RECENT TECHNIQUES OF PHARMACEUTICAL SOLVENTLESS COATING: A REVIEW

RECENT TECHNIQUES OF PHARMACEUTICAL SOLVENTLESS COATING: A REVIEW

Shital Dhuppe ¹, S.S. Mitkare*¹, D.M. Sakarkar ²

School of Pharmacy, S. R. T. M. University, Nanded-431 606, Maharashtra, India

S. N. Institute of Pharmacy, Pusad- 445 204, Maharashtra, India

ABSTRACT

The  coating  of  solid  pharmaceutical  dosage  forms  began  in  the  9th  century  B. C.,  with the  Egyptians.  Conventional coating techniques are based on solvents or water. Solventless coatings are alternative technique of coating. In  solventless  coating,  the coating  material  is  directly  spread  on  the  core  and  then  it  is  cured  by  special  method to  form  coat.  Solventless  coating  avoids  the  use  of  water  or  it  reduces  to  very  small amounts  with respect  to  the  coating material  hence  it  overcomes  the  limitations  of conventional  coating such  as  need  for  time,  energy  consuming,  drying  steps  and  the most  important  drug  stability  issues.  A variety of solventless coating  approaches  are described  in  this  review  as  powder  coating,  hot melt  coating,  supercritical  fluid coating,  magnetically  assisted  impaction  coating,  Plasma  enhanced  chemical  vapor deposition.  This review summarizes basic principle and process of the coating techniques.

Powder coating

INTRODUCTION:Pharmaceutical  solid  dosage  forms  such  as  tablet,  pellets,  pills,  beads,  spherules are  coated  for  different reasons  such  as  aesthetic  property, to enhance drug stability (from light,  moisture,  oxygen),  to  separate  reactive  components  in  formula,  modified drug  release,  identification,  prevention  from  gastric  acid  and  enzyme,  improved mechanical  strength ¹.  Film  coating  can  be  carried  out  using  either  an  organic  solvent or  water ².  The  liquid  coating  technology  can  obtain  extremely  uniform  smooth, gleaming  coating  surface ^{3, 4}.

Organic solvents are  toxic,  flammable,  vapor of  organic solvent causes environmental pollution and  hazard to coating equipment operator, long processing time due to evaporation of solvent,  vaporization of organic solvents is energy  consumptive, high  cost  of  solvent,  strict  environmental  regulation  placed  on  use  of  organic  solvent ^5,6.

USFDA,  Environmental  Protection  Agency  and Occupational  Safety  and  Health  administration  (OSHA)  have  strict  requirement regarding  use  of  solvent  in  pharmaceutical  industry ^{7, 8}.  Thus, aqueous  based  coating  is  increasingly  used  compared  to  organic  based  coating. However aqueous based coating also having following drawbacks:

• Degradation  of  certain  drugs  due  to  use  of  heat  and  water.
• Validation of coating dispersion for controlling microbial presence.
• High energy consumption and long processing time ⁶.

In order to overcome the drawbacks of liquid coating technology, solventless coating has emerged.  Solventless coating eliminates many problems associated with the use of solvent i.e., residual solvent, solvent exposure, solvent disposal in coating. As there is no use of solvent, it eliminates the solvent  evaporation step and thus reduces the processing time  also solventless  coating reduces overall cost  because  it  eliminates  the  tedious  and costly  process  of  solvent disposal and treatment. Solventless  coating  can  be  applied  to thermosensitive  drugs  except  hot  melt  coating ^{5, 9, 10}.

It  can  obtain much  thicker coat than conventional  liquid  coating  and  Process  can  be  recycled.  The  main  aim of this review is to discuss mechanism,  current status and future development of the solventless coating techniques such as powder  coating, hot melt coating, photocurable coating,  magnetically  assisted  impaction  coating,  supercritical  fluid  coating,  Plasma enhanced  chemical  vapor  deposition ¹².

Techniques of Solventless Coating:

Powder/dry coating: The  concept  of  powder  coating  originated  in  the  USA  in  1950s ¹¹.  The principle  of   powder coating  involves  spraying  of  mixture  of  powdered  coating  material along  with  polymer  and  then  heated  in  curing  oven  to  form  a  coat.  Application  of  the  powder  coating  technology  has  been  booming  in  metal  and  wood  coating,  which has  a  new  application  in  the  pharmaceutical  industry  to  coat  solid  dosage  forms. Several  dry  coating  has  developed  depending  on  the  method  of  particle  adhesion  on solid  dosage  forms  such  as  Plasticizer-dry-coating,  Heat  Dry  Coating,  Plasticizer-electrostatic-heat  dry  coating,  and  Electrostatic  coating.  Dry  coating,  a  novel  coating technology  for  solid  pharmaceutical  dosage  forms ¹².

Plasticizer- Dry Coating:

FIGURE 1: PLASTICIZER COATING

The  first  dry  coating  technology  is  mainly  based  on  the  usage  of  plasticizers.  Here, this technology is referred to as “plasticizer-dry-coating. In this  technology, powdered materials  and  plasticizer  are  injected  onto dosage  surface  simultaneously  from  separate spraying nozzle. The sprayed liquid  plasticizer  would  wet  the  powder particles  and  the  dosage  surface  promoting  the adhesion  of particles  to  dosage  surface. The  coated dosage  forms  are  then  cured  for  predetermined  time  above  the  glass  transition temperature  (Tg)  of  the  polymer,  forming  a  continuous  film ^13-16.

By  means  of  the  plasticizer-dry-coating  technology  both   tablets  and  pellets could  be  coated.  The former were generally coated in a pan coater.  However, for  the latter  a   fluidized  bed  coater  is  required  in  order  to  avoid  formation  of  agglomerates caused  by  the  smaller  size  and  higher  specific  surface  area  of  pellets  and  thus  strong interactions ^15-17. The  adhesion of  particles  to  dosage  surface  is  primarily by wetting of  particles  and  dosage  surfaces by plasticizers and the  film  formation  is  the collective  response  of  improved  viscous  flow  and  particle  deformation  resulted  from plasticizer  and  heat ¹³.  Moisture  would  significantly  accelerate  the  film formation and optimize the  film  smoothness  and  integrity of ethylcellulose-coated pellets  during  the heat  curing  phase ¹⁵.

