pharmaceutics Flashcards

1
Q

Different routes of administration used in analgesia

A
Oral
Transdermal
Transmucosal
Intravenous
Epidural
Intrathecal
Nasal
Rectal
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2
Q

Intravenous

A

-Rapid action from drug being presented directly to the circulation.
No lag time between administration and action.

-Physician= titrate the dose
-More predictable response compared to routes
Incomplete absorption and variability in absorption is eliminated.
-Require trained medical staff to administer so only used in acute care.

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3
Q

Transmucosal

A

-Absorption through the oral mucosa (oral cavity).
-Oral cavity rich in blood vessels.
Rapid onset of action and high blood levels.
Absorbed directly into the systemic circulation via the jugular vein (no 1st pass metabolism)

-SA limited only 100cm2.
Only small lipophilic drugs absorbed.

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4
Q

Transdermal

A

-Drug diffusion from the delivery system containing a drug reservoir.
Through the epidermis (main barrier is the stratum corneum) and dermis (rich blood supply).

-2 routes through the stratum corneum:
Hydrophilic keratinised cells and lipid channels.
Main route of absorption is lipid channels (mainly for small molecular weight lipophilic drugs).

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5
Q

Pharmacokinetic advantage of transderma

A
  • Maintain sustained drug plasma profile over several days in therapeutic window.
  • No dips in dose overnight/dose dumping (oral tablets).
  • Good patient compliance (e.g single patch applied every few days)

-Removal of the device causes the plasma levels to fall shortly afterwards.
Some drugs can be stored in hydrophobic regions of the skin.

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6
Q

Transdermal patches

A
  1. Matrix or monolith systems (drug suspension)

2. Rate limiting membrane

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7
Q

Rectal route

A
  • For systemic absorption of drugs and bypasses the hepatic first-pass metabolism.
  • Used when oral route not appropriate (e.g presence of N/V, upper GI disease affects absorption of drug)
  • Widely administer drugs that are affected by pH or enzymatic activity of the GI tract.
  • For drugs that cause gastric/GI irritation when taken orally.

-Drug absorption:
Drug has to dissolve in rectal fluid (only 1-3ml)
Reduced by degradation by luminal contents, adsorption to luminal contents and defaecation.
Absorbed by passive diffusion.

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8
Q

Advs of rectal route

A

route
-Useful for infants, geriatrics and unconscious patients.

  • For drugs with unacceptable taste.
  • For drugs that are candidates for abuse.
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9
Q

Disadvs for rectal route

A
  • Unpredictable, erratic and incomplete absorption in vivo.
  • Inter and intra-subject variation
  • May be difficult to self-administer by arthritic or physically compromised patients.
  • Popularity of dosage form varies culturally, maybe unacceptable to certain patients.
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10
Q

Intrathecal

A

-Administration of drugs in solution by intrathecal catheter to the spinal cord.

  • More invasive route
  • Cerebrospinal fluid (CSF)= fluid that cushions the brain and spinal cord
  • Bulk flow of CSF maybe dominant in determining distribution and pharmacokinetics.
  • Used for chronic pain management, spinal anaesthesia and chemotherapy.
  • Spinal anaesthetic- local anaesthetic plus opioid
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11
Q

`Epidural

A

-Injection of drug via catheter into the epidural space.
(outermost part of the spinal canal, lying outside the dura mater)

  • Can result in a loss of sensation (including sensation of pain) by blocking the transmission of signals through nerve fibers in or near the spinal cord.
  • To achieve epidural analgesia (opioid) or anaesthesia (local anaesthetic + opioid), a larger dose of drug is necessary than with spinal analgesia or anaesthesia.
  • Onset of analgesia= slower with epidural than spinal analgesia/anaesthesia
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12
Q

Other different drug delivery systems available for chronic pain management

A
  • Percutaneous catheter used with external pump
  • Totally implanted catheter with a subcutaneous injection port connected to external pump
  • Fully implanted fixed rate and programmable intrathecal drug delivery systems.
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13
Q

Nasal. route of administration

A

-Small drugs rapidly absorbed from the nasal cavity at rates comparable to IV drugs.
Easier= no medically trained staff required
More comfortable for than IV.

