Pharmaceutical solid dosages such as tablets, capsules and pellets are often coated with a thin layer coating material for many purposes. Esthetically, the coating improves the appearance, market image and brand recognition of the products. The coatings also serve many practical functions such as ease of packaging, ease of swallowing and improved physical and chemical stability of the products. Applying functional coatings on solid dosage forms is an important and versatile tool to modify the drug release profiles. There are many pharmaceutical products in the market with functional coatings for taste masking, odor masking, enteric release and extended release applications.
Pharmaceutical coating technologies have evolved over the years from sugar coating to solvent coating to more environmentally friendly aqueous coating. These coating processes are liquid based processes. For solvent coating, the polymeric coating materials are dissolved in the organic solvent for spraying onto the substrate. Polymeric materials are either suspended or dissolved in water for aqueous coating. Due to strict environmental regulations, aqueous coating has quickly replaced solvent coating for a majority of liquid coating processes except for some controlled released applications such as osmotic delivery and pellet formulations which still require solvent coating processes.
The major limitations associated with liquid coating processes are:
- Microbial contamination in aqueous coating processes
- Aqueous coating is not suitable for moisture sensitive drugs
- Potential moisture related product stability issues of the finished products
- Expensive air handling systems are required to remove water vapor and solvents
- Strict solvent emission regulations limiting the use of solvent coating processes
Electrostatic Powder Coating for Solid Pharmaceutical Dosage Forms
Solvent free and water free powder coatings are desirable alternatives to overcome the short comings of liquid based coating. A patented electrostatic powder coating technology for pharmaceuticals was invented by Professor Jesse Zhu at Western University after over two decades of research in powder coating.1-6 The technology utilizes pharmaceutically acceptable materials and a combination of electrostatic force, thermal energy, hydrodynamic force from the powder spray and mechanical energy from the rotation of a coating pan to coat pharmaceutical substrate directly with dry powder. The electrostatic powder coating technology has overcome the major technical challenges facing pharmaceutical powder coating to make the coating process amendable for commercial use. The challenges include powder flow, reduction of glass transition temperature of the polymer used and powder adhesion to the substrate and curing to form a uniform coat.
The electrostatic powder coating process is shown schematically in Figure 1. The substrate is loaded into a pan coater and pre-heated to approximately 60°C. A suitable plasticizer is sprayed onto the substrate to lower the glass-transition temperature of coating polymer to soften it and facilitate powder adhesion on the substrate. Ultrafine powder is sprayed onto the substrate using an electrostatic spray gun. The coating pan is grounded to create a potential difference leading to electrostatic attraction between the substrate and the charged powder. The coated substrate cures at a temperature slightly above the glass-transition temperature of the polymeric coating material to form a uniform film coat.
Many commercially available pharmaceutical coating materials from major coating materials suppliers such as Evonik, Colorcon, Dow Chemical and Kodak for controlled release applications have been successfully applied on tablets, HPMC capsules and pellets using the electrostatic powder coating technology. Immediate release coating materials include Eudragit® EPO (taste masking), as well as Opadry® II and Opadry® AMB (moisture barrier). Enteric release coating materials include Eudragit® L100 and Acryl-EZE® MP. Extended release coating materials include Eudragit® RL100 and Eudragit®RS100, ETHOCEL™ and Cellulose Acetate from Kodak (Omotic delivery devices). Other coating materials to target drug release at the lower GI track can also be used in the electrostatic powder coating.
A comparison of powder coating and liquid coating for pharmaceutical applications is shown in Table 1. Key advantages of powder coating are listed below.
- Avoid moisture related problems
- Energy efficient and environmentally friendly
- No need for expensive exhaust equipment and air handling system to remove water vapor or solvent. The equipment and facility costs are significantly reduced.
- Opens up new possibility of using powder coating to the development of controlled release formulations that traditionally requires solvent coating.
The use of ultrafine powder in electrostatic powder coating enables the formation of smooth coatings comparable or smoother than liquid coating processes. The amount of coating material deposited on the substrate; and hence, the thickness of the coating, can be controlled by the electrical voltage setting of the powder spray gun. The electrostatic repulsion of the charged powder particles promotes even distribution of the powder on the surface to form a uniform smooth coating.
