1. + Drug release and dissolution 2. + USP Disintegration
Apparatus Drug release and dissolution 3. + Video 4. + The five
types of dosage forms that can be characterized by release in vitro
1. Solid oral dosage forms 2. Rectal dosage forms such as
suppositories 3. Pulmonary (lung delivery) dosage forms ( orally
inhaled products) 4. Modified-release dosage forms 5. Semisolid
products such as ointments, creams,and transdermal products. 5. +
Drug release and dissolution 6. + Drug release and dissolution 7. +
SUPAC (Scale Up Post Approval Change) guidances Drug release and
dissolution Biopharmaceutics Classification System (BCS) 8. + Drug
Product: A drug product is a finished dosage form (e.g., tablet and
capsule) that contains a drug substance, generally, but not
necessarily in association with one or more other ingredients (21
Code of Federal Regulations 314.3(b)). Drug Substance: An active
ingredient that is intended to furnish pharmacologic activity or
other direct effect in the diagnosis, cure, mitigation, treatment,
or prevention of a disease, or to affect the structure of any
function of the human body, but does not include intermediates used
in the synthesis of such ingredient (21 Code of Federal Regulations
314.3(b)). Drug release and dissolution 9. + Drug release is the
process by which a drug leaves a drug product Immediate release
drug products allow drugs to dissolve with no intention of delaying
or prolonging dissolution or absorption of the drug Delayed release
is defined as the release of a drug at a time other than
immediately following administration. (Enteric Coated) Enteric
Coated: Intended to delay the release of the drug (or drugs) until
the dosage form has passed through the stomach. Enteric-coated
products are delayed-release dosage forms. Repeat action two single
doses of medication; one for immediate release; another one for
modified release Targeted release drug release directed toward
isolating or concentrating a drug in a body region, tissue or site
of absorption or for drug action Drug release and dissolution 10. +
Extended-release products are formulated to make the drug available
over an extended period after administration. Prolonged-release
dosage forms Prolonged-release dosage forms are modified-release
dosage forms showing a slower release of the active substance(s)
than that of a conventional-release dosage form administered by the
same route. Equivalent term: extended-release dosage form.
Pulsatile release involves the release of finite amounts (or
pulses) of drug at distinct time intervals that are programmed into
the drug product. Modified-Release Dosage Forms: Dosage forms whose
drug-release characteristics of time course and/or location are
chosen to accomplish therapeutic or convenience objectives not
offered by conventional dosage forms such as a solution or an
immediate- release dosage form OR Modified-release dosage forms are
preparations where the rate and/or place of release of the active
substance(s) is different from that of a conventional- release
dosage form administered by the same route. Modified-release dosage
forms include both delayed and extended-release drug products
controlled release includes extended-release and pulsatile-release
products. Drug release and dissolution 11. + 1. Immediate release
(IR) 2. Sustained Release (SR) 3. Sustained Action (SA) 4. Extended
Release (ER) 5. Long Acting (LA) 6. Prolong Action (PA) 7.
Controlled Release (CR) 8. Timed Release (TR) Drug release and
dissolution 12. + 13. + Osmotically Controlled Systems 14. +
Dissolution Dissolution Dissolution refers to the process by which
a solid phase (e.g., a tablet or powder) goes into a solution phase
such as water. It is the process for which drug molecules leave the
boundary surrounding the dosage form and diffuses into the
dissolution media. 15. + Drug release and dissolution 16. + 17. +
Different controlled release systems Time of release Cumulative
release Diffusion controlled release Zero order (linear) release
Burst like release Pulsatile release Lag followed by Burst release
18. + Mechanism aspects of Oral drug delivery formulation
1.Dissolution : 1.Matrix 2.Encapsulation 2.Diffusion : 1.Matrix
2.Reservoir 3.Combination of both dissolution & diffusion.