-Physiological conditions of the nose will affect the rate of absorption.
Vascularity, mucus flow, atmospheric conditions

-Formulation= influence absorption
pH, vol conc, viscosity, tonicity

-Slower clearance of the drug more time available for absorption

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14
Q

Multiple dosing regimens

A

Aim of drug therapy:
To maintain the drug within the therapeutic range.

  1. Time between doses allows for elimination of each dose.
    Drug plasma conc only maintained within the therapeutic window for short time intervals.
    Long time intervals with patient undermedicated.
  2. Equal doses at shorter time intervals. (e.g 4 hrs)
    Max and min plasma conc increase with each successive dosing interval.
    Time between doses less than that required for elimination.
    Drug plasma conc maintained within the therapeutic window= multiple dosing for patient compliance
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15
Q

Extended release dosage forms

A

A single dose:
(A)-Prompt achievement of plasma conc of drug remains constant value within therapeutic range for a satisfactory amount of time.

(B)-Prompt achievement of plasma conc of drug and declines at a slow rate within the therapeutic range

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16
Q

Sublingual tablets

A
  • Used as dosage form for transmucosal delivery.

- Small/porous fast disintegrating tablet placed under the tongue

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17
Q

Dispersible tablet

A

-Useful= patients having difficulty in swallowing (dysphagia)

-Dropped into a glass of water, CO2 liberated
Reaction of carbonate/bicarbonate with a weak acid (e.g citric acid)
Includes a flavour.

-Fast disintegration and dissolution of the drug

-Buffered water increases the pH of stomach faster emptying time/shorter residence.
Reaches small intestine quicker (main site of absorption= SA, rapid onset of action)
Gastric irritation can be avoided

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18
Q

Suspensions

A

Solid-in-liquid colloid.
-Drug in solid phase (powder)
Liquid= easy to administer to children

Widely used for oral formulations:

  • Antacids (e.g Aluminium hydroxide, calcium carbonate)
  • Antibiotics (e.g amoxycillin, erythromycin)
  • Antifungals (e.g amphotericin, nystatin, fluconazole)
  • Analgesics (e.g paracetamol, ibuprofen)

-Physical instability in suspensions
Flocculation, aggregation
Sedimentation, Ostwald ripening

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19
Q

Fast dissolving oral delivery systems

A

-Solid dosage form= dissolves rapidly in oral cavity
=results in solution/suspension without the need for water
e.g Calpol Six Plus Fast Melts

-Drug dissolves/disperses in the saliva.
Portion of drug maybe absorbed in the mouth, pharynx or oesophagus (potential for increased absorption).

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20
Q

Different dosage forms of Fentanyl

A
  • Transmucosal lollipop

- Transdermal patch

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21
Q

colloid

A

disperse system in which one phase is in the form of tiny particles or droplets

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22
Q

emulsion system

A

liquid in liquid

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23
Q

suspension

A

solid in liquid

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24
Q

Why use disperse systems?

A

-Single phases may not be able to provide all the formulation requirements.

e.g Diprivan
Drug is very hydrophobic.
Cannot be dissolved in water.
Dissolve in oil and oil is dispersed in isotonic water carrier to form an emulsion.

