Lecture 17 Novel Drug Delivery System I_2024.pdf

PHA 339 Identify various drug delivery systems currently available and future trends in this area. Appreciate the advantages and disadvantages of drug delivery systems Understand the mechanisms of controlled drug delivery in solid dosage forms. Know the theoretical basis for preparing and using oral...

PHA 339 Identify various drug delivery systems currently available and future trends in this area. Appreciate the advantages and disadvantages of drug delivery systems Understand the mechanisms of controlled drug delivery in solid dosage forms. Know the theoretical basis for preparing and using oral controlled release dosage forms. Drugs were dispensed in the powder form i.e we dispensed DRUGS Now we dispense DOSAGE FORMS containing the drugs ✓ ✓ ✓ ✓ ✓ Examples: Tablets Capsules Suspensions Emulsions Suppositories Conventional Dosage Forms: Have a high initial release followed by exponential decay Results in peak and trough patterns of drug concentration in plasma/tissue Drug Delivery System: Desired release profile Control of timing and target *Basic Principles and application of Pharmacy Practice, Dash et. al. The drug delivery system is the optimized drug product which is designed to release the drug(s) to produce the maximum safety, efficacy, and reliability DRUG DELIVERY SYSTEMS Advantages: ✓Fewer side effects ✓Rate controlled delivery ✓Increased efficacy ✓Constant delivery Optimized drug therapeutic effects Targeted drug delivery Controlled drug delivery Improved solubility, permeability and stability of drug Improved patient compliance Reduce toxicity 1. Oral drug delivery systems: ▪ Dissolution-diffusion controlled release systems Examples matrix systems, reservoir systems ▪ Osmotic pressure-controlled drug delivery systems 2. GI specific drug delivery systems: ▪ Use of delaying excipients ▪ Colon targeting systems: pH-controlled release coatings are insoluble at low pH of stomach but dissolve and releases drug in the small intestine due to increased pH. ▪ Gastro Retentive Systems ▪ Effervescent tablets 3. Solubility Improving drug delivery systems: ▪ Self emulsifying drug delivery systems ▪ Amorphous systems ▪ Solid dispersions 4. Targeted drug delivery systems: ▪ Monoclonal antibodies: act directly by binding to a cancer specific antigen and induce immunological response to cancer cells such as inducing cancer cells apoptosis, inhibiting specific functions etc. ▪ Nanotechnology ▪ Liposomes 5. Prodrugs 6. Injectable drug delivery systems: ▪ Insulin Pens ▪ Insulin Pumps 7. Inhalation drug delivery systems: ▪ Metered dose inhalers ▪ Dry powder inhalers ▪ Inhalation Nasal sprays 8. Transdermal drug delivery systems: ▪ the drug is mixed with a polymer or contained within a membrane. Drug incorporated polymeric material is then casted to a suitable sized patch which when applied allows penetration into the systemic circulation via transdermal absorption. Ex. Nitro-Dur, scopolamine, nicotine patches ▪ Transdermal Patch: Single layer drug in adhesive, Multilayer drug in adhesive, Matrix system, reservoir systems 9. Specific drug delivery systems Monolithic devices: matrix systems: the drug is mixed with a polymer and forms a complex maze of pores. The diffusion of the drug is controlled by the time it takes to travel through the polymer network. Reservoir devices: rate controlling membranes Degradable systems: polymers degrade due to chemical action. the polymer is degraded in the body releasing the drug(s) at a constant or predetermined rate ORAL DRUG DELIVERY SYSTEMS: DISSOLUTION-DIFFUSION CONTROLLED Bulk degradation Surface degradation Monolithic systems Reservoir systems Biodegradable systems Osmotic pumps/drug delivery system -- the drug is mixed with the core material and place inside a semipermeable membrane. A fine laser hole is drilled through the membrane at one position. When the system is placed in an aqueous environment, water enters through the membrane and increased pressure within the core forces some of the drug solution out through the small hole. *Oros is