Novel Ophthalmic Drug Delivery Approach: An Ophthalmic Inserts

 

Anjali Patel*, Dhara Patel, Nimisha Patel, Jayvadan Patel, Manish Patel, Anita Patel

Department of Pharmaceutics, Nootan Pharmacy College, Visnagar-384315,Gujarat,  India,

*Corresponding Author E-mail: anju27789@gmail.com

ABSTRACT:

Ophthalmic drug delivery system is one of the most interesting and challenging approach facing the Pharmaceutical Scientist. The conventional ophthalmic drug delivery system like solution, suspension. Which shows poor bioavailability and therapeutic response because of rapid precorneal drug loss? Utilization of novel ophthalmic drug delivery system an ophthalmic inserts offers an advantage to prolonged drug residence time and a higher bioavailability with respect to conventional ophthalmic drug delivery system. Ocular inserts are sterile preparations, with a thin, multilayered, drug-impregnated, solid or semisolid consistency devices placed into cul-de-sac or conjunctiva sac. They are usually made up of polymeric vehicle containing drug. The therapeutic efficacy of an ocular drug can be greatly improved by prolonging its contact with the corneal surface. Newer ocular drug delivery systems are being explored to develop extended duration and controlled release strategy.

 

KEYWORDS: Ocular inserts, Swelling index, Solvent casting method, Bio-erosion, Semi synthetic polymer.

INTRODUCTION:

History of ocular inserts

The first solid medication (precursors of the present insoluble inserts) was used in the 19th century, which consisted of squares of dry filter paper, previously impregnated with dry solutions (e.g., atropine sulphate, pilocarpine hydrochloride). Small sections were cut and applied under eyelid. Later, lamellae, the precursors of the present soluble inserts, were developed.¹

Ocular inserts are defined as preparations with a solid or semisolid consistency, whose size and shape are especially designed for ophthalmic application (i.e., rods or shields). These inserts are placed in the lower fornix and, less frequently, in the upper fornix or on the cornea. They are usually composed of a polymeric vehicle containing the drug and are mainly used for topical therapy.² The figure 1 shows the schematic diagram of ocular inserts.

 

Ocular inserts offer several advantages ^{3, 4}

·        Increased ocular residence, hence a prolonged drug activity and a higher bioavailability with respect to standard vehicles;

·        Possibility of releasing drugs at a slow, constant rate;

·        Accurate dosing (contrary to eye drops that can be improperly instilled by the patient and are partially lost after administration, each insert can be made to contain a precise dose which is fully retained at the administration site);

·        Reduction of systemic absorption (which occurs freely with eye drops via the naso-lacrimal duct and nasal mucosa);

·        Better patient compliance, resulting from a reduced frequency of administration and a lower incidence of visual and systemic side-effects;

·        Possibility of targeting internal ocular tissues through non-corneal (conjunctival scleral) routes;

·        Increased shelf life with respect to aqueous solutions;

·        Exclusion of preservatives, thus reducing the risk of sensitivity reactions;

·        Possibility of incorporating various novel chemical/technological approaches.

·        Such as pro-drugs, mucoadhesives, permeation enhancers, microparticulates, salts acting as buffers, etc.

 

Disadvantages of ocular inserts:

The disadvantages of ocular inserts are as follows: ^{3, 4}

a.       A capital disadvantage of ocular inserts resides in their 'solidity', i.e., in the fact that    they are felt by the (often oversensitive) patients as an extraneous body in the eye. This may constitute a formidable physical and psychological barrier to user acceptance and compliance.

b.      Their movement around the eye, in rare instances, the simple removal is made more difficult by unwanted migration of the insert to the upper fornix,

c.     The occasional inadvertent loss during sleep or while rubbing the eyes,

d.      Their interference with vision, and

e.     Difficult placement of the ocular inserts (and removal, for insoluble types).

