Despite of progression and  inventions in  new  administration of  medicines, regulation of constant livery  tube  remedial  indicator of  medicines is still a big concern. The  implicit  detriment of using periodic oral or IV  medicine administration  comprises of elevated  attention of  drug( peaks)  which contribute to adverse  goods or  shy   attention of  drug( troughs) which can lead to  failure of  remedy. The old way to overcome the issue of the  variable  attention of  drug includes constant  intravenous infusion rate dependent on  drug  pharmacokinetic profile. In order to minimise these unwanted   issues, there's a need of  ultramodern approach in achieving  optimised rate of  medicine discharge.¹

Implantable  medicine delivery systems have implicit superiority  in indigenous administration with better pharmacologic   issues at  minimal boluses. Due to which, they lower  possible  venom thereby  perfecting liability for   drug adherence. This kind of administration enables  accessible delivering of  specifics that are  naturally   inharmonious to be taken by oral way, escapes presystemic  elimination as well as enzymatic destruction in  tummy,  therefore,  remarkably enhancing bioavailability.²

  Implantable  bias have capability to minimise the need of  frequent  medicine input as well as authorize  drug needs  with approachable way. At present, these  bias are  generally employed in  numerous  remedial areas  similar as  contraception, chemotherapy, dentistry etc. The expanding   product and  request bareness of implants are apparent  of immense growth in this sector( figure 1).³

Classification Of Implantable Polymeric Drug Delivery System:- 

Passive Polymeric Implant: -

They're simple, singular and  invariant  bias,  substantially  contains simple  medicine loaded in biocompatible matrix. They do  not have any mobile part or  fashion and depend on  unresistant   prolixity for release of  medicine  cargo. Passive  bias can be  subcategorised asnon-biodegradable and biodegradable.⁵

Non -Biodegradable Polemeric implant system-

The most common  marketable forms are matrix- controlled or  polymeric system and membrane enclosed  force.  Polymers like polyurethanes, polyacrylates, silicones or  heteropolymers like polyethylene vinyl acetate( PEVA) are  extensively used. In the matrix- controlled organisation, a  cure is slightly distributed across the base. Gradational   dissipation of bedded cure gives sustained release  from delivery system. The dynamics of  expatriation and release  rate of cure is inconstant and relies on  quantum of  substance in the base. A  force type system contains  compact  medicine  defended bynon-biodegradable  pervious subcaste  whose periphery as well as penetrability  rates  impact  release kinetics.⁶,⁷ These  bias are durable during their  lifetime but need to be  replaced after the  medicine  cargo is exhausted to avoid any negative  impacts like infection, towel  detriment and  ornamental  defects.  These types of systems are extensively  employed in contraception.  Norplant is one of the  foremost, extensively advanced  force  implant.⁸

Biodegradable polymeric implant system-

These systems offer advantages over nonbio-degradable bones and hence are more popular. Polymeric substances  similar as  polycaprolactone( PCL), polylactic acid( PLA), or polylactic- coglycolic acid( PLGA) are  generally used for  expression. The  most desirable property is that it uses inert polymers that  resolve  into small pieces and  farther  immersion and elimination takes  place inside body  therefore do n't bear any gash to  prize  out the device thereby  perfecting patient acceptance and  compliance. But these systems bear the degeneration of  base of polymer for release of cure which is dependent  on  colorful factors like any change in body pH or temperature  and  thus extremely variable in  individualities.( Table 1) 7 9, Their  expression is  likewise intricate than that of nonbiodegradable bones multitudinous factors are taken in view for  their  expression. Decomposition profile of polymeric base  inside the body should be stable for keeping  nonstop  medicine  discharge. To  gain more  invariant and constant  medicine release,  a flattened arbor- suchlike design without edge  corrosion offers zeroorder profile is preferred. Two types ofbio-degradable  bias are present. They are   force system and monolithic types( figure 2). Reservoir  system is  analogous in construction and medium of  medicine  release as described innon-biodegradable systems. still,  these bio disintegrated systems contain  external membranous  subcaste of polymer which disintegrates at moderate pace than  that of  dissipation across membrane. As a result, membrane  stays  innocent releasing behind the cure entirely.  This  complete membrane gets deteriorated inside the body which  is eventually excreted out. The other kind is monolithic where  cure is  circulated in a polymeric substance and  shows gradational  corrosion with a steady release inside the body

Active or dynamic polymeric implants-

This kind of Implantables use definite propulsion in regulating  discharge of  drug across the aid. therefore it offer advanced  standard in  medicine discharging. They use some  feathers of energy  dependent  styles for positive impulse to regulate discharge.  The power origin can range different from bibulous pressure grade to electromechanical forces. 

