To overcome these challenges, we developed novel amphiphilic electrospun nanofibers nfs loaded with hae, phosphatidylcholine pc and. The technical properties of these solidstate materials will be important in formulation and manufacture, e. To fulfill this purpose, preformulation scientists induce degradation of test materials by raising temperature, by increasing humidity when relevant eg, solid state chemical and physical stability, by subjecting materials to sheer or compressive forces eg, solid state physical stability, by exposing the test materials to various ph. In contrast, derived preformulation pre formulation properties are carried out to learn about the issues related to development of a particular dosage form like solid oral. Solidstate preformulation studies of amiodarone hydrochloride. The solidstate properties of crystalline and amorphous salts of procaine are highly dependent on the nature of the counterion. Recently, an alternative api solid state form, namely the pharmaceutical cocrystal, has witnessed increasing academic and industrial interest due to its potential to deliver bespoke physical properties in the pharmaceutical drug product. Key issues include investigation of polymorphism, the ability of a compound to exist in more than one crystalline form, and careful selection of the solid form for further. These polymorphs show different physical properties which can affect. During preformulation stage solid state properties of active pharmaceutical ingredient api and the conditions under which the candidate drug should be. Selection of the optimum solid form is a critical aspect in the development of pharmaceuticals, due to their ability to exist in more than one form or crystal structure polymorphism.
Pdf pharmaceutical preformulation studies in formulation. Preformulation study of electrospun haemanthamineloaded. The overall objective of preformulation study is to generate information useful to the formulator. Serving as a handbook or standalone reference, this text equips those in academia and the pharmaceutical industry with both basic and applied principles for the characterization of drugs, excipients, and.
Solubility, dissolution behaviour and bioavailability of. Solid state properties of pharmaceutical materials in. These polymorphs show different physical properties which can. May 08, 2016 preformulation it is defined as the phase of research and development in which preformulation studies characterize physical and chemical properties of a drug molecule in order to develop safe, effective and stable dosage form. At normal room temperature and pressure the majority of drugs and excipients exist as solids, and so the study of solid state properties is of. Examples of physicochemical and biological properties that should be examined as appropriate include solubility. Solid state characteristics powders are masses of solid particles or granules surrounded by air or other fluid. Solid state characterization allows scientists to understand the properties of formulation and formulation components, the first step in rational formulation development. Solidstate characterization allows scientists to understand the properties of formulation and formulation components, the first step in rational formulation development. Important properties including aqueous solubility, melting point, hygroscopicity, and glass transition temperature were found to vary considerably between the different salts.
Preformulation it is defined as the phase of research and development in which preformulation studies characterize physical and chemical properties of a drug molecule in order to develop safe, effective and stable dosage form. Covering every topic of critical importance to the preformulation stages of development, this guide equips those in the pharmaceutical industry with basic and applied principles for the characterization of new drug compounds and substancesconsidering the identification, stability, structure, and mechanisms of drug candidates during preformulation through phase i of. Bulk characterization of drug molecules involves the characterization of various solid state properties that could change during process development. Preformulation molecular properties pka logplogd equilibrium solubility forced degradation and chemical stability excipient compatibilities solid state properties characterization of selected form solid state stability studies. The drug polymer compatibility was defined by the ftir studies in preformulation. Analytical technique measures responses to perturbations of the objects under examination. Solid state properties polymorphism preformulation 2. Physicochemical properties in preformulation studies. The chemical structure of hae and the geometric properties, molecular interactions and physical solidstate properties of the nfs were. Preformulation is the stage of development during which the physicochemical properties of the drug substance are characterised and established. Every drug has intrinsic chemical and physical properties which has. The chemical structure of hae and the geometric properties, molecular interactions and physical solid state properties of the nfs were investigated using nuclear magnetic resonance nmr spectroscopy, scanning electron microscopy sem, photon correlation spectroscopy pcs, fourier transform infrared ftir spectroscopy, xray powder.
