Fundamentals of Pharmacy & Pharmacology Lecture 4 (2023-24) PDF

Fundamentals of Pharmacy & Pharmacology: The Science of Medicines SL12102 / SL12011 Lecture 4: Role of dosage forms and excipients. Why different dosage forms Dr C POURZAND  A Formulation Principle “The more trivial the complaint, the more...

Fundamentals of Pharmacy & Pharmacology: The Science of Medicines SL12102 / SL12011 Lecture 4: Role of dosage forms and excipients. Why different dosage forms Dr C POURZAND  A Formulation Principle “The more trivial the complaint, the more demanding the consumer” There are 22 types of Nurofen on the UK market!!  The Australian federal court ruled that the company had misled consumers after it was discovered that Nurofen Back Pain, Nurofen Period Pain, Nurofen Migraine Pain and Nurofen Tension Headache are all the same pill, all containing the same active ingredient, ibuprofen lysine 342mg. In the UK, Nurofen is £2 for a packet of 16, compared to £2.85 for a packet of 12 Nurofen Tension Headache and Nurofen Migraine Pain.  How to make a medicine? Why are drugs not administered as pure substances? Need to Formulate the Dosage Form  Types of dosage forms: Definition: Dosage forms are the means by which drug molecules are delivered to sites of action within the body. What do we need in a dosage form: 1. Accurate dosing 2. Protection and Shelf-life 3. Protection from gastric juice 4. Masking taste and odour 5. Placement of drugs directly within body tissues 6. Sustained release medication. 7. Controlled release medication. 8. Insertion of drugs into body cavities 9. Use of desired vehicle for insoluble drugs  What is an excipient? “All the other components of a formulation other than the active drug” Each component requires an appropriate evaluation for safety. An excipient should be chemically and physiologically  Uses for excipients Aid processing of the system during manufacture and accurate dose control Control rate of absorption Protect, support or enhance stability, bioavailability or Difference in in-vivo absorption is due to the Excipients used in the Formulation  Dose Control Why formulate to control dose? Aspirin tablet typically has 300 mg API Patient unlikely to be able to measure this amount Many drugs have lower doses Ethinyl estradiol - 0.01 mg or 10µg tablet Alfacalcidol – 0.001mg or 1µg capsule Difficult to manufacture - blend uniformity  Dose Equally, high dose (low potency) drugs can be a problem to formulate If drug has poor flow/compressability cannot make a tablet  Why are Ibuprofen tablets film coated? Avoiding gastric mucosal irritation- peptic and mucosal ulcers, dyspepsia, severe gastric pain and bleeding…  Taste Very subjective and difficult to quantify Many drugs extremely bitter Can be mitigated by film-coating  Types of dosage forms Dosage Forms Route of administration Physical form Oral Solid Topical Semisolid Transdermal Liquid Rectal Parenteral Vaginal Inhaled Ophthalmic Otic Solid oral dosage forms: Tablet/Caplet A tablet is a hard, compressed medication in round, oval or square shape. Excipients include Diluents (Compressible bulking agents), binders, glidants (flow aids) and dry lubricants to ensure efficient tabletting. Disintegrants to ensure that the tablet breaks up in the GI tract. Sweeteners or film coatings for taste masking active pharmaceutical ingredients.  Solid Oral Dosage Forms 90 % of medicines are taken orally Requirements for an ideal oral solid dosage form: – drug must remain stable – drug must be bioavailable (formulation reliably releases drug in GIT) – uniform drug content (reproducible dose) – robust and resistant to disintegration during handling – easy and cost effective to mass produce – pleasant to take  Buccal and Sublingual Tablet Sublingual and buccal medications are administered by placing them in the mouth, either under the tongue (sublingual) or between the gum and the cheek (buccal). The medications dissolve rapidly and are absorbed through the mucous membranes of the mouth, where they enter into the bloodstream. Bypasses the stomach and liver. Examples  Effervescent Tablet Effervescent tablets are uncoated tablets that generally contain acid substances (citric and tartaric acids) and bicarbonates and which react rapidly in the presence of water to effervesce by releasing carbon dioxide. They are intended to be dissolved or dispersed in water before use providing: Very rapid tablet dispersion and dissolution. Pleasant tasting carbonated drink by addition of sodium saccharin (sweetener) Lubricants need to be water soluble Tablet packaging is critical for stability  Capsule A capsule is a dosage form in which a formulation is contained in a gelatin or a Hydroxypropyl methylcellulose matrix. Hard gelatin capsule Advantage: mask the unpleasant taste of its contents. The two main types of capsules are: 1. Hard-shelled capsules, which are normally used for dry, powdered ingredients, 2. Soft-shelled capsules, primarily used for oils and for active ingredients that are dissolved or suspended in oils or emulsions. Soft gelatin capsule  Oral Granules Consist of solid, dry aggregates of powder particles often supplied in single-dose sachets. Some granules are placed on the tongue and swallowed with water, others are intended to be dissolved in water before taking. Effervescent granules evolve carbon dioxide when added to water.  