These  phenomena  are  similar  to  those  observations  for  film formation  of  aqueous  dispersions ^{18, 19}.  The  application  of  liquid  plasticizer  has  to  be considered  influencing the film formation by temporarily  building capillary forces between the polymer  particles  before  the  plasticizer  will  have  been  taken  up  by  the polymer ¹³. The heat-humidity curing condition suppresses the evaporation of the plasticizer,  resulting  in higher plasticizer levels  remaining  in  the  films,  as  compared  to the  heat-only  curing  condition.  The heat humidity curing also significantly increased the mechanical strength and decreased the water vapor permeability of the films ²⁰.Plasticizer  dry  coating  is  the  technique  that  looks  promising,  from  all  points  of  view, for  coating  food  ingredients  (time,  energy  savings  and  high  productivity) ²¹. This technique has a low moisture level compared with aqueous coating systems.

However, quite  a  small  level  of  water  was  detected  in  the  granules  [2%],  and  this  is  not acceptable  for  applications  to  some  sensitive  products  such  as  probiotics ²².  Coat thickness increases with increasing plasticizer concentration.  Adversely, additional plasticizer leads to very soft or sticky films. It is difficult to balance the plasticizer concentration  for a sufficient coat  thickness  and  that  for  a  flexible  and  dry  coat ²¹.

Heat Dry Coating: This method is named as Heat dry coating by Y Luo et al (2008) ²³.  In this technique heat was used as a binding force to realize the dry coating of tablets.  Heat dry coating was developed by Cerea et al (2004). In  this  coating  technology,  Eudragit  EPO (a  copolymer based on dimethylaminoethylmethacrylate  and  methacrylates) particles  were  constantly  spread onto  the  tablets contained in  a  lab-scale  spheronizer  by  means  of a motorized  single screw  powder  feeder,  with an  infrared  lamp  positioned  on  the  top  of  the  spheronizer as  a  heating  source,  without  using  any  solvent  and  plasticizer.

Recently,  tablets  were pre-plasticized  before  the  coating  process  by  mixing  polymer  powder with  plasticizer and  then  sieving ²⁴. Powder adhesion  onto  the  tablet  surface  is  enhanced  only  by  the partially  melted  polymer  that generates  binding  forces  between  the particles and between  the  tablet  surfaces ²⁵.

Bodmeier  R et al (2005) showed  that  spray-dried  surelease  as  a  pre-plasticized ethylcellulose  powder  required only mild curing conditions to achieve  extended  drug release  from  dry  polymer   powder  coated  pellets ²⁶.

The heat dry coating process occurs in the three stages:

1. Pre-heating:  In  this  stage  the  uncoated  tablets  are  heated  to  the  predetermined temperature.
2. Powdering:  In  this  stage  the  powder  is transferred  into  the  coating  equipment  and distributed  onto  the cores.
3. Curing:  Here  polymeric  particles  adhere  to  the  surface  of  the  substrate  to  form  a Polymeric  film  coating ²⁷.

In  these  processes, dry coating technique was  proved  to  provide  both  bead  and tablet  products  having  sufficient gastric resistance, with a substantial  reduction  of processing  time ¹. The  advantage  of  heat  dry  coating  includes  abandoning  plasticizers for  lower  Tg  film  forming  polymers,  or  avoiding  high  concentrations  of  plasticizers because  of  pre-plasticization.  However,  it  is  a  challenge  for  heat  dry  coating  to  get a smooth,  uniform  and  thick  coating  only  by  the  help  of  heat  based  adhesion ²⁸.

Electrostatic Coating: Electrostatic coating is  extensively used in  the painting industry and the  snack food industry, metal coatings,  finishing  industry  and  coating of living  cells as an alternative  to  traditional powder  coating ^29-33.

The  principle  of  electrostatic powder coating  involves  spraying  of  finely grounded  particles  and  polymers simultaneously onto a substrate surface  without  using any  solvent  and  then  heating  the  substrate for curing on oven until the powder mixture  is  fused  into  film.  There  are  two  types  of  spraying  units,  generally  in  the form  of  powder  coating  guns,  as  per  their  charging  mechanism( corona  charging  and Tribo  charging) ^{11, 34}.

Electrostatic  coating  promotes  an  even  dispersion  of  the  powder over  all  the  surfaces  of  the  products  ²⁹. Coating efficiency during  electrostatic  coating is  enhanced  by  a  large  charge  to  mass  ratio.  The  larger  the  charge  during  electrostatic  coating,  the  greater  the  improvement  seen  with  the  process ³⁴.  Phoqus Pharmaceuticals  Limited,  an  oral  drug  delivery  and  development  company  has  invented  both  apparatus  and  formulations  of  powdered  coating  materials  based  on electrostatic  coating  of  solid  dosage   forms ³⁵.

Corona Charging Mechanism: The  corona  spray  gun  has  an  electrode  located   near  the  tip  of  the  gun,  which emits  a   field  charge  that  imparts  a  negative  charge  onto  the  particles  of  powder  as they  penetrate  this  field  that  results  in  the  powder  being  attracted  to  the  grounded work  piece ³⁴.

This  leads  to  more  consistent  film  thickness  control  and  makes  it easier  to  powder  coat  complex  shapes.  The  movement  of  particles  between  the charging  gun  and  the  substrate  is  derived  by  the  combination  of  electrical  and mechanical  forces.  The  mechanical  forces  produced  by  the  air  blows  the  powder towards  the  substrate  from  spray  gun  and  electrical  forces  are  produced  from  the electrical  field  between  the  charging  tip  of  spray  gun  and  earthen  substance  and  from the  repulsive  forces  between  the  charged  particles ^{23, 34, 36, 37}.

Tribo- Charging Mechanism: Tribo- charging use  frictional  charging  techniques  to  charge  the  powder  particles Tribo-charging  guns  create  a  charge  on  the  powder  particles  via  intimate  contact  with the  gun  walls.  Principle of  friction charging associated  with  the  dielectric  properties of  solid  materials  and  therefore  no  free  ions  and  electrical  field  will  be  present between  spray  gun  and  substance ^{34, 36}.

For  tribo  charging  guns,  the  electrical  forces  are  only  regarded  to  the  repulsive  forces between  the  charged  particles.

Steps  in  the  deposition  of  charged  particles  onto  the  substrate  are;

Charged particles  are  uniformly  sprayed  onto  the  earthen  substrate  in  virtue  of mechanical  forces  and  electrostatic  attraction,

Particles  accumulate  on the substrate before the repulsion force of the deposited particles   against  the  coming  particles  exceeds  and  increases  the  electrostatic  attraction,

Finally, once  the  said  repulsion  becomes  equivalent  to  the  said  attraction,  particles cannot adhere  to  the  substrate  any  more,  and  the  coating  thickness  does  not  increase any  more.

After  spraying  charged  particles  move  into  the  space  adjacent  to  the  substrate, the  particle  to  deposit  on  the  substrate  due to the attraction forces  between the charged particles  and the  grounded substrate. Charged particles are homogeneously sprayed onto the earthen substrate in virtue of mechanical forces and electrostatic attraction.