The study on solid state properties of pharmaceutical materials, including drug substances and excipients, is essential for pharmaceutical research and development involving solid dosage forms. A literature search providing stability and decay data. Preformulation in solid dosage form development covers every topic of critical importance to the preformulation stages of drug development. Preformulation study is the first step in the rational development of dosage forms of a drug substance. General considerations of design and development of. Polymorphism in physics and chemistry of the organic solid state, ed by. In contrast, derived preformulation preformulation properties are carried out to learn about the issues related to development of a particular dosage form like solid oral. Preformulation in drug product design springerlink. It can be defined as an investigation of physical and chemical properties of a drug substance. Physical characteristics of the particles, such as size, shape, angularity, size variability, and hardness will all. Better knowledge of physiochemical properties help us to create better formulation. Presents a detailed discussion of important solid state properties, methods, and applications of solid state analysis illustrates the various phases or forms that solids can assume and discussesvarious issues related to the relative stability of solid forms and tendencies to undergo transformation covers key methods of solid state analysis including xray powder diffraction, thermal analysis. General considerations of design and development of dosage. Presents a detailed discussion of important solidstate properties, methods, and applications of solidstate analysis illustrates the various phases or forms that solids can assume and discussesvarious issues related to the relative stability of solid forms and tendencies to undergo transformationcovers key methods of solid state analysis.
Such material represent the highest energy state and can be considered as super cooled liquid. Physicochemical properties of api impact on formulation. Special aspects of solid state chemistry close relationship to solid state physics and materials science importance of structural chemistry knowledge of several structure types understanding of structures physical methods for the characterization of solids xray structure analysis, electron microscopy. Illustrates the various phases or forms that solids can assume and discussesvarious issues related to the relative stability of solid forms and tendencies to undergo transformation. Vxp pharma provides manufacturing, testing and stability services for preformulation and solid state chemistry development of your product. Differential scanning calorimetry dsc it allows to differentiate polymorphs on the bases of their melting point and heat of fusion i. Solidstate properties of powders in the formulation and processing. Knowledge of the relevant physiochemical and biopharmaceutical properties determines the appropriate formulation and delivery method for preclinical and phase 1 studies. During preformulation, the physicochemical properties of drug candidates are determined. Means it is the solid plus fluid combination, which significantly affects the bulk properties of the powder.
This paper deals with the application of fast screening tools such as ftir, thermal analysis and dsc in the evaluation of compatibility between the active pharmaceutical ingredient amiodarone hydrochloride and different pharmaceutical excipients used in tablet formulations, such as polyvinylpyrrolidone, microcrystalline cellulose, starch, talc and anhydrous lactose. The field of solid state characterization is central to the pharmaceutical industry, as drug products are manufactured as solid materials. Solid state properties characterization of selected form. Preformulation is a group of studies that focus on the physicochemical properties of a new drug candidate that could affect the drug performance and the development of a dosage form. Pdf preformulation commences when a newly synthesized drug shows sufficient pharmacologic promise in animal models to warrant evaluation in man. Aug 03, 2010 the solid state properties of crystalline and amorphous salts of procaine are highly dependent on the nature of the counterion. These studies are specific to candidate drug molecules and it include solubility analysis e. Case studies these studies describe some approaches to solidstate characterization and formulation of poorly soluble apis.
These studies include both solution and solid state. An overview on preformulation for pharmaceutical product. The study on solidstate properties of pharmaceutical materials, including drug substances and excipients, is essential for pharmaceutical research and development involving solid dosage forms. Presents a detailed discussion of important solidstate properties, methods, and applications of solidstate analysis. Solidstate properties of pharmaceutical materials wiley. Pharmaceutics free fulltext preformulation study of. In this post, the discussion is focused on bulk characterization of candidate drug molecules in a drug discovery setting. Fundamental preformulation properties are specific to the drug molecule and are dependent on the chemical structure of the drug molecule. It can be defined as an investigation of physical and chemical properties of a drug substance alone and when combined with excipients. Potency relative to the competit ive products and the dosage form.
