Pharmaceutics & Drug Delivery Systems PDF

PHARMACEUTICS & DRUG 5) DELIVERY SYSTEMS...

PHARMACEUTICS & DRUG 5) DELIVERY SYSTEMS 22 Evaluating Exam Preparatory Course 15 :1 (ID ad Ri 1 e yc TABLE OF CONTENTS Jo Types of Chemical Bonds Solid-Liquid Solutions to Crystallization Gas-Liquid Solutions Crystallinity Factors Affecting Solubility ed Polymorphism Dissolution Theory Hydrates and Solvates Partition Eutectic Mixtures Surface Chemistry ns Solid Solution Emulsions Properties of Powders Suspensions ce Particle Size Analysis Drug Stability Tableting Chemical Stability Li Tablet Coating Pulmonary Drug Delivery Capsules Dermal and Transdermal Drug Delivery Evaluation Tests Parenteral Drug Delivery Sustained/Controlled Release Ophthalmic, Otic, Nasal Drug Delivery Effervescent Powders and Tablets Rectal and Vaginal Drug Delivery Thermodynamic of Pharmaceutical Solutions Controlled/Targeted delivery Pharmaceutical Solvents Protein Drug Delivery Aqueous and Non-Aqueous Solutions Good Manufacturing Practices Solvent/Solute Interactions Product Quality Control and Risk Management Liquid-Liquid Solutions Copyright © 2024 PharmAchieve Corporation Ltd. Private and Confidential. 2 Copyright © 2024 PharmAchieve Corporation Ltd. Private and Confidential. 1  LEGEND G: Gibbs Free Energy GMP: Good Manufacturing Practice H: Enthalpy HFA: Hydrofluoroalkane P*i: Vapour Pressure of Pure Component P ISO: International Organization for Standardization IV: Intravenous IVIVCs: In Vitro-In Vivo Correlations 5) PICC: Peripherally Inserted Central Catheter MDI: Metered Dose Inhaler 22 PI: Partial Vapour Pressure PO: Peroral/Per Os Q: quantity 15 RH: Relative Humidity S: Entropy :1 TPN: Total Parenteral Nutrition XI: Mole Fraction μ: chemical potential (ID ad Copyright © 2024 PharmAchieve Corporation Ltd. Private and Confidential. Ri 3 e yc STATES OF MATTER SOLID Jo Fusion: a solid to changes to the Deposition: gas liquid form changes to solid ed (e.g. heating solid (e.g. water vapour ice to water) changes to ice) Sublimation: ns Solidification: solid changes liquid changes to to gas (e.g. dry ce solid (e.g. water ice subliming freezes to ice) to gas form) Li Vaporization: liquid changes to gas (e.g. water is vaporized to steam) LIQUID GAS Condensation Condensation: gas changes to liquid (e.g. water drops form on a glass with a cold drink on a hot day) Copyright © 2024 PharmAchieve Corporation Ltd. Private and Confidential. 4 Copyright © 2024 PharmAchieve Corporation Ltd. Private and Confidential. 2  CHEMICAL BONDING – VAN DER WAALS Van Der Waals are weak, attractive forces between uncharged molecules There are two types of Van Der Waals forces: London Forces Temporary dipoles in adjacent symmetric molecules causing them to attract one another 5) e.g. London forces occur in halogens molecules - F2 and I2 Dipole-Dipole Interactions 22 Exist between 2 dipolar molecules e.g. Partial negatively charged chlorine atom attracts a partial positive hydrogen atom to form 15 HCl :1 Copyright © 2020 PharmAchieve Corporation Ltd. Rowaida Hussein (ID ad Copyright © 2024 PharmAchieve Corporation Ltd. Private and Confidential. Ri 5 e yc CHEMICAL BONDING – HYDROGEN BONDING Jo Type of dipole interaction to Attractive force between a hydrogen atom and an electronegative atom such as F, O, N ed Hydrogen bonding can be intermolecular (between different molecules) Hydrogen bonding can be intramolecular (within a molecule) ns ce e.g. Hydrogen bonding occurs between water Li molecules. The oxygen of one water molecule hydrogen bonds with the hydrogen of an adjacent water molecule Copyright © 2020 PharmAchieve Corporation Ltd. Rowaida Hussein Intermolecular H-Bond Intramolecular H-Bond Copyright © 2024 PharmAchieve Corporation Ltd. Private and Confidential. 6 Copyright © 2024 PharmAchieve Corporation Ltd. Private and Confidential. 