Preparation of green and gelatin-free nanocrystalline cellulose capsules
Introduction
Capsule provides a tasteless and odorless delivery system for medicine in form of power since the late nineteenth century (Yang et al., 2016). At present, most of the capsules are prepared using gelatin as raw material. It has been reported that a number of factories produced the so-called pharmaceutical gelatin and edible gelatin from waste leather which had been treated by toxic and harmful materials (Mokrejs et al., 2009), and the chromium content in these gelatin exceeds 16 times the standard content. With the world of mad cow disease and other serious events, people had a certain sense of insecurity to the gelatin which was produced from cattle, pigs and other animals’ bones. At the same time, some special populations, such as Buddhists, Muslims and vegetarians, desperately need capsules of non-animal ingredients (Sattar, Ahmed, Majeed, & Petty, 2004). It has also been reported that gelatin will partially be insoluble in water due to the cross-linking reaction at certain conditions, such as the existence of aldehydes in the capsule fill material or hot and humid storage (Brown, Cole, Wilding, & Cade, 1998). Due to the various origins and preparation methods, the structure and composition of gelatin are different, and the gelatin capsule dissolution is not well controlled (Hanani et al., 2012, Samal et al., 2015). Many experts have begun to focus on the development of gelatin substitutes (Bae et al., 2008, Bhatt and Kumar, 2015, Nagata, 2001, Zhang et al., 2013a). Chitosan, starch and regenerated cellulose are attempted to prepare capsules (Yang et al., 2016). However, their potential applications in pharmaceutics are limited by several facts, such as the poor mechanical properties of starch, the exceeded metal ions in chitosan, and the insolubility of regenerated cellulose in aqueous solution, etc. (Cheng, Zhang, Cha, Yang, & Jiang, 2016).
Nanocrystalline cellulose (NCC), which consists of a highly crystalline rod-like particles with the average length of 100–400 nm and diameter of 5–10 nm, is prepared from natural cellulose. It has good hydrophilicity and can be evenly dispersed in water, so it has the same excellent performance as gelatin. (Beltramino et al., 2015, Cha et al., 2012, Filson and Dawson-Andoh, 2009, Hu et al., 2015, Lin et al., 2009, Spinella et al., 2016, Sun et al., 2014, Tang et al., 2015, Zhang et al., 2015, Wang et al., 2014, Wang et al., 2016a). NCC has many unique characteristics, such as high strength, high aspect ratio, high specific surface area, low density and so forth (Cha et al., 2014, Kumar and Singh, 2008, Liu et al., 2010a, Liu et al., 2010b, Rao et al., 2015, Soeta et al., 2015, Tang et al., 2014, Yu et al., 2014, Zaman et al., 2012, Zoppe et al., 2009). It has been reported that NCC has low concern level and does not have the potential to harm aquatic organisms at concentrations that could occur in receiving water (Sirvio et al., 2015, Tibor et al., 2010, Wang et al., 2015, Wang et al., 2016b, Yanamala et al., 2014).
In this study we developed green capsules based on NCC. The effect of PEG and glycerol loading on rheological properties of NCC gel was evaluated. The mechanical property, surface morphology, swelling property, disintegration time and drug release of the capsule were also studied in detail.
Section snippets
Materials and Instruments
NCC was prepared from Northern bleached hardwood pulp (NBHK) by sulfuric acid hydrolysis (concentration: 60.0%, time of treatment: 4 h) according to the method described previously (Wang et al., 2014). The content of NCC was 6.02 wt% (zeta potential: −45 mV).
PEG-4000 and NaCl were purchased from Sigma Co. Ltd. Glycerol, pepsin, salicylic acid and sodium dodecylsulphate were purchased from Aladdin Co. Ltd. Hydrochloric acid (36.5%) and sulfuric acid (64%) were purchased from Cloning biological
Rheological properties of the NCC gel
PEG and glycerol was plasticizer in the NCC gel. Effect of PEG and glycerol on the elastic modulus of the gel was shown in Fig. 2a. The effect of PEG on the elastic modulus of NCC gel did not change over time. When the content of PEG increased, the elastic modulus of the gel system decreased, the value of which was lower than that of pure NCC gel. This shows that the number of hydrogen bonds in the system is reduced, while PEG can destroy the stable hydrogen bonds in NCC gel system.
The elastic
Conclusions
In this work, NCC capsule was rapidly prepared by dipping method with PEG and glycerol as plasticizer in a one-step manner. The NCC capsules can completely disintegrate before 300 s which can fulfill the requirement of USP32-701. The cumulative release percentage of SA can up to 50% in 16 min, and there is no significant difference in the release of SA between gelatin capsule and NCC capsule. Importantly, NCC is produced from natural plant fibers. Therefore, this kind of capsule supplies a green
Acknowledgements
Financial support was provided by the Independent Innovation and Achievement Transformation Project in Shandong Province (2014CGZH0303) and the CAS (XDA09030305). We also thank the Beijing Petrochemical Research Institute and Beijing Silliker Co., Ltd for fruitful discussions and tests of the film.
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These authors contributed equally to this work.