Pharmacy Lecture Notes: Pharmaceutics III (PIP 315) Fall 2024-2025 PDF

Pharmacy Bachelor of Pharmacy –PharmD program Pharmaceutics III (PIP 315) Lecture 1: Introduction to Solid Dosage Forms Fall 2024-2025 Associate Professor : Dr. Sally A. El-Zahaby  2 Course Desc...

Pharmacy Bachelor of Pharmacy –PharmD program Pharmaceutics III (PIP 315) Lecture 1: Introduction to Solid Dosage Forms Fall 2024-2025 Associate Professor : Dr. Sally A. El-Zahaby  2 Course Description  The course introduces the students to the kinetics of drug decomposition including rate and order of the reaction, determination of the half-life, expiry date and shelf-life by different methods, stability testing, and in-vitro possible drug/excipients interactions.  It also describes the principles and techniques involved in the formulation, and manufacturing of solid dosage forms including powders, granules, tablets, capsules and suppositories. Assoc. prof. Dr. Sally El-Zahaby  3 Course Title & Code  Course Title: Pharmaceutics III  Course Code: PIP 315  Credit hours: 3 Assoc. prof. Dr. Sally El-Zahaby  4 Recommended text books & references: ▪ Ansel's Pharmaceutical Dosage Forms and Drug Delivery Systems, Eighth Edition, Loyed V.Allen Jr, Nicholas G. Popovich and Howard C. Ansel, David B. Troy editor (10th Edition), Lippincott Williams & Wilkins 2013. https://books.google.com.eg/books?hl=en&lr=&id=JteCAwAAQBAJ&oi=fnd&pg=PR1&dq=Ansel%27s+Pharmaceutical+Dosage+Forms+a nd+Drug+Delivery+Systems&ots=j07i1x_Ba9&sig=4l1MG4umY4VVtaRsjTKyUZXhf- k&redir_esc=y#v=onepage&q=Ansel's%20Pharmaceutical%20Dosage%20Forms%20and%20Drug%20Delivery%20Systems&f=false ▪ Aulton’s Pharmaceutics. The Design and Manufacture of Medicines. Edited by Michael E. Aulton, Kevin M.G. Taylor (5th Edition), Elsevier, 2018. http://dl.konkur.in/post/Book/MedicalScience/Aulton-Pharmaceutics-The-Design-and-Manufacture-of-Medicines-5th-Edition- %5Bkonkur.in%5D.pdf ▪ Egyptian Knowledge Bank: www.ekb.eg Assoc. prof. Dr. Sally El-Zahaby  5 Learning outcomes (LO’s) After finishing this lecture , you will acquire the following: 1. List the different types of solid dosage forms; powders, granules, tablets, capsules and suppositories. 2. Understand the reasons for the incorporation of drugs into various dosage forms. 3. Understand the general considerations for dosage form design. 4. List the advantages and disadvantages of solid dosage forms. 5. Identify the excipients used in formulating various solid dosage forms. Assoc. prof. Dr. Sally El-Zahaby  6 Introduction to Solid Dosage Forms Definitions  A drug substance: It is the unformulated drug substance that may subsequently be formulated with excipients to produce the dosage form.  It is an agent intended for use in the diagnosis, treatment, or prevention of disease in humans or in animals.  e.g.: Drugs may be used to reduce pain, to treat fever or blood pressure, etc… Assoc. prof. Dr. Sally El-Zahaby  7 Definitions  To facilitate administration of the drug by the selected routes, appropriate dosage forms, such as tablets, capsules, suppositories, and others, are prepared. Dosage forms  Dosage forms are pharmaceutical drug products in the form in which they are marketed for use, with a specific mixture of active ingredients and inactive components (excipients).  Dosage forms can be in the form of liquid, semi-solid or solid. Assoc. prof. Dr. Sally El-Zahaby  8 Definitions  Drug product: The dosage form in the final immediate packaging intended for marketing.  Drug products contain both drug substance (commonly referred to as active pharmaceutical ingredient or API) and excipients.  Excipient: Anything other than the drug substance in the dosage form. Assoc. prof. Dr. Sally El-Zahaby  9 Solid dosage forms 1-Powders 3- Tablets 2- Granules 4- Capsules 5- Suppositories Note: suppositories can be also classified as semi-solid dosage form. Assoc. prof. Dr. Sally El-Zahaby  10 Reasons for the incorporation of drugs into various dosage forms 1. To mask the bitter, salty, or offensive taste or odor of a drug substance (e.g. by formulating flavored syrups). 2. To provide liquid preparations of drug substances, either as dispersions (suspensions) or as clear preparations (solutions). 3. For insertion of a drug into one of the body’s orifices (rectal or vaginal suppositories). 