Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University PH931 Instructor: M. Savva, Ph.D. 1CHAPTER I STATES OF MATTER INTRODUCTION Advanced Physical pharmacy is a required three credit-hour course offered to the MS students of the Pharmaceutics & Industrial Pharmacy program. The course discusses states of matter, ideal and real gases, enthalpy and thermochemistry, introduction to thermodynamics, intermolecular forces in liquids and solids, chemical equilibria and entropy, Gibbs free energy, kinetics, solution theory, diffusion and dissolution principles. The application of these subject areas to the preparation of solid and liquid dosage forms, aerosol and other rate-controlled and targeted drug delivery systems is discussed in subsequent courses. The material presented in this chapter aims to help the students: 1. Learn about and distinguish between the different forms and the three different states of matter. 2. Understand that conversion of a drug molecule into a different state is due to physical changes that are intimately related to intermolecular forces. Physical changes are reversible. Chemical changes are usually related to the spatial arrangement of atoms within the molecule (interatomic or intramolecular forces) and they always result in the creation of a new substance. 3. Develop critical thinking of how the physicochemical properties of a formulated drug product can be affected by the “inert” excipients and how one can go about detecting the drug in a particular dosage form.Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University PH931 Instructor: M. Savva, Ph.D. 24. Understand the interplay between molecular structure, physical properties and pharmacological action of a drug. STATES OF MATTER Matter is the material of the universe and it can be defined as anything that has mass and occupies space. Based on its composition and properties, matter can be classified as mixtures, pure substances, pure compounds and elements. A substance is a form of matter that has a constant composition. The physicochemical properties of a substance are dependent on the way its atoms are organized. For example, n-butane has exactly the same chemical formula as iso-butane, C4H10. Their physical properties, e.g., boiling and melting point as shown in Table I, vapor pressure at a given Matter Mixtures of substancesPure substancesHeterogeneous mixtures Homogeneous mixturesCompounds ElementsArnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University PH931 Instructor: M. Savva, Ph.D. 3temperature, and their chemical properties, e.g., reactivity to a carbocation or a free radical, differ due to a different organization of the same atoms in each molecule, that is, they have different structural formulas (n-butane: CH3-CH2-CH2-CH3; iso-butane: CH3-CH(CH3)-CH3. Table I. Physical Constants for n-butane and isobutene* n-butane isobutane Boiling point 0 ˚C -12 ˚C Melting point -138 ˚C -159 ˚C Relative density at -20 ˚C 0.622 0.604 * Values are adopted from: Morrison, R.T., and Boyd, R.N., Organic Chemistry, 5th Edition, Allyn and Bacon Inc.: Massachusets, 1987. Nitrogen (gas), water (liquid), glucose (solid) are examples of three different substances existing in different physical states under normal conditions (1 atmosphere, 22 ˚C). Ice water, liquid water and vapor water, are examples of a substance in the three different states. Reversible changes of the physical states of a substance are physical changes. Physical changes are due to reorganization of the molecules in a substance. Contrary to that, chemical changes are due to the way the substance’s atoms are organized. Chemical changes may be irreversible, fully or not fully reversible (the majority of chemical reactions are reversible only to some extent) and they always result in a change of a substance to a new one having different properties. An example of an irreversible chemical change is decomposition of water causing the molecules to break apart and form hydrogen and oxygen, two new substances. The esterification of salicylicArnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University PH931 Instructor: M. Savva, Ph.D. 4acid with malonic anhydride to form aspirin (Fig. 1) is a reversible chemical change. The product to reactant’s ratio of a reversible chemical reaction under a given set of conditions at equilibrium, is always the same and is expressed by the equilibrium constant, K of the reaction. OHOOH+OOOOHOOCH3O Fig. 1. Synthesis of aspirin from salicylic acid and malonic anhydride. A compound is a form of substance in which two or more atoms (elements) are chemically linked. Molecular compounds can be broken down to pure elements only by chemical means. An element is a substance that cannot be further divided by chemical means. It is defined by its atomic number. Elements have isotopes. For example, the radioactive 125I that is frequently used in thyroid cancer treatment is an isotope of the stable 127I. All isotopes have the same atomic number but they have a different mass number (different number of neutrons). Pharmaceutical scientists frequently use radioisotopes as a means toArnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University PH931 Instructor: M. Savva, Ph.D. 5follow the in vivo fate of (tagged) biologically active macromolecules and synthetic drug compounds. A mixture is a combination of two or more substances in which the substances may or may not retain their physicochemical properties intact. Mixtures are classified as homogeneous and heterogeneous mixtures. In homogenous mixtures of solids and liquids, the chemical and physical properties of the individual substances cannot be detected (intact) by any method of instrumental analysis. Fig. 2 shows the melting point of solid crystalline aspirin centered around 135 ˚C. Melting-point curve of aspirin0204060801001204080120134134.2134.6135150170200Temperature% of crystals remainingaspirin, crystalsaspirin, solution Fig. 2. Melting of aspirin crystals as determined by a scanning calorimeter that measures the heat of fusion. No melting of aspirin can be detected in the aspirin solution since the forces that hold the aspirin crystal have been destroyed by the solvent, during a process called dissolution. Notice that the