Once the said repulsion becomes  equivalent  to  the said  attraction,  particles cannot  adhere  to  the  substrate  any  more,  and  the  coating  thickness  does  not  increase to  any  further  extent ²³.

Measurement of the electrostatic powder coating  properties  for corona and triboelectric coating guns  can  be done by using  the  Electrostatic Powder  Coating Diagnostic Instrument (EPCDI). EPCDI  analyses  the electrostatic powder coating deposition efficiency  by measuring the  powder  adhesion  properties  in  the  pre-cured state  and  it  also  measures  the  uniformity  of  the powder coating  by  moving  the powder  sample  and measuring the infrared  light  transmission through it ³⁸.

Further methods of adhesion measurements are drop test rig and virtual oscilloscope ³⁹.

Plasticizer-Electrostatic-Heat Dry Coating (PEH): Plasticizer-electrostatic-heat  dry  coating  is  named  here  primarily  because  this technology  is  combined  practice  of  plasticizer,  electrostatic  attraction  and  heat.  In this technology, the steps of coating process consists of, ⁴⁰

• Positioning  preheated  solid  dosage  form  in  a  chamber  of  the  rotatable,  electrically grounded  pan coater,
• Spraying powdered coating materials  and  plasticizer  simultaneously on  the  solid  dosage  forms  in the pan coater,  during  rotation  using  an  electrostatic  sprayer,
• Curing the coated solid  dosage  forms  to  form  continuous,  uniform  and  flexible  coats.

During the whole coating  process, the solid  dosage  forms  and  the chamber  are always kept  in  hot  state by heating the air in the coater or directly  heating in the coater. According to the coating  process, PEH-dry-coating is characteristics of integration of five kinds of forces, softening or  melting  effects  of  particles  by  heat, wetting  of  dosage  surface  by  a  plasticizer,  electrostatic  attraction  forces,  hydrodynamic force  due  to  spraying  and  mechanical force  due  to  rotation  of  pan coater. They are combined to develop the adhesion of powdered coating materials to solid dosage surface.

Firstly,  the  movement  of  the  powdered  particles  from  the  charged  gun  to  the dosage  surface  is  promoted  by  the  combination  of  electrical  and  hydrodynamic  forces. The  adhesion  of  the  powder  particles  on  to  the  dosage  surface  is  by  means  of electrostatic  attraction  between  the  charged  powder  particles  and  earthed  dosages. Softening  effect  of  the  powder  is  due  to  heat  from  preheating  and  heating  during coating.  Wetting effect is due to plasticizers.

Secondly, the  hydrodynamic  forces  from compressed  air  and  mechanical  forces  from  the  tumbling  effects  of  the  pan  coater  are both  helpful  to the  adhesion of powders  on the earthed surface due to  the combination of electrostatic attraction and heat. Finally, the repulsion between the  same charged  particles on the dosage surface support the even  distribution of the  particles on  the  dosage  surface  and  prevent  the  coalescence  between  solid  dosage ²³.

Hot Melt Coating: The  hot-melt  coating  techniques  have  been  shown  to  avoid  the  use  of  solvents  and show  promising  for taste masking,  gastric resistance,  acid  resistance, sustained release or bioavailability  enhancement, based upon type of coating polymer ⁴¹.  It  has been adopted because it  is faster and cheaper  than the conventional coating techniques where  evaporation  and/or  recovery  of  solvent  can  be  expensive,  tedious  and  time consuming ⁴².

In  this  method,  the  coating  material  is  applied  in  its  molten state  on  the substrate. Thermostable  materials  with  a  relatively  low  melting  point  (<80°C)  such  as lipid,  waxes  and  fatty  bases  high  molecular-weight  polyethylene  glycols  are  the  most suitable  coating  material  in  hot  melt  coating.  Examples  of  some  marketed  hot  melt coating  excipients  are  Gelucires,  Precirol,  Stearines,  Myvaplex,  and  Compritol 888ATO ^{41, 46, 48}.

It  offers  several  benefits  and  potential  for  a  wide  variety  of  application  in pharmaceutical  formulation ^43-46.  The most common applications of this technique consist of the coating of pellets, granules and powder particles, particularly to obtain moisture-protected or modified-release dosage forms ⁴⁷. The various  technologies  of hot  melt  coatings  are  fluidized  bed  coating (top spray and bottom spray), spray congealing/coating,  and  pan  coating  (pan  spray  and  pan  pour) ⁴⁶.

Jannin  V  et  al  (2003)  carried  out  the  comparative  study  of  the  lubricant  performance  of  Compritol®888 ATO  on  Lactose  either  used  by  blending  or  by  hot melt  coating  and  found  that  the  hot  melt  coating process  induces  a  homogenous repartition  of  the  lubricant  on  the  lactose  surface  in  a  lower  concentration  as  compare to  classical  blending  procedure ^46,50,51.

TABLE1: LIST OF HYDROPHOBIC SUBSTANCES USED AS COMPONENTS OF EDIBLE FILMS AND COATINGS, BASED ON RESEARCH AND PATENTS PUBLISHED IN THE LAST 15 YEARS ⁴⁹

Supercritical Fluid Coating:  A new method for  coating polymeric  thin  films  on  particles  has  been  achieved by  simultaneous  nucleation  of  polymeric  material  out  of  a  supercritical  fluid, encapsulating  the particles  fluidized  in  the  supercritical  fluid,  and  further  curing  and binding  the  material  coated  on  the particles ⁵². Microencapsulation  using  supercritical  fluid  technology  combines  a  liquid- like density  and  solvating  power  with  gas-like  transport  properties  (like  viscosity, diffusivity). Carbon  dioxide  is  the  most  widely  used  supercritical  fluid  because  of  its relatively  low  critical  temperature  (31°C) and  pressure  (74 bars). The  use  of supercritical  fluid  technology,  especially CO₂ for encapsulation  purposes  is  mainly  due to  the  mild  processing  condition,  allowing  microencapsulation  of  sensitive  ingredients for  cosmetics,  pharmaceuticals ⁵³.

The coating method involves an enclosed system that provides;

• For suspension of the solid particles to be coated,
• For  dissolution  of  the  coating  material  in  the  supercritical  fluid  solvent,
• For temperature or  pressure  swing  operations  causing film deposition/coating of the   suspended solid particles and,
• Additional  chemical  addition  and/or  thermal  cycles  providing  for  any  additional reactions  required  (such  as  polymerization) ⁵⁴.

