Parenteral Route of Administration PDF

1 Parenteral Routes of Administration Dr Laxmi Kerai-Varsani Learning outcomes 2 Discuss the different routes of parenteral administration. Discuss the advantages and disadvantages of oral vs parenteral admini...

1 Parenteral Routes of Administration Dr Laxmi Kerai-Varsani Learning outcomes 2 Discuss the different routes of parenteral administration. Discuss the advantages and disadvantages of oral vs parenteral administration. Discuss the requirements of parenteral formulations and how they are administered. Understand the differences in the pharmacokinetic behaviour of a drug delivered by different routes of administration. Appreciate the range of pharmaceutical queries likely to be encountered during practice. Be able to carry out isotonicity calculations based on the freezing point depression method. Why do you need to know about parenteral products? 3 NOT just for hospital pharmacists!!! Often more complex, ‘higher risk’ patients with lots of scope for pharmacists to use their scientific knowledge in a clinical setting: ▪ Compatibility ▪ Sterility ▪ Formulations ▪ Calculations ▪ Manufacture/reconstitution ▪ Dosing ▪ Monitoring Definition of parenteral 4 ‘Located outside the alimentary canal’ ‘Taken into the body or administered in a manner other than through the digestive tract, as by intravenous or intramuscular injection’ Types of parenteral formulations 5 Why administer via injection? 6 Provides a localised effect E.g. steroids Produces a rapid clinical effect E.g. Intravenous (IV) administration Produces a delayed/prolonged effect E.g. Intramuscular (IM) administration Useful when the oral route is not practical Alternative to oral route when a drug molecule degrades in the GI tract E.g. gentamicin Injection routes 7 Intravenous (IV) administration 8 Injections vs infusions Intravenous (IV) administration 9 Peripheral vs central Intravenous (IV) administration 10 Can deliver medicines in a variety of ways: ▪ Produce a rapid effect (bolus doses) ▪ Slow controlled effect (infusions) Formulation & administration considerations 11 Extremes of pH or osmolarity may cause thrombophlebitis Formulations are usually solutions or aqueous emulsions (in which the size of the disperse phase is small). ▪ Water in oil emulsions or suspensions should not be administered by the IV route ▪ Incompatibility Rate of administration must not be too quick ▪ an excessive concentration of drug at the target organ Correct administration into the vein Advantages of IV administration 12 100% bioavailability compared with other routes of administration ▪ no absorption phase Fastest and most certain parenteral route of administration Rate of administration can be controlled (can achieve both rapid onset or controlled over time) ▪ Allows a range of volumes to be used Suitable route for medicines that degrade orally Disadvantages of IV administration 13 Any side effects will occur rapidly Some medicines must be administered very slowly with constant monitoring of patient response Aseptic technique is essential Increased risk of infections/complications Intra-arterial injections 14 Similar to IV administration except into an artery rather than a vein More invasive than IV and greater risk Only for high-risk patients/used when absolutely necessary Intramuscular (IM) administration 15 Small volumes only (1.5ml – 5ml) Relatively rapid absorption Systemic effects within 15 to 30 minutes IM route often used for controlled release formulations Intramuscular (IM) administration 16 Rate of drug absorption depends on: ▪ Vascularity of muscle site ▪ Drug’s lipid solubility ▪ Vehicle in which drug is contained ▪ Injection technique and depth of needle IM depot injections 17 Depo-Provera ▪ Suspension containing medroxyprogesterone acetate for contraception ▪ Given via deep IM injection (buttock) every 12 weeks Antipsychotic IM depot ▪ Flupentixol decanoate (Depixol) ▪ Given via deep IM injection into buttock/thigh every 2-4 weeks IM disadvantages 18 May be painful Expensive Hard to retrieve once administered Difficult to self-administer Atrophy if given repeatedly Cannot administer large volumes Subcutaneous (SC) administration 19 Also known as hypodermic Injected into the loose connective and fatty (adipose) tissues immediately