DISSOLUTION OF ACTIVE

INGREDIENT FROM DOSAGE FORM

Group 1
Habibie Deswilyaz Giffari (1311011039)
Nadia Putri Inanta (1411011001)
Annisa Fitri Febrianti (1411011004)
Stefany Faula Rendy Putri (1411011007)
Wira Wahyudi Nandayasa (1411011009)

INTRODUCTION
The solubility of a compound depends on its structure and
solution conditions. Structure determines the lipophilicity, hydrogen
bonding, molecular volume, crystal energy and ionizability, which
determine solubility. Solution conditions are affected by pH,
cosolvents, additives, ionic strength, time and temperature. Poorly
soluble compounds can dramatically reduce productivity in drug
discovery and development (Savjani et al., 2012).

IMPORTANCE OF SOLUBILITY

Oral ingestion is the most convenient and commonly

employed route of drug delivery (easy administration, high
patient compliance, costeffectiveness, least sterility
constrains and flexibility in the design of dosage form)2
However, the major challenge with the design of oral
(Yellela et al., 2010).

TECHNIQUES FOR SOLUBILITY

ENHANCEMENT

A. Physical Modifications
Particle size reduction
Nano suspension
Solid dispersion
Cyrogenic techniques
Crystal engineering
(Ziegler, 2010).

C. Miscellaneous Methods

Supercritical Fluid (SCF) Fluids

Hydrotropy
Inclusion complex-formation techniques
Micellar solubilization

(Ziegler, 2010).

B. Chemical Modifications

Change of pH,
Use of buffer,
Derivatization
Complexation
Salt formation.

(Desiraju et al., 2012).

MECHANISM OF SOLUBLE

 Solubility is the capacity of a solute to dissolve in a pure

solvent
Solubility is the thermodynamic process : the system will

tend to arrive at the point of lowest potential energy (PE)

(gibbs free energy), which is most thermodynamically
stable.

(Pharmaceutical press,
2016)

 If solvent

sufficiently
interracts with
solvent particles,
the solutes
intermingles with
the solvent. The
crystalline
structure of the
solute is reduced
and separated by
the solvent into
ions, atoms or
molecules.
(Pharmaceutical
press. 2016)

(Sharpe,2004)
.

 There are 3 steps in

soluble procces :
First is the

separation of the
solvent molecules
Second is the

separation of solute
molecules
Third is the mixing

of the solvent and

solute molecules

(Chang,R.
2005)

HOW TO DISSOLVE THE

DRUG

 Dissolution of a tablet involves its disintegration into smaller and smaller

particles from which the medicinal drug is released more and more
rapidly.
The rate of dissolution of the solute is equal to its rate of separation from

the solution
The theory of dissolution has been studied for over a century and it is a

century since it was established that dissolution takes place in two stages.
The first is the separation of drug molecules from the surface of the solid to

form a solution saturated with drug at the solid-liquid interface

The second stage is the mass transport of the drug from this saturated layer into

the bulk solution

(McMahon,Nia
ll. 2008)

 The mechanism of dissolution, is not affected by the strength of the

chemical or particles dissolved into the liquid, with two successive steps:
1.

A solution of solids on the surface to form a thick layer fixed or films

around the particles

2.

Diffusion of the coating on the mass of the liquid.

The first step occurs fast, and the second step occurs more slowly

(Partang, 2008).

 At the time of drug particles undergo dissolution, drug molecules on

the surface into the solution creating a layer of drug-saturated solution

wraps the surface of the solid drug particles. This solution layer known
as layer diffusion. From this diffusion layer, the molecules of the liquid
passing out medicine which dissolves and is associated with a
biological membrane and absorption.

(Partang, 2008)

 There are 2 type of tablet dissolve procces:

Surface erossion

Surface eroding systems have an advantage in that

they can potentially achieve zero order drug
release if the surface area of drug does not change
during erosion. Surface eroding systems also
minimise the risk of dose dumping
Bulk erossion

the degradation occurs throughout the whole

material equally, depends on volume of the
material, its difficult to control since its not zero
order

(McMahon,Nia
ll. 2008)

 An example of tablet

dissolve in
pharmacokinetic process

(McMahon,Nia
ll. 2008)

DRUGS MUST TEST BY

DISSOLUTION TEST AND
MUSTNT

 Dissolution of the drug is an active compound dissolution

process of a solid dosage form into the carrier solvent.

Solvents an active substance is very important for the
availability of a drug depends on the ability of these
substances dissolved into the solvent medium before it is
absorbed into the body. Dosage should be tested dissolution
is solid or semi-solid form, such as capsules, tablets or
ointments (Ansel, 1989).

 In order for a drug is absorbed, initially the drug should be a

solution in the liquid in place of absorption. For example, a drug

that is given orally in tablet or capsule form can not be absorbed
until the particles dissolve in the liquid drug at a point in the
gastrointestinal tract.
In cases where the solubility of a drug depends on whether the

medium acidic or alkaline medium, the drug is dissolved in a row

in the stomach and the small intestine. The process of dissolution
of a drug called dissolution (Ansel, 1989).