an example of drug delivery systems based on osmotic pressure *Current status of drug delivery systems and future directions by Rajan sharma *Current status of drug delivery systems and future directions by Rajan sharma   OSMOTIC PRESSURE Vanthoff’s Equation  = CRT C = molarity  Cg   =  RT M  grams ( solute ) Cg = 1LSolution *Basic Principles and application of Pharmacy Practice, Dash et. al. Isotropic mixtures of oil, surfactant, co-solvents and drug Spontaneous formation of fine oil-in-water emulsions when introduced into aqueous phases under conditions of gentle agitation Advantages – Improve solubility Enhance lymphatic transport and Increase bioavailability Can be used for acidic, basic and neutral compounds Oral route of administration Ref: Porter et al., Adv. drug del.rev., 60, 2008, 673-691 17 Low Crystal Lattice energy Amorphous Drug Metastable form Crystallizes High Crystal Lattice energy Drug In Solution Crystalline form: ▪Thermodynamically stable ▪Molecules packed in a repeating pattern ▪Low Solubility, More Stable Crystalline Drug Amorphous form: ▪Thermodynamically unstable ▪Molecules packed in random pattern ▪High Solubility, Low Stable J. Breitenbach, M. Mägerlein “Melt-Extruded Molecular Dispersions", I. Ghebre Sellassie, C. Martin (ed.), Pharmaceutical Extrusion Technology, Marcel Dekker, 2003, 133, 245-260; Chiou and Riegelman, J. Pharm. Sci. 60: 1281 (1970). 18 Solid Dispersions refers to a group of solid products consisting of at least two different components, generally a hydrophilic matrix and a hydrophobic drug. Hydrophobic Drug Hydrophilic Polymer Dissolution Advantage Reduce Particle Size Increase Solubility – Amorphous state Enhance wettability- Hydrophilic matrix Stability Advantage High Tg - Low molecular mobility Drug – Polymer Interaction ( e.g. Hydrogen bonds) J. Breitenbach, M. Mägerlein “Melt-Extruded Molecular Dispersions", I. Ghebre Sellassie, C. Martin (ed.), Pharmaceutical Extrusion Technology, Marcel Dekker, 2003, 133, 245-260; Chiou and Riegelman, J. Pharm. Sci. 60: 1281 (1970). 19 *Source: Sanvicens et al, 2008. *Basic Principles and application of Pharmacy Practice, Dash et. al. Hydrophilic Spherical vesicles with a phospholipid bilayer Inactive: Unmodified liposomes gather in specific tissue reticulo-endothelial system Hydrophobic Active: alter liposome surface with ligand (antibodies, enzymes, protein A, sugars) Physical: temperature or pH sensitive liposomes Prodrugs: Prodrugs are defined as compounds that undergoes biotransformation before exerting pharmacological effects. Prodrugs are usually inactive compared to the release drugs. *Basic Principles and application of Pharmacy Practice, Dash et. al. 23 *Basic Principles and application of Pharmacy Practice, Dash et. al. 24 PROCARDIA capsules are formulated as soft gelatin capsules for oral administration, each containing 10 mg nifedipine. Inert ingredients in the formulation are glycerin; peppermint oil; polyethylene glycol; soft gelatin capsules (which contain Yellow 6, and may contain Red Ferric Oxide and other inert ingredients); and water. 25 PROCARDIA XL® Extended Release Tablet is similar in appearance to a conventional tablet. It consists of a semipermeable membrane surrounding an osmotically active drug core. The core itself is divided into two layers: an “active” layer containing the drug, and a “push” layer containing pharmacologically inert (but osmotically active) components. As water from the gastrointestinal tract enters the tablet, pressure increases in the osmotic layer and “pushes” against the drug layer, releasing drug through the precision laser-drilled tablet orifice in the active layer. 26 PROCARDIA XL Extended Release Tablet is designed to provide nifedipine at an approximately constant rate over 24 hours. This controlled rate of drug delivery into the gastrointestinal lumen is independent of pH or gastrointestinal motility. PROCARDIA XL depends for its action on the existence of an osmotic gradient between the contents of the bi-layer core and fluid in the gastrointestinal tract. Drug delivery is essentially constant as long as the osmotic gradient remains constant, and then gradually falls to zero. Upon swallowing, the biologically inert components of the tablet remain intact during gastrointestinal transit and are eliminated in the feces as an insoluble shell. 