There are primarily four ways of  drug discharge  through the implant  bias – polymer decomposition,  optimised expansion, osmosis and simple  prolixity. Implants  amusement by optimised expansion, water  immersion in device  controls  medicine discharge which is generally  shy over  normal  dissipation and  therefore contributes to a steady proportion  of release. The decomposition of expanded matrix allows   prolixity of  medicine  substantially and  perfecting the disintegrating  capacity of the matrix significantly enhances the  effectiveness of  the implant. Osmosis  intermediated release and free  prolixity  ways of   medicine release are applicable for delivering  medicines linearly  where the  volume of delivered  medicine relies proportionally to  square root of discharge duration. Osmosis is simple passage  of waterless  motes from an area of low  attention to a  lesser  attention via a semipermeable membrane which  creates a pressure  grade. prolixity  workshop by process in  which solute moves voluntary in all areas to  souse chemical  composition. The mobile substances are called diffusants and  a membrane through which diffusants  peregrination is known as  diffusional  hedge. The  attention  grade is the  impulsion for the release of cure from system. However the discharge profile of  medicines depends upon  contents of delivery system which in turn relies on factors like  imbibition, bibulous pressure, and  unresistant  prolixity, and   motes stability,  prolixity measure in polymer,  medicine  content, and decomposition rate of polymer in vivo( figure 4)¹⁰

1.Hot melt extrusion:

To create a solution mixture, the medication is prepared to dissolve in the proper solvent. After that, the polymer is gradually added and left to soak for 15 to 20 minutes. The product that is swollen is   mixed well until it takes the consistency of dough, then it is transferred into an ejection cylinder to create an elongated rod-like structure using a showerhead. After being allowed to cure overnight at room temperature, the product is cut to the necessary size. The final product is obtained by dehydrating it at 41 degrees Celsius.

Effective output is possible when extrusion is done concurrently (figure 5A). Thermoplastic polymeric materials, such as polyamide aliphatic polyesters like PLA, PGA, and PLGA, are necessary. Non solvents are necessary for it. However, this may result in degeneration of heat sensitive medications. Zoladex® and Implanon® like devices are produced by this technique.

2.Compaction:

The medication and polymer are lyophilised to create a cake after being dispersed to create a suspension.  Carver   exposes           it          to more            compaction     in                     order       to create          an        implant.   hydraulic device having a metric tonne of force. It has the benefit of not requiring heating or solvents, making it perfect for creating implants with thermolabile materials, particularly proteinaceous content. Because of their rapid release profile, these implantables must be optimised by stacking. Furthermore, the uneven look of the manufactured implants and their many cavities may be further factors in their erratic discharge.^{11 10}

Moulding:-

After being heated and put into a mould, the polymeric material is allowed to solidify. The relative molecular mass of the polymers decreases. because of the intense heat that was used. This technique amplifies molecular mass and dispersability, which can be reduced in a variety of ways. Therefore, in contrast to factory-made mistreatment injection moulding, these implantable dissolved earlier (figure 5B). 12

3D Printing :-

It is a low-cost, reliable, and adaptable process that may prove helpful in the future, particularly for the rapid production of standard units for research. But it's not utilised in large quantities, but when the FDA authorised one such substance in 2015, its applicability advanced. This method is mostly utilised to create implants and prostheses for orthopaedics and dentistry.¹³

       
           
       
 Fig.5 Method of Manufacture of implant-(A)Hot melt extrusion¹⁴  (B) moulding method ¹⁵

In order to properly manage drug distribution, it might be challenging to exactly modify the geometry of drug-loaded system susing standard drug delivery techniques. Microfabrication technology for MEMS, which uses the same processing techniques used to create microprocessors for computer microchips has been used for drug delivery systems¹⁶ as one of the most advanced ways to get around these restrictions. Device circuitry can be constructed and programmed to open seals on individual reservoirs and release medicament, and reservoirs on silicon chips can be filled with medication and sealed to safeguard and confine it thanks to MEMS technology.

Polymers used for implantable polymeric drug delivery devices:- 

Biodegradable and non-biodegradable polymers are the two types of polymers used to make implantable drug delivery systems . The requirement for surgical removal or the buildup of polymer in the body following use are two significant drawbacks of non-biodegradable implants ¹⁷. A research by Odom et al. ¹⁸ found that the surgical removal of non-biodegradable implants is frequently more traumatic than their insertion ¹⁹. The study looked into the removal of the Nexplanon® non-biodegradable contraceptive implant and came to the conclusion that a multidisciplinary care team and a peripheral nerve surgeon's experience might help remove these implants successfull¹⁸. As an alternative, biodegradable polymers have the important benefit of not requiring surgical removal after use. They are made to break down organically into goods that.  The application of polymers in medication delivery and tissue engineering has been extensively studied. Polymers, both synthetic and natural, have been studied ²⁰. In contrast to natural polymers, synthetic polymers are often biologically inert, have predictable chemical and physical characteristics, and do not exhibit batch-to-batch variability²¹. When creating a medication delivery system, the material's biodegradability and biocompatibility are crucial²². All materials must be completely biocompatible, and any modifications to the properties of the polymer that arise during degradation must be thoroughly examined and described.  Any biodegradable polymer should ideally be highly replicable, quickly metabolized and eliminated by physiological processes, degradable to non-toxic compounds, and immune to inflammation in vivo.²² There isn't a single perfect polymer; instead, the mechanism and intended rate of release will determine which polymer is best. A combination of polymers may be needed to get the desired properties. 

