Drug Delivery - Modified Release

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  • Created by: LBCW0502
  • Created on: 09-11-19 11:14
Outline the history of modified release formulations (1)
Discovery of beta blockers to treat HTN, incidence of MI due to sub-therapeutic levels (patients taking medication before going to sleep). MR allows a reduction in frequency of dosing. Combine medication with materials to form MR formulation
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Outline the history of modified release formulations (2)
Concept applied to other medicines/disease treatments
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What is the aim of the ideal dose regimen?
To achieve a therapeutic concentration immediately. Therapeutic concentration is maintained for the desired duration of treatment
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What are the issues with repeated dosing of a normal formulation? (1)
Repeated dosing (absorption, distribution, elimination repeated on graph). First dose (absorption peak shows minimum therapeutic effect, short duration). Within certain period of time, patient only has therapeutic doses after subsequent repeated dose
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What are the issues with repeated dosing of a normal formulation? (2)
Aim to have administration, rapid absorption with continuous and constant therapeutic levels (graph). (At the peak, the absorption rate is equal to the elimination rate)
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What does modified drug release achieve?
Able to smooth out variations in plasma concentration and give a constant therapeutic effect. Reduce frequency of dosage (aid compliance). Promote drug absorption
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Which process needs to occur for absorption of the drug to take place?
Need dissolution before absorption. Dissolution test - release of drug from dosage form
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State features of the idealised drug delivery system
Drug in reservoir (energy source present), rate controller, drug entering portal, drug at desired location in desired amount, sensor and programmer (diagram)
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What are the advantages of MR dosage forms? (1)
Improve treatment of chronic illness. Maintenance of therapeutic effect overnight. Reduction of incidence of systemic side effects (due to the plasma concentration being within the therapeutic window)
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What are the advantages of MR dosage forms? (2)
Reduction of total amount of drug administered over the period of treatment
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What are the MR oral drug delivery terms? (1)
Delayed release (lag time e.g. enteric coating, pulsatile release). Repeat action (doses released at intermittent intervals). Prolonged release (drug provided for absorption over longer period of time)
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What are the MR oral drug delivery terms? (2)
Sustained release (initial release to reach therapeutic concentration and then gradual release). ER (slow release for Cp maintenance over 8-12 h, allows 2 fold reduction in dosing frequency). CR (drug release at constant rate and steady Cp)
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What are the MR oral drug delivery terms? (3)
MR (dosage forms whose drug release characteristics of time course and/or location are chosen to accomplish therapeutic or convenience objectives not offered by conventional forms)
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What is enteric coating?
Coated with film (polymer) – insoluble at low pH, at a pH over 6, film dissolves (not broken down in the stomach, breaks down in the SI) e.g. enteric coated aspirin, avoids stomach irritation, improve absorption
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What is pulsatile release?
One compartment breaks down and releases the drug, another compartment breaks down and releases more of the drug
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What is sustained release?
System releases active agent over extended period of time, avoiding undesirable sawtooth kinetic patterns in plasma concentration profile (e.g. change salt, mix active agent with polymer)
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What is controlled release?
System controls active agent's rate of release over time usually maintaining constant drug concentrations in the target tissue or cells. Release profile is determined by design of system itself
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What is zero-order release?
System releases a constant amount of active agent per unit of time from dosage form. Release rate is independent of remaining dose/amount that needs to be released
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What is first order release?
System releases a percentage amount of its remaining active agents from dosage form per unit of time
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State features of the drug level vs time graph (1)
Plasma concentration against time. Levels (toxic range, therapeutic range, sub-therapeutic range). Zero-order release (sharp increase, remains in therapeutic range). Immediate release (log normal/bell curve)
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State features of the drug level vs time graph (2)
SR (slow absorption, longer in therapeutic range, decreases) - diagram
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What are the mechanisms of modified release?