There  has  been  a  continuing  growth  of  interest  in   replacing  conventional organic  solvents  with  environmentally  friendly  supercritical  fluids  in  chemical processes. Among them, supercritical  carbon  dioxide  emerged  as  an  excellent  candidate  due  to  its  superb  characteristics  and  properties:  it  is  inexpensive,  nontoxic, nonflammable, readily  available,  easily  recycled,  and  as  a  solvent,  it  possesses  both gas-like diffusivities  and  liquid-like  densities  and  solvencies ^{55, 56}.

A  number  of approaches  to  the  use  of  supercritical  technologies  for the  deposition of  modifying coatings  on  solid  substrates  are  described  in  the  literature  such  as  Rapid  expansion  of supercritical  fluid  (RESS), supercritical antisolvent (SAS),  Aerosol  solvent  extraction system  (ASES), solution enhanced  dispersion by supercritical fluid (SEDS), Gas Antisolvent  (GAS)  etc ⁵⁷.

The  two  methods  that  are  most  widely  used  for  applying  SC  Co₂  to  the formation  of  thin  layer  coatings  are  the  rapid  expansion  of  supercritical  solutions  or suspensions  (RESS)  ^58-64 and  the  method  involving  supercritical  antisolvent (SAS) ^65-70. In RESS method polymer  is  dissolved  in  supercritical  carbon  dioxide  with  or without  cosolvent.

Then,  it  is  injected  through  nozzle  (depressured),  generating microparticles with  a  polymer  coating  on  the  surface.  Due  to  rapid  de-pressurization of  the  supercritical  solution  polymer looses  it's  solubility  and is  deposited on substrate  surface ^{71, 72}. However,  the  application  of  the  RESS  process  is severely limited  by  the fact  that  polymers  because they  have  very  limited solubility in SC CO₂ at temperatures  below 80°C ⁷².

Kim et al., reported the microencapsulation of naproxen using rapid expansion of supercritical solutions (RESS) ⁶⁰.

In  the  SAS  method,  a homogeneous  solution  of  various  solutes  and  polymer  is injected  into  the  SC CO₂,  which  in  this  case  acts  as  an  antisolvent.  Co-precipitation  of  the  solutes  and  polymer occurred  and  composite  microspheres  or  microcapsules  were  formed ⁷³.  An  important  feature  of  the  SAS  process  is  that the organic  solvent can  be  almost  completely  removed  by  simply  flushing  with  pure  CO₂.

Thus,  dry particles  are  produced  after  a  CO₂  extraction  step  (flushing)   following  feeding  of  the organic  solution ^{73, 76}.  SAS provides wide range of solvent choice ^{73, 77}. Ribeiro  D et al (2002)  performed  the  encapsulation  of  the  bovine  serum  albumin  with  lipidic compound  (Dynasan  114  or  Gelucire 50-02)  using  supercritical  process  and  determined the  release  kinetic  and  found  that  smooth  and  uniform  coating  can  be  obtained  by  this  method ⁷⁹.

Photocurable Coating: This is a chemical advance anticipated to rapidly coat tablets at or below room temperature ^{80, 81}.  Photocuring as a process of rapid conversion of especially formulated (usually liquid) solventless compositions into solid films by irradiation with ultraviolet or visiblelight ^82-85.Photocuring has wide commercial application in dental and medical fields. It is also used to form films of varnishes, paints, and coatings for paper, plastic, wood, metal surfaces, Composite dental fillings, preventive treatment for caries, assembly of medical devices, and wound dressing ⁸⁷.The UV-curable coating is strong and photostable. By changing the pore-forming agent and with choice of material, number of layers and thickness of the coating it was reasonable to produce immediate as well as sustained release ⁸⁴.

• Photocuring systems have four major components:
• UV-visible light source,
• Liquid prepolymers or monomers,
• Pore forming agent,
• An initiator ⁸⁸.

UV-visible Light Source: An often-used lamp type is the 80 W/cm medium-pressure mercury lamps, which emits a broad spectrum in the short wavelength range from 200 to 320 nm but also at discrete wavelength numbers of 360, 410, and 430 nm ⁸⁹.

Liquid Prepolymers or Monomers: Primary component in a photocuring system is the photocurable film-former a polymer or monomer ⁹⁰. It includes a meth acryloyl monomer, a meth acryloyl oligomer, an organic solvent, epoxy acrylate, polyester acrylate, polyurethane acrylate, hexanediol diacrylate, unsaturated polyester, trimethylolpropane triacrylate, tripropyleneglycol diacrylate, which provides heat resistance, storage stability and high light transmission while having a low viscosity sufficient to avoid discoloration of the optical product.

Tetraethyleneglycol dimethacrylate (TEGDMA) and bisphenol A-glycidyl methacrylate (Bis-GMA) are two photocurable monomers that are comprehensively used in dental composites ^{89, 91-95}. Polydimethylsiloxane is extensively used as a photocuring material because of its good thermal stability and extraordinary flexibility additionally it is used in transdermal drug delivery systems, composite dental fillings and other medical products ⁹³.

Pore Forming Agent: Ratio of solid pore forming agent(S) to liquid pre-polymer (L) is the most important parameter which determines the coating efficiency and uniformity of coating. When wider range of S/L ratio was investigated, good coating efficiency was favored by the lower particle size, and in case of larger particle sizes there is sharp decline in the coating efficiency at low S/L ratios ⁵. The initial study performed by Wang and Bonger, where UV light was used to cure derivatized silicon polymer films on non-pareil beads but film formed by this method is complete and almost perfect barrier to drug diffuse, such drug release depend on defects or weak points in the coating. Hence, they realized to incorporate pore forming agents in the polymeric film to prepare functional coatings. Pore forming agents are Lactose, sodium chloride, Explotab, Ac- Di-Sol, PEG 800, etc ^{92, 96}.

Photoinitiator: The Photoinitiator is an important ingredient of UV-curable coatings and has to have sufficient absorption in the 250~400 nm range, high reactivity, and high thermal stability, in addition to being nonyellowing, and nonodorous ⁹⁹. The photo initiator absorbs the UV-radiation and generates free radicals. The free radicals start and propagate chemical reactions that convert the reactive compounds into a cured film ^{97, 98}. Ciba spatiality chemicals provide Photoinitiator under various brand names such as IRGACURE184, IRGACURE500. Monomolecular-type photoinitiators are Benzoin ether, Diethoxy aceto phenone, Hydroxyketones, Aminoketones, Bisacyl phosphine oxides, etc ^{89, 101}.

Magnetic Assisted Impaction Coating (MAIC): Many food and pharmaceutical ingredients, being organic and moderately soft, are very sensitive to heat and can easily deform by severe mechanical forces. Magnetic Assisted Impaction Coating method can attach the guest (coating material) particles onto the host (material to be coat) particles with a least degradation of particle size, shape and composition caused by heat and mechanical forces. The rise in temperature is negligible; this is an additional benefit with thermosensitive powders such as pharmaceuticals ¹⁰².

