(51c) Tablet Coating By Injection Molding Technology: Characterization of Coating Materials for Optimal Process and Product Performance

ablet coating is one of the most commonly used pharmaceutical unit operations in tablet manufacturing. It renders possible advantages of taste and odor masking, physical and chemical protection, product differentiation, and elegant look to the finished tablet products. Spray coating is the most frequently used film coating process which involves organic and aqueous solvent based polymer systems. The organic solvents can be flammable, costly, and toxic in nature, whereas moisture sensitive drugs cannot be coated with aqueous coating systems. Longer drying time and resulting higher energy costs are other disadvantages of aqueous systems. We have developed a tablet coating process using solvent-free injection molding (IM) technology that can address the limitations experienced by other coating processes. Also, IM technology could be suitable for continuous manufacturing if incorporated with a continuous IM tableting platform. The aims of this research were to 1) optimize coating formulation attributes and process parameters of IM technology, 2) characterize physical properties, process performance and resulting quality attributes of pharmaceutical coating materials, and 3) evaluate the suitability and applicability of IM coating for pharmaceutical tablets.

Methods

Coating formulations (coating polymer and plasticizer in particular ratios) were fed to a vertical, miniature, twin-screw extruder and the generated extrudates were collected through the exit port. Dogbone shaped specimens were created with a microinjector and tested on a universal testing machine. Major mechanical test parameters, like Young’s modulus, percentage elongation at the break, toughness, tensile stress at break and tensile strength were determined. A melt flow analysis was conducted using the microinjector with some modifications in the original instrument. Various coating formulations were fed into the heated IM barrel until it was completely filled. A pressure of 600-630 psi was applied by the injection piston onto the coating formulation and the material coming out from heated barrel was then collected in a container to measure the melt flow (g/min). Based on the mechanical properties and melt flow analysis, coating formulations were selected to coat tablets using an in-house built vertical IM machine in a 2-step process. Briefly, the temperature controlled injection barrel was first filled with a coating formulation and the uncoated tablet was placed inside the cavity of the mold inserts. Next, an injection piston applied pressure to the coating formulation and allowed the softened coating material to flow from the barrel to the mold insert. The coating material solidified inside the mold cavities and rendered a smooth coating layer attached to the first half of the tablet surface (step 1). Mold halves were opened, tablet was flipped over and step 2 coating was performed similar as step 1 to obtain fully coated IM tablet. Process parameters (barrel temperature, injection pressure, mold temperature, and cooling time) were optimized for different coating formulations. Coated tablets were stored in various storage conditions and evaluated after 8 weeks to evaluate the coat stability. Drug release from uncoated and coated griseofulvin (GF) tablets was studied, as per GF tablets USP monograph - test 1 dissolution methodology.

Results

Coating formulations suitable for IM process were ranked by evaluating different material properties (Young’s modulus, toughness, percentage elongation, and tensile strength/Young’s modulus ratio) acquired from the stress-strain analysis. The melt flow property of the coating formulations played a crucial role in IM processing. IM process parameters like injection pressure, barrel temperature, and mold temperature were critical for successful IM coating and were evaluated in depth. Sufficient room humidity (>30% RH) was required while employing polyethylene oxide (PEO) based formulations to avoid immediate cracks, whereas other formulations were insensitive to the room humidity. Tested formulations based on Eudragit E PO and Kollicoat IR did not have the desired tensile properties. Based upon this study, hydroxypropyl peastarch + 30% glycerol, PEO 1,000,000 + 30% PEG and Opadry + 25% glycerol were proven to be viable coating formulations for IM based tablet coating. These formulations had favorable tensile (<700 MPa Young’s modulus, >30% elongation, > 95x10⁴ J/m³ toughness) and melt flow (>0.4 g/min) properties, that provided suitable IM coats. These three formulations increased the dissolution time by 10, 15 and 35 minutes respectively (75% drug release) compared to the uncoated tablets (15 minutes). Coated tablets stored in several environmental conditions remained stable to cracking for the studied 8-week time period.

Conclusions

The study confirmed IM as a viable technology for tablet coating. The study serves as a model for product development with specifications of excipients in ranges within the designed acceptance space for optimal product performance.