 

Criteria for successful ocular insert ⁵ :

·      Comfort and noninterference with vision

·      Successful oxygen permeability

·      Biocompatibility and stability

·      Reproducibility of release kinetics

·      Applicability to a variety of drugs

·      Ease of sterility and nontoxicity

·      Ease of handling ( insertion and removal)

· Ease of manufacture and low cost

 

 Mechanism of drug release ⁶:

The mechanism of controlled drug release into the eye is as follows:

A. Diffusion,

B. Osmosis,

C. Bio-erosion.

 

Diffusion:
In the Diffusion mechanism, the drug is released continuously at a controlled rate through the membrane into the tear fluid. If the insert is formed of a solid non-erodible body with pores and dispersed drug. The release of drug can take place via diffusion through the pores. Controlled release can be further regulated by gradual dissolution of solid dispersed drug within this matrix as a result of inward diffusion of aqueous solution. In a soluble device, true dissolution occurs mainly through polymer swelling. In

swelling-controlled devices, the active agent is homogeneously dispersed in a glassy polymer. Since glassy \polymers are essentially drug-impermeable, no diffusion through the dry matrix occurs. When the insert is placed in the eye, water from the tear fluid begins to penetrate the matrix, then swelling and consequently polymer chain relaxation and drug diffusion take place. The dissolution of the matrix, which follows the swelling process, depends on polymer structure: linear amorphous polymers dissolve much faster than cross-linked or partially crystalline polymers. Release from these devices follows in general Fickian 'square root of time' kinetics; in some instances, however, known as case II transport, zero order kinetics has been observed.

 

Osmosis:
In the Osmosis mechanism, ⁷ the insert comprises a transverse impermeable elastic membrane dividing the interior of the insert into a first compartment and a second compartment; the first compartment is bounded by a semi-permeable membrane and the impermeable elastic membrane, and the second compartment is bounded by an impermeable material and the elastic membrane. There is a drug release aperture in the impermeable wall of the insert. The first compartment contains a solute which cannot pass through the semi-permeable membrane and the second compartment provides a reservoir for the drug which again is in liquid or gel form. When the insert is placed in the aqueous environment of the eye, water diffuses into the first compartment and stretches the elastic membrane to expand the first compartment and contract the second compartment so that the drug is forced through the drug release aperture.

 

Bio-erosion:
In the bioerosion mechanism, the configuration of the body of the insert is constituted from a matrix of bioerodible material in which the drug is dispersed. Contact of the insert with tear fluid results in controlled sustained release of the drug by bioerosion of the matrix. The drug may be dispersed uniformly throughout the matrix but it is believed a more controlled release is obtained if the drug is superficially concentrated in the matrix. In truly erodible or E-type devices, the rate of drug release is controlled by a chemical or enzymatic hydrolytic reaction that leads to polymer solubilization, or degradation to smaller, water-soluble molecules. These polymers, as specified by Heller, ⁸ may undergo bulk or surface hydrolysis. Erodible inserts undergoing surface hydrolysis can display zero order release kinetics; provided that the devices maintain a constant surface geometry and that the drug is poorly water-soluble.

 

Figure 1: Schematic diagram of ocular inserts Advantages of ocular inserts

 

 

Classification of ocular inserts ⁹:

1)  Insoluble ocular inserts                    

a)  Diffusion based

b)  Osmotic based

c)  Soft contact lenses

2)  Soluble ocular inserts

3)  Bioerodible ocular inserts

The following figure 2 shows the classification of ocular inserts.

 

1. Insoluble ocular inserts

The insoluble inserts have been classified into three groups:-

a) Diffusion systems

b) Osmotic systems

c) Hydrophilic contact lenses.

 

The  first  two  classes  include  a  reservoir  in  contact  with  the inner surface of the rate controller and supplying drug thereto. The reservoir contains a liquid, a gel, a colloid, a  semisolid,  a  solid  matrix  or  a  carrier-containing  drug  homogeneously  or heterogeneously  dispersed  or  dissolved  therein.¹⁰ Carriers  can  be  made  of  hydrophobic,  hydrophilic,  organic,  inorganic,  naturally  occurring or synthetic material.

 

The third class including the contact lenses. The insoluble  of  these  devices  is  their  main  disadvantages,  since  they  have to be removed after use.

 

a)      Diffusion inserts :

The diffusion systems are compared of a central reservoir of drug enclosed in specially designed semi permeable or micro porous membranes, which allow the drug to diffuse the reservoir at a precisely determined rate.  The drug release from such a system is controlled by the  lachrymal fluid permeating through the membrane until a  sufficient  internal  pressure  is  reached  to  drive  the  drug  out  of  the  reservoir.  The  drug  delivery  rate  is  controlled  by  diffusion  through  the  membrane,  which  one  can  be Controlled. ¹¹ The components of the diffusional inserts are given in table 1.