4. To protect the drug substance from the destructive influences of atmospheric oxygen or humidity (e.g. coated tablets). 5. To protect the drug substance from the destructive influence of gastric acid after oral administration (e.g. enteric-coated tablets) Assoc. prof. Dr. Sally El-Zahaby  11 What are the general considerations for dosage form design?  The principal objective of dosage form design is to achieve a predictable therapeutic response to a drug included in a formulation which can be manufactured on a large scale with reproducible product quality. Assoc. prof. Dr. Sally El-Zahaby  12 What are the general considerations for dosage form design?  To ensure product quality, numerous features are required: 1. Chemical and physical stability, with suitable preservation against microbial contamination if appropriate. 2. Uniformity of the dose of the drug. 3. Acceptability to patient, and suitable packaging and labelling. Assoc. prof. Dr. Sally El-Zahaby  13 What are the general considerations for dosage form design?  To formulate certain dosage form:  Some data must be determined like the routes of administration (e.g., oral, rectal, parenteral, topical), the age of persons (e.g., neonates, children, adults, elderly), and states of illness.  If the medication is intended for systemic use and oral administration is desired, tablets and/or capsules are usually prepared because they are easily handled by the patient and are most convenient in the self-administration of medication. Assoc. prof. Dr. Sally El-Zahaby  14 What are the general considerations for dosage form design?  Examples of state of illness affecting dosage form design:  If a drug substance has application in an emergency in which the patient is in coma or unable to take oral medication, an injectable form of the medication may be prepared. Assoc. prof. Dr. Sally El-Zahaby  15 What are the general considerations for dosage form design?  For treatment of nausea and vomiting, suppositories and injections are better used than oral dosage forms. Assoc. prof. Dr. Sally El-Zahaby  16 What are the general considerations for dosage form design?  The age of the intended patient also plays a role in dosage form design. For infants and children younger than 5 years of age, pharmaceutical liquids rather than solid forms are preferred for oral administration.  These liquids, which are flavored aqueous solutions, syrups, or suspensions, are usually administered directly into the infant’s or child’s mouth by dropper, spoon, or oral syringe or incorporated into the child’s food. Assoc. prof. Dr. Sally El-Zahaby  17 Advantages of solid dosage forms 1- Solid dosage forms are more stable than other dosage forms (It allows less microbial contamination). 2- They are easy to handle and more easy to transport (Less product spoilage during transportation). 3- Less space is required to store. 4. More accurate dosing (Single dose). Assoc. prof. Dr. Sally El-Zahaby  18 Disadvantages of solid dosage forms 1-Difficult to swallow (Some patient particularly children and old age ill persons). 2-Unconscious or breathing tube patients cannot swallow pills. 3- Takes longer time to be absorbed in the body. Assoc. prof. Dr. Sally El-Zahaby  19 Dosage Forms ▪ Drugs are rarely administered as pure chemical substances alone and are almost always given as formulated preparations that generally consist of a drug (or drugs) together with a varied number of other substances (excipients). Active Pharmaceutical Ingredient + Excipients ▪ The product should be packaged in containers that keep the product stable. ▪ The product should be labeled to promote correct use and be stored under conditions that contribute to maximum shelf life. Assoc. prof. Dr. Sally El-Zahaby  20 Excipients Definition:  Excipients are non-medicinal agents that have specialized pharmaceutical functions and produce effective and appealing dosage forms.  So “Excipients” are substances other than the drug.  Excipients are added to the formulation to facilitate the preparation, patient acceptability and functioning of the dosage form as a drug delivery system. Assoc. prof. Dr. Sally El-Zahaby  21 Excipients  Excipients are sub-divided into various functional classifications, depending on the role they play in the resultant formulation.  