Solid Dispersion: Techniques, Stability, and Permeation Enhancement

This assignment delves into the realm of solid dispersion techniques, addressing key aspects such as the impact of cooling rates on system properties during fusion methods and how solid dispersion enhances the dissolution rate of poorly water-soluble drugs through particle size reduction. It explores various methods for solvent removal in the solvent evaporation technique, including steam bath application and spray drying. The assignment also discusses the reasons behind the withdrawal of Ritonavir capsules due to drug crystallization and its effect on dissolution, while highlighting the role of carriers like Polyvinylpyrrolidone (PVP) in retarding crystallization. Furthermore, it explains the differences in permeation enhancer effectiveness between in vitro and in vivo conditions, the reasons for low membrane permeability in certain compounds, and formulation strategies to improve the bioavailability of proteins and peptides using transient permeability enhancers (TPE). The mechanisms by which absorption promoters enhance absorption in the gastrointestinal membrane, targeting specific channels and tight junctions, are also discussed, along with the role of sodium caprate in enhancing oral absorption through increased exposure time and surface area. This comprehensive overview provides a detailed understanding of solid dispersion and its challenges.

Running head: SOLID DISPERSION
Solid Dispersion
Name of the Student
Name of the University
Author Note

1SOLID DISPERSSION
Question 1.
The step of cooling is very much important in pursuing the method of fusion to form
solid dispersions. In preparation of nifedipine–PEG 6000 solid dispersion, at first, physical
mixtures of the drugs were melted at 80-85 degree centigrade temperature. After that, it was
rapidly cooled by using mixture of sodium chloride and ice. Then the solids were stored for 24
hours before sieving and pulverization.
Question 2.
Lower water solubility is one of the major hindrances in the way of developing new
drugs. However, the solubility can be enhanced by several methods like solubilization, reducing
the particle size of the drug, salt formation. Solid dispersion technique is quite effective in
increasing the dissolution rate of the water soluble drugs. Commonly, process of particle size
reducing is used to enhance the solubility. Poorly water soluble drug when taken with solid
dispersion/ solution, the drug particles are disintegrated. As a result the size of the drug particles
are reduced to a very size that is the size almost become < 1 micron. This size reduction helps in
increasing the dissolution rate and ultimately the absorption rate increases. In this way, solid
dispersion enhances the dissolution rate.
Question 3.
Different researchers had used different techniques to remove solvent. Ethanolic solvent
can be evaporated by steam bath technique and residual solvent can be removed by application
of low pressure. In addition, ethanolic solution can be removed by drying from a solution of
griseofulvin and PEG 6000 can be removed by applying 115 degree centigrade temperature in an
oil bath until ethanol bubbles appear. After that, viscous mass is kept to be in a solid condition by

2SOLID DISPERSSION
keeping it in a flow of cold air. Along with this, spray drying, lyophilization, vacuum-drying,
sugarbeads spray by the help of fluidized bed-coating system. This techniques can be used to
remove solvents from in solvent evaporation method.
Question 4.
It is reported that, in the solid dispersion, the drug particles stay in an unchanged
condition if it is mixed with the carrier. However, if it is dissolved in the carrier, the state of the
particle will be changed. In addition, if heat is applied to dissolve the drug particle into the
carrier, it will be crystalized and may come out from the carrier. This crystallization of the drug
negatively affect the dissolution of the capsule. Along with this, the capsule produced a solution
which was thermodynamically stable. As a result the main purpose that is the enhancement of the
dissolution rate was hampered. That was the reason behind the withdrawal of the Ritonavir
capsule from the market.
Question 5.
The conversion of the drug into a crystalize form is the crucial step of drug stability with
solid dispersion that is prepared by the solvent method. In this case, Polyvinylpyrrolidone,
commonly known as PVP is very much useful carrier in retardation of crystallization process to
amorphous drugs. PVP is not converted into the crystalize form. In a study it was seen that, there
was no crystallization in the furosemide-PVP dispersion method in the temperature range of 6-45
degree centigrade in relative humidity of 45% (for 1 year). So it was assumed that PVP is
responsible for retardation of crystallization in the solid dispersion method.

3SOLID DISPERSSION
Question 6.
The permeation enhancers was less effective in the in vivo condition than that of the in
vitro condition. In an in vitro study, a researcher could easily control the environment of the
research and even the micro environment of the research could also be controlled. The actual
concentration of the drug was also remain same in case of in vitro condition. However in case of
the in vivo condition that is the actual target side inside the body, the condition cannot be
controlled. The original concentration of the delivered drug could be also diluted by the fluids
present in that region. This one of the reasons of less functioning of drugs in a in vivo condition.
Moreover it was seen that, the permeation enhancer could be more effective in the excised
membrane than that of the intact membrane that was in the in vivo condition.
Question 7.
There were several molecules that have lower membrane permeability due various
reasons. One of the major reason is the size of the molecules. The larger molecule weight of the
orally administered drugs is the most common issue due to their larger molecular weight and
alongbwith this, they have a lot of hydrogen bonding groups that is also responsible for the poor
membrane permeation. Along with this, the hydrophilic nature of the compounds, strong
ionization capacity are the barrier for the membrane permeation. In case of paracellular
absorption, the membrane permeation is restricted as the molecular size is higher than that of the
effective pore size.
Question 8.
The permeation of the peptides or proteins can be enhanced by using a formulator. In this
context, formulation technology such as transient permeability enhancer (TPE) system can be

4SOLID DISPERSSION
used. This formulation may include protease inhibitor, bile salt, EDTA, bile acids and those are
responsible for the enhancing permeation through the membrane.
Question 9.
The enhancement of the absorption in the gastrointestinal membrane by using absorption
promoters is completed by targeting specific channels present on the gastrointestinal membrane.
In this scenario, mainly zonula occludens is first identified and then a peptide fragment helped to
enhance the absorption mechanism of intestinal membrane. Along with this, modulation of the
tight junctions that are present in that region are also responsible for the increment of the
absorption through the gastrointestinal membrane. However, the enhancement using tight
junction modulation had not have enough evidence in in vivo condition.
Question 10.
Sodium caprate is one of the important absorption promoter and it has been used to
enhance the oral absorption of drugs. It is thought that, sodium caprate enhanced the exposure
time of the gastrointestinal membrane to the absorption promoter. As a result, the promoter can
affect the permeation for long time. Along with this, enhancer also increase the surface area of
the membrane. By this mechanism, sodium caprate enhances the absorption.