 

Table1:Componentsof diffusional inserts

 

b) Osmotic inserts

The  osmotic  inserts  are  generally  compared  of  a  central  part  surrounded  by  a  peripheral  part. ¹²  The  first  central  part  can  be  composed  of  a  single  reservoir  or  of  two  distinct compartments.

 

In first case, it is composed of a drug with or without an  additional  osmotic  solute  dispersed  through  a  polymeric  matrix,  so  that  the  drug  is  surrounded  by  the  polymer  as  discrete  small  deposits. In  the  second  case,  the  drug  and  the  osmotic  solutes  are  placed  in  two  separate  compartments, the drug reservoir being surrounded by an  elastic  impermeable  membrane  and  the  osmotic  solute  reservoir  by  a  semi  permeable  membrane.  The  second  peripheral  part  of  these  osmotic  inserts  comprises  in  all  cases  a  covering  film  made  of  an  insoluble  semi permeable polymer .The tear fluid diffuse into peripheral deposits through the semi permeable polymeric membrane wets them and  induces their dissolution. The  solubilized  deposits  generate  a  hydrostatic  pressure  against  the  polymer  matrix  causing  its  rupture  under  the  form  of  apertures.  Drug  is  then  released  through  these  apertures  from  the  deposits  near  the surface of the device which is against the eye, by the  sole  hydrostatic  pressure. This  corresponds  to  the  osmotic  part  characterized  by  zero  order  drug  release  profile. The table 2 shows the components of osmotic inserts.    

 

c) Soft contact lenses:

These are shaped structure made up of a covalently cross-linked  hydrophilic  or  hydrophobic  polymer  that  forms  a  three-dimensional network or matrix capable of retaining  water, aqueous solution or solid components  .  When  a  hydrophilic  contact  lens  is  soaked  in  a  drug  solution, it absorbs the drug, but does not give a delivery  as  precise  as  that  provided  by  other  non-soluble  ophthalmic systems. The drug release from such a system is generally very rapid at the beginning and then declines exponentially with time.  The  release  rate  can  be  decreased  by  incorporating  the  drug  homogeneously  during  the  manufacture  or  by  adding  a  hydrophobic  component. Contact lenses have certainly good prospects as ophthalmic drug delivery systems.

 

Figure 2: Classification of ocular insert

 

Table 2: Components of osmotic inserts

 

2. Soluble ocular inserts:

These soluble inserts offer the advantage of being entirely soluble so that they do not need to be removed from their site of application, thus limiting the intervention to insertion only.They can be broadly divided into two types, the first one being based on natural polymers and the other on synthetic or semi-synthetic polymers.

 

A. Natural polymer:

The first type of soluble inserts is based on natural  polymer.¹³ Natural polymer used to produce soluble ophthalmic inserts is preferably collagen. The therapeutic agent is preferably absorbed by soaking the insert in a solution containing the drug, drying, and re-hydrating it before use on the eye. The amount of drug loaded will depend on the amount of binding agent present, the concentration of the drug solution into which the composite is soaked as well as the duration of the soaking. As the collagen dissolves, the drug is gradually released from the interstics between the collagen molecules.

 

B. Synthetic and semi-synthetic polymer;

The second type of soluble insert is usually based on semi-synthetic polymers (e.g., cellulose derivatives) or on synthetic polymers such as polyvinyl alcohol. A decrease of release rate can be obtained by using Eudragit, a polymer normally used for enteric coating, as a coating agent of the insert. Saettone et al. ¹⁴ have observed in rabbits that Eudragit coated inserts containing pilocarpine induced a miotic effect of a longer duration, compared to the corresponding uncoated ones. However, the inherent problems encountered with these soluble inserts are the rapid penetration of the lachrymal fluid into the device, the blurred vision caused by the solubilization of insert components and the risk of expulsion due to the initial dry and glassy consistency of the device. Ethyl cellulose, a hydrophobic polymer, can be used to decrease the deformation of the insert and thus to prevent blurred vision. The soluble inserts offer the additional advantage of being of a generally simple design, of being based on products well adapted for ophthalmic use and easily processed by conventional methods. The main advantage is decreased release rate, but still controlled by diffusion. The table 3 shows the components of soluble inserts containing synthetic polymer.