3  CHEMICAL BONDING – METALLIC BONDING An ordered Positively charged atoms share free electrons in a lattice of cations arrangement of Ionic/covalent bonding exists between 2 atoms positively charged ions Forms between metal atoms 5) 22 Sharing of free electrons in a lattice 15 of cations. Metallic bonding :1 occurs in metals like iron Copyright © 2020 PharmAchieve Corporation Ltd. Rowaida Hussein (ID ad Copyright © 2024 PharmAchieve Corporation Ltd. Private and Confidential. Ri 7 e yc CHEMICAL BONDING – ELECTROSTATIC BONDING Jo Forms between a positive and negative ion to Electron is donated by one ion to another ion Also known as an ionic bond This example shows a positive ed sodium ion forming an ionic bond with a negative chlorine ion. The ns sodium donates an electron to chlorine to make NaCl ce Li Copyright © 2020 PharmAchieve Corporation Ltd. Rowaida Hussein Copyright © 2024 PharmAchieve Corporation Ltd. Private and Confidential. 8 Copyright © 2024 PharmAchieve Corporation Ltd. Private and Confidential. 4  CHEMICAL BONDING – COVALENT BONDING Electrons are shared between two atoms e.g. Hydrogen atoms form a covalent bond to make a hydrogen molecule 5) 22 15 :1 (ID Copyright © 2020 PharmAchieve Corporation Ltd. Rowaida Hussein ad Copyright © 2024 PharmAchieve Corporation Ltd. Private and Confidential. Ri 9 e yc CHEMICAL BONDING Jo to Chemical Bond Description Example Strength Weak electric forces, ed Van Der Waals includes London Forces Weak attractions often found Weak Forces and Dipole-Dipole in halogens like F2 and I2 ns Interactions Forms between hydrogen ce Hydrogen atom and electronegative Between water molecules Bonding atoms: F, O, N Li Metallic Sharing of electrons in a Metallic bonding is found in Bonding lattice of cations metals like iron Electrostatic One ion donates electrons Na donates an electron to a Cl Bonding to another ion to make NaCl Two hydrogen atoms share Covalent Sharing of electrons electrons to make a hydrogen Bonding Strong molecule Copyright © 2024 PharmAchieve Corporation Ltd. Private and Confidential. 10 Copyright © 2024 PharmAchieve Corporation Ltd. Private and Confidential. 5  CRYSTALLIZATION Atoms or molecules arrange themselves into a well-defined crystal structure The process of ice INDUCING CRYSTALLIZATION formation is an 5) example of crystallization 22 Methods to induce crystallization: 15 Evaporating the solvent :1 Filtering the solvent Freezing the solvent (ID Adding other components (solvent or salt) to reduce solubility ad Copyright © 2024 PharmAchieve Corporation Ltd. Private and Confidential. Ri 11 e yc SATURATED VS SUPERSATURATED SOLUTION Jo Solutions often have a limit for the amount of solute than can be dissolved into the solvent to ed ns Saturated Supersaturated ce Solution contains Solution contains maximum amount of more than maximum Li Saturated solute at given amount of solute at a temperature given temperature Stable Unstable Unsaturated Supersaturated Copyright © 2020 PharmAchieve Corporation Ltd. Rowaida Hussein Copyright © 2024 PharmAchieve Corporation Ltd. Private and Confidential. 12 Copyright © 2024 PharmAchieve Corporation Ltd. Private and Confidential. 6  SATURATED VS SUPERSATURATED SOLUTION Saturated solution: solution that contains Supersaturated solution: no more solute maximum amount of dissolved solute under the dissolves, and is considered unstable set condition and is considered stable 5) 22 15 :1 Copyright © 2020 PharmAchieve Corporation Ltd. Rowaida Hussein Copyright © 2020 PharmAchieve Corporation Ltd. Rowaida Hussein e.g. When dissolving sugar in a solvent, the (ID e.g. When dissolving sugar in a solvent solution is supersaturated when the solvent the solution is saturated when the solvent can not dissolve anymore sugar and any can not dissolve anymore sugar sugar added will precipitate out of solution ad Copyright © 2024 PharmAchieve Corporation Ltd. Private and Confidential. Ri 13 e yc CRYSTALLINITY Jo to Amorphous solids form when molecules or atoms are not organized into an organized lattice structure ed e.g. glass Degree of crystallinity refers to how close a crystal is ns to perfection Perfect crystals only at absolute zero temperature, 0 ce K, has entropy of zero Crystals can have the following defects: Li Extended defects: defects within the individual grains of a crystal Point defects: occur at isolated atomic positions Copyright © 2020 PharmAchieve Corporation Ltd. Rowaida Hussein Copyright © 2024 PharmAchieve Corporation Ltd. Private and Confidential. 