E.g.: solubilize, suspend, preserve, emulsify, improve the flavor of drug, impart color, etc…  So, Excipients include: solubilizing agents, suspending agents, chemical stabilizers, preservatives, emulsifying agents, disintegrating agents, diluents, lubricants, flavoring agents, and coloring agents. Assoc. prof. Dr. Sally El-Zahaby  22 Excipients  The excipient must be: 1. Non-toxic 2. Non-sensitizing and non-irritating 3. Compatible with all the other components of the formulation.  The drug and pharmaceutical materials must be compatible with one another to produce a drug product that is stable, effective, attractive, easy to administer, and safe. Assoc. prof. Dr. Sally El-Zahaby  23 Excipients  Some excipients are acceptable by certain but not all routes of drug administration.  For example, the preservative benzalkonium chloride is used in oral solutions, but not in nebulizer solutions as it causes bronchoconstriction. Assoc. prof. Dr. Sally El-Zahaby  24 Excipients  Although historically excipients were considered to be inert in that they themselves should exert no therapeutic or biological action or modify the biological action of the drug present in the dosage form, they are now regarded as having the ability to influence the rate and/or extent of absorption of the drug. Assoc. prof. Dr. Sally El-Zahaby  25 Excipients  For instance, the potential influence of excipients on drug bioavailability has already been illustrated by the formation of poorly soluble, nonabsorbable drug–excipient complexes between: 1- Tetracyclines and dicalcium phosphate (Tetracyclines are broad-spectrum antibiotics, Dicalcium phosphate is a commonly used filler in tablet). 2- Amphetamine and Sodium Carboxymethylcellulose (CMC) (Amphetamine is used to treat attention-deficit/hyperactivity disorder (ADHD), CMC is used for example as suspending agent) 3- Phenobarbital and Polyethylene glycol 4000 (PEG 4000). (Phenobarbital used to manage insomnia, PEG 4000 can be used as solvent for example). Assoc. prof. Dr. Sally El-Zahaby  26 Examples of excipients: Diluents/Fillers  Filler(or diluent or bulking agent): such as lactose, is included in tablets and capsules formulations when the drug dose is insufficient to generate the bulk, which means the amount of active ingredient is so small to produce a tablet or capsule. Assoc. prof. Dr. Sally El-Zahaby  Examples of excipients: 27 Surfactants  Surfactants are often used in dosage forms as: Emulsifying agents Solubilizing agents Wetting agents The release of poorly soluble drugs from tablets and capsules may be increased by the inclusion of surfactants in their formulations. Assoc. prof. Dr. Sally El-Zahaby  Examples of excipients: 28 Lubricants  Both tablets and capsules require lubricants in their formulation.  Lubricants reduce friction between powder and metal surfaces during the manufacture process.  Lubricants are often hydrophobic.  Magnesium stearate is commonly included as a lubricant during tablet compaction and capsule- filling operations. Assoc. prof. Dr. Sally El-Zahaby  29 Video about Tablet machine Assoc. prof. Dr. Sally El-Zahaby https://www.youtube.com/watch?v=7BeKzjWB_XU  Examples of excipients: 30 Lubricants  Reduction in the dissolution rate is observed when magnesium stearate is included in tablets or capsules.  This effect can be avoided by: 1. Addition of a wetting agent (i.e. a water-soluble surfactant) 2. The use of a hydrophilic diluent (e.g. stearic acid) 3. or can be minimized by decreasing magnesium stearate content in the formulation. Assoc. prof. Dr. Sally El-Zahaby  31 Examples of excipients: Disintegrants  Disintegrants are required to break up capsules, tablets into particles in order to increase the surface area of the formulation exposed to the gastrointestinal fluids.  A tablet that fails to disintegrate or disintegrates slowly may result in incomplete absorption or a delay in the onset of action of the drug.  The compaction force used in tablet manufacture can affect disintegration.  In general, the higher the force, the longer the disintegration time. Assoc. prof. Dr. Sally El-Zahaby  32 Examples of excipients: Disintegrants  There are two classes of Disintegrants:  Traditional Disintegrants: such as Starch  Super Disintegrants: such as Croscarmellose sodium, Crospovidone, and sodium starch glycolate. Assoc. prof. Dr. Sally El-Zahaby  33 Examples of excipients: Disintegrants Assoc. prof. Dr. Sally El-Zahaby  34 Associate Professor/ Sally El-Zahaby