 

Table 3: Components of soluble inserts containing synthetic polymers

 

 

3. Bioerodible ocular inserts ¹⁵:

This type of device is fabricated from bio- erodible or bio- degradable polymer of hydrogel or non hydro gel type. The mechanism of drug release in this  system  is  dependent  on  rate  of  erosion  or  rate  of  degradation.  Several  erodible  type  of  ocuserts  have  been  prepared  using  polymer  like  carboxymethyl  cellulose,  poly  vinyl  alcohol,  collagen  etc.  Containing drug like pilocarpine, gentamicin etc in the form of disc and wafers. Some of the products are also marketed recently as,

Ø  Lacrisert

Ø  Soluble ocular drug insert, (SODI)

Ø  Ocular therapeutic system or (minidisk)

Ø  Corneal collagen shield

 

Lacrisert:

·      It  is  sterile  rod  shaped  device  made  of  hydroxypropyl  cellulose  without  any  preservative. i.e. used for the treatment of dry eye syndrome.

·      It weighs 5 mg and measures 1.27 mm in diameter with a length of 3.5 mm.

·      It  is  inserted  into  the  inferior  fornix  where  it  imbibes  water  from  conjunctiva  and  forms  a  hydrophilic  film  which  stabilizes  the  tear    film  and hydrates and lubricates the cornea.

·      Day long relief from dry eye syndrome has been reported from a single insert placed in the eye early in the morning.

 

Advantages :

Replacement of 4 times an hr regimen by once or twice  daily  regimen  is  the  benefit  achieved  by  this  dosage  forms.

 

Soluble ocular drug insert (SODI) :

·        The insert is small oval wafer.

·        It  is  in  the  form  of  sterile  thin  film  of  oval  shaped Weighing 15-16 mg .

·        After introduction into the inferior cul-de-sac where wetted by tear film, it soften in 10-15 seconds and assumes the curved configuration of globe.

·        During the following 10-15 min. the film is turn into viscous polymer mass, thereafter in 30-60 min it becomes a polymer solution.

 

Advantages:

Single SODI application has been reported to replace 4-12 drops instillation or 3-6 applications of ointment before treatment of glaucoma and trachoma.

 

Ocular therapeutic system (minidisk) :

·     Consist of countered disc with a convex front and concave back surface in contact with eyeball.

·     It is like a miniature contact lenses with a diameter of 4-5mm.

·     The major component of it is silicone based prepolymer.

·     The OTS can be hydrophilic or hydrophobic to permit extended release of both water soluble and insoluble drugs.

 

Corneal collagen shield:

Prepared  by  molding  collagen  mixed  with  the  drug  into  a  contact  lens  configuration  is  dehydrated  and  sterilized by gamma radiation and packed. Drugs like antibiotics, steroids have been reported (Bloomfield, 1978).

The  biodegradable  inserts  are  composed  of  homogeneous  dispersion  of  a  drug  included  or  not  into  a  hydrophobic  coating  which  is  substantially  impermeable to the drug. They are made of the so-called biodegradable polymers.  Successful  biodegradable  materials  for  ophthalmic  use  are  the  poly  (orthoesters)  and  poly  (orthocarbonates).  The  release  of  the  drug  from  such  a  system  is  the  consequence  of  the  contact  of  the  device  with  the  tear  fluid  inducing  a  superficial  diversion  of  the  matrix.

 

Method of preparation of ocular inserts ¹⁶;

1. Solvent casting method:

In  this  method  using  different  ratios  of  drug  and  polymer  a  no. of batches  are  prepared.  The polymer is dissolved in distilled water.  A plasticizer is added to this solution under stirring conditions. The weighed amount of drug was added to above solution and stirred to get a uniform dispersion.  After  proper  mixing  the  casting  solution  was  poured  in  clean  glass  petridish  and  covered  with  an  inverted  funnel to allow slow and uniform evaporation at room temperature for 48 h. The dried films thus  obtained  were  cut  by  cork  borer  into  circular  pieces  of  definite  size  containing  drug.  The  ocular  inserts  were  then  stored  in  an  airtight  container  (desiccator)  under  ambient  condition .

