FORM 2
THE PATENT ACT, 1970
(39 OF 1970)
AND
THE PATENTS RULES, 2003
PROVISIONAL/COMPLETE SPECIFICATION
(See section 10; rule 13)
TITLE OF THE INVENTION : NanoNizer

APPLICANT(S)
(a) Name : Ms. Kaudanya Anju Gupta,
(b) Nationality: Indian
(c) Address: 802/A wing, 8th floor President Park, Plot No. 77 & 77A, Sector 29, Opp. Rajiv Gandhi Udyan, Vashi, Navi Mumbai
APPLICANT(S)
(d) Name : Mr. Iyer Natrajan S.
(e) Nationality: Indian
(f) Address: 403 Kaveri, K. Raheja Residential Complex, Balkum Pipe road,
Thane (W)-400 008. India
3 PREAMBLE TO THE DESCRIPTION
PROVISIONALThe following specification describes theinvention.See Annexure 1 as attached COMPLETEThe following specificationparticularly describes the inventionand the manner in which it is to beperformed. :NA
DESCRIPTION (Description shall start from next page)
See the Annexure 1
CLAIMS (not applicable for provisional specification. Claims should start with the preamble - "I/We claim" on separate page)
NA
DATE AND SIGNATURE (to be given at the end of last page of specification)
See the Annexure 1
ABSTRACT OF THE INVENTION (to be given along with complete specification on separate page) See the attachment Annexure II Note-
* Repeat boxes in case of more than one entry
* To be signed by the applicant(s) or by authorized registered patent agent.
* Name of the applicant should be given in full, family name in the beginning.
* Complete address of the applicant should be given stating the postal index no. / code State ad country.
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NanoNizer
Think Small Think Really, Really Small - smaller than anything you ever saw through a microscope at school. Think atoms and molecules, and now you're there. You're down at the nanoscale, where scientists are learning about these fundamental components of matter and are putting them to use in beneficial ways.
Relatively new area of science that has generated excitement worldwide. Working ai the nanoscale, scientists today are creating new tools, products and technologies to address some of the world's biggest challenges, including :
• Clean, secure affordable energy
• Stronger, lighter, more durable materials
• Low-cost filters to provide clean drinking water
• Medical devices and drugs to detect and treat diseases more effectively with fewer side effects
• Lighting that uses a fraction of the energy
• Sensors to detect and identify harmful chemical or biological agents
• Techniques to clean up hazardous chemicals in the environment
Micro - Prefix meaning one millionth, 1/1,000,000
Nano - Prefix meaning one billionth, 1/1,000,000,000
Mono composite of titamine allay is used to improve bio compatability of inserts. Nano means Dway in Greek.
'Nanotechnology' literally means technology that is very small. One nanometer is one-billionth of a meter or the width of about 5 atoms. 'Nanotechnology' refers to technology that takes place at this very tiny, sub-atomic level in robotics, chemistry, physics, information and communication technology, and molecular biology. Nanotechnology is revolutionary, because at the nano-scale all matter is the same. All things, both living and non-living, are constructed of atoms.
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NanoNizer
The nano-scale sparks so much interest because when a substance is artificially created, structured atom by atom, it can have different or enhanced properties compared with same substance as it occurs naturally, including increased chemical reactivity, optical, magnetic, or electrical properties.
Nanotechnologies have numerous and widespread applications but their earliest commercial impact is likely to occur in the field of biotechnology and medicine. Biopharmaceutics Classification System (BCS) with which to identify expendable clinical bioequivalence tests. The BCS recommends a class of immediate-release (IR) solid oral dosage forms for which bioequivalence may be assessed based on in vitro dissolution tests. Thus all poorly water-soluble drugs are classed as BCS II or IV.
In contrast, poorly soluble drugs present big challenges for the formulation scientist. Compounds with solubilities below O.lmg/ml face significant obstacles, and often even those falling below lOmg/ml present formulation difficulties related to solubilisation. Those compounds with poor water solubility that do get through to the market are frequently prone to suboptimal performance owing to low levels of absorption, and the effects of food intake when delivered orally. One answer is to give a higher dose to treat the patient's condition effectively, but this almost inevitably invites increased toxic side effects and introduces the need for co-therapies to manage idiopathic conditions. There is always a risk for the patient in that the 'cure' might prove worse than the disease.
Poorly soluble marked drugs are clearly good candidates for reformulation using the emerging range of different technologies available to target these issues. A recent BCS classification of the 130 orally administered drugs on the WHO model list of essential medicines found that, of the 61 that could be classified
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NanoNizer
with certainty, about one-quarter were poorly soluble (10[17%] class II and six [10%]class IV).
Conventional approaches to enhancing the solubility enhancement of hydrophobic drugs include:
• Synthesis of molecular species such as salts to facilitate dissolution.
• Drug particle size reduction by physical grinding and milling.
• Amorphous crystal formation for production of solid/resin dispersions: typically melt extrusion technology, in which supra-melt temperatures are used to produce a more soluble amorphous dispersion of chemical drug molecules in a polymer diluent such as polyethylene glycol (PEG).
• Use of surfactants/excipients, e.g. in self-emulsi-fying/micro-emulsifying systems: anhydrous lipid-based formulations containing drug dissolved in oil/s, together with surfactants and co-solvents; generally administered in soft gel capsules for spontaneous emulsion on contact with GI fluids.
• Conjugation/derivation (surface chemistry) of delivery system.
Furthermore, permeability of micro- and nano-sized drug particles is enhanced using a combination of :
• Enteric coating/muco-adhesive.
• Excipient/surfactants.
• Liposome/polymer delivery vehicles.
Nanotechnology-based approaches to the enhancement of drug solubility are
summarized.
Let us do simple exercise of taking a sphere and dividing it in a way given
below. Initial sphere of diameter'd' and radius V is divided into r/2 in the first
stage and r/4 (r/2 is again divided into £). When such divisions are done the
increase in the surface area can be calculated as follows. Please remember
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calculations are done for only understanding the increase in surface area. Actually particles are not absolutely spherical in nature and does not get divided
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in \.