Diffusion based systems. Dissolution based systems. Ion exchange systems. Osmotically controlled systems
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Describe features of the diffusion system - reservoir device (1)
Drug contained in reservoir surrounded by insoluble polymer membrane. Release rate determined by type of membrane. Fick's law (J = -D dc/dx). dM/dt = (A DKdeltaC)/d, membrane characteristics (polymeric membrane)
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Describe features of the diffusion system - reservoir device (2)
Amount of drug released (M) depends on SA of device (A), diffusion coefficient of drug (D), partition coefficient (K), conc difference of drug across membrane (deltaC) and membrane thickness (d). If drug cannot partition in membrane/cannot diffuse
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Describe features of the diffusion system - matrix device (monolithic devices) - 1
Drug dissolved/dispersed in a water insoluble polymer matrix. As drug dissolves, matrix is emptied. M = [ Dse/τ (2Co-eS) t ]1/2. Amount of drug released (M) depends on diffusion coefficient of drug in polymer matrix (D), solubility of drug (S)
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Describe features of the diffusion system - matrix device (monolithic devices) - 2
Initial concentration of drug in matrix (Co), porosity (e) and tortuosity (τ) - Equations - able to predict drug release rate/bioavailability
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Describe features of the diffusion system - matrix device (monolithic devices) - 3
After drug is released, matrix/reservoir insoluble polymer is excreted out of the body in the same conformation as it was administered
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What are dissolution based systems?
Either drug particles or inert particles coated with drug or concentration tablet surrounded by a dissolving film. Or drug embedded/dispersed in a slowly dissolving matrix
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Describe features of the dissolution controlled systems (1)
Drug release is sustained according to the different dissolution rates of the coating around the active ingredient. dM/dt = AD/h (Cs - Cb). Dissolution rate of coating (dM/dt). Depends on SA of device (A), diffusion coefficient of drug (D)
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Describe features of the dissolution controlled systems (2)
Thickness of coating (h), concentration of drug at solid surface (Cs), concentration of drug in bulk solution (Cb)
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Describe features of the dissolution controlled systems (3)
Dissolution/release rate are equal. Able to change thickness of coating (thicker coating, longer duration).
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Why is the concentration of drug in the bulk solution minimum (very small to 0)?
Drug is absorbed (assume drug is absorbed/released, sink conditions)
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What is the difference between a diffusion system and a dissolution system?
In a diffusion system there is no dissolving of material
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Describe features of osmotically controlled systems (1)
Osmotically active drug is surrounded by a semi-permeable membrane (permeable only to water). Drug pumps out of the system through the orifice at the same rate of the volume flow rate of the water into the core multiplied by drug concentration
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Describe features of osmotically controlled systems (2)
dV/DΠ = Ak/h (delta Π - delta P). Depends on membrane permeability (k), area of membrane (A), membrane thickness (h), osmotic pressure difference (delta Π) and hydrostatic pressure difference (delta P)
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Describe features of osmotically controlled systems (3)
Drug with coating (semi-permeable membrane), high osmotic pressure in system (contains salt solution/drug), tendency for drug to be released through orifice. Good bioavailability
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What was the main issue with osmotically controlled systems when it was discovered?
Drilling a hole into every tablet (required different QC). Now have modern technology to put holes in the tablets (e.g. use a laser)
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What are the requirements of an implantable controlled release drug delivery system? (1)
Facilitate compliance over an extended time period. Capable of delivering a drug at a controlled rate. Readily implanted without a major surgical procedure. Free of potential medical complications
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What are the requirements of an implantable controlled release drug delivery system? (2)
Minimum risk of misuse or unauthorised termination by non-medical personnel. Readily retrievable by medical personnel. Simple to procedure and relatively inexpensive. Biostable, biocompatible, non-toxic, non-carcinogenic
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What are the types of release for controlled drug delivery from implants? (1)
Release by diffusion (permeation form matrix e.g. vaginal rings, permeation across membrane e.g. Progestasert IUD, hybrid system e.g. Norplant). Release by activation (Alzet osmotic pumps, long term release of peptides/proteins)
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What are the types of release for controlled drug delivery from implants? (2)
Release by erosion (Gliadel implants for treatment of brain tumours)
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What are the types of non-degradable polymeric implants (release by diffusion)?
