The term silica is otherwise known as silicon dioxide or quartz. Silicon dioxide is a substance which occurs naturally in the earth and it consists 12 percent of the earth crust. Since the availability of silica is known from several years it is most frequently found in the nature as crystal quartz. As we know silicon dioxide have divergent properties it has been used in different fields. Silicate glasses and ceramics are produced from many materials but silica is the first material through which silicate glasses and ceramics had been produced. Silicon dioxide is one of the most frequently used substances in our day to day life and in the manufacturing of electronics. Silicon dioxide usually occurs in crystalline and amorphous form. Crystalline silicon dioxide is one of the key ingredient in the preparation of many minerals and gem stones.
There are many forms of silica out of which mesoporous silica is none of the form and it is one of the recent improvement or evolution in nanotechnology. The actual intention of the scientists who found the mesoporous silica particles is to use them as the medicine, bio fuels and for imaging purposes.
Physical properties of silica:
1. It is white in colour.
2. The chemical formula of silicon dioxide is sio2.
3. The molar mass of silicon dioxide is 60.0843 g/mol.
4. The melting point of silicon dioxide is 17100c.
5. The boiling point of silicon dioxide is 22300c.
6. The density of silicon dioxide is 2.634 g/cm3.
7. It is soluble in water.
8 .Natural abundance of silicon dioxide is 2.2 mg/l.
9. Percentage composition of silicon dioxide by mass is that silica contains 47.644% and oxygen contains 53.255%.
10. Percentage composition of silicon dioxide by number is that silica contains 33.33% and oxygen contains 66.6%.
1.1.2 USES OF SILICON DIOXIDE:
1.Silicon dioxide is one of the most important compound which is used for the manufacture of electronics i.e silicon dioxide has piezoelectric property which means it has the ability to convert mechanical energy to electrical energy and vice versa.
2. Silicon dioxide is used as a sand for foundations.
3.Silicon dioxide is used as a sealant.
4. Silicon dioxide is used as a petroleum product.
5. It is used as a thickening agent in medicines.
6. It is used as a detergent.
SILICA GEL STRUCTURE:
Explanation about the silica gel from the figure:
The silica gel essentially consists of a group of silicon atoms united together with oxygen atoms by siloxane bonds.There are several silicon atoms of silica gel of which on each of the particle surface uncondensed hydroxyl groups are formed from origina polymersilici acid remain which is knon as residue . The residue formed suggests polar properties of silica. The surface of the silica is obscure and contains more than one hydroxyl group which makes us difficult to understand .There are three types of hydroxyl groups in silica gel.
1.First hydroxyl group has three siloxane bonds joining it to gel matrix which is attached to silicon atom.
2. Second hydroxyl group has two siloxane bonds in this out of the two hydroxyl groups, one of the hydroxyl group is attached to silicon atom.
3.The third hydroxyl group has only one siloxane bond which is attached only to the silica matrix.
1.1.3 SILICA NANOPARTICLES:
The particles with the size ranging from 1 to 100 nm are known as nanoparticles. Nanoparticles are also called as nanospheres when drug is binded with polymer matrix and when drug is incorporated in to the polymer matrix nanoparticles are called as nanocapsules.Nanoparticles cannot be measured because of their tiny size and also they possess surface area per unit volume which is immeasurable due to this large number of atoms are produced in the surface area and hence it produces quantum effect.
The main objective for abstract art of silica nanoparticles is to control the particle size and surface properties.
Silica nanoparticles have played vital and divergent role in each and every product because the product quality is dependent on the size of the particles. From the simple projection of the bulk material we cannot expect the universal properties of the nanoparticles. The physical properties such as surface area and particle size will be changed where microparticles are converted in to nanoparticles. Silica nanoparticles are present in the form of metals, metal oxides, semiconductors, carbon materials with varied chemical and morphological properties. Silica nanoparticles generally have low luminescent or optical property, by adding various functional groups like phenols, amines, thiols and carboxyls to improve luminescent property because luminescent property is helpful in bio analysis and when compared with traditional fluorescent technique luminescent nanoparticles are precise in improving the detectable signals. The differences between silica particles modified with the polymer and those of non modified are:
1. There will be more weight loss of the particle in the modified one's when compared with non-modified.
2. There will be low water vapour adsorption due to hydrophobic surface property resulting from polymers that are being adsorbed on to the silica when compared with non modified one's.