NanoNizer
An above-mentioned example shows us the increase in surface area and numbers of particles after each division. Let us do same theoretical calculation
as we reduce the size from micrometer to nanometer scale.


Diameter = 1 micrometer
Radius = | micrometer
Volume = 4/3 p(l/2)3 microm3
Surface area = 4p (1/2)2 microm2
How many spheres of diameter 1/1000 micrometer (1/2000 micrometer radius)
can be made.
4/3 pCl/2)3 microm3 - n 4/3p (1/2000)3
Therefore, n = 2000 x 2000 x 2000
= 1,000,000,000 particles of nanometer size
8
Surface area of micrometer particle = 4p (1/2)2
Surface area of total nanoparticles generated from 1 microparticle =
1.000.000.000x471 x (1/2000)2
The surface area theoretically increases by 1000 folds.
You can clearly see increase in surface area gives better solubility of drug, which is shown in the following example.
The rate of dissolution (dM/dt)---
dM = DS(Cs - Cb)
dt h
Where:
M = amount of drug (material) dissolved (usually mg or mmol)
T = time (seconds)
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D = diffusion coefficient of the drug (cm2/s)
S - surface area (cm2)
11 = thickness of the liquid film
Cs & Cb = concentrations of the drug at the surface of the particle (surface = Cs)
and the bulk medium (bulk medium = Cb)
e.g. calculate the dissolution rate of a hydrophobic drug having the following
physicochemical characteristics:

.Surface area = 2.5 x 103 cm
Saturated solubility = 0.35 mg/mL (at room temperature)
Diffusion coefficient = 1.75 x 10-7 cm2/s
Thickness of diffusion layer = 1.25 um
[Note: need to convert to cm, so 1 um = 1 x 10-4 cm and 1.25 x 10~4 cm] Concentration of drug in bulk = 2.1 x 10~4 mg/mL