Reservoir devices (drug and rate controlling membrane). Matrix devices (biodegradable polymeric implants, implantable pumps)
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Describe features of the reservoir type non-degradable polymeric implants (solution diffusion) (1)
Drug contained in reservoir surrounded by rate controlling polymeric membrane. For diffusion of drugs barriers to be circumvented - reservoir membrane interface, rate controlling membrane, membrane-implantation site interface
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Describe features of the reservoir type non-degradable polymeric implants (solution diffusion) (2)
Use silicone polymer (silicone fluid, silicone foam elastomer, medical grade). PEVA. Ease of fabrication (co-polymers, thermoplastic, manufacturing performed by extrusion film casting or injection molding)
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Describe features of the reservoir type non-degradable polymeric implants (solution diffusion) (3)
Versatility (mwt, ethylene/vinyl acetate ratios (content of ethylene unit increases crystallinity therefore solubility parameter and release profile)
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Describe features of the steady state concentration profile of a drug in a reservoir type polymeric implant (1)
Drug reservoir (donor) Cr, polymer membrane, implantation site (receptor) Ci. Fick's law (equation and components). Sink conditions apply
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Describe features of the steady state concentration profile of a drug in a reservoir type polymeric implant (2)
In a reservoir type polymeric implant reservoir consists of solid drug particles or suspension of solid drug particles in dispersion medium so that Cr is constant. Zero order CR, release rate doesn't vary with time
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Describe features of the steady state concentration profile of a drug in a reservoir type polymeric implant (3)
Lag time due to interphases (drug reservoir-polymer membrane and membrane-implantation site)
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Describe features of reservoir type non-degradable polymeric implants - pore diffusion (1)
Rate controlling polymer membrane is porous. Microporous membranes can be prepared by making hydrophobic polymer membranes in the presence of PEG which can be removed in water. Drug molecules are released by diffusion through pores
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Describe features of reservoir type non-degradable polymeric implants - pore diffusion (2)
Pores filled with water or oil (depending on drug properties e.g. hydrophobicity, facilitate diffusion of drug). Pathway of drug transport in membrane is tortuous. Porosity and tortuosity are considered (equation)
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Describe features of Norplant I (1)
Six capsules of levonorgestrel implanted in the upper arm, 34 mm long, 2.4 mm diameter. 5 years ago - 70 mcg/day initially followed by 30 mcg/day. Membrane permeation device. Membrane made of silastic (poly dimethylsiloxane), cross linked, non-porous
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Describe features of Norplant I (2)
Hydrophobic, impermeable to ions, release zero order (membrane diffusion)
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Describe features of Norplant II (1)
Hybrid membrane permeation controlled matrix diffusion controlled. Constant kinetics while minimising dose dumping, drug reservoir is formed by homogenous dispersion of drug solid particles through a polymer matrix
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Describe features of Norplant II (2)
Further encapsulated by a rate controlling polymeric membrane. 2 rods, 4.4 cm length x 2.4 mm diameter. Norplant subject to controversy. Irregular bleeding, occasional challenging removal, coercive application
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Describe features of the Vitrasert (1)
Implant for the eye (for HIV patients with CMV retinitis), local release inside the eye, layers of polymers to control the release.