3. Lower electrical conductivity will be there when compared with non modified ones.
Of all the materials that have been studied mesoporous nanoparticles are one of the prominent materials with structures that are well defined and particles with good surface properties that are considered to be the best material as drug delivery system. Silica nanoparticles are much suitable for drug delivery system because :
1. They are cheaper [inexpensive]
2. Thermally balanced.
3. They are inert chemically.
4. They are biocompatible.
There are so many advantages of using silica nanoparticles as a drug delivery system. They are
1. In order to achieve both active and passive targeting of the drug after parenteral administration, the physical properties of mesoporous silica particles such as particle size and surface area can be arranged
2. The defects such as decomposition of the particle and controlled release can be easily controlled by matrix components.
3. The other advantage of using silica nanoparticles as a drug delivery system is that large amount of drug can be loaded in to the system such that no reaction occurs thus preventing the decomposition of the particle due to this the activity of the drug will not be changed.
4.Specific targeting of the drug at a site can be obtained by using magnetic guidance.
Beside the advantages there are some disadvantages.
When the size of the particle is small and the surface area is more, then particle -particle interaction occurs which leads to agglomeration.
The other disadvantage is that when particle size is small and surface area is large amount of drug cannot be loaded.
From the past few years the techniques which are based on nanoparticles had shown good improvement in the applications of medicines and bio analysis and also based on the properties of inorganic nanoparticles and the polymer, nanoparticles hybrids have become advanced development in recent technology.
1.1.4 TYPES OF NANOPARTICLES:
Nano particles are divided in to several types. They are
1. Quantum dots.
3. Fullerenes: Bucky balls and carbon tubes
7. Super paramagnetic nanoparticles.
8. Nano rods.
1.1.5 GENERAL METHOD OF SYNTHESIS OF SILICA NANOPARTICLES:
Synthesis of silica nanoparticles can be made by several methods but out of which the most general method used for the synthesis of silica nanoparticles are stober and sol-gel methods.
SYNTHESIS: Hydrolysis and condensation reactions are very important in these two methods for the preparation of silica nanoparticles .In this tetra ethyl oxy silicate is used as a precursor.
Hydrolysis and condensation reactions:
Si (OR) 4 + 4 H2O → Si (OH) 4+ 4 ROH
Si (OH) → SiO2+ 4H2O
REFERENCE; STOBER W.FINK,A.J BOHN, EJ.COLLOD INTERFACE SCIENCE 1968.
METHOD OF PREPARING SILICA NANOPARTICLES FROM SILICEOUS MUDSTONE:
As we know siliceous mudstone is a mineral source of the silica,silica nanoparticles are prepared from siliceous mudstone bu using a chemical reaction.First aqueous solution of sodium silicate is prepared and after that ingredient of silica is added to the aqueous solution which involves sodium hydroxide reaction of siliceous mudstone [s100]. This is done to remove the sodium from the aqueous solution and after removing the siliceous mudstone [s200] is and after preparing s200 silica nanoparticles are prepared from aqeous solution by conducting flame spray analysis.
1.1.6 APPLICATIONS OF SILICA NANOPARTICLES:
Cancer can be detected and diagnoised by the application of silca nanoparticles
Silica nanoparticles are useful in the application of biosensing.
Silica nanoparticles are used as biomarkers for leukamia cells
Silica nanoparticles are used in the application of bioanalytics
These are useful for drug delivery systems
They act as support for the catalyst
Silica nanoparticles are used as antibacterial agents
Silica nanoparticles are used for imaging purpose.
Silica nanoparticles are used as magenetic reasonance agents
It is used as a cell marker in both cancer and stem cell.
They are used for targetting cell specification
For many organic compounds it is used as a stabilising agent
It is used in the manufacture of tablets as a glidant
It is used as antiviral agents for in vivo gene delivery
These are useful in diagnosis for colon diseases
These are used for controlled release for drugs.
1.1.7 STRUCTURE OF SILICA:
Amorphous structure of silica:
Iler, R.K., The Chemistry of Silica (Plenum Press, New York 1979)
The drug used is paracetamol.It is nonsteroidal antiinflammatory drug.It acts as analgesic and antipyretic.
Ref : Pharmaco dynamic series by DR James Mitchell
CHEMICAL CHARACTERISTICS OF PARACETAMOL:
The chemical characteristics of paracetamol are
Chemical formula C8H9 NO2
The molecular weight of paracetamol is 151.17 g/mol.
The density of paracetamol is1.263 g/cm3
The melting point is 1680c
It is soluble in water.
The bioavailability of the drug is 80%
The half life is 1-4 hours
Peak plasma level is 40 to 60 minutes.
The administration of the drug is through oral, rectal and intravenous route.