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NOTE!!!! The concentration in bulk solution is generally much lower than the saturated solubility. See the example above, (0.35 mg/mL - 0.00021 mg/mL), and the Ci, term can sometimes be ignored.
Problem: What would the rate of dissolution if the surface area was increased to 4.3 x 10^ cm2?
Answer: 4.3 x 10~4 cm2 is a 17.2-fold increase over the prior surface area (2.5 x 103 cm2). Therefore, multiply the rate 1.22 mg/sec x 17.2 = 20.98 mg/sec (Approx). Or you can recalculate the rate by substituting all the valves into the equation.
This clearly indicates dissolution increases as particles size goes down.
One of the current challenges in pharmaceutical product development is dealing with low solubility and/or low permeability compound, i.e., class II, III, and IV active pharmaceutical ingredients (API).
Descriptive Solubilities :

Description Approximate weight of solvent (g necessary dissolvelg of solute Solubility (% w/v)
Very soluble < 1 10-50
Freely soluble 1 - 10 3.3- 10
Soluble 10-30 1 -3.3
Sparingly soluble 30- 100 0.1 - 1
Slightly soluble 100 - 1000 0.01 -0.1
Very slightly soluble 1000- 10000 0.01 -0.1
Practically insoluble > 10000 < 0.01
A common strategy here is to go to smaller particle sizes, thereby increasing the specific surface area (SSA) and solubility of the product. For the manufacturing of very small particles with a nano or submicron size either a bottom up or a top
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down approach can be applied. Solid dispersions (e.g. melt extrusion or spray drying) are typically manufactured according to a bottom up approach (e.g. spray freezing), or a top down approach (e.g. milling)
Nanoparticles are produced by following method :
1. Colloidal process
2. Liquid-phase synthesis
3. Gas-phase synthesis
4. Vapor-phase synthesis
5. Sono-fragmentaion
Out of the above mention processes we will talk in detail about Sono-fragmentaion.
The use of ultrasound in chemistry is called "Sonochemistry". Offers the synthetic chemist a method of chemical activation which has a broad application and uses equipment which is relatively inexpensive. The driving force for sonochemistry is cavitations and so a general requirement is that at least one of the phases of the reaction mixture should be a liquid. Fundamental aspects ultrasound is defined as sound of a frequency beyond that to which the human ear can respond. The normal range of hearing is between 16 Hz and about 18 kHz and ultrasound is generally considered to lie between 20 kHz to beyond 100 MHz.
Human Hearing 16 Hz - 18 kHz
Conventional power ultrasound 20kHz - 40 kHz
Sonochemistry 20kHz - 2MHz
Diagnostic ultrasound 5MHz - 10MHz
Sonochemistry uses frequencies between 20 and 40 kHz because this range is employed in common laboratory equipments. In this frequencies acoustic cavitation can be generated well above this frequencies. High frequency
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ultrasound above 5 MHz does not produce cavitation; hence it is used for medical imaging.
Ultrasound behaves in a similar manner to audible sound, it has much shorter wavelength. Ultrasonic vibration travel in the form of a wave, similar to the way like travels. However light wave does not require any medium but ultrasonic wave requires elastic medium for propagation.
■ 1 cycle/second = 1Hz
■ 1000 cycles/second = 1 KHz
■ 1,000,000 cycles/second = 1 MHz Ultrasound is propagated via a series of compression and rarefaction waves induced in the molecules of the medium through which it passes. At sufficiently high power the rarefaction cycle may exceed the attractive forces of the molecules of the liquid and cavitation bubbles will form, these bubbles will grow over a few cycles taking in some vapour or gas from the medium (rectified diffusion) to an equilibrium size which matches the frequency of bubble resonance to that of the sound frequency applied. The acoustic field experienced by the bubble is not stable because of the interference of other bubbles forming and resonating around it. As a result some bubbles suffer sudden expansion to an unstable size and collapse violently. It is the fate of these cavities when they collapse which generates the energy for chemical and mechanical effects (Fig.3). There are several theories, which have been advanced to explain the energy release involved with cavitation of which the most understandable in a qualitative sense is the 'hot spot' approach. Each cavitation bubble acts as a localised micro-reactor, which in aqueous systems generates temperatures of several thousand degrees and pressures in excess of one thousand atmospheres.
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In addition to the generation of extreme conditions within the bubble there are also major mechanical effects produced as a result of its rapid collapse. These are also of significance in synthesis and include very rapid degassing of the cavitating liquid (in the rarefaction cycle the newly formed bubbles will fill with gas and be expelled from the liquid) and rapid crystallisation (brought about through seed crystal generation on implosion).