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Describe features of the Vitrasert (2)
Ganciclovir tablet initially coated with PVA then coated with discontinuous film of hydrophobic dense PEVA. Entire assembly coated with PVA. Diffusion through PVA then through pores of PEVA and through PVA outer membrane. Rate - 1 mcg/h for 7-8 month
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Describe features of the NuvaRing
Ethylene vinyl acetate co-polymer. 54 mm in diameter. Cross-sectional diameter 4 mm. Systemic control for 1 month. 0.12 mg of etonogestrel and 0.015 mg of ethinyl estradiol per day over 3 weeks
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Describe features of matrix type non-degradable polymeric implants (1)
Drug dissolved/dispersed within matrix. Polymer matrix. Physical mixing polymer and drug. Total payload of drug determines drug's stable in polymer. Dissolved (drug soluble in polymer matrix low payload). Dispersed (drug above saturation level)
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Describe features of matrix type non-degradable polymeric implants (2)
Porous when drug occupies more than 30% volume. dm/dt = kd/t^1/2 where kd is proportionality constant dependent on the implant properties (graph - cumulative % release vs time)
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Describe features of matrix type non-degradable polymeric implants (3)
Compudose, microcrystalline, estradiol dispersed in silicone rubber (under skin for animal weight gain, duration of 200 days). Syncro-mate-B, estradiol valerate and cross-linked ethylene glycomethacrylate (ear implant, synchronise ovulation, 16)
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Describe features of reservoir/matrix hybrid polymeric implants
Implanon - membrane/matrix system, not biodegradable (needs to be removed from the body). Rate controlling membrane, core (EVA and etonogestrel) and membrane (EVA). Following implantation, releases etonogestrel at 30 mcg/day over 3 years
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Describe features of biodegradable polymer matrices
Bioerosion (gradual dissolution of a polymer matrix). Biodegradation (degradation of polymer caused by chemical or enzymatic process). Drug delivery from biodegradable systems (bulk eroding or surface eroding). System is absorbed
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What are the biodegradable polymeric implants?
Water soluble (polyacrylic acid, PEG, PVP). Degradable (polyhydroxybutyrate, polylactide-co-glycolide, polyanhydrides). Polymers with mwt <40,000 Da can be excreted out of the body
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Describe features of biodegradable PLGA (1)
PLA and PLgA are degraded by homogenous bulk erosion. Zoladex (PLA/PLGA implant to deliver goserelin for 1-3 months, endometriosis). Lupron Depot (PLA/PLGA implant for leuprolide for 3-4 months, prostate cancer)
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Describe features of biodegradable PLGA (2)
Excreted in urine, metabolised by liver, expired by CO2 by the lung. Liquid at room temperature, forms gel within the body (body temp)
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Describe features of the GLIADEL wafer (1)
Polyanhydride implant used in treatment for malignant glioma, anti cancer agent (carmustine) incorporated into co-polymer matrix consisting of CPP and sebacic acid in a 20:80 molar ratio. Wafers dissolve (surface erosion), release BCNU locally
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Describe features of the GLIADEL wafer (2)
Provide direct delivery of chemotherapy to the tumour cavity
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Describe features of osmotic implantable pumps (1)
Driving force for drug release is the difference in pressure that causes the bulk flow of a drug or a drug solution (movement of water molecules from high to low osmotic potential via semi-permeable membrane)
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Describe features of osmotic implantable pumps (2)
Alzet - semi-permeable membrane, osmotic chamber, reservoir wall, drug reservoir, flow moderator
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Which regions of the GI tract affect drug absorption?
Stomach (gastric emptying), SI (duodenum, jejunum, ileum, high SA, no tissue between epithelium and blood capillary, tight junction/barrier for lipophilic drugs and peptides). Large intestine/colon (absorption of water/electrolytes)
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Which biological factors affect oral sustained release dosage forms?