Overdose of the drug leads to liver damage
1.It is used in the treatment for relief of pain.
2.It is used for the symptomatic treatment for fever
AIM OF THE PROJECT:
The aim of the project is to synthesise silica using tween 40 and to study its use as a drug delivery system.
2.1 CHEMICALS USED:
The chemicals used are:
Tetra ethyl oxy silicate
2.2 SYNTHESIS OF SILICA:
To prepare silica we need a surfactant and silica source so we take tween 40 as a surfactant and tetra ethyl ortho silicate as a silicate source. Firstly in the preparation of the silica we should weigh 4 grams of tween 40 and after that in a measuring cylinder, measure accurate volume of 65 ml of 2M [molar ] hydrochloric acid .Now hydrochloric acid and tween 40 are mixed to make a solution. To the resulting solution 35 ml of deionised water is added with continuous stirring to make up the volume and now we should add 9.1 ml of tetra ethyl oxy silicate with continuous stirring. By continuous stirring homogeneity and twisted oil water interface is obtained and keep the solution aside for 24 hours. The product obtained is filtered, washed with plentiful volume of water to remove the gritty particles. Then the product obtained is silica which is dried at a room temperature and it is stored in a plastic bottle. Thus, this is the way I had prepared silica in the laboratory.
2.3 CHARACTERISATION OF SILICA:
Silica characterisation is done by different methods .They are
1.Scanning electron microscopy
2. Transmission electron microscopy
3.X-ray powder diffraction
4. Surface area by nitrogen adsorption
5. Particle size measurement.
The characterisation of silica is mainly done because the silica particles are immeasurable due to their tiny size that is their size will be in the sub micrometer range. Based on the size of the particles, the characterisation of silica particles is mainly done by electron microscopy to know the mesostructure of the sample.
SCANNING ELECTRON MICROSCOPY:
Scanning electron microscopy is one of the important method to know the characterisation of silica. By using this method we can know overall form and structure of the product without considering its function. Scanning electron microscopy is done by mr.Ian Slipper of university of Greenwich at medway.This experiment is done by using stereo scan 90 scanning electron microscope operated at 37 kv and it is magnified 3700 times. To characterise the silica by scanning electron microscope the silica particles must possess the capacity of the conductance. So, the particles need to be gold coated to get the conductance .
TRANSMISSION ELECTRON MICROSCOPY:
This method is done by Mr.Ian Slipper of university of Greenwich at medway by sing HRTEM, JEOL, 200 CX equipment operated at 200k. This is an advanced technology over scanning electron microscopy that is if scanning electron microscope does not provide the clear cut structure of the sample then this method will be used. In this method as we know the silica particle size is very small, small amount of sample is taken and it is placed on the sample holder which is rod shaped and then the sample containing sample holder is adjusted in the instrument and thus by analysing the sample particle size and shape is determined. This is the process how we characterise silica by using transmission electro microscope.
3. X-RAY POWDER DIFFRACTION:
X-ray powder diffraction is one of the important method to characterise the silica. Mainly this method is used to know the structural conformation and porous behaviour of the particle.Although they are having long range order they are amorphous in nature, x-ray diffraction is generally measured at low angles for this reason.
4.Surface area by nitrogen adsorption:
Nitrogen adsorption is the method used to measure not only surface area but also structural and morphological properties of the sample. At liquid nitrogen 78k nitrogen absorption of the sample was determined by using micromeritics Gemini 6 analysers.There are two important methods to determine the surface area by nitrogen adsorption. They are
Stephen brunauer, p.h Emmett
By measuring the adsorption of non polar gases surface area is determined in BET.
5.Particle size measurement:
Particle size measurement is done by taking small amount of sample in a test tube and degassing is done for two hours in flowing nitrogen.
DRUG ADSORPTION STUDIES:
PREPARATION OF DRUG SOLUTION
Paracetamol is the drug used in this experiment.The study of absorption drug standard solution and sample solution are prepared.
PREPARATION OF STANDARD DRUG SOLUTION
In a clean and dried conical flask we should take 0.1 ml of crude paracetamol drug and it is diluted with 100 ml of water and it is agitated thoroughly.The prepared standard drug solution was used and labelled.
The prepared o.5 ml of standard paracetamol drug solution was taken in a dried conical flask and it is made up to 2.5ml with distilled water and labelled as 0,.5 ml standard paracetamol solution.In the same way 1ml, 1.5 ml,2.0ml, 2.5ml paracetamol drug solutions are prepared and labelled in the same way.