The following steps involved in the mechanism of coating in the MAIC process:

1. Excitation of magnetic particle
2. De-agglomeration of guest particles
3. Shearing and spreading of guest particles on the surface of the host particles
4. Magnetic-host-host particle interaction
5. Magnetic–host–wall interaction and;
6. Formation of coated products ¹⁰²

The surrounding electromagnetic coil creates a magnetic field. It is used to accelerate and spin the large magnetic particles mixed with the host and guest particles promoting collisions between the particles and with the walls of the vessel, creating a fluidized state. During collision there is de-agglomeration of guest particles since the magnetic particles ‘‘fluidize’’ the host and guest powders, ‘‘soft’’ coating occurs by powder impaction ^{103, 104}. There are several unique features of MAIC that make it advantageous as a dry particle coating device. Firstly, the MAIC can coat soft organic host and guest particles without causing major changes in the material shape and size ¹⁰³.

Secondly, although there is some heat generated on a microscopic level due to the collisions of particles, there is negligible heat generation on a macroscopic level and hence no increase in temperature of the material during processing by MAIC. This is desirable when processing temperature sensitive powders such as pharmaceuticals. Lastly, the device can be operated both as a batch and continuous system making it versatile in the amount of material it can process ¹⁰⁵.

According to Singh P et al (2001) model, the coating time in the MAIC device depends on the number density of host particles, the diameters of the host and guest particles, the initial and final bed heights, and the material properties of the host and guest particles ¹⁰⁶. Yang J et al (2005) observed that the reduction in the cohesion force for the coated particles is inversely proportional to the size ratio of the guest and the host particles, indicating that smaller guest particles provide a larger reduction in the cohesive force ¹⁰⁴.

Plasma enhanced Chemical Vapor Deposition (PECVD):

FIGURE 2: PLASMA ENHANCED CHEMICAL VAPOR DEPOSITION

Plasma polymerization is also known as plasma-enhanced chemical vapor deposition (PECVD) ¹⁰.It involves the fragmentation of gaseous monomers into activated species, generally free radicals and ions, which then recombine and condense on the surface of the substrate as a solid polymer film (i.e. in situ polymerization). The plasma energy is provided for monomer activation, which can be induced by a range of sources including radiofrequency and microwave radiation ¹⁰⁸. These techniques originally from semiconductor industry, such as chemical vapor deposition (CVD), atomic layer deposition(ALD) used to coat particle. Use of non-thermal plasma creates the possibility to treat heat sensitive material with combination of charged particles, which preventing agglomeration before and during the coating process ^{109, 110}.

Specifically, PECVD allows deposition of thin films on a wide variety of substrates, including sub-micron particles ¹⁹. PECVD has become an attractive tool in the food, biomedical and pharmaceutical fields and has been used for a wide variety of applications from increasing biocompatibility and cell adhesion to controlling drug release ^{109, 112-114}.

Plasma polymerization, also known as plasma-enhanced chemical vapor deposition (PECVD), a dry coating method, was chosen to deposit thin hydrophobic polymer films on the surface of amorphous ketoprofen (KET)/ Methocel™ E5 aggregate particles ¹⁰⁷.

CONCLUSION: Solventlesscoating technologies are having many advantages over conventional liquid coating such as solventless coating does not emits volatile organic compounds, it can achieve much thicker coat, produce less hazardous waste, having less operating coat, less recovery time, less processing time. The equipment is needed for pan coater, fluidized bed coater, spray coater with slight modification. However, for magnetically assisted impaction coating, electrostatic coating special equipments are required. Solventless coatings produce uniform thick coating. Electrostatic coating is able to apply different color coating on tablet. But before commercialization of these techniques, additional research is to be made on scale up test evaluation for drug release profile, clinical test.

REFERENCES:

