Three new hydrochlorothiazide cocrystals: Structural analyses and solubility studies (original) (raw)
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Molecular Pharmaceutics, 2015
Hydrochlorothiazide (HCT) is a diuretic and a BCS class IV drug with low solubility and low permeability, exhibiting poor oral absorption. The present study attempts to improve the physicochemical properties of the drug using a crystal engineering approach with cocrystals. Such multi-component crystals of HCT with nicotinic acid (NIC), nicotinamide (NCT), 4aminobenzoic acid (PABA), succinamide (SAM) and resorcinol (RES) were prepared using liquid assisted grinding and their solubilities in pH 7.4 buffer were evaluated. Diffusion and membrane-permeability were studied using a Franz diffusion cell. Except the SAM and NIC cocrystals, all other binary systems exhibited improved solubility. All the cocrystals showed improved diffusion/membrane-permeability compared to HCT with the exception of the SAM cocrystal. When the solubility was high, as in the case in PABA, NCT and RES cocrystals, the flux/permeability dropped slightly. This is in agreement with the expected interplay between solubility and permeability. Improved solubility/permeability is attributed to new drug-coformer interactions. Cocrystals of SAM, however, showed poor solubility and flux. This cocrystal contains the primary sulfonamide dimer synthon similar to HCT polymorphs which may be a reason for its unusual behavior. A Hirshfeld surface analysis was carried out in all cases to correlate cocrystal permeability with drug-coformer interactions.
Pharmaceutical Co-crystal : An Emerging Technique to enhance Physicochemical properties of drugs
International Journal of ChemTech Research, 2020
Major constraints in development of new product are poor aqueous solubility, stability and low oral bioavailability, low permeability. As majority of drugs marketed worldwide are administered by oral route and about 40% -50% of the new molecular entities were never invade into the market because of such biopharmaceutical issues.So issues related to poor physiochemical property of an active pharmaceutical ingredient (API) can be resolved using cocrystallization approach.Crystallization emerge as potential technique for enhancement of solubility of poorly aqueous soluble drugs also helps to improve physicochemical with preserving the pharmacological properties of the API . Cocrystals are solids that are crystalline single-phase materials composed of two or more different molecular and/or ionic compounds generally in a stoichiometric ratio which are neither solvates/hydrates nor simple salts. It is multicomponent system in which one component is API and another is called coformer. Cofo...
Recent Updateson Cocrystals Technologieson Enhancement of Solubilityofthe Drugs
Pharmaceutical co-crystals have acquired vast improvement in recent years due to its ability to change physicochemical properties of drugs. Pharmaceutical co-crystal consists of active pharmaceutical ingredient (API) and coformers. Co-crystals can be utilized to improve imperative physicochemical attributes of a medication, including solvency, disintegration, bioavailability and solidness of API while keeping up its therapeutic activity. Expanded commercialization of cocrystals has thus required extra research on techniques to make cocrystals, with specific highlight put on rising innovations that can be produced naturally attractive and efficient choices. In this review, well-organized and ordered overview of pharmaceutical cocrystal is provided, focusing on the solids forms of API, design strategy, its method of preparation, physicochemical properties, mechanism of enhancing solubility and its characterization technique. An overview of applications and marketed drug products of cocrystals is also described.
American Journal of PharmTech Research
Co-crystallization is an emerging approach for enhancing physicochemical properties like solubility, stability, bioavailability of poorly soluble drugs of BCS class II in pharmaceutical development without changing the chemical composition and considered better alternatives to optimize drug properties. Co-crystal is a crystalline entity consists of API and a stoichiometric amount of a pharmaceutically acceptable co-crystal former formed by intermolecular interactions like Hydrogen bonding, π-π stacking and Van der Waals forces. In this article, an overview of pharmaceutical cocrystals will be presented along with the intermolecular interactions (Chemistry of Co-crystals), methods of their preparations, characterization of co-crystals altered physicochemical properties. Furthermore, this article also gives a brief explanation about newer trends in co-crystals with application of co-crystals in medicines and industries.
AN OVERVIEW ON PHARMACEUTICAL COCRYSTALS
Padala Alekya*, Jagadeesh Panda, D. Komali, S. Neeraja Sukanya
The cocrystal production and properties are intricate in different ways. It exhibits properties corresponding to dissolution rate, melting point, solubility, chemical stability etc. The crystal engineering has been applied to API’s as an implication to pharmaceutical cocrystal which has been increasingly recognized as an attractive option to polymorph, salts, solvates and crystal habit modifications in dosage form design. Pharmaceutical cocrystals formation has been manifested to influence the solid-state properties (solubility and bioavailability) of poorly water-soluble drugs without compromising its pharmacological activity. To date, there is no agreeable definition, what a cocrystal constitutes. This article intended to presents an overview of pharmaceutical cocrystals with different preparation methods, physicochemical properties and analytical characterization methods. KEY WORDS: cocrystal, API, crystallization, solubility, bioavailability
A Review on Pharmaceutical Cocrystals
2020
Pharmaceutical cocrystals are solid substances and a promising technology which are used to improve the solubility of poor aqueous compounds. They are a very interesting and useful product for improving different properties of drug substances such as dissolution rate, melting point, solubility, chemical stability, etc on the other hand we can say that they are drug pharmacological action modification agents. In the present paper, we review the pharmaceutical co-crystals. Cocrystals are multi-component molecular design allows us to change in the physicochemical properties of solids according to the need, through manipulation of various intermolecular interactions. In this short review, we focus on some recent reports on pharmaceutical co crystals and their emerging subclasses as Charge transfer co-crystals, Energetic co-crystals, and Ternary cocrystals and discuss their methods of characterization and applications of importance in the industrial pharmacy. KeywordCocrystals, solubilit...