Fast Dissolving Oral Delivery Formulations Solid dosage form that dissolves or disintegrates rapidly in oral cavity, resulting in solution or suspension without the need of water Also known as: Orodispersible tablets, melts Tablet disperses in saliva – for some drugs a portion may be absorbed from the mouth, pharynx and oesophagus as the saliva passes towards the stomach (potentially increased absorption/bioavailability) – formulations are either very porous or soft moulded matrices or compressed into tablets with very low compression force – Tablets difficult to handle - often require specialized ‘peel-off blister’ packaging  Liquid preparations Solutions Oral solutions are clear liquid preparations for oral use containing one or more APIs dissolved in a solvent. Solvents include diluted alcohol, glycerin or propylene glycol and purified water. Emulsions Oral emulsions are stabilized oil-in-water dispersions, either or both phases of which may contain dissolved solids. Suspensions Oral suspensions are liquid preparations for oral use containing one or more APIs suspended in a suitable vehicle. Liquid vehicles include purified water with cellulose derivative polymers and thickening agents (e.g. Xanthan  Liquid preparations Syrup It is a concentrated aqueous solution of a sugar. Flavored syrups are a convenient form of masking disagreeable tastes. Elixir It is pleasantly flavored clear liquid oral preparation of potent or nauseous drugs. The vehicle may contain a high proportion of ethanol in purified water and sucrose together with antimicrobial preservatives which confers the stability of the preparation.  Liquid preparations Linctus Linctuses are viscous, liquid oral preparations that are usually prescribed for the relief of cough. They usually contain a high proportion of syrup and glycerol which have a demulcent effect on the membranes of the throat. The dose volume is typically small Oral drops Oral drops are liquid preparations for oral use that are intended to be administered in small volumes with the aid of a suitable measuring device. They may be solutions, suspensions or  Topical dosage forms Ointments Ointments are viscous, semi-solid, greasy preparations (oil 80% to 20% water) for application to the skin, rectum or nasal mucosa. The base is usually anhydrous and  Topical dosage forms: Creams Creams are semi-solid emulsions, that is mixtures of oil and water. They are divided into two types: 1. Oil-in-water (O/W) creams: O/W are more comfortable and cosmetically acceptable as they are less greasy and more easily washed off using water. 2. Water-in-oil (W/O) creams: W/O creams more difficult to handle but many drugs which are incorporated into creams are hydrophobic and will be released more readily from a water-in-oil cream than an oil-in- water cream. Water-in-oil creams are also more moisturising as they provide an oily barrier which reduces water loss from the stratum corneum.  Topical dosage forms: Gels Gels are semisolid system in which a liquid phase is constrained within a 3D polymeric matrix (consisting of natural or synthetic polymer) having a high degree of physical or chemical cross-linking. They are used for medication, lubrication and some miscellaneous applications like carrier for spermicidal agents to be used intra vaginally.  Transdermal dosage forms: Patch A transdermal patch or skin patch is a medicated adhesive patch that is placed on the skin to deliver a specific dose of medication through the skin and into the bloodstream. An advantage of a transdermal drug delivery route over other types such as oral, topical, etc is that it provides a controlled release of the medicament into the patient. The first commercially available patch was scopolamine for motion sickness.  Rectal/Vaginal dosage forms: Suppositories/Pessaries Suppositories are solid dosage forms intended for administration of medicine via the rectum, vagina (pessaries) or urethra (bougies) that melt, soften or dissolve in the body cavity. Suppositories are made by dissolving or dispersing the active ingredient(s) in a base at an elevated temperature, the mix is then poured into a mould and solidifies at room temperature. The quantity of fluid available for drug dissolution in the rectum is very small - approximately 3 ml and 100mm thick layer.  Parenteral dosage forms An injection is an infusion method of putting liquid into the body, usually with a hollow needle and a syringe which is pierced through the skin to a sufficient depth for the material to be forced into the body. All requires the preparation of a sterile product Intravenous (IV) injection It is a liquid administered directly into the bloodstream via a vein. It is advantageous when a rapid onset of action is needed. 100% of drug is bioavailable Intramuscular injection It is the injection of a substance directly into a muscle. Many vaccines are administered intramuscularly. Depending on the chemical properties of the drug, the medication may either be absorbed fairly quickly or more gradually. Injection sites include the deltoid muscle of the arm, the  Parenteral dosage forms Subcutaneous injections are given by injecting a fluid into the subcutis, the layer of fatty tissue directly below the dermis and epidermis. Subcutaneous injections are highly effective in administering vaccines and such medications as insulin.  Inhaled dosage forms Inhaled drug delivery is any drug or solution of drug administered by the nasal or oral respiratory tract Inhalers are prepared either as solutions, suspensions or a dry powder formulation. There is a need to deliver the drug in an aerosol form (less than 5µm)  Drug Delivery Liquid Dose inhaler Devices LDI Pressurised metered dose inhaler Dry Powder inhaler pMDI DPI Nebuliser Standard Spacers Active Passive Pneumatic Ultrasonic Inhalers Inhaler Inhalers Breath Activated Inhalers  Ophthalmic dosage forms Eye drops are saline-containing drops used as a vehicle to administer medication in the eye. Depending on the condition being treated, they may contain steroids, antihistamines or topical anesthetics. Eye drops sometimes do not have medications in them and are only lubricating and tear-replacing solutions. Ophthalmic ointments These are sterile semi-solid preparations intended for application to the conjunctiva or eyelid margin.  Otic dosage forms Ear drops - Ear drops are solutions, suspensions or emulsions of drugs that are instilled into the ear with a dropper. - It is used to treat or prevent ear infections, especially infections of the outer ear and ear canal.  References