27 Lozenges are solid oral dosage forms that are designed to dissolve or disintegrate slowly in the mouth. They contain one or more APIs that are slowly liberated from the flavored and sweetened base. NicoDerm CQ features Extended Release SmartControl® Technology. A unique patch that helps prevent the urge to smoke, all day long when worn for 24 hours. https://www.nicodermcq.com/how-nicoderm-cq-works.html https://www.youtube.com/watch?v=pTKuiJyW7-k CQ (Committed Quitters) 28 Review Question1 Which of the following is an example of a prodrug A) B) C) D) Levodopa Procardia XL NicoDerm Lidocaine Review Question 2 Which is an example of a drug delivery system based on osmotic pump A) B) C) D) Levodopa Nitro-Dur OROS Scopolamine Review Question 3 Spherical vesicles with phospholipid bilayer utilized for targeted delivery of drug are A) Liposome B) Micelles D) Amorphous dispersion E) Dendrimers Review Question 4 Which is not true for Amorphous systems? A)They are thermodynamically unstable B) Molecules are packed in a repeated pattern C) They have high Solubility D) Have Low stability Osmotic Pumps https://www.youtube.com/watch?v=QOOQ5pOZyWU Gastro-retentive System https://www.youtube.com/watch?v=MmGCJEqZkOY Liposomes https://www.youtube.com/watch?v=pSCv5_41j88 33 Ansel’s Pharmaceutical Dosage Forms and Drug Delivery Systems; ▪ Chapter 20- Novel Dosage Forms and Drug Delivery Technologies Pharmaceutics: Basic principles and application to pharmacy practice ▪ Chapter 12- Special dosage forms and novel drug delivery systems 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. Ointments, Creams and Gels: Semi-Solid dosage forms USP Chapters: Pharmaceutical Dosage Forms USP Chapters: Qualitative and Quantitative Evaluation Suppositories: Rectal and Vaginal drug delivery systems Nebulizers and Inhalers: Pulmonary drug delivery systems Patches: Transdermal drug delivery systems Novel Drug delivery systems I Novel Drug delivery systems II Calculations: Dosage form Design and Delivery Systems Pharmaceutical Excipients Expectation: More application based (both theoretical and calculation based problems) compared to straightforward questions. 35 A 75:25 mixture of propane and isobutane were mixed in an aerosol container. Calculate the pressure inside the container using the properties given in the following table. Assume ideal solution model. A 75:25 mixture of propane and isobutane were mixed in an aerosol container. Calculate the pressure inside the container using the properties given in the following table. Assume ideal solution model. Ratio: 75:25 Molecular Weight: Propane (44.1) and Isobutane (58.1) Vapor pressure (pure): Propane (110) and Isobutane (30.4) No. of moles of propane No. of moles of isobutane Mole fraction of propane Mole fraction of isobutane Vapor pressure of propane Vapor pressure of isobutane Total pressure in the aerosol container No. of moles of propane No. of moles of isobutane Mole fraction of propane Mole fraction of isobutane Vapor pressure of propane Vapor pressure of isobutane Total pressure in the aerosol container Equation Sheet No. of moles of propane = 75gms/44.1 = 1.7 No. of moles of isobutane = 25 gms/58.1 = 0.43 Mole fraction of propane = 1.7/(1.7+0.43) = 0.798 Mole fraction of isobutane = 0.43/(1.7+0.43) = 0.202 Vapor pressure of propane = 0.798 x 110 = 87.78 psig Vapor pressure of isobutane = 0.202 x 30.4 = 6.14 psig Total pressure in the aerosol container = 87.78 + 6.14 = 93.92 psig No. of moles of propane = 75gms/44.1 = 1.7 No. of moles of isobutane = 25 gms/58.1 = 0.43 Mole fraction of propane = 1.7/(1.7+0.43) = 0.798 Mole fraction of isobutane = 0.43/(1.7+0.43) = 0.202 Vapor pressure of propane = 0.798 x 110 = 87.78 psig Vapor pressure of isobutane = 0.202 x 30.4 = 6.14 psig Total pressure in the aerosol container = 87.78 + 6.14 = 93.92 psig