Preformulation in solid dosage form development moji c. Most drug substances that are chosen for final product development will be in powder form. Initially, there may be a number of potential drug candidate molecules, each with a unique set of physicochemical properties and each showing activity towards a particular biological target. Solid state 1 water and other solvents 1 temperature 2 phsolubility profile 2. If a company patents one form of a solidstate molecule, but their competitor discovers another form with the same or better properties, the original developer may have no legal recourse against that competitor. Haemanthamine hae has been proven as a potential anticancer agent.
Polymorphs show the same properties in the liquid or gaseous state but they behave differently in the solid state. Solid state stability polymorphism ku scholarworks. Presents a detailed discussion of important solidstate properties, methods, and applications of solidstate analysis illustrates the various phases or forms that solids can assume and discussesvarious issues related to the relative stability of solid forms and tendencies to undergo transformation covers key methods of solid state analysis including xray powder diffraction. The chemical structure of hae and the geometric properties, molecular interactions and physical solidstate properties of the nfs were investigated using nuclear magnetic resonance nmr spectroscopy, scanning electron microscopy sem, photon correlation. Solidstate characterization and techniques sciencedirect. Polymorphism as a part of preformulation study list of contents 1. It can be defined as an investigation of physical and chemical properties of new drug substance alone or in combination with other excipient. Hence, the current project work deals with the improving of the dissolution rate and solid state stability by restricting the movement of atorvastatin calcium atc using gel liquisolid compact systems. This is presented in the contest of dosage form type. Whats more, each new polymorph of a solidstate molecule requires specialized screening for pharmacokinetics and toxicology. Solid state 1 water and other solvents 1 temperature 2 phsolubility profile.
Formulation development of atorvastatin calciumtablets by gel. Amorphous solid dispersions formulatability assessmentrisk analysis services. Formulation development of atorvastatin calciumtablets by. However, the therapeutic use of this plantorigin alkaloid to date is limited due to the chemical instability and poorly watersoluble characteristics of the agent. Presents a detailed discussion of important solid state properties, methods, and applications of solid state analysis. When the material is in the solid state but the molecules are not packed in a repeating long range ordered fashion, it is said to be amorphous. In a second module, automation and downscaling of preformulation assessments will be discussed. During preformulation stage solid state properties of active pharmaceutical ingredient api and the conditions under which the candidate drug should be formulated are examined. For example, properties of polymers used in delivery devices molecular weight, degree of crosslinking, crystallinity can have a signiicant effect on drug release. Chapter 1 preformulation studies rsc publishing doi. This could provide important information for formulation design or support the need for molecular modification.
Analysis of relationships between solidstate properties. Illustrates the various phases or forms that solids can assume and discussesvarious issues related to the relative stability of solid forms and tendencies to. Preformulation stability studies of drug under the following categories. Physicochemical properties of api impact on formulation development duk soon choi, ph. The effect is not only on the physical properties of solid drugs but also, in some. The data generated at this stage allow decisions to be made on the likely ease of formulation of. Formulation is the process of developing a drug candidate into a drug product. To fulfill this purpose, preformulation scientists induce degradation of test materials by raising temperature, by increasing humidity when relevant eg, solidstate chemical and physical stability, by subjecting materials to sheer or compressive forces eg, solidstate physical stability, by exposing the test materials to various ph. Preformulation perspective solid drug drug in solution hydrolysis into active general circulation hydrolysis absorption waste.
Case studies these studies describe some approaches to solid state characterization and formulation of poorly soluble apis. Active pharmaceutical ingredients apis are most commonly formulated and delivered to patients in the solid state. Preformulation is the stage in drug and dosage form development before formulation proper. Pdf every drug has intrinsic chemical and physical properties which has been consider. Almost all drugs are marketed as tablets, capsules or both.
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