4.Osmotic pressure controlled system 19. + Dissolution controlled
systems In dissolution controlled systems, the rate controlling
step is dissolution. The drug is embedment in slowly dissolving or
erodible matrix or by coating with slowly dissolving substances
There are basically two types of dissolution devices Controlled
Release Systems Encapsulation dissolution controlled system Matrix
dissolution controlled system Soluble drug Slowly dissolving matrix
Soluble drug Slowly dissolving or erodible coat 20. + Controlled
Release Systems Diffusion controlled systems Diffusion systems are
characterized by release rate of drug is dependent on its diffusion
through inert water insoluble membrane barrier. There are basically
two types of diffusion devices. (I)Reservoir devices (II)Matrix
devices 21. + Dissolution & Diffusion Controlled Release system
Drug encased in a partially soluble membrane. Pores are created due
to dissolution of parts of membrane. It permits entry of aqueous
medium into core & drug dissolution. Diffusion of dissolved
drug out of system. Insoluble membrane Pore created by dissolution
of soluble fraction of membrane Entry of dissolution fluid Drug
diffusion Controlled Release Systems 22. + Controlled Release
Systems Osmotic pressure controlled system 23. Swelling vs. Erosion
Diffusion controlled systems and / or Dissolution & Diffusion
Controlled Release system Dissolution controlled systems Controlled
Release Systems 24. + Drug dissolution and release commonly fall
into two groups: zero-order release and first-order release.
Typically in the pharmaceutical sciences, zero-order release is
achieved from non-disintegrating dosage forms such as topical or
transdermal delivery systems, implantable depot systems, or oral
controlled release delivery systems oral osmotic tablets matrix
tablets with low-soluble drugs Drug release and dissolution 25.
zero-order release tKQQt 00 where Q is the amount of drug released
or dissolved (assuming that release occurs rapidly after the drug
dissolves) Q0 is the initial amount of drug in solution (it is
usually zero), and K0 is the zero-order release constant. tKQt 0
Constant release is defined in this context as the same amount of
drug release per unit of time 26. First-order release. Kt Q Q eQQ
tkt t )ln( 0 0 Where Qt is the amount of drug released or dissolved
Q0 is the initial amount of drug in the device and K is the
First-order release constant. 27. + Absorption depends some what on
1- The rate of disintegration of the dosage forms 2- Deaggregation
of the granules 3- More importance is the dissolution rate of the
solid drug. Frequently, dissolution is the limiting or
rate-controlling step in the absorption of drugs with low
solubility Dissolution 28. Mathematical model for drug dissolution
Noyes-Whitney equation 29. + Chemical photography of drug release
Mathematical model for drug dissolution Noyes-Whitney equation 30.
The equation describes the rate of release of the drug from its
solid state. )( )( CCs Vh DS dt dC CCs h DS dt dM M: mass of solute
dissolved in time t. D: is the diffusion coefficient. S: is the
surface area of dissolution. (concentration of a saturated
solution) h: is the diffusion layer thickness Cs: is the solubility
of drug in the dissolution medium. C: is the concentration of drug
in the bulk. V: is the volume of solution. dC/dt is the dissolution
rate, Mathematical model for drug dissolution Noyes-Whitney
equation 31. + An aqueous diffusion layer or stagnant liquid film
of thickness h exists at the surface of a solid undergoing
dissolution. This thickness, h, represents a stationary layer of
solvent in which the solute molecules exist in concentrations from
