Recent Advancements in Pharmaceutical Cocrystals, Preparation Methods and Their Applications

2021 ◽  
Vol 27 ◽  
Author(s):  
Deeksha Manchanda ◽  
Arun Kumar ◽  
Arun Nanda
Keyword(s):  
Aqueous Solubility ◽  
Active Pharmaceutical Ingredient ◽  
Preparation Methods ◽  
Pharmaceutical Dosage Forms ◽  
Physiochemical Properties ◽  
Pharmaceutical Cocrystals ◽  
Regulatory Guidelines ◽  
Development Pipeline ◽  
Covalently Linked ◽  
Further Development

The issue of poor aqueous solubility is a major hurdle in pharmaceutical dosage forms design. A large number of active molecules in the research and development pipeline are known to possess poor aqueous solubility and hence are not suitable for further development. Therefore, the pharmaceutical industry is continuously in search of techniques to tackle the issue of poor solubility. Cocrystallization has gained popularity as one such technique for the modulation of physicochemical properties of an active pharmaceutical ingredient (API). Pharmaceutical cocrystals consists of an API non-covalently linked to a crystal former or coformer that plays an important role in the imparting the desired properties to the cocrystal. Cocrystallization of an API with a suitable coformer not only enhances solubility but also helps in tweaking other physiochemical properties such as stability, bioavailability, mechanical properties, etc. without any change in the pharmacological activity of the API. The past decade saw an enormous growth in cocrystal research which paved the way for drug-drug, higher order and nano-sized cocrystals and further exploration of the applications of cocrystals is still going on. Recently FDA and EMA released regulatory guidelines for pharmaceutical cocrystals which grant them a status similar to that of polymorphs and salts which in turn opened a wider prospect for pharmaceutical cocrystals in terms of intellectual property.

scholarly journals Recent Advances in Pharmaceutical Cocrystals: From Bench to Market

2021 ◽  
Vol 12 ◽  
Author(s):  
Ravi Kumar Bandaru ◽  
Smruti Rekha Rout ◽  
Gowtham Kenguva ◽  
Bapi Gorain ◽  
Nabil A. Alhakamy ◽  
...  
Keyword(s):  
Pharmacokinetic Profile ◽  
Pharmaceutical Compounds ◽  
Dosage Forms ◽  
Active Pharmaceutical Ingredients ◽  
Design Development ◽  
Pharmaceutical Dosage Forms ◽  
Pharmaceutical Cocrystals ◽  
Pharmaceutical Ingredients ◽  
Regulatory Guidelines ◽  
Pharmaceutical Industries

The pharmacokinetics profile of active pharmaceutical ingredients (APIs) in the solid pharmaceutical dosage forms is largely dependent on the solid-state characteristics of the chemicals to understand the physicochemical properties by particle size, size distribution, surface area, solubility, stability, porosity, thermal properties, etc. The formation of salts, solvates, and polymorphs are the conventional strategies for altering the solid characteristics of pharmaceutical compounds, but they have their own limitations. Cocrystallization approach was established as an alternative method for tuning the solubility, permeability, and processability of APIs by introducing another compatible molecule/s into the crystal structure without affecting its therapeutic efficacy to successfully develop the formulation with the desired pharmacokinetic profile. In the present review, we have grossly focused on cocrystallization, particularly at different stages of development, from design to production. Furthermore, we have also discussed regulatory guidelines for pharmaceutical industries and challenges associated with the design, development and production of pharmaceutical cocrystals with commercially available cocrystal-based products.

scholarly journals A Novel In Vitro Approach for Simultaneous Evaluation of CYP3A4 Inhibition and Kinetic Aqueous Solubility

2014 ◽  
Vol 20 (2) ◽  
pp. 254-264 ◽  
Author(s):  
José Pérez ◽  
Caridad Díaz ◽  
Francisco Asensio ◽  
Alexandra Palafox ◽  
Olga Genilloud ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Physicochemical Properties ◽  
Safety Concern ◽  
Aqueous Solubility ◽  
Cyp3a4 Inhibition ◽  
Use Of Resources ◽  
Simultaneous Evaluation ◽  
New Chemical Entities ◽  
Further Development

In the early stages of the drug discovery process, evaluation of the drug metabolism and physicochemical properties of new chemical entities is crucial to prioritize those candidates displaying a better profile for further development. In terms of metabolism, drug–drug interactions mediated through CYP450 inhibition are a significant safety concern, and therefore the effect of new candidate drugs on CYP450 activity should be screened early. In the initial stages of drug discovery, when physicochemical properties such as aqueous solubility have not been optimized yet, there might be a large number of candidate compounds showing artificially low CYP450 inhibition, and consequently potential drug–drug interaction toxicity might be overlooked. In this work, we present a novel in vitro approach for simultaneous evaluation of CYP3A4 inhibition potential and kinetic aqueous solubility (NIVA-CYPI-KS). This new methodology is based on fluorogenic CYP450 activities and turbidimetric measurements for compound solubility, and it provides a significant improvement in the use of resources and a better understanding of CYP450 inhibition data.

