Preparation of green and gelatin-free nanocrystalline cellulose capsules

Highlights

• The green and gelatin-free capsules were prepared using NCC.

• The disintegration time of NCC capsule meets the criteria in USP32-701.

• No significant difference in drug release between NCC capsule and gelatin capsule.

• NCC capsule supplies a green platform for applications in drug delivery.

Abstract

The ambiguous source and uncontrolled solubility of gelatin make it crucial to develop gelatin capsule substitutes. Nanocrystalline cellulose (NCC) of excellent mechanical performance, good biocompatibility and green origin has drawn many attentions as a new class of biomaterials. In this work, NCC capsule was prepared by dipping method with PEG and glycerol as plasticizer. The effect of PEG and glycerol on the rheological property of NCC gel and the surface morphology of NCC capsule was evaluated. The disintegration time of NCC capsule meet the criteria in United States Pharmacopoeia (USP32-701).There is no significant difference in the release of sulfuric acid between gelatin capsule and NCC capsule. NCC capsule thus has the potential as a green platform for biomedical applications in drug delivery.

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.