14 Copyright © 2024 PharmAchieve Corporation Ltd. Private and Confidential. 7  AMORPHOUS SOLIDS VS CRYSTALLIZED SOLIDS Comparison Amorphous solids Crystalline solids Repeating Units Irregular Regular Shape No shape Characteristic shape Melting point Over a range of temperature Specific temperature Symmetry Unsymmetrical Symmetrical 5) Examples Glass, plastic Diamond, table salt 22 15 :1 (ID ad Copyright © 2024 PharmAchieve Corporation Ltd. Private and Confidential. Ri 15 e yc CRYSTALLINITY Amorphous solids, degree of crystallinity, crystal defects Jo Oppositely charged atoms leave the lattice structure to Due to vacancies and cause vacancies in the caused in the lattice lattice ed structure ns Schottky Vacancies in lattice ce Intrinsic Vacancy created by atom Frenkel or ion moving into Li Defects interstitial position Foreign atom is Extrinsic inserted into lattice Vacancy: a defect in Atom or ion leaves its the crystal structure original position in a lattice where an atom is and moves to an interstitial missing from the position. Atoms still reside lattice site within the crystal Copyright © 2024 PharmAchieve Corporation Ltd. Private and Confidential. 16 Copyright © 2024 PharmAchieve Corporation Ltd. Private and Confidential. 8  CRYSTALLINITY 5) 22 15 :1 Copyright © 2020 PharmAchieve Corporation Ltd. Rowaida Hussein Copyright © 2020 PharmAchieve Corporation Ltd. Rowaida Hussein Schottky defect: oppositely charged Frenkel defects: atom or ion leaves its (ID atoms leave the lattice structure and original position in a lattice and moves cause vacancies in the lattice to an interstitial position. Atoms still reside within the crystal ad Copyright © 2024 PharmAchieve Corporation Ltd. Private and Confidential. Ri 17 e yc POLYMORPHISM – EFFECTS ON FORMULATION, BIOAVAILABILITY Jo Polymorphism: drug substances exist in many forms and packing arrangements in the crystal to lattice structure ed They are prepared by varying the conditions during the crystallization process such as temperature ns At a given temperature and pressure, only one form of the pure drug substance is stable The unstable forms are called metastable ce Metastable forms convert to the stable form at differing rates Polymorphisms differ in their drug physicochemical properties - affects ease of formulation, Li dissolution rates and solubility, melting point and biological activity Copyright © 2024 PharmAchieve Corporation Ltd. Private and Confidential. 18 Copyright © 2024 PharmAchieve Corporation Ltd. Private and Confidential. 9  HYDRATES AND SOLVATES Liquid Phase diagrams show the different physical states of a Pressure (kPa) substance when temperature and/or pressure are changed Temperature is on the x-axis Solid Pressure is on the y-axis 5) At 100 °C and 0.6 kPa, 0.6 water exists in the water Vapour 22 vapor (gas) form. 100 Temperature (°C) 15 Common Terminologies: Hygroscopicity: take up and retain moisture :1 Deliquescence: tendency to melt or dissolve by absorption of moisture Lyophilization: process of removing water to preserve solids (ID Drug requires aqueous system for solubility and good bioavailability ad Copyright © 2024 PharmAchieve Corporation Ltd. Private and Confidential. Ri 19 e yc EUTECTIC MIXTURES Jo Any of these Eutectic mixtures: solid substances that become liquid when mixed