DISSOLUSION PROFILE

Dissolution and Solubility

Dissolution is the process by which a solid drug substance becomes

dissolved in a solvent. Solubility is the mass of solute that dissolves in a

specific mass or volume of solvent at a given temperature (eg, 1 g of
NaCl dissolves in 2.786 mL of water at 25C).

Solubility is a static property; wheareas dissolution is a dynamic property.

In biologic systems, drug dissolution in an aqueous medium is an

important prior condition for systemic absorption.

(Shargel et al., 2004).

 The rate at which drugs with poor aqueous solubility dissolve from an intact

or disintegrated solid dosage form in the gastrointestinal tract often controls

the rate of systemic absorption of the drug.
Thus, dissolution tests may be used to predict bioavailability and may be

used to discriminate formulation factors that affect drug bioavailability.

The dissolution test is required for all U.S. Food and Drug Administration

(FDA)-approved solid oral drug products.

(Shargel et al., 2004).

The overall rate of drug dissolution may be described by

the NoyesWhitney equation

where dC/dt = rate of drug dissolution at time t, D

= diffusion rate constant, A = surface area of the

particle, C S = concentration of drug (equal to
solubility of drug) in the stagnant layer, C =
concentration of drug in the bulk solvent, and h =
thickness of the stagnant layer.
The rate of dissolution, dC/dt, is the rate of drug

dissolved per time expressed as concentration

change in the dissolution fluid.

(Shargel et al., 2004).

 The NoyesWhitney equation shows that dissolution in a flask may be influenced by

the physicochemical characteristics of the drug, the formulation, and the solvent.
Drug in the body, particularly in the gastrointestinal tract, is considered to be
dissolving in an aqueous environment. Permeation of drug across the gut wall (a
model lipid membrane) is affected by the ability of the drug to diffuse (D) and to
partition between the lipid membrane. A favorable partition coefficient (K oil/water) will
facilitate drug absorption.
In addition to these factors, the temperature of the medium and the agitation rate also

affect the rate of drug dissolution. In vivo, the temperature is maintained at a constant
37C, and the agitation (primarily peristaltic movements in the gastrointestinal tract)
is reasonably constant. In contrast, in-vitro studies of dissolution kinetics require
maintenance of constant temperature and agitation. Temperature is generally kept at
37C, and the agitation or stirring rate is held to a specified rpm (revolutions per
minute). An increase in temperature will increase the kinetic energy of the molecules
and increase the diffusion constant, D. Moreover, an increase in agitation of the
solvent medium will reduce the thickness, h, of the stagnant layer, allowing for more
rapid drug dissolution (Shargel et al., 2004).

 Factors that affect drug dissolution of a solid oral dosage

form include:
(1) the physical and chemical nature of the active drug

substance,
(2) the nature of the excipients,
(3) the method of manufacture.
(Shargel et al., 2004).

Dissolution testing can be used to support the bioavailability of a new

pharmaceutical product, the bioequivalence of an essentially similar product.
In summary, dissolution testing is performed :
As an essential part of product development
In support of an application for a waiver of bioequivalence testing
To obtain information on test batches used in bioavailability/bioequivalence

studies and pivotal clinical studies to support specifications for quality control
To demonstrate batch-to-batch and lot-to-lot consistency during manufacture,
and to indicate potential problems of bioavailability i.e. as a tool in quality
control

(Desiraju et al., 2012).

References
Ansel, H.C., 1989. Pengantar Bentuk Sediaan Farmasi. Jakarta: Universitas Indonesia
Press.
Chang, Raymond. 2005.Kimia Dasar: Konsep-konsep Inti Jilid I. Jakarta: Erlangga.

Desiraju,Sharma Soni M, Kumar S, Gupta GD. (2009). Solubility enhancement

eminent role in poorly soluble drugs. Research Journal of Pharmacy and
Technology ;2(2):220224.
Leon Shargel., Andrew B.C.,
Susanna WuPong. (2004). Applied
Biopharmaceutics
and
Pharmacokinetics
5th
edition;
Department
of
Pharmaceutics; Virginia Commonwealth University
McMahon,Niall. 2008. The Mechanics of Drug Dissolution : A demonstration of the
potential of mathematical and numerical methods for solving flow related
problems in pharmaceutics. Dublin City University
Partang,Alfian. 2008. Dissolusi Obat. Makassar. Universitas Hasanudin
Pharmaceutical press. 2016. Remington education : Physical pharmacy Solubility
and dissolution. Pharmaceutical Press
Sharpe,AG. 2004 . Solubility Explained. Great Britain: Cambridge University Press
Yellela SRK. (2010). Pharmaceutical technologies for enhancing oral bioavailability
of poorly soluble drugs. Journal of Bioequivalence & Bioavailability; 2(2):2836.
Ziegler, G. R., & Hogg, R. (2009). Particle size reduction. Industrial Chocolate
Manufacture and Use, Fourth Edition, 142-168.

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