 

2. Glass substrate technique:

Drug  reservoir  film:  1%  w/w  polymer  for  example  chitosan  was  soaked in 1%v/v Acetic acid solution for 24hrs, to  get  a  clear  solution  of  chitosan  in  acetic  acid  solution.  The  solution  was  filtered  through  a  muslin  cloth  to  remove  undissolved  portion  of  the polymer (chitin). Required quantity of drug-β  CD  complex  was  added  and  vortexed  for  15minutes  to  dissolve  the  complex  in  chitosan  solution.  1%w/v  propylene  glycol  (plasticizer)  was  added to  it and  mixed  well  with  stirrer.  The  viscous  solution  was  kept  aside  for  30  minutes  for  complete  expulsion  of  air  bubbles.  The rate controlling films were prepared.  The  films  were  casted  by  pouring  solution  into  the  center  of  leveled  glass  mould  and  allowing  it  to  dry  at  room  temperature  for  24hrs.  After  drying,  films  were  cut  into  ocuserts  of  desired  size  so  that  each  contains  equal  quantity  of  the  drug.  Then,  the  matrix  was  sandwiched  between  the  rate  controlling  membranes  using  non-toxic,  nonirritating,  water  insoluble  gum.  They were wrapped in aluminium foil separately and stored in a desiccator.

 

3. Melt extrusion technique:

Drug for example  acyclovir  and  the  polymer  were  sieved  through  60#,  weighed  and  blended  geometrically.  The plasticizer was added and blended.  The blend was then charged to the barrel of Melt Flow Rate apparatus and extruded.  The  extrudate  was  cut  into appropriate size and packed in polyethylene  lined  aluminium  foil,  heat  sealed  and  sterilized  by gamma radiation (2.5 Mrad for 4 h) .

 

Evaluation of ocular inserts ^{5, 15, 17, 18}:

1.      Thickness of ocular inserts

2.      Weight variation test

3.      Surface pH determination

4.      Drug content uniformity

5.      Swelling index

6.      Folding endurance

7.      Tensile Strength

8.      Hardness

9.      In vitro drug release

10.    In vivo drug release

11.    Accelerated Stability study

12.    Ocular irritation test

 

1. Thickness of ocular inserts:

Thickness of the inserts is measured using dead weight thickness gauge. After initial settings, the foot is lifted with the help of the lifting lever fixed on the side of the dial gauge. Insert is placed on the anvil such that the area where the thickness is to be measured lies below the foot. Readings of the dial gauge are recorded after gentle lowering of foot. 

 

2. Weight variation test:

Inserts  from  each  batch  are  randomly  selected  and  weighed  individually  on  electronic  balance.  Mean weight of inserts of each formulation is recorded.

 

3. Surface pH determination:

Inserts are left to swell for 5 h on agar plate prepared by  dissolving  2%  (w/v)  agar  in  warm  simulated  tear  fluid  (STF;  sodium  chloride:  0.670  g,  sodium  bicarbonate:  0.200  g,  calcium  chloride.  2H 2 O:  0.008 g, and purified water q.  s.  100  g)  of  pH  7.4  under  stirring  and  then  pouring  the  solution  into  Petri  dish  till  gelling  at  room  temperature.  After  the  time  of  soaking,  the  pH  of  the  wet  surface  is  measured  by  placing  the  electrode  in  contact  with  the  surface  of  the  insert.

 

 

4. Drug content uniformity:

Uniformity  of  the  drug  content  is  determined  by  assaying  the  individual  inserts.  Each  insert  is  grounded  in  a  glass  pestle  mortar  and  STF  is  added  to  make  a  suspension.  The  suspension  so  obtained  is  filtered  and  the  filtrate  is  assayed  spectrophotometrically.

 

5. Swelling index:

Swelling  of  the  polymer  depends  on  the  concentration  of  the  polymer,  ionic  strength,  and  the  presence  of  water.  To  determine  the  swelling  index  of  prepared  ocular inserts (n = 3), initial weight of insert is taken, and  then placed in agar gel plate (2% w/v agar in STF, pH 7.4)  and incubated at 37ºC ± 1ºC. For 5 h, insert is removed  from  plate  after  every  1  h,  surface  water  is  removed  with  help  of  filter  paper,  and  insert  is  reweighed.

  

% swelling index = [wt − wo/wo] Χ 100

 

Where, wt = weight of swollen insert after time t,

 wo= original weight of insert at zero time

 

6. Folding endurance:

Folding  Endurance  of  the  film  was  determined  by  repeatedly  folding  the  inserts  at  the  same place till it breaks. The ocuserts was folded in the center, between finger and thumb and then opened. This was one folding. The number of times, the film could be folded at the same place without breaking gave the value of folding endurance.