Biological half life, absorption, metabolism (and other factors)
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Describe features of biological half life
To achieve sustained therapeutic levels the drug must enter circulation at the same rate as it is eliminated (half life t 1/2, elimination = metabolism and clearance)
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Describe features of biological half life (1)
Therapeutic compounds with short half lives are good candidates (more frequent dosing) but dose is a limitation (furosemide and L-DOPA have half lives <2 h, not good candidates). Drugs with half lives >8h e.g. digoxin, warfarin, phenytoin - not good
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Describe features of biological half life (2)
Long half-life - may have adverse effects, may not be able to control behaviour of CR system
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Describe features of absorption (1)
Transit time in absorptive areas of GIT is 8-12 h. Max half life for absorption should be 3-4 h, corresponds to a min absorption rate constant of 0.17-0.23/h. Compounds demonstrating lower absorption rate constant are poor candidates
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Describe features of absorption (2)
Maintenance in stomach, gastroretentive systems, p-aminobenzoic acid could be an alternative. Mucoadhesive delivery systems
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Describe features of metabolism (1)
Local metabolic activity can show decreased bioavailability when in a sustained release dosage form. E.g. aloprenolol extensively metabolised when given as a sustained release preparation, L-DOPA metabolised by DOPA-decarboxylase in intestinal wall
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Describe features of metabolism (2)
Low metabolic activity can show decreased bioavailability in SR system (metabolism in GIT, hepatic metabolism, use of local enzymes)
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What are the other physicochemical factors affecting oral drug absorption from SR dosage form? (1)
Dose size (max dose 0.5-1 g). Ionisation, pKa, aqueous solubility (pH-partition hypothesis). Lower solubility of a drug to be formulated as a SR system is 0.1 mg/mL. Partition coefficient would affect diffusion through polymer membranes
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What are the other physicochemical factors affecting oral drug absorption from SR dosage form? (2)
Stability (acid base hydrolysis and enzymatic degradation)
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Give examples of unsuitable candidates (1)
Digoxin, amitriptyline (long t1/2). Riboflavin, iron (window of absorption). Furosmide (short t1/2). Gentamicin (drugs with narrow therapeutic range). Warfarin (dose titration required). Griseofulvin (poorly soluble)
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Give examples of unsuitable candidates (2)
Analgesics (drugs which need to produced a prompt effect)
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Describe features of monolithic matrix delivery systems for oral delivery (1)
Lipid and insoluble polymer matrices (drug dispersed in an insoluble matrix, drug becomes available as solvent enters matrix and dissolves drug)
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Describe features of monolithic matrix delivery systems for oral delivery (2)
Hydrophilic colloid matrices (drug dispersed in a soluble matrix, drug becomes available as matrix dissolves). Drug release from typical matrix drug delivery system (diagram)
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Describe features of matrix devices (1)
Water soluble drugs dispersed in hydrophobic (polymer) matrix such as fatty alcohols, acids or esters, granulated and compressed to form tablet e.g. Voltarol ****** (100 mg diclofenac in hydrophilic matrix with cetyl alcohol, OD)
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Describe features of matrix devices (2)
Hydrophilic matrices made from high viscosity grade HMPC also used. 1000-1500 cPs HPMC can be used to prepare matrix tablets using dry granulation
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Describe features of matrix devices (3)
MS Continus - combination matrix, hydrophilic granular system inserted in hydrophobic matrix. Theo-dur made of 2 components (matrix of compressed drug and coated theophylline granules embedded in matrix)
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Describe features of matrix devices (4)
1/3 dose in matrix and remainder is present as pellents
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Give examples of matrix diffusional products
Desoxyn gradumet (methamphetamine HCl). Tral-film tab (hexocyclium methylsulfate). Procan SR (procainamide HCl)
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Describe features of lipid matrices (1)
Matrix formers (hydrophobic materials solid at RT and don't melt at body T, hydrogenated vegetable oils, microcrystalline wax, carnauba wax (20-30% formulation). Channeling agents (soluble in GIT
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Describe features of lipid matrices (2)
Leach out formulation leaving tortuous capillaries, through which the drug diffuses, NaCl, sugars, polyols 20-30% of formulation). Solubilisers, pH modifiers (PEG, polyols, surfactants, buffers or counter ions for ionisable drugs)
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Describe features of lipid matrices (3)
Anti-adherent/glidant (to prevent hot melted wax to stick to punches/diet, talc, colloidal, silica)
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What are the types of hydrophilic matrix?