Pharmaceutical Cocrystals: A Novel Approach for Oral Bioavailability Enhancement of Drugs
Critical Reviews in Therapeutic Drug Carrier Systems, 2012
Solid dosage forms are by far the preferred drug delivery systems. However, these often face the problem of poor and erratic bioavailability during the drug development process. Numerous formulation strategies for drug delivery are currently under development, among which the solid forms such as polymorphs, solvates, salts, and cocrystals have been considered to be the most important for improving dissolution rate and bioavailability. Cocrystallization is a fairly new approach in pharmaceutical industry that can improve the solubility and, consequently, the bioactivity of the active pharmaceutical ingredient (API) without compromising its structural integrity. Pharmaceutical cocrystals have found their place in drug delivery, primarily due to their ability to produce alternative, viable solid forms when a more standard approach of salt and polymorph formation fails to deliver the desired objectives. Over the past few years, a number of papers have been published focusing on a broad range of subjects, from traditional crystal engineering to structure-property relationships of cocrystals. The present review, however, illustrates how the cocrystalline forms of APIs have improved their in vitro dissolution rate and in vivo bioavailability, often correlating well with their improved solubility as well.
2017
The increasing frequency of drugs which have poor aqueous solubility, manufacturability and stability in development offers risk of new drug products with low and variable bioavailability particularly for those drugs administrated by the oral route, with consequences for safety and efficacy. Although number of strategies exists for enhancing the bioavailability of these drugs, newer strategies, dependent on the physical and chemical nature of the molecules are being developed. Crystal engineering approach presents a number of routes such as co-crystallization, polymorphism and salt formation to improve physicochemical properties of drugs, which can be implemented through a detailed knowledge of crystallization processes and the molecular properties of drugs. Pharmaceutical co-crystals are emerging as a new class of solid drugs with improved physicochemical properties, which has attracted increased interests from both industrial and academic researchers. In the present review, the co...
Indian Journal of Pharmaceutical Sciences, 2009
Yadav, et al.: Co-crystals to Modify Physicochemical Properties of API's Crystal form can be crucial to the performance of a dosage form. This is especially true for compounds that have intrinsic barriers to drug delivery, such as low aqueous solubility, slow dissolution in gastrointestinal media, low permeability and first-pass metabolism. The nature of the physical form and formulation tends to exhibit the greatest effect on bioavailability parameters of water insoluble compounds that need to be given orally in high doses. An alternative approach available for the enhancement of drug solubility, dissolution and bioavailability is through the application of crystal engineering of co-crystals. The physicochemical properties of the active pharmaceutical ingredients and the bulk material properties can be modified, whilst maintaining the intrinsic activity of the drug molecule. This article covers the advantages of co-crystals over salts, solvates (hydrates), solid dispersions and polymorphs, mechanism of formation of co-crystals, methods of preparation of co-crystals and application of cocrystals to modify physicochemical characteristics of active pharmaceutical ingredients along with the case studies. The intellectual property implications of creating co-crystals are also highly relevant.
Formulation and Evaluation of Cocrystals of a BCS Class II Drug Using Glycine as Coformer
International Journal of Applied Pharmaceutics, 2022
Objective: Development of pharmaceutical co-crystals is an interesting area of research as co-crystals are unique because they have the advantages of maintaining drug's intrinsic properties along with improvement in its physicochemical attributes. Objective of this research was to improvise solubility of a Biopharmaceutics Classification System (BCS) class II drug (Ezetimibe) along with better dissolution profile using cocrystallization technique. Methods: In the present study, pharmaceutical cocrystals of a BCS class II drug, Ezetimibe, were prepared using glycine as coformer using neat grinding method. Prepared cocrystals were characterized using Hot Stage Microscopy (HSM), Differential Scanning Calorimetry (DSC), Fourier Transform Infrared (FTIR) and Powder X-Ray Diffract meter (PXRD). In addition, solubility and dissolution studies were also performed. Results: HSM study and DSC study represented melting at Ezetimibe (166 °C), Glycine (233 °C) and cocrystals (174 °C), respectively. Melting point of cocrystal is between API and coformer, indicating towards interaction. During XRD studies, a new peak was observed at 14.7193 and 23.3211 at position 2θ in comparison to parent peaks of