FORM 2
THE PATENT ACT 1970
(39 of 1970)
&
The Patents Rules, 2003
PROVISIONAL SPECIFICATION
(See section 10 and rule l3)
1. TITLE OF THE INVENTION:
"Smart Drug Delivery System"
2. APPLICANT (S):
(a) NAME: FDC Limited
(b)NATIONALITY: Indian company incorporated under the Companies Act 1956
(c) ADDRESS: 142-48, S.V. Road, Jogeshwari (W), Mumbai - 400 102, Maharashtra, India.
3. PREAMBLE TO THE DESCRIPTION
The following specification describes the invention.

Field of invention
The invention discloses a smart drug delivery system, which releases the drug into a cavity/affected area that contains water molecules/body fluids. It obviates the need for an injection into such a cavity /affected area. The difference in pH of the substrate that deliver the medicine and the cavity surrounding the drug allows the drug to be taken up by the water molecules in the cavity/affected area quickly and efficiently.
Background of the invention
The terms "cavity as well as drug" referred by http:/'/medical-dictionary. thefreedictionary.com/ is defined as a hollow place or space, or a potential space and a (i) a substance used in the diagnosis, treatment, or prevention of a disease or as a component of a medication or (ii) such a substance as recognized or defined by the U.S. Food, Drug, and Cosmetic Act, respectively.
Drug delivery systems are essential components of drugs release at a specific targeted site. Several drug delivery technologies have emerged including tablets capsules, liposomes, microparticles, nanoparticles, and polymers. These in turn involve various routes of administration such as oral, intramuscular, intravenous, rectal, transdermal, transmucosal etc. Drugs are delivered by various drug delivery systems as mentioned above. The commonest example is a tablet, which, when swallowed, releases a drug which has been compressed to form it. Such a tablet may be coated so that it releases a drug only at a certain pH by dissolving the coating or due to matrix mechanism. An injection consists of a syringe and a needle, and the drug is delivered by penetrating a surface by needle, which is sharp, and then pressing the plunger of a syringe. There are sophisticated drug delivery systems, where drug may be delivered by tubes, with sheaths, by devices which can open electronically when triggered from a remote site, and pumps which can deliver precise amounts of drug by use of sensors. There are plugs with different appropriate shapes and handles, which, can block a passage, and therefore increase the amount of fluid that would have otherwise flown out of the passage. Such plugs are commonly used in dry eye disorder, to block lacrimal secretions from wasting


into the nasal cavity. Spheres of polymers have been patented. These spheres are hollowed, penetrated with the drug, and released into a space where the drug needs to be delivered. Sprays as drug delivery systems are well known. There are few prior arts suggesting various routs, devices and mechanisms well known in drug delivery system.
US2007129793 discloses an expandable biodegradable polymeric stent fabricated with biodegradable polymer fibers (Poly-L-lactic acid, PLLA) in a coil shape that is constructed with both central and external or internal peripheral lobes. It is delivered and expanded using a conventional angioplasty balloon system. The disclosed stent can serve as a temporary scaffold for coronary vessels after PTCA or for peripheral endovascular stenting, or it can provide mechanical palliation for strictures of ductile organs (trachea, esophagus, bile and pancreatic ducts, ureter etc.). The disclosed stent also serves as a unique device for specific local drug delivery. Therapeutic agents (chemical compounds, protein enzyme and DNA sequences) and cells can be loaded into the stent and gradually released to target tissues. Local radiation therapy can also be delivered by a specially adapted stent.
EP1790362 relates to an implantable medical drug delivery system like stent, stent-graft or anastomotic device comprising a) an implantable structure; b) a combination of anti-restenotic agent and phosphoinositide (PI) 3-kinase inhibitor directly affixed to the medical device in a single multiple polymeric layer architecture; and c) an additional polymeric coating for controling the elution rate of the ant-restenotic agent and PI 3-kinase inhibitor. These therapeutic agents can reduce a biological organism's reaction to the introduction of the medical device to the organism.
CA2554394 relates to medical devices, and in particular implantable medical devices which may be coated to minimize or substantially eliminate a biological organism's reaction to the introduction of the medical device to the organism. The medical devices may be coated with any number of biocompatible materials. Therapeutic drugs, agents or compounds may be mixed with the biocompatible materials and affixed to at least a portion of the medical device. These therapeutic drugs, agents or compounds may also further reduce a biological organism's reaction to the introduction of the medical device