True gels (movement of chains, cross-links chemical or physical bonds e.g. gelatin). Viscous materials (increased viscosity as a result of entanglement of adjacent polymer gels, dynamic system e.g. HPMC). Drug release depends on type of polymer used
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Give examples of matrix forming agents for hydrophilic matrices
Hydrated gels should remain sufficiently intact during passage through GIT. E.g. HPMX (high viscosity grade), sodium carboxy-methyl-cellulose, alginates, xanthan gum, carbopol/carbomer (polyacrylates, synthetic polymers)
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Describe features of the the hydrophilic matrix in drug release formulation (1)
Single bead with alternating layers of drug and rate controlling coats. Beads 1-2 mm diameter particles divided into 10 groups. First group with one coat, second group with two cats etc. Thickness of 10 coats about 0.1 mm. Pellets mixed/taken as dose
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Describe features of the the hydrophilic matrix in drug release formulation (2)
Coating materials are cellulose/esters/ethers with or without resins/fats/keratin/gluten. Coatings such as carnuba wax and shellac used. Release is dissolution controlled but if resistant coat is used then release is diffusion controlled. Spansules
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Give examples of encapsulation dissolution products available in the market
Ornade spansules (phenylpropanolamine HCl). Diamox sequels (acetazolamide). Deamazin repetabs (chlorpheniramine maleate, phenylephrine HCl)
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Give examples of matrix dissolution products available in the market
Demetane exetabs (brompheniramine maleate). Mestinon timespan (pyridostidmine bromide). Disophrol chronotabs (dexbrompheniramine maleate, pseudofedrine sulfate). Mestinon tablets
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Describe features of MS Continus
Coated with polymer, CR, control system depend on dissolution of higher aliphatic alcohol and diffusion of active principle through in vivo hydration of hydroxylalkyl cellulose (slide)
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State features of membrane controlled delivery systems
Membrane is the rate controlling part. Membrane should become permeable (through hydration, drug being soluble in a membrane component e.g. plasticiser). Membrane polymer doesn't swell and doesn't erode
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What are the components of a membrane controlled system?
Core (active drug, filler, solubiliser, lubricant, glidant). Coating (membrane polymer, plasticiser, membrane modifier, colour/opacifier)
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Describe the effect of storage on release from a reservoir device
(Graph). Diffusion system freshly made, formulation stored over extended period, drug on surface of membrane (burst effect), fresh batch (membrane empty, takes time for drug to diffuse into membrane)
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What are the two types of core of a membrane controlled system? (1)
Single unit (tablet cores should not disintegrate by dissolve, fillers should be chosen to have minimum osmotic effect)
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What are the two types of core of a membrane controlled system? (2)
Multiple unit systems (coated spheroids 1 mm filled in a hard gelatin capsule, inert sugar/lactose spheres coated with drug then with membrane, spheroids containing the drug)
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Describe features of the release controlling membrane
Polymer should remain intact during release with no swelling. Ethyl-cellulose. Acrylate copolymers: Eudragit RL and RS. Plasticiser is used to affect the glass transition T (Tg) e.g. PEG 400 or for ethylcellulose films: dibutyl pthalate
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What are the advantages of membrane controlling systems? (1)
Multiple unit system have more consisted GIT transit time compared to single-unit. Multiple unit system are less likely to dump the whole dosage due to failure of the film around the monolith
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What are the advantages of membrane controlling systems? (2)
Multiple unit systems allow the release mechanism to be optimised for individual drugs if in a delivery system there is more than one active ingredient
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What are the disadvantages of membrane controlling systems?