PREPARATION OF SAMPLE SOLUTION:
We should take 50 mg of silica in 5 small glass bottles and to it we should add o.5 ml of standard paracetamol drug solution and labelled as 0.5 ml of paracetamol sample solution. In the same way the other solution 1, 1.5, 2.0 and 2.5 ml solutions are prepared and labelled respectively.
Standard Paracetamol drug solution concentration is 100ppm. 0.5ml of standard paracetamol drug solution was taken which is of 20 ppm concentration. The absorbance of the standard drug solution was measured and recorded known as absorbance of standard.
The absorbance of the standard paracetamol drug solution was 1.907nm.
5ml of standard paracetamol drug solution was taken and add 0.05g of silica made with tween 40 was added to it. Record the absorbance of the sample solution from the aqueous layer.
The absorbance of sample containing silica tween 40 was recorded as 1.350nm.
The absorbance of another silica prepared from CTAB [cetyl trimethyl ammonium bromide] by the same process as mentioned above and it was recorded as 1.619nm.
we can calculate the amount of drug adsorbed on the silica by subtracting the standard drug solution and sample solution absorbance values from the above recorded absorbance values.
Absstd - Abssam = measurement of the adsorbed drug
Absorbance of standard drug solution is Absstd
Absorbance after addition of silica is Abssam
The amount of paracetamol drug adsorbed on the silica tween 40 is
Absstd - Abssam = adsorbed drug measrement
Absstd - Abssam = 1.907-1.350
The mount of drug paracetamol adsorbed on the silica CTAB is
Absstd - Abssam = 1.907-1.619
Absorbance A = E C l
Where E = molarity
C = concentration
l = path length
Absstd = E Cstd l and
Abssam = E Csam l
Absstd / Abssam = E Cstd l / E Csam l
Absstd / Abssam = Cstd / Csam
From this the concentration of the sample can be calculated as
Csam = Cstd X Abssam / Absstd
Since concentration of the standard used was 20 ppm
The concentration of the sample containing silica TWEEN 40 and std drug solution
Csam = 20 X 1.350 / 1.907
= 14.15 ppm
The concentration of the sample containing silica CTAB and drug solution
Csam = 20 X 1.619/ 1.907
= 16.97 ppm
1 ppm = 1mg / 1 lit
= 1 µg / 1 ml
For 20 ppm
20ppm = 20 µg / 1 ml
5ml of drug solution is added to the samples.
So, the total amount of drug added was
5 X 20 = 100 µg
Then the concentration of the silica TWEEN 40 is
Csam = 100 X 1.350 / 1.907
= 70.79 µg
The concentration of the silica CTAB is
Csam = 100 X 1.619 / 1.907
= 85.2 µg
The amount of drug adsorbed by 50mg of silica tween 40 is
100 - 70.79 = 29.21 µg
The amount of drug adsorbed by 50 mg of silica Tween 40 is
100 - 85.2 = 14.8 µg
From the above calculations the amount of drug adsorbed by the 1 gm of silica can be determined.
The amount of drug adsorbed by the 1gm of silica tween 40 is
= 1000/50 X 29.21
The amount of drug adsorbed by the 1gm of silica CTAB is
= 1000/50 X 14.8
3.0 RESULTS AND DISCUSSION:
CHARACETERISATION OF SILICA:
The characetersiation of silica is done by the following methods:
1.Scanning electron microscopy
2. Transmission electron microscopy.
3. Particle size measurement.
4. Surface area by nitrogen adsorption.
5.Powder x-ray diffraction.
The amount of drug adsorbed on 1 gram of silica tween40 was found to be 0.58 mg and in the same way i have compared with my friend silica cetyl trimethyl ammonium bromide found to be o.29 mg when compared with my friend silica my silica tween 40 was found to be well adsorbed and it can be applied efficiently in drug delivery system.
The particle size measurement was found by using the equipment malver master sizer and it was found to be 6.651µm to 231.280 µm.
The surface area was determined by nitrogen adsorption method and it was found to be 0.14 m2/g which is less than 1 and from the results we can say that my silica is nonporous in nature and it is less efficient for drug delivery system because the surface area is less than 1.Hence sustained release of loaded drug in drug delivery system is obtained.
From the results and discussion we can say that the surface area of the silica is less than 1 m2/g .So the resulted silica obtained is nonporous in nature.
From experimental data the wavelength was found to be 242.2nm.
SUGGESTIONS FOR THE FUTURE WORK:
The surface area of the silica that i have prepared in the laboratory is less than 1 m2/g so I suggest that care should be taken while preparing the silica and accurate measurements should be taken to avoid the loss and degradation of sample.