1. Remington’s. The Science and Practice of Pharmacy, Volume-I. 21st ed. Indian Edition, Lippincot Williams And Wilkins, 2005, p. 929-938
2. Joseph L. Johnson Aqualon Company, Coatings Technology Handbook, Third Edition.  In: Pharmaceutical Tablet Coating. 2005. p. 112-1,112-3.
3. Wheatley, T.A., Steuernagel, C.R, Latex emulsion for controlled drug delivery. In: McGinity, J.W. (Ed.), Aqueous Polymeric Coatings for Pharmaceutical Dosage Forms. Marcel Dekker. New York: 1997. p. 1–54.
4. Belder EG, Rutten HJ J, Perera DY. Cure characterization of powder coatings. Prog Org Coat. 2001; 42:142–9.
5. Lachman L, Lieberman HA, Kiang JL. The Theory and Practice of Industrial Pharmacy. 3rd ed. Varghese Publication House, Bombay. 1987, p. 346-373.
6. Thomas M. Solvent film coating, aqueous Vs organic. Midwest Regional Meeting, Academy of Pharmaceutical Sciences. Industrial Pharmaceutical Technology Section, 1978 April 10.
7. National Advisory Committee for Acute Exposure Guideline Levels (AEGLs) for Hazardous Substances, Proposed AEGL Values. Environmental Protection Agency, OPPTS-00312, FRL-6776-3.
8. U.S. Department of Labor, Occupational Safety and Health Administration. 1999, OSHA 3160 (Revised).
9. Zhu J, Zhang H. Ultrafine powder coatings: An innovation. Powder Coat 2005; 6: 39-47.
10. Cole G, Hogan J, Aulton M, Pharmaceutical Coating Technology, Taylor and Francis, London, 1995. p. 1-5.
11. Bailey, A.G. The science and technology of electrostatic powder spraying, transport and coating. J Electrostat 1998; 45: 85–120.
12. Yanfeng Luoa, b Jesse Zhub, Yingliang Mab, Hui Zhangb. Dry coating, a novel coating technology for solid pharmaceutical dosage forms. Int J P'ceutics 2008; 358:  16–22.
13. Kablitz C, Urbanetz N. Characterization of the film formation of the dry coating process. Eur J Pharm Biopharm 2007; 67(2): 449-457.
14. Obara S, Maruyama N, Nishiyama Y, Kokubo. H. Dry coating: an innovative enteric coating method using a cellulose derivative. Eur J Pharm Biopharm 1999; 47: 51-59.
15. Pearnchob N, Bodmeier R. Coating of pellets with micronized ethylcellulose particles by a dry powder coating technique. Int J Pharm 2003; 268: 1-11.
16. Pearnchob N, Bodmeier R. Dry polymer powder coating and comparison with conventional liquid-based coatings for Eudragit RS, ethylcellulose and shellac. Eur J Pharm Biopharm 2003; 56: 363-369.
17. Pearnchob N, Bodmeier R. Dry powder coating of pellets with micronized Eudragit® RS for extended drug release. Pharm Res 2003; 20: 1970-1976.
18.  Liu J, Williams III RO. Long-term stability of heat-humidity cured cellulose acetate phthalate coated beads. Eur J Pharm Biopharm 2002; 53: 167-173.
19. Williams III RO, Liu J. Influence of processing and curing conditions on beads coated with an aqueous dispersion of cellulose acetate phthalate. Eur J Pharm Biopharm 2000; 49: 243-252.
20. Jiping L, Robert O, Williams III. Properties of heat-humidity cured cellulose acetate phthalate free films. Eur J Pharm Sci 2002;17(1-2): 31–41.
21. Bodmeier R, Terebesi I. Pre-plasticized vs. simultaneously plasticized ethylcellulose powder for dry polymer powder coating. AAPS annual meeting and exploration, Nashiville, USA. 2005: Article -1674.
22. Ivanova E, Teunou E, Poncelet D. Encapsulation of water sensitive products: effectiveness and assessment of fluid bed dry coating. J Food Eng 2005; 71: 223–230.
23. Luo Y, Zhu J, Ma Y, Zhang H. Dry coating, a novel coating technology for solid pharmaceutical dosage form. Int J Pharm 2008; 358(1-2): 16-22.
24. Cerea M, Zheng W, Christopher R, McGinity J. A novel powder coating process for attaining taste masking and moisture protective films applied to tablets. Int J Pharm2004; 279(1-2): 127–139.
25. Pagliai P, Simons SJR, Rhodes D. A novel experimental study of temperature enhanced cohesive interparticle forces. Powder Technol 2007; 174: 71-7.
26. Bodmeir R, McGinity JW. Dry coating of solid substrate with polymeric powders. Drug Deliv Technol 2005; 5(19).
27. Caroline Desir ee Kablitz, Kim Harder, Nora Anne Urbanetz. Dry coating in a rotary fluid bed. European journal of pharmaceutical sciences 2006; 27: 212–219.
28. Dorothea S, Weijia Z, Lonique B, McGinity J. Influence of processing parameters and formulation factors on the drug release from tablets powder-coated with Eudragit L100-55. Eur J Pharm Biopharm 2007; 67(2) : 464-475.
29. Akou E, Amefia, Jareer M. Abu-Ali, Sheryl A, Barringer. Improved functionality of food additives with electrostatic coating. Inno Food Sci Techn 2006; 7: 176–181.
30. Barletta M, Gisario A, Rubino G, Tagliaferri V. Electrostatic spray deposition (ESD) of self-organizing TiO2-epoxy powder paints, Experimental analysis and numerical modeling. Sur Coat Tech 2006; 201(6): 3212-3228.
31. Aline T, Khashayar S, Pierre G, Czechowski C. Characterisation of electrostatic properties of powder coatings in relation with their industrial application. Powder Technol, 2009; 190: 230-235.
32. Siebers MC, Walboomers XF, Leeuwenburgh SCG, Wolke JGC, Jansen JA. Electrostatic spray deposition (ESD) of calcium phosphate coatings, an in vitro study with osteoblast-like cells. Biomaterials 2004; 25: 2019-2027.
33. Beucken J, Vos MR, Thune PC, Hayakawa T, Fukushima T, Okahata Y. Fabrication, characterization and biological assessment of multilayered DNA-coatings for biomaterial purpose. Biomaterials 2006; 27(5): 691-701.
34. Mazumder M, Sims R, Biris A. Twenty-first century research needs in electrostatic processes applied to industry and medicine. Chem Eng Sci 2006; 61: 2192- 2211.
35. Phoqus Group plc, Annual Report and Accounts. 2006.
36. Nick Liberto, P.E. Powder coatings: Not just another pretty finish, Powder Coating Consultants, Powder Coating, December 2010, 23.
37. Zhu J, Luo Y, Ma Y. Dry powder coating of pharmaceutical tablets by electrostatic pan coating. AAPS J 2006, 8(S2), Article -02674.
38. Puntarika R, Sheryl B. Particle size, cohesiveness and charging effects on electrostatic and nonelectrostatic powder coating. J Electrostatics 2007; 65: 704-708.
39. Dastoori K, Makin B. Adhesion measurements for electrostatic powder coatings using drop test rig and virtual oscilloscope. J Electrostatics 2001; 51-52: 509-510.
40. Zhu J, Zhang H. Fluidization additives to fine powders. U.S. Patent 6833185, 2004, December 21.