Biodegradable Polymer:- 

Thermoplastic Aliphatic Polyesters:- 

Poly (lactic acid) (PLA), poly(glycolic acid) (PGA), and poly(lactic-co-glycolic acid) (PLGA) (Figure 3) are examples of thermoplastic aliphatic poly(esters) that have been extensively studied because of their advantageous properties, which include mechanical strength, biodegradability, and biocompatibility²³. These polymers have been effectively employed in solid and microparticle parenteral implants as well as drug delivery systems based on nanoparticles . These polymers can degrade over a period of one month to more than six months ²⁴. Figure 4 depicts the PLA, PGA, and PLGA degradation mechanisms. Hydrophilicity, glass transition temperature, molecular weight, and environmental parameters including pH and temperature all have an impact on degradation rate ²⁴.

The polymerization of lactic acid derived from natural feedstock (such as corn starch, rice, or potatoes, among others) yields poly(lactic acid) (PLA), a biodegradable and bioresorbable polymer with promising qualities for medical applications ²⁵. The mechanical properties of PLA are comparable to those of other synthetic polymers, including polypropylene, although PLA is more abundant, less expensive, and biodegradable . PLA is more likely to biodegrade than other biomedical polymers because it is semipermeable to both oxygen and water . Being a generally recognized as safe (GRAS) material, PLA has been approved by the US Food and Drug Administration (FDA) for use in direct contact with biological fluids . Because PLA is so thermally processable, it can be processed in a wide range of ways ²⁵.  PLA is a white powder at ambient temperature with melting and glass transition temperatures of approximately 175 and 55 °C, respectively. The characteristics of PLA with a high molecular weight are comparable to those of polystyrene. Both kinds of monomers can be used to create PLA since lactic acid has two stereoisomers (d and l) . Because of its regular chain structure, PLA made from d-lactic acid, or PDLA, is a crystalline substance. The PLA produced using l-lactic acid, or PLLA, will, nevertheless, have a hemicrystalline structure . Furthermore, an amorphous polymer can be produced by preparing PLA with a combination of both (PDLLA) . A broad range of organic solvents, including acetonitrile, tetrahydrofuran, dioxane, benzene, and chloroform, can dissolve all of these polymers²⁶.

Poly (gycolic acid):

A polyester known as poly(glycolic acid) (PGA) is created by polymerizing glycolic acid units. In terms of biomedical applications, it was among the earliest biodegradable polymers. Only one extremely crystalline version of the polymer PGA is known to exist . It has outstanding mechanical qualities (better than PLA) and a melting point above 200 °C . Dexon® and other biodegradable sutures derived from PGA have been effectively employed. PGA is insoluble in a wide range of common solvents and shows a rapid degradation profile. Therefore, this polymer hasn't been employed by itself to deliver drugs. Glycine is produced when PGA is broken down in bulk by the scission of its ester backbone and is eliminated by the citric acid cycle or urine.²⁰

Non -Biodegrable Polymer

Poly (siloxanes) :- 

Organosilicon polymeric compounds made of silicon and oxygen atoms are known as poly(siloxanes) or silicones . The chemical structure of this kind of polymer is depicted in Figure 5. Methyl, vinyl, or phenyl groups are examples of lateral groups . These groups will affect the polymer's characteristics. Because of their special blend of elastomeric, chemically inert, thermal, and biocompatible qualities, poly(siloxanes) have found widespread application in medicine. At room temperature, silicones that are frequently employed in medical equipment are vulcanized. They are made with a catalyst (a chemical based on platinum) and a two-component poly(dimethylsiloxanes) (PDMS) . An addition hydrosilation process creates the final substance ²⁰.

       
           
       
Cellulose: - 

The most prevalent organic substance in the world is cellulose, which is mostly made by plants. The structure of cellulose, a naturally occurring linear polymer (polysaccharide), is made up of lengthy chains of repeating ?-d-glucopyranose units that are covalently joined by acetal functionalities between the equatorial ?OH group of C4 (?-1,4-glycosidic bonds) and the C1 carbon atom ²⁰.

Current Therapeutic Application:-

Implantable drug delivery devices have the potential to be used for a wide variety of clinical applications in areas including, but not limited to: women’s health, oncology, ocular disease, pain management, infectious disease and central nervous system disorders ¹⁷. Examples of implantable drug delivery devices for each of these areas are summarised in Tables 1–4. Women’s health is one area where implantable drug delivery devices have had a large impact, particularly in their use for contraception. In 1990, Norplant became the first implantable contraceptive device to be approved. Implantable long acting contraceptives have been shown to be the among the most effective method of birth control, with women who use these methods experiencing a pregnancy rate of less than 1% year. Examples of implantable medication delivery systems for women's health are displayed in Table 1.  The most popular method of administering chemotherapeutic drugs is systemic distribution. 

Nevertheless, it frequently entails administering the drugs at the highest dose that can be tolerated, which may result in serious adverse effects as cardiomyopathy and neutropenia²⁸. installation of a medication delivery 

 Table 1:- Example of Implantable drug delivery devices use in the area of woman’s health.