beneath the dermis Subcutaneous (SC) administration 20 Usually small volumes (up to 1ml) Hypodermoclysis ▪ Large-volume electrolyte or dextrose solutions, (up to 1000 ml) may be infused (rarely however) ▪ Employed when there is difficulty in accessing a vein Syringe drivers For non-irritating drugs only Well vascularised, fairly rapidly absorbed ▪ Slower onset of action and sometimes less total absorption of therapeutic agents when compared to the IV or IM routes. Subcutaneous formulation issues 21 Usually aqueous solutions or suspensions ▪ nature of the formulation directly affects the rate of drug absorption ▪ oily solutions or aqueous suspension of therapeutic agents exhibit slower drug absorption Viscous formulations are not generally administered Rate of drug absorption depends on: ▪ Vascularity of site ▪ Drug’s lipid solubility ▪ Vehicle in which drug is contained SC formulation examples 22 Insulin ▪ Injected SC for long and short acting insulins ▪ Injection devices – pens, cartridges, metered doses. Low Molecular Weight Heparins (LMWH) ▪ E.g. enoxaparin ▪ Administered regularly on hospital wards for patients at risk of developing DVT Zoladex ▪ Goserelin for the treatment of prostate cancer and breast cancer ▪ SC injection into anterior abdominal wall every 28 days or 12 weeks depending on formulation Intradermal administration 23 Between the epidermal and dermal skin layers Very small volumes only (up to 0.2ml) Absorption rate is very slow Used for immunological tests ▪ Allergy tests ▪ TB reactivity test ▪ BCG vaccine Intrathecal administration 24 Injection of a drug into the cerebrospinal fluid (CSF) Volumes up to 10ml Used for: ▪ Substances that do not cross the BBB ▪ Cerebral infections/tumour ▪ Anaesthesia Other direct injection sites 25 Intra-osseous ▪ Administration into the bone marrow ▪ Emergency or short-term treatment when access by the vascular route cannot be achieved and the patient’s condition is considered life threatening (infants and children) Intra-articular ▪ Administration into the synovial fluid of joint cavities ▪ E.g. knee for arthritis/sports injuries Specialist administration sites: alprostadil 26 Intracavernosal Intra-urethral administration ▪ Along the dorsolateral aspect of the proximal ▪ Administered to the urethra third of the penis (visible veins should be ▪ Discontinued avoided) ▪ https://www.medicines.org.uk/emc/PIL.3367.latest.pdf  27 Break time herts.ac.uk Oral route of administration 28 Advantages Disadvantages Most commonly used Drug degradation due to pH, bile, enzyme in GI tract Preferred by patients and clinicians Variable absorption across the GI tract Safer, more convenient and economical Patient co-operation and compliance than parenteral route required Self-administration is possible Emesis Drugs with range of physiological properties First pass metabolism for some drugs can be delivered limits the bioavailability (e.g. fentanyl citrate, furosemide, morphine) Parenteral (injection) route of administration 29 Advantages Disadvantages Avoidance of pre-systemic and first pass Painful – poor patient compliance, needle metabolism - increased bioavailability phobia Expensive, strict control of environment More rapid and predictable absorption - during manufacturing, storage and more accurate selection of the effective handling required - aseptic controlled dose environment is must and important to Local effects may be achieved maintain Important in emergency therapy, Difficult to self-administer, requires uncooperative patients (coma), swallowing administration by a healthcare difficulties, emesis etc. professional Difficult to reverse the effects of drugs Parenteral formulations 30 Injections ▪ available as ampoules, vials with rubber head Solutions, emulsions or suspensions, liposomes, microspheres, nanosystems, and powders to be reconstituted as solutions All formulations must be: ▪ Sterile – free of microorganisms (microbiological tests) ▪ Pyrogen-free (test for pyrogens) ▪ Isotonic (NaCl usually as the additive) ▪ Free from visible particulate matter ▪ Stable - chemical, physical and microbiological ▪ Compatible with other sterile diluents and co- administered drug(s). Needles & administration 31 Diameter and length of needle Needles & administration 32 Angle of injection Summary of