scholarly journals CO-CRYSTALS: A REVIEW

2018 ◽  
Vol 8 (6-s) ◽  
pp. 350-358 ◽  
Author(s):  
Shilpa Chaudhari ◽  
Sarika Ankushrao Nikam ◽  
Neetu Khatri ◽  
Shubham Wakde
Keyword(s):  
Melting Point ◽  
Physicochemical Properties ◽  
Spray Drying ◽  
Supercritical Fluid ◽  
Oral Bioavailability ◽  
Aqueous Solubility ◽  
New Product ◽  
Active Pharmaceutical Ingredient ◽  
Pharmacological Properties ◽  
Hot Melt

In development of new product major constraints are poor aqueous solubility and low oral bioavailability. Crystallization is one the approach has been used for enhancement of solubility of poorly aqueous soluble drugs also helps to improve physicochemical properties such as melting point, tabletability, solubility, stability, bioavailability and permeability with preserving the pharmacological properties of the active pharmaceutical ingredient. Different methods have been used for the synthesis of cocrystal such as grinding, slurry, antisolvent, hot melt extrusion, sonocrystallization, supercritical fluid, spray drying etc. The article highlights the co-crystallization, its methods and significance.  

Review on Pharmaceutical Co-Crystals and Design Strategies

2021 ◽  
pp. 175-180
Author(s):  
A.V.S. Ksheera Bhavani ◽  
A. Lakshmi Usha ◽  
Kayala Ashritha ◽  
Radha Rani E.
Keyword(s):  
Aqueous Solubility ◽  
Active Pharmaceutical Ingredient ◽  
Crystal Formation ◽  
Stoichiometric Ratio ◽  
Design Strategies ◽  
Great Opportunity ◽  
Drug Products ◽  
Drug Substances ◽  
Component Systems ◽  
Physical And Chemical

Poor aqueous solubility and low oral bioavailability of an active pharmaceutical ingredient are the major constraints during the development of new product. Various approaches have been used for enhancement of solubility of poorly aqueous soluble drugs, but success of these approaches depends on physical and chemical nature of the molecules being developed. Co-crystallization of drug substances offers a great opportunity for the development of new drug products with superior physicochemical such as melting point, tabletability, solubility, stability, bioavailability and permeability, while preserving the pharmacological properties of the active pharmaceutical ingredient. Co-crystals are multi component systems in which two components, an active pharmaceutical ingredient and a coformer are present in stoichiometric ratio and bonded together with non-covalent interactions in the crystal lattice. This review article presents a systematic overview of pharmaceutical co-crystals, differences between co-crystals with salts, solvates and hydrates are summarized along with the advantages of co-crystals with examples. The theoretical parameters underlying the selection of coformers and screening of co-crystals have been summarized and different methods of co-crystal formation and evaluation have been explained.

scholarly journals Analytical Dissection of an Automotive Li-Ion Pouch Cell

Batteries ◽  
2019 ◽  
Vol 5 (4) ◽  
pp. 67 ◽  
Author(s):  
Kovachev ◽  
Schröttner ◽  
Gstrein ◽  
Aiello ◽  
Hanzu ◽  
...  
Keyword(s):  
State Of The Art ◽  
Measured Data ◽  
Li Ion Batteries ◽  
Complete Sample ◽  
Analytical Methodology ◽  
Preparation Methods ◽  
Analysis Techniques ◽  
Sample Preparation Procedure ◽  
Li Ion ◽  
Further Development

Information derived from microscopic images of Li-ion cells is the base for research on the function, the safety, and the degradation of Li-ion batteries. This research was carried out to acquire information required to understand the mechanical properties of Li-ion cells. Parameters such as layer thicknesses, material compositions, and surface properties play important roles in the analysis and the further development of Li-ion batteries. In this work, relevant parameters were derived using microscopic imaging and analysis techniques. The quality and the usability of the measured data, however, are tightly connected to the sample generation, the preparation methods used, and the measurement device selected. Differences in specimen post-processing methods and measurement setups contribute to variability in the measured results. In this paper, the complete sample preparation procedure and analytical methodology are described, variations in the measured dataset are highlighted, and the study findings are discussed in detail. The presented results were obtained from an analysis conducted on a state-of-the-art Li-ion pouch cell applied in an electric vehicle that is currently commercially available.

