about nanodrugs are summarized. Finally, the specific challenges and opportunities of nanocrystals technology for pharmaceutical science are summarized and discussed. Conclusion: This review will provide a comprehensive guide for scientists and engineers in the field of pharmaceutical science and biochemical engineering.

Fats are essential nutrients that have a significant role in the human diet and are essential to provide energy. Fatty acids are present in several types of lipids, such as triglycerides and phospholipids. Fatty acids differ among them, depending on the number of double bonds and on the length of the hydrocarbon chains. If there are no double bonds, the fatty acids are considered saturated and show a linear structure. Compounds with double bonds are unsaturated and have bent structure. The saturated fatty acids are usually solid at room temperature and the unsaturated fatty acids are liquid at that very same temperature. These compounds are of recognized value as raw materials for drug delivery systems, such as lipid nanoparticles. The behaviour of the macroscopic aspects of fat polymorphisms is directly influenced by the melting point, the crystallization and their polymorphic transformations. In this work, we revise the most critical factors contributing for the long-term stability of lipid nanoparticles, as well as the influence of the polymorphism on the loading capacity for drug molecules.