Dose dumping can occur from single-unit systems as a result of film failure. Multiple unit systems are less retained in higher GIT. Control of membrane characteristics can be difficult. Filling of multi-units spheroids into capsule may be problematic
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Describe features of the ion exchange systems - acidic drug (1)
Electrostatic interactions between API and vehicle. Resin salt (attracts molecules with opposite charge). Formation - basic ion-exchange resin + acidic drug = resin salt, liberation. In stomach - resin salt + HCl = resin chloride + acidic drug
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Describe features of the ion exchange systems - acidic drug (2)
In intestine - resin salt + NaCl = resin chloride + sodium salt of drug (Cl ions displace drug). Na salt more soluble (better absorption). Drug release in site depending on pKa/pH (acid or base)
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Describe features of the ion exchange systems - basic drug
Formation - acidic ion-exchange resin + basic drug = drug resinate, liberation. In stomach - drug resinate + HCl = acidic resin + basic drug HCl. In intestine - drug resinate + NaCl = sodium resinate + basic drug
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Outline the release of a drug from the resin in the body
Drug displaces counterion on polymer, able to isolate drug (separation of drug and resin depends on pH - stomach or SI), drug displacement, drug released, Cl ions replace drug, resinate excreted out of the body
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The complexation and formulation of the resin/drug depends on which factors?
Ion-exchange capacity, particle size of resin (smaller size, less molecules associated with it), size of drug ion, drug solubility, pH and ionic strength, temperature
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The drug release and absorption depends on which factors?
Ionic strength and pH, cross linking of the resin (affecting binding of drug in polymer, lots of cross-linking/not porous, few cross links/more of drug in pores of polymer), drug solubility, binding sites, membrane permeability at the site
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Excretion and elimination depends on which factors?
Biodegradation and biocompatibility, site of administration
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What are the factors which affect the performance of the resinate?
pH and temperature of drug solution, mwt and charge intensity of the drug and IER, geometry, mixing speed, ionic strength of the drug solution, degree of cross linking and particle size of IER, nature of solvent, contact time between drug species/IER
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Give examples of the types of ion exchangers (1)
Cation/anion exchangers, inorganic/organic, natural/synthetic. E.g. modified greensand clays, zeolites, peat, lignite, sephadexion-exchangers, zeocarb, acrylic acid copolymers, tannin, formaldehyde resin, dolomite, heavy metal silicates
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Give examples of the types of ion exchangers (2)
Sephadex anion exchange resins, amine formaldehyde resin
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Give examples of ion exchange products
Biphetamine capsules (amphetamine dextroamphetamine). Tussionex suspension (hydrocodone chlorpheniramine). Ioanamin capsules (phenteramine) - not favoured due to no zero-order kinetics
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Describe features of colon specific systems (1)
Not possible to have site specific release in SI - rely on timed release instead. Large intestine - responsible for water absorption (not designed to absorb drugs). Lot of colon, constant transit time. Colonic environment is benign
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Describe features of colon specific systems (2)
Allows for pH controlled drug delivery (7.5-8), low number of enzymes (specific to colon, azoreductases - cleaves N=N bond to form NH + NH). Coat tablet with polymer containing azo groups for site specific drug release (suitable for UC/CD, IBD)
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Describe features of colon specific systems (3)
Future development - use colon specific system to deliver antibodies (use polymers containing N=N bonds) - potential oral administration
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Describe features of the OROS osmotic pump (1)
OROS push-pull (osmotic drug core, semi-permeable membrane, polymeric push compartment, delivery orifice). L-OROS (liquid drug formulation, soft gelatin capsule, barrier inner membrane, rate controlling membrane, osmotic push layer, orifice)
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Describe features of the OROS osmotic pump (2)
OROS tri-layer (drug compartment 1, drug compartment 2, drug overcoat, push compartment, orifice). Tegretol-XR (seizure control GI transit <12h), carbamazepine bioavailability up to 32%, ADALAT OROS, nifedipine for HTN/angina OD
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Describe features of the OROS osmotic pump (3)
Small orifice allows drug to be delivered when water enters, drug dissolved in water, drug release via orifice (central compartment expands)
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