Progress in the Preparation of Silver Nanometer Antibacterial Material

2020 ◽  
Vol 996 ◽  
pp. 76-81
Author(s):  
Ben Jiao Li ◽  
Song Li ◽  
Bin Rong Ma ◽  
Yong Jing ◽  
Zhe Ming Zhang ◽  
...  
Keyword(s):  
Chemical Method ◽  
Antibacterial Agents ◽  
Antibacterial Properties ◽  
Physical Method ◽  
Biological Method ◽  
Preparation Methods ◽  
Antibacterial Materials ◽  
Development And Utilization ◽  
Antibacterial Material ◽  
Further Development

Silver inorganic antibacterial agents have been widely used inbiotechnology, bioengineering science, electronics, optics and water treatment because of their strong bactericidal ability, high safety and durable antibacterial properties. In this paper, the preparation methods of silver nanoparticles are reviewed, including physical method, chemical method and biological method, in order to provide a reference for the further development and utilization of silver nano-antibacterial materials.

Crystal structure of pharmaceutical cocrystals of 2,6-diaminopyridine with piracetam and theophylline

2017 ◽  
Vol 73 (10) ◽  
pp. 767-772 ◽  
Author(s):  
Melissa Hidekel Durán-Palma ◽  
Sonia Sanet Mendoza-Barraza ◽  
Nancy Evelyn Magaña-Vergara ◽  
Francisco Javier Martínez-Martínez ◽  
Juan Saulo González-González
Keyword(s):  
Self Assembly ◽  
Active Pharmaceutical Ingredient ◽  
Two Dimensional ◽  
X Ray Diffraction ◽  
Orthorhombic Space Group ◽  
Hydrogen Bond Interaction ◽  
Pharmaceutical Cocrystals ◽  
Space Group ◽  
X Ray ◽  
Grinding Method

Pharmaceutical cocrystals are crystalline solids formed by an active pharmaceutical ingredient and a cocrystal former. The cocrystals 2,6-diaminopyridine (DAP)–piracetam [PIR; systematic name: 2-(2-oxopyrrolidin-1-yl)acetamide] (1/1), C5H7N3·C6H10N2O2, (I), and 2,6-diaminopyridine–theophylline (TEO; systematic name: 1,3-dimethyl-7H-purine-2,6-dione) (1/1), C5H7N3·C7H8N4O2, (II), were prepared by the solvent-assisted grinding method and were characterized by IR spectroscopy and powder X-ray diffraction. Cocrystal (I) crystallized in the orthorhombic space group Pbca and showed a 1:1 stoichiometry. The DAP and PIR molecules are linked by an N—H...O hydrogen-bond interaction. Self-assembly of PIR molecules forms a sheet of C(4) and C(7) chains. Cocrystal (II) crystallized in the monoclinic P21/c space group and also showed a 1:1 stoichiometry. The DAP and TEO molecules are connected by N—H...N and N—H...O hydrogen bonds, forming an R 2 2(9) heterosynthon. A bidimensional supramolecular array is formed by interlinked DAP–TEO tetramers, producing a two-dimensional sheet.

scholarly journals Nanosuspension Technologies for Delivery of Poorly Soluble Drugs

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Roya Yadollahi ◽  
Krasimir Vasilev ◽  
Spomenka Simovic
Keyword(s):  
Aqueous Solubility ◽  
Drug Formulation ◽  
Preparation Methods ◽  
Administration Routes ◽  
Drug Molecules ◽  
Advanced Therapies ◽  
Poorly Soluble ◽  
Minimal Damage ◽  
Processing Techniques ◽  
Cancer Tissues

Poor aqueous solubility of some drug molecules is a major problem in drug formulation. Drug nanosuspensions emerged as one solution to delivering such hydrophobic drugs. Scaling down to nanoparticles enhances drug aqueous solubility and bioavailability by increasing drug surface area that comes into contact with biological media. Nanosuspensions that have attracted particular attention are those sterically stabilised by steric polymers such as polyethylene glycol (PEG) with a typical size range of 10–100 nm. These nanoparticles are capable of accumulating in targeted areas such as cancer tissues and infarct zones with minimal damage to healthy tissues. Nanosuspensions are often prepared by commercially available methods such as high pressure homogenization, media milling, emulsification, and melt emulsification. Solidification and surface modification methods are post-processing techniques used to add particular properties for advanced therapies. In this review, we firstly describe preparation methods for nanosuspensions. Secondly, we highlight typical characterization techniques. Finally, we describe several practical application of applications for drug delivery design and different administration routes such as parenteral, pulmonary, oral, and ocular.

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