Fig. 2 Sound propagation in liquid showing cavitation bubble formation and collapse
The Gold, Co, Fe, Pg, Ni, Au/Pd, Fe/Co and homogeneous liquids were particles sizes can be reduced to nanoparticle by use of Sonochemistry. The first step as soon as we introduced ultrasound at sonic chemistry frequency the bubbles gets generated and explodes near the particle as shown in the figure (Fig. 3)
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Fig. 3 Sono-Fragmentation (Size Reduction)
The bubbles collapse clue to implosion because of this particle fragments and the fragmented particles gets separated (Fig 4).

Fig 4 Bubble Implosion
The feed sample consist of distilled water (Fig 5) and micron sized feed particles on application of 20 kHz, 1 Kvv transducer (Fig 6) for some time and then it is transferred to the tank having 58 kHz, 500 W transducer to produces Sub-micron/Nono Sized particles. (Fig 7)
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DESCRIPTION :
The first requirement for sonochemistry is a source of ultrasound and whatever type of commercial instrument is used the energy will be generated via an ultrasonic transducer - a device by which mechanical or electrical energy can be converted to sound energy. There are three main types of ultrasonic transducer used in Sonochemistry:
1. Liquid-driven (effectively liquid whistles)
2. Magnetostrictive (based on the reduction in size of certain metals, e.g. nickel, when placed in a magnetic field)
3. Piezoelectric
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Most of the current equipment used for Sonochemistry utilizes transducers constructed of piezoelectric ceramics. These are brittle and so it is normal practise to clamp them between metal blocks for protection. The overall structure is known as a piezoelectric 'sandwich'. Usually two ceramic elements are combined so that their overall mechanical motion is additive (Fig. 8). Piezoelectric transducers are very efficient and, depending on their dimensions, can be made to operate over the whole ultrasonic range.

rig. o Construction of a piezoelectric sandwich transducer
The two most common sources of ultrasound for laboratory sonochemistry are the ultrasonic cleaning bath and the ultrasonic horn or probe system. These generally operate at frequencies of around 40 and 20 kHz, respectively.
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Patent Applied for :
1. One lab model of 5 litres
2. Manufacturing model of 50 litres General Setup :

1. Suspended probes
2. VSL Internal surface is electro polished.
3. The probe can be fed into the VSL from top or through dip pipe.
•1. Magnetic stirren at the bottom to keep the probe in continuous motion and proved with valuable required necessary drive.
This is helpful to keep the slowely in motion without settling this gives better size distribution
- As the temperature is increased effect of ultrasonic is more prayed effect of ultrasonic is kept at 60° - 80° according to product.
- Temperature increase by electrical blanket or steam jacket controlled
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- Different probes will be fixed in the boundary to given frequency/bubbles of all ranges by which nano particles of required bandwidth can be made.
PLC Logic
1. CHK for temperature increase feedback from PT-100
2. Temperature compared with set value
3. Probe to set time and frequency
4. Set the rpm of mag stirren (direction) clockwise or anti clockwise
5. Setting the Hz of external transducer and time can be adjusted.
6. Process starts and end of each process alarm is generated
7. Program can be done for changing/sweeping at regular internals
8. CIP/SIP cycle can be program
9. Different process can be stored in saftyware and when processing it can be recalled.

NAME DATE 8B SIGNATURE
Ms. Anju Gupta Kaudanya
Mr. Natrajan S. Iyer
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