Concept of diffusion: Drug release from polymer matrices (Part – I) and MCQs for GPAT, NIPER, Pharmacist and Drug Inspector exam
DRUG RELEASE FROM POLYMER MATRICES:
When the conventional dosage forms (i.e. tablets, capsules, ointment or creams) are administered orally or topically, the active drug in the dosage form is immediately released and absorbed into the systemic circulation. The release of the drug can occur immediately (i.e. less than 45 min) and consequently the drug concentration in the blood quickly reaches a maximum level followed by an exponential decrease due to the elimination of the drug. To maintain the therapeutic level of the drug in the blood for an extended period of time, either frequent dosing or use of novel controlled release dosage forms is required. Diffusion is the most common mechanism controlling drug release through a polymer matrix or a polymeric membrane. Diffusion-controlled systems include reservoir, monolithic and membrane-matrix devices. For a water-insoluble polymer, either the solubility of the drug in polymer drives the diffusion or a channeling agent in the film dissolves and allows the diffusion to occur. For a partially water-soluble polymer, either swelling of polymer or erosion of polymer drives diffusion.
Reservoir Systems – In a nonporous reservoir device, the drug is contained in a core that is surrounded by a rate controlling layer of the insoluble polymer. Release of drug from a reservoir device occurs through the penetration of the drug into the membrane from the high-concentration core with subsequent release into the low-concentration medium. In case where the drug is surrounded by a partially water-soluble polymer membrane, the release of drug occurs through channels or pores formed due to dissolution of polymer upon exposure to water. The release rate (J) of drug from both nonporous and porous reservoir devices can be described by integrating Fick’s first law of diffusion equation for thickness l and the concentration gradient ‘C as mentioned in the following equation:
J = DK∆C/l (1)
where D is the diffusion coefficient, K the distribution coefficient, ‘C the concentration difference across the membrane and l the diffusion length. Ethyl cellulose and polyvinyl acetate are commonly used as nonporous polymers whereas hydroxypropylcellulose (HPC) is commonly used as porous polymer. The release rate from such devices can be adjusted by changing coating thickness, partition coefficient and diffusion coefficient through polymer composition.
Matrix/monolithic Systems – In a monolithic system, the drug is distributed within a polymer matrix or dissolved in a polymer. When the matrix is in contact with a solvent (i.e. water), the drug starts diffusing out through the interstices of the polymer structure. If the distributed drug is a solid, then the solvent rapidly penetrates the polymer, dissolves the entire drug and forms an unsaturated drug solution. The drug may be dispersed either in an insoluble matrix of rigid non swellable hydrophobic materials or in swellable hydrophilic substances. Rigid non-swellable matrix comprises insoluble plastics such as polyvinyl chloride (PVC) or fatty materials such as stearic acid, beeswax, etc. Swellable hydrophilic substances comprise hydrophilic gums of natural origin (guar gum, gum tragacanth), semi-synthetic origin (HPMC, carboxymethyl cellulose (CMC), xanthan gum) or synthetic origin (polyacrylamides). The release of drug occurs through absorption of water (resulting in hydration, gelling and swelling of gum) and desorption of drug via a swelling-controlled diffusion mechanism. Drug release follows Fickian first-order diffusion under equilibrium conditions. The systems where the drug is dissolved in the polymer matrix, release kinetics can be calculated by two equations:
dMt/dt = 2Mx(D/πl2t)1/2 (2)
dMt/dt = 8DMx/l2expπD2t/l2 (3)
These equations predict drug release from a slab of thickness l, where D is the diffusion coefficient, M x the total amount of drug dissolved in the polymer and Mt the quantity released at time t.
When the active agent is dispersed in the polymer, release kinetics are explained by the Higuchi equation, i.e.
dMt/dt = A/2(2DCsC0/t)1/2 (4)
where A is the area, Cs the solubility of the drug in the polymer matrix and Co the total concentration in the matrix (dissolved and dispersed).
Fig 1 – Reservoir system and monolithic system (taken from mathematical analysis of some models for drug delivery)
Multiple choice questions:
1.Which of the following are conventional dosage forms?
a)tablets
b)capsules
c)ointment
d)all of these
2.Diffusion is the most common mechanism controlling drug release through
a)polymer matrix
b)polymeric membrane
c)both of these
d)only a
3.Diffusion-controlled systems include
a)reservoir
b)monolithic
c)membrane-matrix devices
d)all of these
4.For a partially water-soluble polymer which of the following drives diffusion?
a)swelling of polymer
b)erosion of polymer
c)both of these
d)only b
5.In which of the following drug is contained in a core that is surrounded by a rate controlling layer of the insoluble polymer?
a)Reservoir Systems
b)Matrix systems
c)Monolithic Systems
d)All of these
6.Release of drug from a reservoir device occurs through the penetration of the drug into the membrane from the high-concentration core with subsequent release into the low-concentration medium.
a)true
b)false
7.The release rate (J) of drug from both nonporous and porous reservoir devices can be described by which of the following equation?
a)J = DK∆C/l
b)dMt/dt = 2Mx(D/πl2t)1/2
c)dMt/dt = 8DMx/l2expπD2t/l2
d)dMt/dt = A/2(2DCsC0/t)1/2
8.J = DK∆C/l In this equation D is
a)diffusion coefficient
b)distribution coefficient
c)concentration difference across the membrane
d)diffusion length
9.Which of the following are commonly used as nonporous polymers?
a)Ethyl cellulose
b)Polyvinyl acetate
c)Hydroxypropylcellulose
d)a and b
10.Which of the following is commonly used as porous polymer?
a)Ethyl cellulose
b)Polyvinyl acetate
c)Hydroxypropylcellulose
d)all of these
11.The release rate from reservoir systems can be adjusted by changing
a)coating thickness
b)partition coefficient
c)diffusion coefficient
d)all of these
12.In which of the following the drug is distributed within a polymer matrix or dissolved in a polymer?
a)Reservoir Systems
b)Matrix systems
c)Monolithic Systems
d)b and c
13.Rigid non-swellable matrix comprises of which of the following?
a)polyvinyl chloride
b)stearic acid
c)beeswax
d)all of these
14.Swellable hydrophilic substances comprise of which of the following?
a)guar gum
b)stearic acid
c)beeswax
d)all of these
15.Which of the following is of semi-synthetic origin swellable hydrophilic substance?
a)gum tragacanth
b)carboxymethyl cellulose
c)polyacrylamides
d)all of these
Solutions:
- d)all of these
- c)both of these
- d)all of these
- c)both of these
- a)Reservoir Systems
- a)true
- a)J = DK∆C/l
- a)diffusion coefficient
- d)a and b
- c)Hydroxypropylcellulose
- d)all of these
- d)b and c
- d)all of these
- a)guar gum
- b)carboxymethyl cellulose
References:
- Gaurav K. Jain Theory and Practice of Physical Pharmacy, 1st edition 2012 Elsevier, page no. 274-276.
- Martins Physical Pharmacy, 6th edition 2011, page no. 465-473.
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