**4. Modifications of pectin for future applications**

The presence of several hydroxyl and carboxyl groups distributed along its backbone as well as a certain amount of neutral sugars presented as side chains gives pectin the capability of producing a broad spectrum of derivatives with modified or new functional properties. Various methods used for pectin modification include substitution (alkylation, amidation, quaternization, thiolation, sulfation, oxidation, etc.), chain elongation (cross-linking and grafting) and depolymerization (chemical, physical, and enzymatic degradation). Saponification (a process catalyzed by mineral acids, bases, salts of weak acids and primary aliphatic amines) can also be used to modify pectin chemically. Modification induced by pH changes can produce new fragments that have their solubility and biological activities altered [86]. Enzymatic modification of pectin has been achieved by using endo-polygalacturonase (Endo-PG), resulting in highly selective and specific structural changes in the polymer backbone. This modification leads to the cleavage of glycosidic linkages between two non-esterified α-D-galacturonic acid residues inside the HG fragment, which is depolymerisation. The enzymatic modification method can alter the macromolecular structure of pectin and can yield modified pectin with newer and improved properties and functionalities [87].

A new hydrolyzed polyacrylamide-graft-sodium alginate (PAAmg-SA) and diclofenac sodium-loaded interpenetrating polymer network (IPN) beads of pectin were developed using the ionic gelation method. The results of the investigation verified that hydrolyzed PAAm-g-SA and pectin cross-linked with aluminum ion (Al3+) and glutaraldehyde could form an optimal matrix material for the production of IPN beads to support the sustained release of diclofenac sodium [88]. In another study, for the nasal administration of tacrine hydrochloride (an anti-Alzheimer drug), mucoadhesive microparticles based on chitosan/pectin polyelectrolyte complexes were prepared. The microparticles were produced by spray drying followed by lyophilization and direct spray drying. The study thus demonstrated the potential of the chitosan/pectin polyelectrolyte complexes to function variously in mucoadhesive microparticles [89, 90]. The chitosan/pectin molar ratio influenced the water uptake and tacrine hydrochloride permeation [90, 91].

Emerging advanced manufacturing technology in the field of tissue engineering and pharmaceutical formulations is the use of 3D bioprinting technology. 3D printing is an additive manufacturing technology in which objects are constructed in a layer-by-layer manner achieved by heat fusion, ultraviolet light (UV), and chemical bonding [91]. Spritam®, a fast disintegrating orodispersible tablet containing levetiracetam for epilepsy was the first 3D printed drug product approved by the US Food and Drug Administration (FDA) in 2015 [91]. To sustain the manufacturing of these types of drugs using this new technique, biomaterials that are green and non-toxic, derived from renewable sources and can be processed through 3D bioprinting are being developed [42, 60]. Common techniques include powder bed printing, vat polymerization (VP), and fused deposition modeling (FDM) [92]. A major disadvantage of the FDM technology is the need to insert printing materials into a nozzle in the form of a solid filament, which is non-existing for many pharmaceutical materials, thus necessitating the transformation of pharmaceutical-grade materials, including active pharmaceutical ingredients (API), into FDM-suitable filaments using techniques like hot-melt extrusion (HME). However, thermolabile therapeutics are not suitable for extrusion via FDM, due to potential degradation concerns [93]. The use of bio-inks for extrusion-based bioprinting at room or body temperature has shown clinical potential in achieving personalized treatment [92]. For example, Long et al. developed a personalized 3D printed wound dressing composed of chitosan and pectin with the ability to

### *Pharmaceutical Applications of Pectin DOI: http://dx.doi.org/10.5772/intechopen.100152*

control dimensional properties such as thickness and pore size using an extrusionbased bioprinter [91, 92], while allowing for facile lidocaine incorporation for immediate pain relief [94]. Pectin from citrus peels has also been cross-linked with (3-glycidyloxypropyl)trimethoxysilane (GPTMS) through a one-pot procedure to obtain freeze-dried porous pectin sponges with varying porosity, water uptake, and compressive modulus [42]. The addition of GPTMS improved the printability of pectin due to an increase in viscosity and yield stress [95]. Without the use of any additional support material, three-dimensional woodpile and complex anatomical-shaped scaffolds interconnected with micro and macro pores were, therefore, bioprinted [96]. Thus showing the great potential of pectin cross-linked with GPTMS as biomaterial ink to fabricate patient-specific scaffolds that could be used to promote tissue regeneration *in vivo* [42]. In another study, gelatin, another natural biopolymer has had its rheological properties improved to aid its bioprinting performance by using pectin as a rheology modifier of gelatin and GPTMS as a gelatin-pectin crosslinking agent [95]. Pectin played a key role in increasing the viscosity and the yield stress of low viscous gelatin solutions as shown through investigation of the rheological properties, as well as bioprinting assessments [96]. Water stable, three-dimensional, and self-supporting gelatin-pectin-GPTMS scaffolds with interconnected micro- and macro- porosity were successfully obtained by combining extrusion-based bioprinting and freeze-drying which did not require any additional temperature control to further modulate the rheological properties of gelatin solutions [95]. Patient-centric dosage forms have been produced through additive manufacturing techniques, which enable its design with precise control over dimension and microstructure, factors that are known to ultimately play key roles in modulating drug release kinetics, a feat not achieved through compression; traditional manufacturing techniques [92, 96, 97].