 

7. Tensile strength:

Ocular insert with good tensile strength would resist tearing due to stress generated by the blinking of eye. The insert was cut into strips. The apparatus consist of a base plate with pulley aligned on it. One aluminium clip was fixed on one end of the base plate to which the insert was clipped. The other end of the insert was clipped to movable aluminium clip. A thread was tied to movable clip and passed over the pulley to which the small pan was attached to hold weights. The weights were gradually added to the pan till the insert was broken. The weight necessary to break the insert was noted as break force.

 

8. Hardness:

Apparatus consist of a wooden stand of 11cm height and top area of 16 x16cm.A small pan was fixed horizontally on one end of the 2mm thick iron rod whose other end is reduced to sharp point. A hole of 0.2cm diameter was made at the centre of the top area of wooden stand for supporting the pan rod. An electric circuit was made through battery in such a way that the bulb lights up only when circuit is completed through the contact of the metal plate and sharp end of the rod. The insert was placed between metal plate and short end of rod. The weights were gradually added to the pan at an interval of 10 seconds  and for the stabilization of force till the bulb was glown. The final weight was considered as measure of hardness.

 

9. In vitro drug release:

In-vitro release studies are carried out using a bi-chamber donor-receiver compartment model design made by using a transparent and regenerated cellulose type of semi-permeable membrane. It is tied at one end of an open cylinder, which acts as the donor compartment. The ocular insert is placed inside the donor compartment. The semi permeable membrane is used to create ocular in vivo conditions, like a corneal epithelial barrier, which simulates the tear volume; 0.7 m1 of distilled water is placed in a donar compartment and maintained at the same level throughout the study. The surface of the membrane is in contact with the reservoir compartment containing 25 ml of phosphate buffer having a pH of 7.4. It is stirred continuously using a magnetic stirrer. Samples of 1 ml are withdrawn from the receptor compartment at periodic intervals and replaced with an equal volume of distilled water. The withdrawn sample is analyzed at 246 nm against the reference standard using a pH 7.4 phosphate buffer as a blank on a UV / visible spectrophotometer.

 

10. In vivo drug release:

The inserts are sterilized by using UV radiation before in-vivo study.  Inserts are taken in a Petri dish along with 100 mg of pure drug, which are spread to a thin layer.  This Petri dish along with polyethylene bags and forceps are place in UV sterilization chamber (hood).  The inserts and other materials are exposing to UV radiation for one hour.  After sterilization, inserts are transferee into polyethylene bag with the help of forceps inside the sterilization chamber itself.  The pure  drugs  which  are  sterilized  along  with  inserts  are  analyzing for potency by UV spectrophotometer after  suitable dilution with pH 7.4 phosphate buffer.  The male albino rabbits, weigh between 2.5-3.0 kg are require for the experiment.  The animals are house on individual cages and customized to laboratory conditions for 1 day. Receive free access to food and water. 

 

The  ocular  inserts  containing  drug  are  taken  for in-vivo study which are previously sterilize on the  day of the experiment and are place into the lower  conjunctivas cul-de-sac. The inserts are inserting into  7  eyes  at  same  time  and  each  one  eye  of  seven  rabbits is serving as control.  Ocular inserts are removing carefully at 2, 4, 6, 8, 10, 12 and 24 hours and analyze for drug content as dilution mention in drug content uniformity.  The drug remaining is subtracted from the initial drug content of inserts which will give the amount of drug release in the rabbit eye.  Observation for any fall out of the inserts is also recording throughout the experiment. After one week of wash period the experiment is repeating for two times as before.

 

11. Accelerated stability study:

The  accelerated  stability  studies  are  carries  out  to  predict  the  breakdown  that  may  occur  over  prolong  periods  of  storage  at  normal  shelf  condition. The films of the formulation are taken in a  separate  Petri  dish  and  are  keep  at  three  different  temperatures 40⁰C, 50⁰C and 60⁰C and the period for break  down  or  degradation  of  the  ocular  inserts  is check.  When ocular inserts show degradation the time in days is note and subject to determine the drug content of each individual film using the drug content uniformity procedure.