to the organism. In addition, these therapeutic drugs, agents and/or compounds may be utilized to promote healing, including the formation of blood clots. The drugs, agents, and/or compounds may also be utilized to treat specific diseases, including vulnerable plaque. Therapeutic agents may also be delivered to the region of a disease site. In regional delivery, liquid formulations may be desirable to increase the efficacy and deliverability of the particular drug. Also, the devices may be modified to promote endothelialization. Various materials and coating methodologies may be utilized to maintain the drugs, agents or compounds on the medical device until delivered and positioned. In addition, the devices utilized to deliver the implantable medical devices may be modified to reduc e the potential for damaging the implantable medical device during deployment. Medical devices include stents, grafts, anastomotic devices, perivascul ar wraps, sutures and staples. In addition, various polymer combinations may be utilized to control the elution rates of the therapeutic drugs, agents and/or compounds from the implantable medical devices.
WO2004045578 discloses a) a medical device, e.g. a coated stent or stent-graft, adapted for local application or administration in hollow tubes; and, in conjunction therewith, b) a therapeutic dosage of an anti-inflammatory ascomycin derivative, such as pimecrolimus, e.g. affixed to the medical device, and use thereof in the preparation of a medicament for the prevention and treatment of inflammatory complications following vascular injury, and method of treatment therewith.
US2004208985 to an implant having a coating comprising a polymer matrix is swollen in a pharmaceutical solution whereby pharmaceutically active compound is imbibed into the polymer matrix. When the product is implanted, release of the pharmaceutically active compound from the coating takes place. The polymer is preferably formed from ethylenically unsaturated monomers including a zwitterionic monomer, most preferably 2-methacryloyloxyethyl-2'-trimethylammoniumethylphosphate inner salt. The monomers from which the polymer is formed may further include surface binding monomers, such as hydrophobic group containing monomers, and crosslinkable monomers, the content of which may be used to control the swellability. Preferably the implant is a stent and the coating of polymer on the exterior wall surface is thicker than the coating of polymer on


the interior surface. Release of the drug may be controlled by selection of comonomers. The implant is suitably a stent for use in the cardiovascular system.
WO03024455 relates to an intraluminal medical device comprising a stent having a coating applied to at least part of an interior surface, an exterior surface, or both. The coating comprises a sustained release formulation of a combination of pharmaceutical compounds dispersed within a biologically tolerated polymer composition. The choice of the combination of pharmaceutical compounds are intended to reduce neointimal hyperplasia restenosis.
US2003004564 reveals a stent based drug delivery system. A biological agent of interest is entrapped within a matrix, which is loaded into channels on the surface of a stent. The matrix allows for release, usually sustained release, of the entrapped agent. The stent and matrix is sheathed with a covalently bound gel. In one embodiment of the invention, the stent is used to deliver therapeutic agents to a patient, providing the advantage of efficient delivery and sustained release of an agent at a localized site. In another embodiment of the invention, the drug delivery system is used for testing and comparison of candidate drugs in an in vivo setting.
WO0032267 relates to a method of site-specifically delivering a therapeutic agent to a target location within a body cavity, vasculature or tissue. The method comprises the steps of providing a medical device having a substantially saturated solution of therapeutic agent associated therewith; introducing the medical device into the body cavity, vasculature or tissue; releasing a volume of the solution of therapeutic agent from the medical device at the target location at a pressure of from about 0 to about 5 atmospheres for a time of up to about 5 minutes; and withdrawing the medical device from the body cavity, vasculature or tissue. In another aspect, the present invention includes a system for delivering a therapeutic agent to a body cavity, vasculature or tissue, comprising a medical device having a substantially saturated solution of the therapeutic agent associated therewith.


In US2006283465 a smart drug delivery system is disclosed. The system includes a sensor component, an analytical component coupled to the sensor component and a drug delivery component coupled to the analytical component for delivering a drug to a host.
US5817332 discloses a controlled release transdermal system for the delivery of at least one therapeutic agent comprises: a reservoir comprising (a) the therapeutic agent in ionized form and (b) a pH adjusting agent which upon uptake of water is converted to a buffer solution and (c) a cyclized polysaccharide selected from a group consisting of cyclodextrin, cyclodextrin derivative and cyclodextrin polymer, the cyclized polysaccharide being capable of improving the solubility of the therapeutic agent in the buffer solution by forming an inclusion complex with the therapeutic agent; and a reservoir wall comprising a polymer being substantially impermeable to the ionized form or to the inclusion complex form of the therapeutic agent but permeable to water and to the unionized form of the therapeutic agent. The system allows the release of a therapeutic agent which may be a weak acid or base in a manner which shows less variation between patients than previous systems.
US5229131 relates to a drug delivery system for administering a drug in controlled pulse doses to an aqueous environment in the body of a living being has one or more, and preferably less than ten, individual drug-containing subunits in a unitary drug depot, such as a tablet or capsule. The individual subunits are designed to dissolve at different sites and/or times in the gastrointestinal tract to release pulse doses of drug into the portal system in an analogous manner to the rate of release from an immediate release dosage form administered according to an appropriate dosing schedule. The dissolution time of the individual subunits can be controlled by several methods including the provision of pH-sensitive enteric coatings and permeability-controlled coatings. The drug delivery system has significant advantages for the oral administration of first-pass metabolized drugs which exhibit a non-linear relationship between input rate of the drug into the portal system and bioavailability.
Despite the above-described approaches there has remained a need for new and improved methods, which could circumvent the problems associated with each of them.