e.g Suspension of paracetamol.
Solid phase (powder)= tablet
Liquid= easy to administer to children
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25
emulsion
dispersion of a liquid in a second immiscible liquid o/w w/w
26
what do emulsions require
emulsifier
27
emulsion stability
to make an emulsion, a large amount of new surface must be formed -(requires energy)
28
what has a higher energu, dispersed or inmixed iol/water
dispersed
29
emulsifier
positions at the interface between two phase for o/w emulsion hydrophobic part-positioned in the oil droplet hydrophilic part oritentates towards surrounding water
30
Emulsion applications
-Intravenous = total parenteral nutrition (TPN), Intralipid: administration of fats (soya bean oil, medium chain triglycerides) =Fat absorbed from GI tract circulates as chylomicrons (tiny droplets of triglycerides coated with lecithins and bile salts). Feeding emulsions attempt to simulate these droplets. Emulsion has a droplet diameter of 0.2-0.3 microm (large droplets harmful). -Oral =oral feeding of fats (enteric feeds) =Oral delivery of hydrophobic drugs -Intramuscular =W/O emulsions for sustained release =Emulsion vaccine adjuvants
31
Acceptable excipients for emulsions
1. IV formulations - very few oils and emulsifiers= used IV - Oil phase: soya bean oil/ medium chain triglycerides 2. Emulsifiers - Phospholipids= (purified) from egg yolk or soya beans - some of the hydrophilic Pluronics - small volume parenterals= polysorbate, bile salts 3. IM formulations - sesame oil - Squalane and Pluronic L121 in Syntex Adjuvant Formulation= induce immune response
32
Emulsions for drug delivery | -drug incorporation
1. Hydrophobic oil= soluble drugs - dissolved in oil which is then emulsified. - drug must be very hydrophobic (log>5) or drug will transfer through aq phase and crystallize out. (e.g Diprivan) 2. Surface-active drugs -adsorbed at the interface -increasing number of complex drugs are insoluble in both oil and water. -more difficult to formulate due to solubility problems (can solubilise drug in emulsifier solution, then use this to emulsify the oil phase) e.g Amphotericin B, Taxol
33
Emulsion examples: | Diprivan injection
-Propofol= most widely used drug for IV anaesthesia -Drug is very hydrophobic. Dissolved in soya bean oil -Oil is dispersed in isotonic water carrier to form an emulsion. Oil droplet sizes ~150nm (small).
34
Importance of emulsion stability
If oil droplet size increase, life-threatening to the patient.
35
Emulsion examples: | Intralipid
Intralipid consists of lecithin emulsifier, soya oil and water. Lethicin= natural emulsifier from eggs (mixture of a group of compounds= phospholipids) Charge on emulsion= enough to make the emulsion stable for several years
36
Consequences of disperse system instability
1. Flocculation 2. Coagulation/ aggregation 3. Coalescence
37
Physical instability of disperse systems: | Flocculation
Particles/droplets cluster together in an open structure. Particles/droplets maintain their individual identity. Can be redispersed to single particles/droplets by shaking. Sometimes flocculation is desirable in a formulation.
38
Physical instability of disperse systems: | Coagulation/Aggregation
Small aggregates form. SA is decreased so surface tension is experienced by fewer molecules. Attractive forces between particles very strong. Cannot be redispersed to single particles by shaking. Permanent failure of the medicine.
39
Physical instability of disperse systems: | Coalescence
Droplet structure lost entirely. Impossible for patient or clinician/nurse to reform the emulsion. Total failure of the medicine. Also known as 'cracking' in emulsions.
40
Forces acting on particles in disperse systems
Particles of <2 microns diameter= constantly moving due to Brownian motion [ -As particles approach they experience: 1. Forces of repulsion due to electrostatic interactions. Energy of electrostatic repulsive interaction= Vr 2. Forces of attraction due to VDWs forces Energy of attractive interaction due to VDWs forces= Va 3. Steric forces if they have a non-ionic surfactant on their surfaces. Energy of steric interactions (hinderance)= Vs Overall potential energy= Vt Vt= Va + Vr + Vs
41
Vt= Va + Vr
All of the forces vary with particle separation distance. When the particles are widely separated the forces are weak, but get stronger as the particles get closer. Diagram= Force (V) against particle separation (H) Steric forces are important for non-ionic surfactants (e.g polysorbate 80)
42
Va= attractive force
Va= -Aa/12H Va changes as a function of 1/H. A= constant of proportionality A depends on the particle material and the suspending fluid. Small separations= very sharp increase in attraction Big separations= small attractive force
43
Vr= repulsive forces source of charge in colloidal particles
-ion distribution =ionic substances acquire charge by uneven dissolution of oppositely charged ions, if more cations dissolve then the surface becomes negatively charged -ion adsorption :
44
Primary Minimum