substances become to eutectic mixtures when Combine to achieve lowest melting point possible mixed Substances forming eutectic mixtures when combined: ed ns ce Phenyl Phenol Camphor Menthol Thymol Aspirin® Salicylate Li An example of a eutectic mixture is sodium chloride and water. A mixture of 23.3% sodium chloride by weight in water has a freezing point of -21.2 °C. This mixture is used to melt ice Itraconazole can be mixed with phenol to produce a eutectic mixture. This eutectic mixture allows drug delivery of itraconazole across the skin Copyright © 2024 PharmAchieve Corporation Ltd. Private and Confidential. 20 Copyright © 2024 PharmAchieve Corporation Ltd. Private and Confidential. 10  SOLID SOLUTIONS Mixture of two crystalline solids, which when mixed form a new single crystal lattice structure The two crystalline solids are melted into liquids at high temperatures and then mixed The mixture is then cooled to form a new crystal lattice structure Solids differ in their solubility – this solubility determines how their atoms fit together Solid solutions include inclusion compounds, clathrate, and clathrate hydrates 5) 22 15 :1 (ID ad Copyright © 2024 PharmAchieve Corporation Ltd. Private and Confidential. Ri 21 e yc SOLID SOLUTIONS, CLATHRATES, INCLUSION COMPOUNDS Jo Solid solutions include inclusion compounds, clathrate, and clathrate hydrates to ed ns ce Li Inclusion compound: where Clathrate: type of Clathrate hydrates: molecule(s) of one inclusion compound inclusion compounds substance are incorporated where one component is formed by guest within crystal lattices or trapped within molecule within molecular cavities of framework of different hydrogen bonded cage another molecule component of solid-state water Copyright © 2024 PharmAchieve Corporation Ltd. Private and Confidential. 22 Copyright © 2024 PharmAchieve Corporation Ltd. Private and Confidential. 11  SOLID SOLUTIONS, CLATHRATES, INCLUSION COMPOUNDS Lattice structure for solid solutions Compound Lattice Structure Inclusion compound Unaffected 5) 22 Clathrate Changed 15 :1 Clathrate Hydrate Changed (ID ad Copyright © 2024 PharmAchieve Corporation Ltd. Private and Confidential. Ri 23 e yc POWDERS – PROPERTIES, HANDLING, DRYING, MIXING, MILLING Jo Many drugs are prepared as powders to Powder: dosage formulation that is in the solid form in its physical state ed Powder formulations may be formed of only the active drug, or a mixture of active drug plus other ingredients ns Powder Properties ce Each dose contains different amounts of the active drug Li Powders can be easily administered to patients who have difficulty swallowing Drugs tend to be stable as solids The following slide represents the properties of good powders It also contains information for the handling, drying, mixing, and milling processes of powders Copyright © 2024 PharmAchieve Corporation Ltd. Private and Confidential. 24 Copyright © 2024 PharmAchieve Corporation Ltd. Private and Confidential. 12  POWDERS – PROPERTIES, HANDLING, DRYING, MIXING, MILLING Properties Morphology, purity, flowability, stability, particle size, uniformity, compatibility, effective surface area, solubility, appearance, colour, odour, moisture Drying Drying trays in oven or air; environment of low humidity 5) Milling 22 Breaking down coarse particles into fine particles using mechanical force Containment system protects environment from chemical dust, reduces 15 product loss and contamination Mixing :1 Spatulation: mix with spatula Trituration: mortar and pestle (ID Sifting: pass through sifters Tumbling: rotating chamber ad Copyright © 2024 PharmAchieve Corporation Ltd. Private and Confidential. Ri 25 e yc PARTICLE SIZE ANALYSIS Jo Particle size analysis: quantitative data on size, distribution, and shapes of drug to components Particle size characteristics: ed Range from extremely coarse (~10 mm diameter) to extremely fine (