Release of a drug without injection and which does not cause pain or bruising is the need of the hour.
Fueled by the promise of needle-free mechanisms for vaccine distribution and other pharmaceutical uses, we have designed a smart drug delivery system comprising a thin rod which when inserted in the required site of action (cavity /affected site) will facilitate the drug release due to the aqueous environment present in the site of action and pH differential existing between the drug formulation and the internal environment in the site of action. The invention has a promising advantage of a painless and bruises free drug delivery in a quick and efficient manner.
Objective of the Invention
The main objective of the invention is to obtain a drug delivery system comprising a thin rod which when inserted in the required site of action (cavity /affected site) will facilitate the drug release due to the aqueous environment present in the site of action and pH differential existing between the drug formulation and the internal environment in the site of action.
Another objective of the invention is to make available a painless and bruise free drug delivery system in a quick and efficient manner.
Summary of the Invention
According to the present invention there is disclosed a smart drug delivery system comprising of a thin rod having a coarse or uneven surface which is coated with the drug composition. The thin rod serves as a delivery system such that when inserted into the cavity /affected area the drug is released as a result of the environment of the cavity / affected area secretions and pH differential.
Detailed Description of the Invention
According to the present invention there is disclosed a smart drug delivery system comprising of a thin rod having a coarse or uneven surface which is coated with the drug composition. The thin rod serves as a delivery system such that when inserted into the


cavity /affected area the drug is released as a result of the environment of the cavity / affected area secretions and pH differential.
The system disclosed here comprises of a micro roughened small rod 0.01 mm to 2 cms in length, the rod being made of metal, glass or plastic, may be made of self dissolving type acrylic material or vicryl, and may or may not be hollow. The surface of the rod is made rough so that there are micro depressions produced on the surface.
The said rod is coated with a drug or chemical which has a different pH compared to the normal pH of the fluid in the cavity to be treated.
The said rod is inserted into the cavity by a forceps or with fingers, or any other appropriate instrument known by those expert in the art either under microscopic supervision or with out it. The rod is removed after five to 60 minutes.
In another embodiment of the invention, a polymer is, it is soft when it comes in contact
with liquids, because of its property of imbibing water molecules. For example, poly
methyl methacrylate which is used to prepare contact lenses may be used.
The said polymer is hydrated with a solution of a drug.
It is allowed to dry, so that it retains a measurable quantity of the drug.
It is shaped in a spindle shaped narrow needle like device.
Being hard, it can be introduced into a space which has a narrow opening.
If the space already contains water, the polymer will imbibe the water, and during the
process of hydration, releases the drug by process of the drug dissolving into the
surrounding water due to the different Ph of the drug and the surrounding medium.
The device may be withdrawn from the cavity in a softened state after certain time, so
that measurable amounts of drug are released into the cavity.
In third embodiment, a self dissolving acrylic material is used. The rod of appropriate size is extruded. The rod is coated with the drug to be introduced into the cavity. Such a rod, once introduced, may not be withdrawn from the cavity.


Although the disclosure herein has been drawn to one or more exemplary systems and methods for drug delivery systems, various modifications thereof will be apparent to those skilled in the art without departing from the spirit and scope of the invention as outlined in the claims appended hereto.
The drug delivery is called "smart" because the pH of the dry drug which is coated on the
surface of the substrate is adjusted to be different from the pH of the contents of the
cavity /affected area.
Example:
Five patients who had chalazion or a meibomian cyst were selected. Betadine ( providone
iodine 10% solution was quoted on a nylon rod 150 microns in diameter and 1 cm in
length.. The nylon rod was roughened by polishing it with 5 micron polishing paper. The
device was sterilized.
Under slit lamp, the duct of the blocked gland in the eyelid margin, was identified. The
nylon rod was held in a plain forceps. The rod was gently inserted into the cyst through
the duct. The opening of the duct allowed insertion of the nylon rod on slight pressure on
the mouth with the tip of the nylon rod.
The rod was kept in the cyst for 30 seconds. The rod was removed and the patient was
asked to go home.
Follow up examination after three days revealed that the cyst had disappeared.
On questioning, the patients reported that the cyst had started reducing in size in one hour
after treatment and was almost gone in first six hours.
The ph of the secretions inside a chalazion is alkaline, where as the ph of povidone iodine
is about 4 to 5.