41. P.H. Barthelemy, J.P. Laforet, N. Farah. Compritol 888 ATO: an innovative hot-melt coating agent for prolonged-release drug formulations.Eur J Pharm Biopharm 1999; 47:  87– 90.
42. J.J. Michael, M.F. Robert, M.J. David, Characterization of a Hot-Melt Fluid Bed Coating Process for Fine Granules. Pharm. Res 1990; 7: 1119– 1126.
43. Ayres J.Hot melt coating by direct blending and coated substances, US Patent application 0141071, 2007.
44. Padsalgi A, Bidkar S, Jadhav V, Sheladity D. Sustain release tablet of theophyllin by hot melt wax coating technology. Asian J P'ceutics 2008; 2(3): 26-29.
45. Jannin V. Berard V, Andres C. Modification of the drug release of ibuprofen by hot-melt coating with mixes of compritol™ 888 ATO and non-ionic surfactants. AAPS J 2005; 7(S1), Article -0853.
46. Sinchaipanid N, Junyaprasert V, Mitrevej A. Application of hot-melt coating for controlled release of propranolol hydrochloride pellets. Powder Technol 2004; 141(3): 203-209.
47. Achanta A, Adusumilli P, James K, Rhodes C. Development of hot melt coating methods. Drug Develop Ind Pharm. 23(5), 1997, 441-449.
48. Gowan, Walter G, Bruce, Richard D, Aliphatic esters as a solventless coating for pharmaceuticals, CIPO 2082137. 1992.
49. Milda E. Embuscado, Frédéric Debeaufort and Andrée Voilley. Edible Films and Coatings for Food Applications, In: Lipid-Based Edible Films and Coatings, 135.
50. Jannin V, Berard V, N‘Diaye A, Andres C, Pourcelot Y. Comparative study of the lubricant performance of Compritol® 888 ATO either used by blending or by hot melt coating. Int J Pharm 2003; 262(1-2): 39-45.
51. Deasy BP. Microencapsulation and Related Drug Process. Vol-20 of Drugs and pharmaceutical sciences. Marcel Dekker, New York. 1984, 182-192.
52. Aydin K. Sunol , John Kosky, Mike Murphy, Eric Hansen,John Jones, Brad Mierau, Sermin Suno. Supercritical Fluid Aided Encapsulation of Particles, Chemical Engineering Department, University of South Florida Tampa FL 33629 USA.
53. Marentis R, James K. Processing pharmaceuticals with supercritical fluids. 4th Brazilian Meeting on Supercritical Fluids EBFS, 2001; TN-17.
54. Thies C, Ribeiro Dos Santos I, Richard J, VandeVelde V, Rolland H, Benoit JP. A supercritical fluid-based coating technology 1: process considerations, J Microencapsul. 2003; Jan-Feb; 20(1):87-96.
55. S.D. Yeo, G.B. Lim, P.G. Debenedetti, H. Bernstein. Formation of microparticulate protein powders using a supercritical fluid antisolvent. Biotechnology and Bioengineering 1993; 41: 341– 346.
56. E. Reverchon, G. Della Porta, S. Pace, A. Di Trolio. Supercritical antisolvent precipitation of submicron particles of superconduct precursors. Indust & Engi Chem Res 1998; 37 (3): 221–236.
57. Jennifer Jung, Michel Perrut. Particle design using supercritical fluid: Literature and patent survey ,J Supercrtical Fluid  2001; 20:179-219.
58. R. C. Peterson, D. W. Matson, R. D. Smith. Rapid precipitation of low vapour pressure solid from supercritical fluid solution: The formation of thin films and Powders. J. Am. Chem. Soc. 1986; 108, 2100.
59. Matson DW, Fulton JL, Petersen RC, Smith RD.  Expansion of supercritical fluid solution: solute formation of powders. Thin films and fibers. Ind Eng Chem Res. 1987; 26:2298-2306.
60. Kim JH, Paxton TE, Tomasko DL. Microencapsulation of naproxen using rapid expansion of supercritical solutions. Biotechnol Prog 1996; 12(5):650-661.
61. J.J. Shim, M.Z. Yates, K. P. Jhonston. Polymer Coatings By Rapid Expansion of suspension in supercritical carbon dioxide. Ind. Eng. Res 1999; 38:3655-3662.
62. G. Tepper, N. Levit. Polymer deposition from supercritical solutions for sensing applications. Ind Eng Chem Res 2000; 39(12): 4445-4449.
63. Chernyak, Y, Henon, F, Harris, R. B, Gould, R. D, Franklin, R. K,  Edwards, J.R,  DeSimone, J. M, Carbonell, R. G. Formation of Perfluoropolyether Coatings by the Rapid Expansion of Supercritical Solutions (RESS) Process. Part 1: Experimental Results. Ind Eng Chem Res 2001; 40: 6118–6126
64. Matsuyama, K., K. Mishima, H. Umemoto and S. Yamaguchi, Environmentally Benign Formation of Polymeric Microspheres by Rapid Expansion of Supercritical Carbon Dioxide Solution with a Nonsolvent. Environ. Sci. Technol 2001; 35: 4149–4155.
65. Mawson, S., Johnston, K. P., Betts, D. E. et al. Stabilized polymer microparticles by precipitation with a compressed fluid antisolvent. 1. Poly(fluoro acrylates), Macromolecules, 1997; 30: 71-77.
66. Reverchon E. Supercritical antisolvent precipitation of micro- and nano-particles. J Supercrit Fluids.1999; 15:1–21.
67. N. Elvassore, A. Bertucco, and P. Caliceti. Production of proteinloaded polymeric microcapsules by compressed CO2 in a mixed solvent. Ind Eng Chem Res 2001; 40:795-800.
68. Chattopadhyay, P, Gupta, R. B. Supercritical CO2-Based Production of Fullerene Nanoparticles. Ind Eng. Chem Res 2000; 39 (7): 2281-2289.
69. Chattopadhyay, P.; Gupta, R. B. Production of Antibiotic Nanoparticles Using Supercritical CO2 as Antisolvent with Enhanced Mass Transfer. Ind Eng Chem Res 2001; 40 (16): 3530- 3539.
70. Wang, Y., Dave, R.N., and Pfetter, R. Polymer coating/encapsulation of nanoparticles using supercritical anti-solvent process. J. Supercrit. Fluids, 2004; vol. 28:  85-99.
71. Corazza ML, Filho LC, Dariva C. Modeling and simulation of rapid expansion of supercritical solutions. Brazilian J Chem Eng 2006; 23(3): 417-425.
72. M.L. O’Neill, Q. Cao, M. Fang, K.P. Johnston, S.P. Wilkinson, C. Smith, J.L. Kerschner, S.H. Jureller. Solubility of homopolymers and copolymers in carbon dioxide, Ind Eng Chem Res 1998; 37:  3067.
73. E. Reverchon, G. Della Porta, I. De Rosa, P. Subra, D. Letourneur. Supercritical antisolvent micronization of some biopolymers. J. Supercrit. Fluids 2000; 18: 239.
74. T.W. Randolph, A.J. Randolph, M. Mebes, S. Young. Sub-micrometer-sized biodegradable particles of poly(l-lactic acid) via the gas antisolvent spray precipitation process. Biotechnol Progress 1993; 9:  429.
75. Florence Marciacq ,chimica oggi . Chemistry Today, Nanotechnologies Coating of nanoparticles by using supercritical CO2 (27) n 1 / Jan. Feb.2009, 31.
76. T.J. Young, K.P. Johnston, K. Mishima, H. Tanaka. Encapsulation of lysozyme in a biodegradable polymer by precipitation with a vapor-over-liquid antisolvent. J Pharmaceut Sci 1999; 88,: 640.
77. R. Falk, T.W. Randolph, J.D. Meyer, R.M. Kelly, M.C. Manning. Controlled release of ionic compounds from poly (l-lactide) microspheres produced by precipitation with a compressed antisolvent. J Control Release 1997; 44: 77–85.