permanent aggregation of particles
45
primary maximum
repulsive barrier to aggregation
46
secondaru minimum
weak attraction cause flocculation
47
Kinetic energy: | Coagulation
High Kinetic energy | Primary max= insufficient to stop particle
48
Kinetic energy: | Flocculation
Low kinetic energy Primary max= Too great a barrier. -Particle has insufficient energy to continue its path towards neighbouring particle. -Insufficient energy to escape the secondary minimum.
49
Kinetic energy: | Stable colloidal formulation
Intermediate kinetic energy. Primary max too great a barrier. Particle has insufficient energy to continue its path towards neighbouring particle. Particle also escapes the secondary minimum (Brownian motion).
50
k
debye-huckel constant
51
1/k
debye-huckle length the diffusuion layer of the electrical double layer
52
Relationship between Vr, 1/k (Debye-Huckel Length), K (Debye-Huckel constant)
Vr decreases with increasing particle separation (H). Vr decreases with increasing k. 1/k decreases, k increases, Vr decreases.
53
Why would the Debye-Huckel length change
changes to the conc of electrolytes. affects the charge distribution changes the k, 1/k impacts the electrical double layer
54
Low [electrolytes] and debye-huckel length
1/k increases Less +ve ions in solution but need the same amount to neutralise the surface. Larger halo. Diffuses longer into the solution.
55
High [electrolytes] and debye-huckel length
1/k decreases | because neutralising the surface is quicker as there are more ions
56
Effect of high electrolyte conc on the electrical double layer
High [electrolytes] Small 1/k Large k Repulsion experienced when electrical double layers overlap. No repulsion until the particles get very close.
57
Effect of low electrolyte conc on the electrical double layer
Low [electrolytes] Large 1/k Small k Repulsion experienced at large particle separations.
58
Effect of low [electrolyte] on Vt
Big primary max No secondary min. Stable formulation even at high kinetic energy.
59
Effect of intermediate [electrolyte] on Vt
Primary max Secondary min. Stable formulation
60
Effect of high [electrolyte] on Vt
No primary max Attraction at all H values Unstable formulation at all kinetic energies. Aggregation
61
Critical Flocculation concentration
An electrolyte conc at which the secondary minimum appears. Particles with same charge are attracted to each other. Flocculation can be useful: - Avoided in injectables - Great in high density suspensions
62
ostwald ripening
Due to their high surface free energy, small particles dissolve preferentially when compared to large particles. Greater solubility of the smaller particles produces solutions supersaturated relative to the larger particles. Dissolved molecules = crystallise on the surface of the large particles =extends the lattices =causes growth of the larger particles
63
why do surfactants icnrease the rate of ostwald ripening
Surfactants can increase the rate of Ostwald ripening. | Increase the solubility of the suspended drug by solubilization.
64
Sedimentation. stokes law
Stokes law describes the velocity of sedimentation.
65
stokes law application. to keep particles suspended
To keep particles suspended: - Reduce particle size - Density match with vehicle - Increase viscosity of the vehicle
66
Consequences of sedimentation-caking
Particles repel each other then they fall and pack into a dense cake. Weight of particles presses down on the particles below. Push through the primary maximum. Forced to aggregate by the primary min.
67
Consequences of sedimentation-redispersed
If particles experience a secondary min, they will form flocculated structures. Flocculated structure= very porous, does not compress into a cake Because the secondary min is a weak attraction, we can redisperse by shaking.
68
thickened suspensions
Delay sedimentation by thickening the suspension with viscosity modifiers: e.g xantham gum Thickeners solution= non-Newtonian Shear stress due to weight of a 10microm particle is extremely small. Particles can remain suspended at quite modest bulk viscosities.
69
disadvantage of thickened suspensions
increased viscosity makes it hard to handle practically
70
Apparent viscosity
Measure of a fluid's resistance to flow. | internal friction of a moving fluid
71
sher thinning and viscosity
shear thinning (shaking) decreases viscosity shear utangles the hydrophilic polymer chains allowing it to flow better
72
Creaming rate: Stokes' Law
Stokes' law describes the velocity of creaming. To keep droplets suspended: - Reduce globule size of droplets. - Decrease density difference between the two phases. - Increase viscosity continuous phase
73
Steric forces (Vs)
Energy of attraction= VDWs forces Steric forces are repulsive due to the interaction between the non-ionic surfactants and block co-polymers on the particles. Vt= Va + Vs Va= van der waals forces
74
What happens when the non-ionic surfactant particles approach each other? 1. Non-penetrational (H>2L)
Particles further apart than non-ionic surfactant/block copolymer layer. No interaction, no steric force.