various parenteral routes of drug 33 administration Routes of administration – rate of drug absorption 34 Intravenous Fastest Inhalational Intramuscular Subcutaneous Intranasal Oral Cutaneous Slowest Rectal Does getting the correct parenteral administration site 35 matter? Intrathecal administration 36 Best practice: https://www.youtube.com/watch?v=oNCObzqSMa0 Pharmaceutical queries 37 Administration of IV drugs ▪ Dose check (BNF or Summary of Product Characteristic (SmPC) www.medicines.org.uk)) ▪ Does the drug need to be reconstituted? Displacement values? ▪ Incompatibilities ▪ Appropriate diluent (BNF or SmPC) ▪ Dilution factor ▪ Does the line need to be flushed (0.9% NaCl pre & post infusion)? ▪ Infusion rate? ▪ Duration of infusion? ▪ Mixing with other diluents e.g. dextrose Calculating displacement values 38 Every powder has a volume that must be accounted for when reconstituting. Displacement value of diamorphine is 0.06 mL per 5 mg Question 1. What volume of water must be added to a 1 mL vial containing 10 mg of diamorphine? Answer: 1 – (0.06 x 2) = 0.88 mL Calculating displacement values 39 Displacement value of bupivacaine is 0.3 mL per 1 mg Question 2. What volume of diluent must be added to a 5 mL vial containing 5 mg of bupivacaine? Answer: 5 – (0.3 x 5) = 3.5 mL Isotonicity 40 Isotonic solution: same osmotic pressure as a body fluid. Ophthalmic, nasal, and parenteral solutions should be isotonic. Hypotonic solution: lower osmotic pressure than that of a body fluid. These solutions lead to swelling and bursting of RBCs, which in turn leads to haemolysis. Hypertonic solution: higher osmotic pressure than that of a body fluid. These solutions lead to shrinkage of the RBCs. Isotonicity 41 Freezing point depression method of calculating isotonicity. Freezing-point depression describes the phenomenon in which the freezing point of a liquid is lowered when another compound is added ▪ solution has a lower freezing point than a pure solvent ▪ the inclusion of ions in a solvent will lower the freezing point of that solvent Isotonicity 42 The freezing-point depression of blood serum/plasma and tears is 0.52°C. An isotonic solution exhibits a freezing-point depression of 0.52°C. Therefore, the solution of drug should be adjusted to produce a freezing-point depression of 0.52°C to render the solution isotonic. The required amount of adjusting substance required to make a hypotonic solution isotonic is given by the equation: 0.52 − 𝑎 𝑊= 𝑏 where W is the weight/volume percentage of adjusting substance in the final solution, a is the freezing point depression of unadjusted solution (i.e. freezing point depression of 1% solution × strength in weight/volume percentage) and b is the freezing point depression of water due to 1% w/v of adjusting substance, usually sodium chloride or glucose. Freezing point depression method 43 Question 3. Calculate the amount of NaCl (% w/v) that should be added to the following formulation in order to make the final solution isotonic: Lidocaine hydrochloride 1.0 g Water to 100 mL 1.0% w/v solution of lidocaine depresses freezing point by 0.338˚C 1.0% w/v solution of NaCl depresses the freezing point by 0.576˚C 0.52−0.338 𝑊= = 𝟎. 𝟑𝟏𝟔% w/v 0.576 Equivalent to 0.316 g per 100 mL Freezing point depression method 44 Question 4. Calculate the amount of anhydrous glucose that should be added to make a solution containing 0.28% w/v potassium chloride isotonic. 1.0% w/v solution of potassium chloride depresses freezing point by 0.439˚C and 1.0% w/v solution of anhydrous glucose depresses the freezing point by 0.101˚C 1% solution of potassium chloride depresses the freezing point of water by 0.439 °C. Therefore, the freezing point depression of unadjusted solution = 0.28 × 0.439 = 0.123 °C. (a) 1% solution of anhydrous glucose depresses the freezing point of water by 0.101 °C. (b) 0.52−0.123 𝑊= = 𝟑. 𝟗𝟑% w/v 0.101 Equivalent to 3.93 g of anhydrous glucose per 100 mL to make the potassium chloride solution isotonic with plasma Recommended reading 45 Aulton, M.E. and Taylor, K.M.G. (2021) Aulton’s Pharmaceutics: The Design and Manufacture of Medicines (6th Edition), Chapter 38. Jones, D.S. (2016) Pharmaceutics - Dosage Form and Design (2nd Edition): FASTtrack, Pharmaceutical Press, Chapter 5.  46 Thank you herts.ac.uk