 

12. Ocular irritation test:

The potential ocular irritation and/or damaging effects of the ocusert under test were evaluated by observing them for any redness, inflammation (or) increased tear production. Formulation was tested on five rabbits by placing the inserts in the cul-de-sac of the left eye. Both eyes of the rabbits under test were examined for any signs of irritation before treatment and were observed up to 12 h.

 

CONCLUSION:

The main efforts in ocular drug drug delivery during  the past two decades has been on the design of systems to increase the residence time of topically applied  drugs in conjuctival sac. Various new approaches like ocular inserts, collagen shield, in-situ activated gel formation, non-corneal route of ocular drug penetration, and nanoparticle-based polymeric solutions and gels are being developed by the pharmaceutical scientists. The advantages gained by ocular inserts are many for the treatment of eye-related problems, but only few gain commercial acceptance.

 

REFERENCE:

1.       Saettone MF. Solid polymeric inserts/disks as ocular drug delivery systems. Biopharmaceutics of ocular drug delivery. Boca Raton, 1993.

2.       Gurtler F, Gurny R. Patent literature review of ophthalmic inserts. Drug Dev Ind Pharm.21; 1995:1-18.

3.       Karthikeyan D, Bhowmick M, Pandey VP, Nandhakumar J, Sengottuvelu S,Sonkar S, Sivakumar T. The concept of ocular inserts as drug delivery systems: An overview. Asian Journal of Pharmaceutics.2; 2008:192-200.

4.       Bawa R. Ocular inserts. In: Ophthalmic Drug Delivery Systems.In Marcel Dekker. Edited by Mitra AK. NewYork. 1993: pp. 223-59.

5.       Renu Kalyanwat, Stuti gupta, Rajendra Kr. Songara, Priyanka Lokwani.Ocular inserts: An overview. International Journal of  Pharmaceutical Research and Development.3(6);2011:141-48.

6.       Korsmeyer RW, Peppas NA. Macromolecular and modeling aspects of swelling- controlled systems. In. Marcel Dekker. Edited by Roseman TJ, Mansdorf SZ. NewYork.1983: pp.77-90.

7.       Darougar Sohrab, Darougar and Dayshad. Patent literature review of ocular Inserts. United States Patent 6,264,971, Appl. No. 428967, Filed on November 4, 1999.

8.       Heller J. Controlled release of biologically active compounds from bioerodible Polymers.Biomaterials.1; 1980:pp.51-57.

9.       Di Colo, Burgalassi S, Chetoni P. Gel forming ocular inserts for Ocular controlled delivery. International Journal of Pharmaceutical Science.215 (1-2); 2001:101-11.

10.     Darougar S. Ocular insert for the fornix, U.S. Patent 5,147, 1992,647.

11.     Bloomfield SE, Miyata T, Dunn MW. Soluble gentamacin ophthalmic inserts as a delivery system. Arch Opthalmol. 98;1978:885.

12.     Bloomfield SE, Miyata T, Dunn MW, Bueser N, Stenzel KH, Rubin AL.Soluble gentamacin ophthalmic inserts as a drug delivery system. Arch Ophthalmol.96;1978:885-887. 

13.     Saettone MF, Chetoni P, Torraca MT, Giannaccini B, Naber L, Conte U. Application of the Compression technique to the manufacture of Pilocarpine inserts. Acta Pharma Technology. 36; 1990:9-15.

14.     Shinde SK, Banerjee SK, Grampurohit ND, Gaikwad DD.Ocular inserts: A rate controlled Drug delivery system. Imperial Journal of Pharmaceutics and Cosmetics.1 (1); 2011:12-23.

15.     Shahwal VK.Ocular Drug Delivery: An overview. International Journal of Biomedical and Advance Research. 2(5); 2011:167-187.

16.     Renu Kalyanwat, Stuti gupta, Rajendra Kr. Songara, Priyanka Lokwani.Ocular inserts: An overview.International Journal of  Pharma Research and Development.3(6);2011:141-48.

17.     Kumari A, Sharma PK, Garg VK, Garg G.Ocular inserts - Advancement in therapy of eye diseases. Journal of Advance  Pharm Tech Research.1;2010:291-296.

18.     Ritu Mehra Gilhotra, Kalpana nagpal, Dina nath mishra. Azithromycin novel ocular drug delivery system for ocular application. International journal of pharmaceutical investigation.1(1);2011:22-28.

 

 

Received on 12.04.2012       Modified on 20.05.2012

Accepted on 24.05.2012      © RJPT All right reserved