(T1330-08-53) Optimization of Tablet Coating Composition and Weight Gain for Moisture Protection Using Optimal Combined Design of Experiments (DOE)

Purpose: The protection of pharmaceutical tablets from moisture through coatings is a crucial element in drug formulation, particularly for hygroscopic drugs or those prone to hydrolysis. Ensuring moisture protection is vital for maintaining the stability of many active pharmaceutical ingredients, thereby preventing their degradation. It also ensures safety by preserving the drug's efficacy and preventing the formation of harmful byproducts¹. Kollicoat^® Protect (BASF) is a film-coating polymer made of 60% polyvinyl alcohol-polyethylene glycol graft copolymer (PVA-PEG) and 40% polyvinyl alcohol (PVA), presenting great coating processability, low viscosity in water, ideal flexibility, and high pigment load capability for moisture protection purposes². This study used an optimal combined model (combination of mixture and process factors) design of experiment (DOE) analysis to evaluate Kollicoat^® Protect’s effectiveness by evaluating and optimizing coating composition and coating weight gain parameters.

Methods: A highly hygroscopic core tablet formulation was prepared mixing 83.5% of sorbitol (Sorbitol DC, LFA Machines), 15% of crospovidone (Kollidon^® CL, BASF), and 1.5% of sodium stearyl fumarate (Pruv^®, JRS). Core tablets were compressed using 10 mm round standard concave punches for tablet weight of 360 mg using a compression force of 8.5 kN. An optimal combined model design of experiment (DOE) was employed using the software Design-Expert (Stat-Ease, Inc.) to design moisture protective film-coating formulations for these tablets using the mixture and process factors and evaluate the results of the trials. Three factors were assessed in the study: amount of Kollicoat^® Protect, as the film-coating polymer, amount of talc (Talc, Spectrum), as a hydrophobic pigment, and coating weight gain weight/weight (w/w). Kollicoat^® Protect was selected at a range from 40 to 100%, while talc was chosen at a range of 0 to 60%. The coating weight gain was examined across the typical coating range of 3% to 10% weight gain w/w. Coated tablets underwent moisture uptake tests from 0 to 90% RH (relative humidity) using a Dynamic Vapor Sorption (DVS) equipment with the equilibrium of mass change over time (dm/dt) method in place. The percentage of tablet mass increase (moisture uptake) at 60% and 70% RH and disintegration time of tablets for the various coating compositions were assessed as the responses for DOE analysis modeling and predictions.

Results: The coating process for all experiments was deemed satisfactory. A summary of core tablets formulation, coating DOE experiments and the resultant responses are presented in Figure 1. A linear X cubic model was found optimal for predicting moisture uptake at 60% RH. Instead, for moisture uptake at 70% RH and disintegration time responses, linear X quadratic models were found more adequate. 3D plots representing these observations and the response surfaces are given in Figure 2. Optimized models were used to define the design space, considering a maximum moisture uptake of 1% w/w at 60% RH and 3% w/w at 70% RH, along with a disintegration time of less than 300 seconds. The design space represented by the overlay plot for the three responses are presented in Figure 3. A mixture ratio of 60% polymer to 40% talc and a 5.5% coating weight gain, as indicated in the overlay plot, was selected for model validation experiments. Two validation experiments were performed using these factor values to evaluate the model’s predictive capability. The results were consistent with the model's predictions, as detailed in Figure 3.

Conclusion: Moisture protective film coating composition and coating weight gain for Kollicoat^® Protect and talc were well evaluated by using optimal combined design. Polymer concentration, talc content, and coating weight gain were determined to be critical parameters influencing the moisture protection of the formulated hygroscopic tablet. The design space illustrates the potential to achieve effective moisture protection through various combinations of Kollicoat^® Protect and talc at different coating weight gain levels. An increase in disintegration time was observed with higher polymer content and greater coating weight gain levels. Nevertheless, all disintegration times were below 6 minutes (360 seconds). Validation experiments using a coating composition of 60% Kollicoat^® Protect and 40% talc, with a 5.5% w/w coating weight gain, demonstrated satisfactory values for both moisture uptake and disintegration time when compared to the predicted means. These results confirm the model’s accuracy in predicting the studied responses. Overall, the findings strongly support the effectiveness of Kollicoat^® Protect as a reliable moisture barrier, making it a valuable excipient for enhancing the stability of moisture-sensitive pharmaceutical formulations.

References: 1. Mwesigwa, T., & Basit, A. W. (2016). An investigation into moisture barrier film coating efficacy and its relevance to drug stability in solid dosage forms. International Journal of Pharmaceutics 497(1-2), 70–77.
2. BASF Pharma Solutions. Kollicoat® Protect. https://pharma.basf.com/products/kollicoat-protect.

Figure 1: Core tablet composition, tableting parameters and DOE results.

Figure 2: 3D Plots representing the response surface for the DOE experiments.

Figure 3: Overlay Plot of optimized models and the DOE validation experiments results.