(T1130-02-14) Low Viscosity Hypromellose for Capsule Banding and Tablet Coating Applications via Ethanol (Isopropanol)/Water Solvent Media

Purpose: It is important to effectively band hard-shell capsules after they are filled with solid, semi-solid and liquid formulations. Good quality banding can reduce defects, increase productivity (reduce cost), and improve the stability of the final dosage form. This ensures that patients receive the correct dosage over the intended period. Low viscosity hypromellose (hydroxypropylmethyl cellulose, HPMC LV) in ethanol/water solvent media has been effectively used for capsule banding to create a tamper-resistant seal and ensure liquid-tight capsules. This is especially important for liquid-filled capsules to prevent leakage and maintain the stability of the formulation. Similarly, HPMC LV in organic solvent media (e.g. ethanol/water) has been used in pharmaceutical tablets/pellets coatings to reduce the interaction of water with moisture-sensitive APIs. The main factors controlling capsule banding formulations as well as coating formulations are the viscosity of polymer solutions and the concentration of polymer solutions. The usage of organic solvent such as ethanol/water in these formulations allowed vary fast drying at relatively low temperatures or air volumes. This study evaluated the rheological behavior of lowest viscosity grades of hypromellose in ethanol/water solvent system and the viscosity-concentration relationship hypromellose in various ethanol/water mixture. Additionally, the effect of plasticizers and surfactants on film performance was also investigated, which correlates the performance of the banding film and coating.

Methods: The polymer solutions with various concentrations were made from low viscosity hypromellose of type 2910 (labeled as E3P), type 2906 (labeled as VLV), and type 2208 (labeled as K3P), in ethanol/water (EtOH/H₂O) or isopropanol/water (IPA/H₂O) solvent. Plasticizers and surfactants such as triacetin, polyethylene glycol (PEG 400), triethyl citrate (TEC), and polysorbate (Tween 20 and Tween 80 etc.) were also used in the formulations. Such polymer solutions were subsequently used to cast films. Rheological experiments were performed on polymer solutions using a StressTech stress rheometer and Anton Paar MCR 702e rheometer. Film puncture strength and distance were measured on a Texture Analyzer (model TA.XT2). Capsule banding operations of HPMC capsules filled with Gellucire 44/14 were performed on a capsule banding equipment, STI Laboratory Capsule Bander by Schaefer Technologies.

Results: A comparison of rheological behaviors of E3P, K3P and VLV in water as well as in ethanol/water mixture were investigated. An example of the comparison is shown in Figure 1.  E3P showed a significantly lower viscosity than that of K3 and VLV in the EtOH/H₂O solvent system. It was found that the addition of surfactant can increase or decrease solution viscosity depending on the surfactant concentration. Similarly, addition of plasticizers can increase or decrease solution viscosity depending on the solvent mixture, plasticizer type and plasticizer concentration. Film mechanical properties were evaluated by puncture testing.  It was found that triacetin and TEC provided higher film puncture strength, elasticity, and work to puncture comparing to the other plasticizers tested, with the film being casted from an ethanol/water solution.

Conclusion: This study successfully evaluated the rheological behavior of hypromellose E3P, K3P, and VLV in EtOH/H₂O or IPA/H₂O solvent systems. The findings demonstrated the effect of polymer, solvent system, surfactant and plasticizers significantly influences the solution viscosity, with variations depending on the type, concentration, and solvent mixture used. The mechanical properties of the films with triacetin and TEC showed better performance compared to other plasticizers tested, with the films that were cast from an ethanol/water solution. These results underscore the importance of selecting appropriate polymer, surfactants and plasticizers to optimize the performance of capsule banding and coating formulations.

Complex viscosity as a function of frequency for different polymer solutions including 23% K3 in water and in EtOH/ H2O (50/50), 24% VLV in water and in EtOH/ H2O (50/50), 23% E3 in water and EtOH/ H2O (50/50).