The coating uniformity of powder coated tablets with different coating polymers has been studied using Laser Induced Breakdown Spectroscopy LIBS. The coating materials usually contain titanium dioxide and sometime magnesium stearate. Upon vaporization by a laser, the titanium and magnesium form excited ions which emit photons. The emission intensity is related to the amount of titanium and magnesium in the coating. By measuring the variability of the ion intensity from different locations or depths of the tablets, the variation of the coating thickness and uniformity can be assessed.
Three ibuprofen tablet batches were coated with three different types of functional coating polymer for taste masking, enteric release and extended release.4 The LIBS data of the three powder coated batches were compared to a marketed ibuprofen product. The Relative Standard Derivation (RSD) of the measured intensity at various locations and depths were compared. The results are shown in Table 2. The inter-tablet variation of the powder coated tablets is better than the commercial product. The intra-site variation of the powder coated tablets is comparable with the commercial product.
Examples of Powder Coating for Controlled Release Applications
Example 1: Powder coating for enteric formulations
Enteric coating is insoluble in low pH and allows coated tablets and capsules to pass through the stomach without releasing the drug. The coating helps to protect the acid labile drugs from hydrolysis by the stomach acid and prevent stomach irritation caused by drugs such as Aspirin. Aspirin tablets and HPMC capsules containing Aspirin (81 mg and 325 mg strengths) have been successfully coated with Eudragit® L100 – 55. The dissolution profiles of the enteric coated Aspirin tablets and capsules and the commercial Bayer Aspirin Tablets are shown in Figure 2. The powder coated tablets and capsules meets the USP dissolution requirement of less than 10% release during the acid stage testing.
Example 2: Powder coating for small pellets
Small pellets pass through the GI track at a steady pace which is very desirable for controlled release applications. Also, multiple coating layers for different functions can be applied on the pellets successively (Figure 3a). Piroxicam pellets with a particle size of 0.9–1.18 mm have been successfully coated in a pan coater with Eudragit® L100 – 55, Eudragit® EPO and Eudragit® RS/RL for enteric release, taste masking and extended release applications respectively. The dissolution profiles of the pellets with the three different polymers are shown in Figure 3b. It is worth noting that coating of small pellets usually requires the use of a fluid bed coater to suspend the pellets in mid air to prevent pellet cohesion.
Example 3: Powder Coating for Osmotic Drug Delivery Systems
Osmotic Drug Delivery Systems are the only true zero order release delivery system and the drug release is independent of food intake. Cellulose acetate has been successfully applied by powder coating onto an osmotic tablet core containing salbutamol to form a semi-permeable coat for osmotic delivery applications. The resulting osmotic delivery system and the dissolution profiles are shown in Figure 4. It is noteworthy that solvent coating is typically required for coating osmotic polymers such as cellulose acetate.
Electrostatic dry powder coating is a promising technology to replace liquid coating for many pharmaceutical applications.
Biography: Dr. Herman Lam was a Principal Investigator at GlaxoSmithKline Canada. Currently, he is the CEO of Powder Pharma Coating Inc.
Email Contact: firstname.lastname@example.org
Dr Herman Lam received his B.Sc. from the University of Toronto and his Ph.D. in chemistry from York University in Toronto. He was a Principal Investigator at GlaxoSmithKline Canada responsible for the implementation of new analytical technologies and laboratory automation. Currently, he is the CEO of Powder Pharma Coating Inc. Dr Lam also serves as the President of the Calibration & Validation Group (CVG), a government registered non-profit professional organization in Canada with focus on the GMP, calibration and validation in pharmaceutical industry. He was appointed Honorary Assistant Professor in the Department of Chemistry at the University of Hong Kong from February 2012 to 2015. He is an Adjunct Associate Professor at the School of Pharmacy of the Chinese University of Hong Kong.Page Break
- J. Zhu, Y. Luo, Y. Ma, H. Zhang, Direct Coating Solid Dosage Forms using Powdered Materials, US Patent 8161904 B2, 2007.
- M.X. Qiao, L.Q. Zhang, Y.L. Ma, J. Zhu, K. Chow, A novel electrostatic dry powder coating process for pharmaceutical dosage forms: immediate release coatings for tablets, Eur. J. Pharm. Biopharm. 76 (2010) 304–310.
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- Y. L. Yang, Y.L. Ma, J. Zhu, Applying a novel electrostatic dry powder coating technology to pellets, Eur. J. Pharm. Biopharm. 97 (2015) 118–124.