Design of medicines_1 and 2 2023.pdf

MPharm Programme Design of Medicines – Lectures 1and 2 Prof. Amal Ali Elkordy Professor of Pharmaceutics Slide 1 of 43 MPharm Design of Medicines OVERVIEW  Introduction  Why design of medicines or medicinal products is important (TO MANAGE DISEASE)  Is that OK to release the medicine?  How...

MPharm Programme Design of Medicines – Lectures 1and 2 Prof. Amal Ali Elkordy Professor of Pharmaceutics Slide 1 of 43 MPharm Design of Medicines OVERVIEW  Introduction  Why design of medicines or medicinal products is important (TO MANAGE DISEASE)  Is that OK to release the medicine?  How a drug can be formulated and manufactured  Examples  Small scale manufacture (FOCUS) Slide 2 of 43 MPharm Design of Medicines Introduction  Pharmaceutical formulations involves the rationale design of dosage forms to ensure that the biological and physical performance of the drug (therapeutic agent) are met.  Formulation converts drug into medicine to achieve bioavailabilty, stability and efficacy.  Formulation includes method of manufacture, ingredients, excipients, appearance, colour and taste.  Small scale manufacture vs large scale manufacture: most medicines are manufactured under well-controlled conditions. Slide 3 of 43 MPharm Design of Medicines  Small scale products (extemporaneous dispensing or compounding) can not be as well controlled, accordingly should be used when medicinal products are not available.  Extemporaneous preparations are medicines prepared depending on a request (a legal prescription) from a prescriber for a specific patient.  The unique role of pharmacists, formulation scientists, they have the knowledge of physical pharmaceutics, chemical pharmaceutics and biopharmaceutics.  PHARMACISTS know the unique risks of medicines which are special products. Slide 4 of 43 MPharm Design of Medicines Why design of medicines is important  Medicines: - Have many functions, therapeutic – prevent, treat and cure disease. - Mode of action can be complex not just pharmacological - Improve patient life style.  MEDICINES ACT 1968: - Controls Manufacture, Distribution and Introduction of medicinal products. - Guarantees Quality, Safety and Efficacy of medicinal products. - Extemporaneous dispensing products are exempt from licence Slide 5 of 43 MPharm Design of Medicines  Is that OK to release the medicine? - Design (Formulation) - Quality - Safety  Factors affect safety of medicines: - Correct DRUG - Correct DOSE - Correct METHOD OF DELIVERY (correct label)  DRUG has therapeutic action - Positive - medicinal purpose - Negative - Side Effects Slide 6 of 43 MPharm Design of Medicines  QUALITY : - By the end the medicines will be taken/used by patients: therefore it is important that medicines are produced with the highest achievable quality. Quality requires operation of a Quality Assurance (QA) programme. - In Specials and large pharmaceutical manufactures , medicines are prepared using strict standards and following Standard Operation Procedures (SOPs): documents that detail every step of manufacture and its approval by one person and checking by another and the final products are released by a qualified person. Slide 7 of 43 MPharm Design of Medicines Slide 8 of 43 MPharm Design of Medicines Slide 8 of 43 MPharm Design of Medicines How a drug can be formulated and manufactured  Key points to be considered: - Equipment to be in working order - Formula is safe (source) - Calculations are correct - All materials are sourced from recognised pharmaceutical manufacturers - Records (all aspects of manufacturing must be checked and signed off, worksheet). Records kept for inspection. - Labelling and packaging Slide 9 of 43 MPharm Design of Medicines How a drug can be formulated and manufactured  How a drug is formulated is dependent on various factors and the same drug may be presented in different dosage forms  For extemporaneous dispensing: detailed preparations can sometimes be found in “Pharmaceutical codex”, if not the application of scientific knowledge, e.g. physical properties of the drug (solubility, viscosity, etc), is required. Slide 10 of 43 MPharm Design of Medicines DOSAGE FORMS  Suspensions  Solutions  Tablets  Capsules  Emulsions  Powders  Inhalers  Linctus Slide 11 of 43 MPharm Design of Medicines  Injections  Lotions  Creams  Suppositories  Ointments  etc Examples for Medicines Slide 12 of 43 MPharm Design of Medicines Examples for Medicines Slide 13 of 43 MPharm Design of Medicines Examples for Medicines Slide 14 of 43 MPharm Design of Medicines Examples for Medicines Slide 15 of 43 MPharm Design of Medicines Small Scale Manufacturing (compounding) Suspensions Powders Topical Slide 16 of 43 MPharm Capsules Design of Medicines Solutions Issues to be considered - Shelf life The shelf life of a pharmaceutical product is the period during which the product is expected to maintain its physical and chemical properties unchanged. Shelf-lives for extemporaneous preparations (small scale manufacture) do not exceed one month. Types of Degradation: - Chemical degradation - Physical degradation - Microbiological degradation Slide 17 of 43 MPharm Design of Medicines Suspensions  Suspensions are preparations that contain fine drug particles distributed uniformally throughout a vehicle (a two phase system: solid particles dispersed in a continuous fluid medium). Particles usually have diameter greater than 0.1 µm.  