78. D.J. Dixon, K.P. Johnston, R.A. Bodmeier, Polymeric materials formed by precipitation with a compressed fluid anti-solvent, AIChE J 1993; 39: 127.
79. Ribeiro I, Richard J, Pech B, Thies C, et al. Microencapsulation of protein particles within lipids using a novel supercritical fluid process. Int J Pharm 2002; 242(1-2): 69.
80. Yang DB.  Direct kinetic measurements of vinyl polymerization on metal and silicon surfaces using real-time FT-IR spectroscopy. Appl Spectrosc. 1993; 47:1425-1429.
81. Yang D. B. Kinetic studies of phtopolymerisation using real time FT-IR spectroscopy. j. Polymer. Sci. Polymer chem. 1993; 31; 199-208.
82. Nakamura, Kenichi K, Hirotoshi K, Toshio S, Shichi. Photocurable paint composition for road marking. US Patent 6211260. 2001.
83. Moore, James E. Photocurable acrylonitrile coated plastic articles. US patent 4557975. 1985.
84. Takahashi, Naoto M, Katsushiro. Process for producing coated plastic lenses and lenses holder. US patent application 0027782. 2009.
85. Biller, Kevin M, Fadder M, Ben A. Radiation curing of powder coating on wood. US Patent 1998; 5824373.
86. S.P. Pappas (Ed.), UV-Curing: Science and Technology, Vol. I, Technology Marketing Corporation, Connecticut, USA, 1980, 2nd printing.
87. Sagarika Bose, Robin H. Bognera, Solventless visible light-curable coating: II. Drug release, mechanical strength and photostability. Int J P'ceutics 2010; 393:  41–47.
88. Pappas SP.  UV curing by radical, cationic and concurrent radical-cationic polymerization. Radia Phys Chem. 1985; 25:633-641.
89. Bieleman JH, Additives for Coating. Wiley-CVH, New York, 2000, 338-348.
90. Jacobine A.F. and Nakos, S.T. Photopolymerizable silicone monomers, oligomers, and resins. In Pappas, S.P. (Ed.), Radiation Curing: Science and Technology, Plenum, New York, 1992; 181-239.
91. Pereira, S.G., Nunes, T.G., Kalachandra, S. Low viscosity dimethacrylate co monomer compositions [Bis-GMA and CH3Bis-GMA] for novel dental composites; analysis of the network by stray-field MRI, solid-state NMR and DSC & FTIR. Biomaterials 2002; 23: 3799–3806.
92. Bose S, Bonger RH. Design And space for solventless photocurable pharmaceutical coating. J Pharma Innov, 2006; 1(1): 44-53.
93. Hiroshi I, Kimihiro M, Yoshiko T, Noboru N. Photo-Curing of Acryl-Functional Alkoxysilane with Benzoin Sulfonates. J Photopoly Sci Tech, 1999; 12 (1): 129-132.
94. Ahmed, Farooq, Faisal. Solvent free silicone coating composition U.S. Patent 2004;6,833,407.
95. Mistv, Toska A. Composition containing UV curable unsaturated monomer and/or oligomers, a Photoinitiator and colloidal silica with an organosilane compound, an application of compositions on coatings. US Patent 1992. 5,086,087.
96. Bose, S., Bogner, R.H, 2007b. Solventless photocurable film coating: evaluation of drug release, mechanical strength and photostability. AAPS Pharm Sci Tech 8, E1–E10.
97. J. Jakubiak, A. Sionkowska, L-A. Linden, J.F. Rabek. Journal of Thermal Analysis and Calorimetry, Isothermal Photo Differential Scannig Calorimetry. Crosslinking polymerization of multifunctional monomers in presence of visible light photoinitiators, 2001; 65: 435-443.
98. C. G. Roffey, Photopolymerization of Surface Coatings, Chap. 4, John Wiley and Sons Ltd., 1982.
99. Salthammer, T. Release of Photoinitiator Fragments from UV Cured Furniture Coatings. J Coat Technol 1996; 68:856, 41.
100. Wang J, Bogner R. Solvent-free film coating using a novel photocurable polymer. Int J Pharm 1995; 119(1): 81-89.
101. Gowarikar V, Polymer Science, 1 st edition, New Edge International Publication, 1986, p. 15- 85.
102. Ramlakhan M, Wu CY, Watano S, Dave RN, Pfeffer R. 90th Annual Meeting, AIChE. Nov 1998.
103. M. Ramlakhan, C.-Y. Wu, S. Watano, R.N. Davé, R. Pfeffer. Dry particle coating using magnetically assisted impaction coating (MAIC): modification of surface properties and optimization of system and operating parameters. Powder Technol. 2000;112: 137–148.
104. J. Yang, A. Sliva, A. Banerjee, R.N. Davé, R. Pfeffer. Dry particle coating for improving the flowability of cohesive powders. Powder Technol Spec. Issue Mem. Prof. Molerus 2005;158:  21–33.
105. Robert Pfeffer, Rajesh N. Dave, Dongguang Wei, Michelle Ramlakhan. Synthesis of engineered particulates with tailored properties using dry particle coating. Powder Techn 2001;117: 40–67.
106. Singh P, Solanky T, Mudryy R, Pfeffer R, Dave R. Estimation of coating time in the magnetically assisted impaction coating process. Powder Technol 2001; 121(2-3): 159-167.
107. Stephanie Bosselmann , Donald E. Owens III , Rachel L. Kennedy , Matthew J. Herpin , Robert O. Williams III. Plasma deposited stability enhancement coating for amorphous ketoprofen. European J Pharma Biopharma 2011;78: 67–74.
108. C. Cavallotti, M. Di Stanislao, S. Carra. Interplay of physical and chemical aspects in the PECVD and etching of thin solid films. Prog. Cryst. Growth Charact. Mater. 2004; 48–49: 123–165.
109. J.Raud van ommenelena Abadjieva Yves l.m.creyghton,ECI conference on the 13th International-new paradigm in fluidization engineering,2010.
110. http://services.bepress.com/eci/uidizationxiii/68.
111. J. Zhang, F. Zhu, C. Shi, L. Sun, Y. Wang, Z. Cheng et.al. Molecular tailoring coating on TiO2 nanoparticle surface by plasma polymerization, In: R. d’Agostino, P. Favia, C. Oehr, M.R. Wertheimer (Eds.), Plasma Processes and Polymers, Wiley-VCH Verlag GmbH, Weinheim, Germany, 2005, 117–128.
112. R. Forch, A.N. Chifen, A. Bousquet, H.L. Khor, M. Jungblut, L.Q. Chu, Z. Zhang, I. Osey-Mensah, E.K. Sinner, W. Knoll. Recent and expected roles of plasma polymerized films for biomedical applications. Chem. Vap. Deposition 2007; 13: 280–294.
113. N. Gomathi, A. Sureshkumar, S. Neogi. RF plasma-treated polymers for biomedical applications. Curr Sci 2008; 94: 1478–1486.
114. C. Susut, R.B. Timmons. Plasma enhanced chemical vapor depositions to encapsulate crystals in thin polymeric films: a new approach to controlling drug release rates. Int J Pharm 2005; 288:  253–261.
     

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     Refaat J, Kamel SM, Ramadan AM and Ali AA: Crinum; an endless source of Bioactive Principles: A Review. Int J Pharm Sci Res, 2012; Vol. 3(7): 1976-1986

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