(M1430-12-78) Investigating the Effect of Plasticizer Type and Concentration on Kollicoat® SR Films Prepared by Film Casting Technique

Purpose: Multiple Unit Pellet Systems (MUPS), a type of extended-release dosage form, present several benefits in comparison to single unit dosage forms such as coated tablets or capsules. MUPS are normally compacted as tablets or filled into hard gelatine capsules to produce a final drug product (1). During compaction there is a significant risk of damaging the film coating, particularly if the coating material is brittle. Recent studies have discussed the properties of various extended-release polymers and the effect of additional excipients such as plasticizers on the flexibility of the MUPS coating layer and their ability to resist fracture during compression, hence maintaining extended-release properties (2-4).The present research work aimed to investigate the effects of plasticizer type (polyethylene glycol 400 (PEG 400) and triethyl citrate (TEC)) and concentration (5,10,15,20%w/w) on the thermal and mechanical properties of the water-insoluble extended-release film forming polyvinylacetate polymers.

Methods: Polymer films were prepared from aqueous dispersions of polyvinyl acetate (Kollicoat® SR 30D,BASF SE,Germany). Plasticizers (TEC(Merck,Germany) or PEG 400(BASF, Germany)) were added at concentrations of 0,5,10,15 or 20% based on the total weight of polymer into the dispersion and stirred for at least 2 hours before casting onto a Teflon plate with dimensions of 10 cmx10 cm. The plates were then incubated at 40°C for 24 hours in an oven (Binder GmbH,Germany) to obtain thin films by solvent evaporation. Thermal analysis of the films was performed using differential scanning calorimeter (DSC 214 Polyma,Netzsch,Germany). The analysis method was adopted from the literature (5) with slight modifications by using a modulation ramp of 2°C/min from−40 to 100°C. Thermograms were analysed using Proteus® Software (Netzsch,Germany). The glass transition temperature (Tg) was recorded as the midpoint of the transition that appeared in the reversible heat flow. The mechanical properties of the dried films were evaluated using a TA.XT Plus texture analyser (Stable Micro Systems,UK), mounted with a 5 N capacity load cell at room temperature. The film samples (5cm×0.5cm) were held in place using tensile grips at the extension speed of 10 mm/min. The resulting stress/strain plots were evaluated and used to determine mechanical properties The viscoelastic properties of the films were evaluated using dynamic mechanical analysis (Q800 DMA,TA Instruments,USA). A frequency sweep method was employed at a constant strain at a temperature of 25°C, across a frequency range from 0.1 Hz to 100 Hz. The applied preload force was 0.01 N, and the oscillating amplitude was 15 µm.

Results: The Tg values of Kollicoat® SR polymer films, with varying concentrations of plasticizers (TEC or PEG 400) are presented in Table 1. The Tg of pure Kollicoat SR without any plasticizer was found to be 28.7°C. However, an increase in the concentration of TEC up to 20%, resulted in a gradual decrease in the Tg, reaching a minimum of 4°C at a 20%w/w loading of TEC. Table 1 shows the comparative mechanical properties of the polymer films with TEC and PEG 400 at various concentrations (5-20% w/w). Values of pure Kollicoat SR films could not be determined accurately due to the highly brittle nature of the films. Films prepared with either 5% TEC or PEG 400, exhibited comparable tensile strength. However, PEG 400 films displayed a higher elongation percentage. On the other hand, the mechanical properties of TEC films improved with increasing concentration, resulting in lower tensile strength but higher elongation at 20%. Surprisingly, the Tg of PEG containing films was relatively constant (~20°C) at concentrations of 10% w/w or higher, whereas the mechanical properties were significantly impacted. For example, the tensile strength of PEG 400 containing films decreased as the concentration of PEG increased from 10% to 15% 20%w/w. However a further increase to 20%w/w had no major impact upon mechanical properties, Table 2 presents the viscoelastic properties of the films with varying concentrations of plasticizers (TEC or PEG 400) at different frequencies, measured using DMTA. As the concentration of plasticizer increased, the tan value approached 1, and even exceeded a value of 1 at 20% TEC concentration. Furthermore, increased tan values were observed with increasing concentrations of TEC. However, at high concentration of PEG, tan delta values of films were similar whereas TEC continued to increase the viscous response, resulting in a loss tangent value that exceeded.

Conclusion: In this work, both PEG and TEC have been shown to positively impact the Tg, mechanical and viscoelastic properties of the Kollicoat® SR polymer. Increasing concentrations of TEC up to 20% w/w resulted in improved mechanical characteristics, whereas PEG reached a plateau point at 15% w/w concentration. Using a lower concentration, e.g., 5%w/w or 10%w/w could serve as a promising plasticizer concentration, thus enhancing the mechanical properties and providing flexibility to the polymer film during tablet compression. The findings from this study serve as a useful insight to the relevance of mechanical and viscoelastic testing of polymer films to be used for micropellet formulation.

References: 1. Roland Bodmeier, Tableting of coated pellets, European Journal of Pharmaceutics and Biopharmaceutics, Volume 43, Issue 1, 1997, Pages 1-8, ISSN 0939-6411, https://doi.org/10.1016/S0939-6411(96)00028-8.
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3. Kaur S, Sivasankaran S, Wambolt E, Jonnalagadda S. Determinants of zero-order release kinetics from acetaminophen-layered Suglet® pellets, Wurster-coated with plasticized Aquacoat® ECD (ethyl cellulose dispersion). Int J Pharm. 2020 Jan 5;573:118873. doi: 10.1016/j.ijpharm.2019.118873. Epub 2019 Nov 22. PMID: 31765772.
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Acknowledgements: This research was funded by BASF.

Table 1. Comparative Tg and mechanical properties of the Kollicoat® SR polymer films with TEC and PEG 400 at different concentration.

Table 2. Comparative viscoelastic properties of the Kollicoat® SR polymer films with TEC and PEG 400 at different concentration.