Particulate Coating – The Cornerstone of Controlled Release Systems

Particulate systems such as pellets, granules, mini-tablets, and microspheres offer several distinct benefits over conventional tablets and capsules – suitability for co-administration of incompatible actives, reduced dose-dumping, uniform drug-release, and improved bioavailability. These particulates are combined in single dosage units such as capsules or compressed into tablets for administration ease.

The drug in the particulate systems is entrapped within the cores or is layered over them. Functional coatings are applied to the particulates to improve physical characteristics, to enhance chemical stability, for taste-masking, but most importantly and frequently to achieve modified drug-release profiles such as sustained, pH-dependent, time-programmed, or targeted release.

Following are the principal methods used for particulate coating:

  1. Air suspension/fluid-bed coatingIn this method, the coating material in liquid form is sprayed as a thin film onto the air-fluidised particulate bed. The liquid coats are dried by hot fluidising air, while the molten coats are dried by cold fluidising air. Powder coating of particulates can also be carried out by alternatively spraying the polymer-talc powder mixture and plasticizer-binder solution on the fluidised particulate bed, followed by curing so that the polymer particles coalesce and form a film.Air suspension coating using fluid bed/Wurster coater is the most widely used method for particulate coating as it is adaptable for different types of functional coatings. Several key process variables must be taken into consideration for particulate coating by the Wurster process:
    1. Distance between the spray nozzle and fluidisation zone should cause minimal attrition by atomising air velocities.
    2. Atomising air pressure of spray nozzles influences the droplet size. Too small droplets dry out before depositing on the cores, while too large droplets form bridges between cores and cause agglomeration.
    3. Lower air-flow rates lead to inadequate drying and agglomeration, while higher air-flow can cause attrition.
    4. Drying temperatures should allow adequate coalescence of coating material on the cores before drying.
    5. Curing temperatures below the glass-transition temperature of the polymer helps to avoid agglomeration.

    Some examples of functional coating of particulates by the Wurster process include duloxetine hydrochloride, meloxicam, and haemoglobin.

  2. Compression CoatingLarger particulates such as mini-tablets are coated by this method. The particulates are immersed in a bed of powder coating material in a tablet press and covered with a layer of coating powder on the top. The mixture is then compressed at a compaction pressure of 10-30 kN to ensure the integrity of the particulates during and after consolidation. The viscoelasticity of the particulates and the excipients used for coating also plays an essential role in maintaining the integrity of the coated particulates. This method is, however, complex. Also, there is the possibility of uneven coating if the core is not appropriately placed. Compression coating has been studied for enteric delivery of drugs like omeprazole, bisacodyl, ibuprofen, diltiazem, and probiotics.
  3. Solvent EvaporationParticulates are placed in a coating polymer solution prepared in a volatile organic solvent. The solvent is evaporated by constant stirring, leaving a film around the particulates. Pellets of melatonin have been coated by this method for oral delivery in a circadian manner over 8 hrs.
  4. 4. CoacervationThe particulates are placed in a coating polymer solution. The polymer is precipitated on the surface of cores by temperature change or by the addition of a precipitating agent. The coated particles are then dried. Coating by coacervation has been reported for drugs like ibuprofen, methoxybutropate, 5-fluorouracil, and ketorolac. This approach has also been explored for taste masking of microparticles and coating of probiotic microbeads.
  5. Spray DryingThis method is suitable for coating micron-sized particulates. The drug in a polymer solution is sprayed and dried in a spraying-chamber at high temperatures to form microcapsules. If the drug is soluble in the polymer solution, it forms a matrix system upon drying. If the drug is insoluble in the polymer solution, coated microcapsules are formed. Microparticles/microcapsules of diltiazem, lycopene, ibuprofen, and theophylline have been prepared by spray drying.
  6. Spray CongealingThis method is similar to spray drying and is also used for coating micron-sized particulates. This method’s advantage is that it is solvent-free, employs molten lipidic coating materials that solidify at lower temperatures, and help achieve high encapsulation efficiencies. This method, however, cannot be used for hydrophilic drugs due to poor encapsulation efficiency. Hydrophilic waxes or polymers like stearyl alcohol, lecithin, or high molecular weight polyethylene glycols.
    Indomethacin, aspirin, ibuprofen], and verapamil hydrochloride have been coated by spray congealing.

Conclusion

Coating of particulate systems offers tremendous opportunities for developing new controlled-release oral formulations. Extensive knowledge and advances in coating processes, equipment, and technologies can further help expand the future development of these reliable and time-tested drug delivery systems.

References
1. Tang, E.S., L. Chan, and P.W. Heng, Coating of multiparticulates for sustained release. American Journal of Drug Delivery, 2005. 3(1): p. 17-28.
2. Dey, N., S. Majumdar, and M. Rao, Multiparticulate drug delivery systems for controlled release. Tropical journal of pharmaceutical research, 2008. 7(3): p. 1067-1075.
3. Kuang, C., et al., Preparation and evaluation of duloxetine hydrochloride enteric-coated pellets with different enteric polymers. Asian journal of pharmaceutical sciences, 2017. 12(3): p. 216-226.
4. Bodmeier, R., Tableting of coated pellets. European journal of pharmaceutics and biopharmaceutics, 1997. 43(1): p. 1-8.
5. El-Mahdi, I. and P. Deasy, Tableting of coated ketoprofen pellets. Journal of microencapsulation, 2000. 17(2): p. 133-144.
6. Fassihi, S.C., R. Talukder, and R. Fassihi, Colon-Targeted Delivery Systems for Therapeutic Applications: Drug Release from Multiparticulate, Monolithic Matrix, and Capsule-Filled Delivery Systems, in Targeted Nanosystems for Therapeutic Applications: New Concepts, Dynamic Properties, Efficiency, and Toxicity. 2019, ACS Publications. p. 309-338.
7. Kapoor, D., et al., Coating technologies in pharmaceutical product development, in Drug Delivery Systems. 2020, Elsevier. p. 665-719.
8. Lee, B.-J. and G.-H. Min, Oral controlled release of melatonin using polymer-reinforced and coated alginate beads. International journal of pharmaceutics, 1996. 144(1): p. 37-46.

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