The formulation of a suspension having optimal physical stability depends on whether the particles are to be flocculated or to remain deflocculated. Slide 18 of 43 MPharm Design of Medicines  Approaches to suspension formulations: Dispersed phase (particles) Addition of wetting agent and dispersion medium Uniform dispersion of deflocculated particles (extemporaneous dispensing – stability only two weeks) Incorporation of structured vehicle (deflocculated suspension) Slide 19 of 43 MPharm Design of Medicines Addition of flocculating agent (flocculated suspension) Slide 19 of 43 MPharm Design of Medicines Preparation of suspensions  In the preparation of suspensions, the pharmacist must be familiar with the properties of the dispersed phase and the dispersed medium: if the powder is not wetted when the medium added, the particles will clump and float on the top of the vehicle uneven suspension. Wetting agent should be used.  During extemporaneous compounding of suspensions: - The pharmacist either adds the contents of the commercially available capsules containing Slide 20 of 43 MPharm Design of Medicines the required prescribed drug into a mortar or crushes tablets containing the drug using a mortar with a pestle. THEN - The selected vehicle is slowly added to the powder and mixed well to create a paste before diluted to the desired volume.  Formulation considerations - Physical (colour, odour, clarity, caking) stability and chemical stability (degradation) of the drug are important (drugs in liquid forms have faster decomposition compared to those in solid forms). Slide 21 of 43 MPharm Design of Medicines Formulation considerations - Expiration dates: calculated from the shelf-life at the time of preparation, short due to product susceptibility to chemical, physical or microbiological challenge. - Storage: exposure of the product to light can have deleterious effects on product integrity. - A preservative may be added to protect against bacterial contamination. Slide 22 of 43 MPharm Design of Medicines Manufacturing considerations - Containers: glass or plastic, must be clean before they are filled. Containers must not physically or chemically interact with the product no change in strength, purity or quality. - Caps should be closed tightly to avoid loss of the drug or any components and to avoid premature degradation. - Storage: any condition should be mentioned Light! Slide 23 of 43 MPharm Design of Medicines Manufacturing considerations - Labeling: All labels must be typewritten or computer generated (now). Details which must appear on the label of a dispensed medicine are: - The name of the preparation - The quantity - Instructions for the patient - The patient’s name - The date of dispensing slide 24 of 43 MPharm Design of Medicines Manufacturing considerations - Labeling (cont.): - The name and address of the pharmacy - “keep out of reach of children” Additional Labelling Requirements: - Warning or advisory labels, “shake the bottle” - A batch or product number - An expiry date Slide 25 of 43 MPharm Design of Medicines Example for a suspension request for a specific patient You are required to prepare 100 mL of 15% Chalk mixture  Formula: adapted from BP 1954 method Master formula (1000 mL) Chalk 150g Powdered tragacanth 2g Concentrated Cinnamon Water 25mL Double strength chloroform water 500mL Water to 1000mL Slide 26 of 43 MPharm Design of Medicines Example for a suspension request for a specific patient You are required to prepare 100 mL of 15% Chalk mixture  Calculation: To prepare (100 mL) Chalk 15g Powdered tragacanth 0.2g Concentrated Cinnamon Water 2.5mL Double strength chloroform water 50mL Water to 100mL Slide 27 of 43 MPharm Design of Medicines Example for a suspension request for a specific patient  Preparation: - Lightly mix 15g Chalk and 0.2g tragacanth in a porcelain mortar. - Add 50mL of double strength chloroform water gradually with mixing. - Pipette in 2.5mL of concentrated cinnamon water - Caliber an amber bottle. - Rinse the mixture into the bottle with water. - Shake well. Slide 28 of 43 MPharm Design of Medicines Example for a suspension request for a specific patient You are required to prepare 100 mL of 15% Chalk mixture  Storage: - Expiry date of 2 weeks, why? - Store in a amber bottle, why?  