75
What happens when the non-ionic surfactant particles approach each other? 2. Penetrational (L
Particles coming closer together. | Overlap of the hydrophilic part of the surfactant chains.
76
What happens when the non-ionic surfactant particles approach each other? 3. Compressional (H
Steric forces increase (repulsion). | Chains are compressed and chain conformation is heavily restricted.
77
3 factors that affects the degree of steric effect
Non-ionic surfactant chain length. Number of chains per unit area of interacting surface. Chain/solvent interactions
78
Nature of the steric force
Entropic stabilisation. Positive value of Gibbs free energy (G). Aggregation not spontaneous process. Polymer chains become compressed (lose conformational freedom) leading to a negative entropy (S). Change of G= Change of H - T(changes of S)
79
Immediate release
Releases whole dose immediately or soon after administration.
80
Modified release
Time course and location of release, modified to achieve therapeutic advantage or convenience.
81
2 types of modified release
1. Delayed release | 2. Extended release
82
Delayed release | enteric coated- e/c
Releases whole dose later. e.g enteric coated aspirin (avoids release in stomach and gastric irritation)
83
Extended release | modified release- m/r
Releases drug slowly over an extended time. | Plasma concentrations maintained at therapeutic level for a prolonged period of time (8-12 hrs).
84
extended release is Designed so that a single dose:
- Prompt achievement of plasma conc of drug remains constant value within therapeutic range for a satisfactory amount of time. - Prompt achievement of plasma conc and declines at a slow rate within the therapeutic range.
85
Benefits of delayed release
- Avoids stomach irritancy. - Minimise drug degradation before reaches absorption site - Targeting of drug release (e.g ileum/colon) - Taste masking
86
Benefits of ER dosage forms
drug plasma cocnenrration is maintained in terapeutic range for extended period of time reduction int he total amount of drug admin over tx period reduced dosing frequency
87
Potential limitations of ER
-Physiological factors= GI pH, enzyme activity, gastric and intestinal transit rates, food and severity of disease can interfere with the control of release and drug absorption -Rate of transit of ER product along GI tract limits max. Period to 12 hrs plus length of time absorbed drug exerts its therapeutic length. - Overdose slow clearance of drug from the body. - Risk of prolonged toxicity if therapeutic index of the drug is too narrow. - Accidental poisoning (e.g chewing)
88
Factors influencing the design of ER oral formulations
1. Physiology of the GIT and absorption - Particulates/pellets leave the stomach rapidly. - Single dose units >7mm can stay in the stomach for up to 10 hrs. 2. Aqueous solubility and permeability - Absorbed by passive diffusion (non site specific absorption) - Ideal= high solubility, no issues of dissolution (low solubility retards dissolutions) - Drugs with low permeability maybe not suitable for MR 3. Lack of pharmacologically active metabolites
89
Technologies to achieve ER
1. Single monolith matrices - inert polymer - lipid/wax hydrophilic matrices 2. Membrane controlled - coated single monolith/tablet/pellets - osmotic pumps 3. Ion exchange resins
90
Monolithic matrix systems
- Drug particles dissolved/dispersed in a matrix | - Matrix controls diffusion and release of the drug.
91
matrix types in monolithic matrix systems
-Matrix types: 1. Hydrophilic swelling matrices Drug particles dispersed in hydrophilic water soluble polymers. e.g carboxymethyl cellulose 2. Hydrophobic matrices Insoluble polymer matrices e.g ethylcellulose polymethacrylate Drug particles dispersed in insoluble polymers. Lipid matrices (e.g stearyl alcohol, Carnauba wax)
92
Hydrophilic swelling matrices
-Tablet produced from water swelling polymer (e.g HPMC) Surface hydrates. Forms viscous gel structure. Matrix swelling. Gel is a barrier to liquid ingress into tablet and drug diffusion out (important for water soluble drugs). Matrix erodes in GI tract. Stage important for release of water insoluble drugs.
93
Models for drug release for hydrophilic swelling matrices
i) Diffusion of water, drug and disentangled polymer chains ii) Polymer swelling iii) Drug and polymer dissolution (erosion)
94
BNF e.g of ER analgesics
-Morphgesic Hydroxyethylcellulose, hypromellose -Filnarine Hypromellose
95
Reservoir (coated) systems
Drug containing core is enclosed within a polymer coating. | -Depending on the polymer used 2 types of reservoir systems:
96
two types of reservoir system for extended release
1. Simple diffusion/erosion systems Drug containing core covered with hydrophilic/and or water insoluble polymer coatings. Drug release by diffusion of the drug through coating. 2. Osmotic systems Drug core is contained within a semi-permeable polymer membrane with a mechanical/laser drilled hole for drug delivery. Drug release is achieved by osmotic pressure generated within the tablet core.
