Pharmaceutics II P224PT PDF

# Pharmaceutics II P224PT ## Introduction - Drug substances are seldom administered in their natural or pure state, but rather as part of a **formulation** in combination with one or more non-medicinal agents that serve varied and specialized pharmaceutical functions. - Pharmaceutical aids, pharma...

# Pharmaceutics II P224PT ## Introduction - Drug substances are seldom administered in their natural or pure state, but rather as part of a **formulation** in combination with one or more non-medicinal agents that serve varied and specialized pharmaceutical functions. - Pharmaceutical aids, pharmaceutical ingredients, excipients or adjuncts result from the selective use of these non-medicinal agents. - Pharmaceutical adjuncts serve to solubilized, suspend, thicken, dilute, emulsify, stabilize, preserve, color, flavor and fashion the many and varied medicinal agents into effective and appealing pharmaceutical preparations. ## A Drug From A to Z - **Active Pharmaceutical Ingredient (API)** is the active substance responsible for the therapeutic effect. - **Preformulation studies** are done to study the physicochemical properties of the API (e.g., solubility, stability, and particle size). - **Formulation studies** are done to develop the final dosage form (e.g., tablets, capsules). - **Non-medicinal agents** (excipients/adjuncts) are added to the formulation to improve its properties (e.g., taste, stability, and dissolution). ## What are the objectives of preformulation studies ? - To establish the physicochemical parameter of new drug substances. - To establish the kinetic rate profile. - To establish physical characteristics. - To establish compatibility with the common excipients. ### Preformulation - Is a stage of development during which the physicochemical properties of drug substance are characterized (the process of optimizing a drug). - Develop a knowledge base. ## Compatibility - Materials used in formulation must be compatible, meaning that they do not interact with each other in a way that would affect the quality or efficacy of the drug product. ## Kinetic rate profile - Is the study of how the drug is absorbed, distributed, metabolized, and excreted in the body. - It helps understand how the drug behaves in the body and how it may be affected by other factors, such as food or other medications. ## Pharmaceutical Product - Is the finished drug product. - It is what is dispensed to the patient. **The proper design and formulation of a dosage form requires consideration of the physical, chemical, and biological characteristics of all of the drug substances and pharmaceutical ingredients (excipients) to be used in fabricating the product.** **The drug and pharmaceutical materials used must be COMPATIBLE and produce a drug product that is STABLE, EFFICACIOUS, PALATABLE, EASY TO ADMINISTER, and WELL TOLERATED.** ## Polymorphism - Polymorphism is the ability of a substance to exist in more than one crystalline form. - The different forms of a polymorph are generally different in stability and solubility. - The stable form is often preferred in pharmaceutical formulations due to its higher stability and lower solubility. - Amorphous form is more soluble and dissolvable than the crystalline form, but it is less stable and less preferred. - Polymorphism can also affect the bioavailability of a drug. ## Melting Point Depression - Is a characteristic of a pure substance. - A pure substance has a defined melting point or melting range. - If the substance is not pure, its melting point will be depressed. - Melting point depression can be useful for determining the purity of a substance. ## Solubility - The maximum amount of solute that dissolves in a solvent at equilibrium. - Factors that affect solubility include temperature, pressure, and the nature of the solute and solvent. - To increase solubility, the following methods can be used: - Addition of co-solvent: Water, alcohol, glycerin - Addition of complexing agent: EDTA - Chemical modification of the drug into salt or ester forms - pH adjustment: The most usable technique - Addition of surfactant: Span, tween, SLS - Particle size reduction: Small increases in solubility can be accomplished by particle reduction. ## Dissociation Constant (pka) - The extent of ionization of a drug is important because it can affect its solubility, absorption and other pharmacokinetic parameters. - Most drugs are weak organic acids or bases, meaning that they are not fully ionized in solution, and their absorption is governed to a large extent by their degree of ionization. - **Henderson Hasselbalch equation** helps to calculate the extent of ionization: - **Weak acid: pka - pH = log [(un-ionized)/(ionized)]** - **Weak base: pk₂- pH = log [(ionized)/(un-ionized)]** - The pH of the environment can affect the ionization of a drug. - **Only unionized drug molecules are absorbed across biological membranes.** ## Dissolution Rate - The time it takes for the drug to dissolve in the fluids at the absorption site. - Factors that affect dissolution rate include particle size, solubility, and the presence of other substances in the formulation. - To increase dissolution rate, the following methods can be used: - Decreasing the drug’s particle size - Increasing drug solubility in diffusion layer. - Using a highly water soluble salt of the parent substance. ## Partition Coefficient (PC or Log P) - The ratio in which a solute distributes itself between two immiscible liquids, mostly between n-octanol and water. - It is commonly used in formulation development to predict the ability of a drug to cross biological membranes, which are generally composed of lipids. - Drugs with a high partition coefficient (lipophilic) are more likely to cross biological membranes. - Drugs with a low partition coefficient (hydrophilic) are less likely to cross biological membranes. ## Macroscopic Examination - **Color:** Result of unsaturation, presence of impurities, or degradation products. - **Odor:** Result of functional groups like sulfides, sulfoxides, sulfhydryl, amines, or solvents. - **Taste:** If a taste is unacceptable, it is generally possible to circumvent this by using less soluble chemical forms, adding flavorants, or coating the solid dosage forms. ## Particle Size - Affects the following properties of drugs: - Flow properties - Content uniformity - Taste, Texture and Color. - Sedimentation rate - Dissolution rate - Absorption - Bioavailability - Stability - Particle size can be analyzed using various methods including - Sieving (screening) - Microscopy - Sedimentation - Stream scanning: Electronic microscopy ## Organoleptic Properties - These are the properties of a drug that can be perceived by the senses, such as taste, touch, smell, and appearance. - The organoleptic properties of a drug are important because they can affect its palatability, ease of administration, and patient compliance.