Labelling, additional information: - Shake well before use. Slide 29 of 43 MPharm Design of Medicines Working Example In 400mL of a suspension there is 200 mL of peppermint water. The peppermint water is only available as concentrated peppermint water. The dilution factor 1+39 is used. How many mL of concentrated peppermint water is required to prepare 200 mL of peppermint water? Slide 30 of 43 MPharm Design of Medicines Magnesium Trisilicate Mixture You are required to prepare 200 mL of 5% Magnesium Trisilicate Mixture  Formula: BP 2001 Master formula (1000 mL) Magnesium Trisilicate 50g Light Magnesium Carbonate 50g Sodium Bicarbonate 50g Concentrated Peppermint Emulsion 25mL Double strength chloroform water 500mL Water to 1000mL Slide 31 of 43 MPharm Design of Medicines Magnesium Trisilicate Mixture You are required to prepare 200 mL of 5% Magnesium Trisilicate Mixture  Calculation: To prepare (200 mL) Magnesium Trisilicate 10 Light Magnesium Carbonate 10 Sodium Bicarbonate 10 Concentrated Peppermint Emulsion 5 Double strength chloroform water 100 Water to 200 Slide 32 of 43 MPharm Design of Medicines  Preparation:  Storage:  Labeling, additional information: Slide 33 of 43 MPharm Design of Medicines Powders  Powders represent one of the oldest dosage forms, due to increased use of highly potent compounds, powders as a dosage form have been largely replaced by capsules and tablets.  Powders are dry mixtures of finely divided medicinal and non-medicinal agents intended for internal or external use.  Powders may be dispensed to a patient and used in a bulk form such as powders measured by spoonful to make a douche solution or they may be divided into single dosage units and packaged in folded papers. Slide 34 of 43 MPharm Design of Medicines Powders  Oral powders: bulk and individually (single-dose) wrapped powders - Bulk to supply non potent drugs, e.g. antacids - Individually wrapped powder to supply potent drugs. - Powders supplied as finely divided powders or effervescent granules. The powders are suspended or dissolved in water or mixed with soft foods before administration. Powdered antibiotics syrup to be reconstituted before administration. Slide 35 of 43 MPharm Design of Medicines Powders  Advantages: - solid preparations are more stable than liquid formulations. - Powders and granules are convenient forms as drugs with large doses can be dispensed easily. - Powders have faster dissolution rates than tablets or capsules. - easy for compounding solids. Slide 36 of 43 MPharm Design of Medicines Powders  Disadvantages: - Less convenient for patients to carry. - Problematic in masking of unpleasant tastes. - Not suitable for administrating potent drugs. - Not suitable for drugs that are inactivated in the stomach. - Not suitable for hygroscopic drugs. slide 37 of 43 MPharm Design of Medicines  Weighing Preparation of powders  Measuring  Sifting  mixing - Reduce particle size by grinding with a mortar and pestle (trituration) - Camphor.. - Levigation: non solvent is added to the solid to form a paste, rubbing the paste in a mortar with a pestle. - When mixing two or more powders the method of uniform distribution geometric dilution is applied Slide 38 of 43 MPharm Design of Medicines Preparation of powders - In case of efflorescent powder (contain water of hydration) e.g. caffeine, citric acid and ferrous sulfate. - Hygroscopic and deliquescent powders should be handled with care, double wrapping is better than single wrapping for protection. Packaging of powders - Divided powders (Chartula) are dispensed in the form of individual doses and are dispensed in folded papers and parchment. - For greater protection: small cellophane or polyethylene envelops can be used. - Capsules. Slide 39 of 43 MPharm Design of Medicines Example of powders to be applied externally - You are required to dispense: Zinc, starch and talc dusting powder BPC. Mitte 100g master formula Zinc oxide Starch 25% 25% Sterilized purified talc 50% Slide 40 of 43 MPharm Design of Medicines for 100g Example of powders to be applied externally - Shelf-life of 4 weeks - Storage: in a cool and dry place - Labels: “For external use only”, “Store in a cool and dry place”. Advise: Lightly dust the powder onto the affected area. The area should not be too wet as the powder will cake and abrade the skin. It should not be applied to broken skin or large raw areas. Slide 41 of 43 MPharm Design of Medicines Example of powders to be taken orally - Calculate the amounts required to make 10 powders each containing 200 micrograms of digoxin. Lactose is used as an inert diluent for the trituration. The weight of each divided powder is 120 mg. - Points to be considered: - Balance class B (100mg) to be used. - A 1 in 10 dilutions will be produced. - The geometric method will be applied for mixing powders. Slide 42 of 43 MPharm Design of Medicines Example of powders to be taken orally - Shelf-life of 2-4 weeks - Storage: if hygroscopic, the storage should be moisture proof and airtight - Labels: powders to be mixed with water References Resources on CANVAS Winfield, A.J. 2009. Powders and granules. In: Winfield, A.J., Rees, J.A. and Smith, I. (Eds.). Pharmaceutical Practice, 4th Edition. Churchill Livingstone, pp. 387-391 Slide 43 of 43 MPharm Design of Medicines