Cs to C h Cd DSK dt dM h CrCd DSK dt dM 32. + 33. Cs Vh DS dt dC Cs
h DS dt dM C 0 Mathematical model for drug dissolution
Noyes-Whitney equation )( )( CCs Vh DS dt dC CCs h DS dt dM Under
sink conditions CCs 2 1 2 tADCQ S 2 1 2 t ADC dt dQ S dQ/dt the
rate of drug released per unit area Cs is the solubility or
saturation concentration of drug in the matrix A is the total
concentration dissolved and undissolved, of drug in the matrix. OR
Total amount of drug in a unit volume of the matrix OR The initial
drug concentration Q amount of the drug release in time t per unit
area D, the diffusion coefficient of the drug in the matrix 50. +
Release from Granular Matrices: Porosity and Tortuosity 2 1 2
tCCADQ SS Sink condition OR A>>>>Cs 2 1 2 tADCQ S dQ/dt
the rate of drug released per unit area Cs is the solubility or
saturation concentration of drug in the matrix A is the total
concentration dissolved and undissolved, of drug in the matrix. OR
Total amount of drug in a unit volume of the matrix Q amount of the
drug release at time t per unit area D, the diffusion coefficient
of the drug in the matrix; is the porosity of the matrix and is the
tortuosity of the capillary system, 51. + Porosity is the fraction
of matrix that exists as pores or channels into which the
surrounding liquid can penetrate Tortuosity is introduced to this
equation to account for an increase in the path length of diffusion
due to branching and bending of the pores as compered to shortest
straight through pores Tortuosity tends to reduce the amount of
drug release in a given interval of time 52. + T(hr) Concent. Drug
release mg/ml 0 0 2 0.42 4 0.59 6 0.74 8 0.876 10 0.98 2 1 tQ The
dissolution in 500 ml water data are found in the table below. 0
100 200 300 400 500 600 0 1 2 3 4 5 6 7 8 9 10 mgdrrugrelease t
(hr) Amount drug release Mg (in 500ml) Qt 0 210 295 370 438 490
T^(1/2) 0.000 1.414 2.000 2.449 2.828 3.162 K mg*^(1/2)/hr 148.4924
147.5 151.0519 154.8564 154.9516 53. + T(hr) Concent. Drug release
mg/ml Amount drug release Mg (in 500ml) Qt T^(1/2) K mg*^(1/2)/hr 0
0 0 0.000 2 0.42 210 1.414 148.4924 4 0.59 295 2.000 147.5 6 0.74
370 2.449 151.0519 8 0.876 438 2.828 154.8564 10 0.98 490 3.162
154.9516 2 1 tQ The dissolution in 500 ml water data are found in
the table below. 0 100 200 300 400 500 600 0.00 0.50 1.00 1.50 2.00
2.50 3.00 3.50 mgdrugrelease t (hr)^(1/2) 54. + Mathematical model
for drug dissolution zero-order release tKQt 0 first-order release.
Kt Q Q eQQ tkt t )ln( 0 0 Noyes-Whitney equation )( )( CCs Vh DS dt
dC CCs h DS dt dM tMM t 3 1 3 1 0 Hixson-Crowell cube root equation
Higuchi (Equation) 2 1 2 tCCADQ SS 2 1 ktQ 2 1 2 SS CCADk 55. + 55
56. + T(hr) Qt Drug release mg 0 0 1 10.02 2 19.8 3 28.78 4 38.54 5
49.05 6 58.78 7 67.99 8 78.12 9 88.04 10 97.58 KtQt hrmgK /749.9 7
24.68 29 8.1904.88 0 10 20 30 40 50 60 70 80 90 100 0 1 2 3 4 5 6 7
8 9 10 11 t(hr) Qtmgdrugrelease K= (Qt)/t Mg/hr 10.02 9.90 9.59
9.64 9.81 9.80 9.71 9.77 9.78 9.76 K=9.78 Mg/hr Average
Mathematical model for drug dissolution zero-order release equation
57. + tMM t 3 1 3 1 0 Mathematical model for drug dissolution
Hixson-Crowell cube root equation T(hr) Concent. Drug release mg/ml
0 0 2 0.159 4 0.288 6 0.39 8 0.468 10 0.528 3 1 3 1 0 tMM A 0.625 g
af paracetamol powder was dissolved in 1000 ml of water. The
dissolution data are found in the table below. 0 100 200 300 400
500 600 0 2 4 6 8 10 12 mgdrugrelease t( hr) Average K= 0.397
Amount drug release Mg / 1lt Wt 0 159 288 390 468 528 Amount of
undissolved drug Mt=625-Wt 0 466 337 235 157 97 0.000 0.797 1.591
2.379 3.155 3.955 K mg*^(1/3)/hr 0 0.399 0.398 0.396 0.394
0.396