97
Membrane controlled systems
1. Single unit - Conventional tablet coated with an insoluble polymer. - Choice of excipients to prevent any osmotic effect (e.g lactose, 2. Multi-particulate systems -Polymer coated Drug coated sugar spheres. Pellets/spheroids manufactured by a wet extrusion -Filled into hard gelatin capsules/compressed into a tablet
98
Release mechanisms of membrane controlled systems
- Water enters interior of particle/tablet by diffusion. - Dissolution of the drug. - Diffusion of the drug through the polymer coating membrane. (normally rate controlling step). - Erosion of the polymer coating.
99
Disadv of multi-particulates
- Dose dumping as a result of film failure in single dose monolith/matrix. - Control of membrane characteristics in film coating can be difficult. - Multi particulates difficult to retain in the higher GIT
100
Advs of multi-particulates
- More consistent GI transit than single dose monolith/matrix - Less likely to suffer from dose dumping from castastrophic failure of monolith/matrix. - Allow release of 2 different actives.
101
Osmotic pumps
1. Drug included in water soluble core= suspend/solubilise drug 2. Tablet coated with semi-permeable membrane= water passes into the core 3. Core dissolves and hydrostatic pressure builds up. Forces drug solution or suspension through a drilled hole in semi-permeable membrane. 4. Drug release governed by: - membrane - viscosity of the solution/suspension - size of the drilled hole
102
Ion exchange resins
- Synthetic organic cross-linked polymers | - Contain basic/acidic groups= can form ionic complexes with oppositely charged drugs
103
ion exhange resin release rate depends on
Diameter of the resin beads Degree of the crosslinking of the resin pKa ionisable group of the resin.
104
Cationic exchange resin. involving morphine
H+ exchange with morphine during processing. Create MST continus suspension. In the GIT morphine exchanges with other cations (e.g Na+, K+) Amine group (protonated) Absorbed into the resin. Enter the GI tract. Morphine displaced by exchanges with other cations. Morphine is attracted to SO3-, displaces H+. Morphine is released.
105
rectal drug delivery
dosage forms administered via anus into the rectum or lower colon
106
why is rectal drug delivery used
local effect systemic effect
107
type of rectal delivery doage forms
suppositories enemas microenemas foams, creams, gels and ointments
108
problems of rectal drug delivery
not popular inconvenient leakage proctitis bowel moevement drug absorption is erratic
109
local therapy for rectal drug delivery. chronic constipation
laxatives suppositories
110
local therapy for rectal drug delivery. bowel evacuation
clear impacted constipation prior to endoscopy
111
what is used for bowel evacuation
enemas
112
local therapy for rectal drug delivery. chronic bowel disease
foams suppositories enemas
113
local therapy for rectal drug delivery. inflammation. haemorrhoids, pruitis
suppositppres soothing agents corticosteroids
114
uses of rectal delivery for systemic therapy
suppositories or enemas for painr eleief nausea after chemotherapy arthititis infection
115
drugs administered high in the rectumand metabolism
drugs adminsitered high in the rectum usually carried direct to liver
116
drugs administered low in the rectum and metabolism
drugs administered low in rectum delibered systemicalluy by inferior rectal vein before passing through the liver
117
rectal absorption of drugs processes
absorption across a mucosal epithelium no villi to increase area lymphatic absorption also takes place
118
what does rectal absorption of drugs depend on
disease state rentention time position of dosage form
119
retention time of dosage form
disease state/ drug irritancy can alter toilet frequency drugs such as opiates can affect GI muscles irritant drugs can stimulate evacuation
120
requirement for rectal drug formulation
must release drug sopread across epithelium non irritant
121
environement in the rectal area
secretions-neutral pH 7, mucin rectal environment has little buffering
122
liquids as rectal formulation designs
immediate availability but leak
123
pastes or suspensions as formulation designs
retained better than liquid
124
foams as rectual formulationn designs
rapid knock down and spreading
125
tabletsas rectal formulation designs
not good little water for disintegration
126
suppositories as rectal formulation designs
melt as body temerpature can give prolongd action if melted slowly viscous and retianed
127
drug release from suppository bases. common bases used
hydrophobic waxes fats gelatin hydrophilic bases are water miscible and mix with secretion
128
issues in rectal formulation drug release
dont want drug retained in base drugs may reduce meltng point surfactants aid spreadang but may irritate
129
how do we counteract drugs retaining in bases
use a base with opposite characteristics to drug so that drug paritions out easily - hydrophobic base release ionised drugs - hydrophilic bases release hydrophobic drugs