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\begin{document}


\def\RunningAuthor{Arun Radhakrishnan and Pradeep Krishna Baskaran}
\firstPage{4261}
\articleType{Review Article}
\receivedDate{20 Feb 2020}
\acceptedDate{04 Apr 2020}
\revisedDate{26 Mar 2020}
\journalVolume{2020, 11}
\journalIssue{3}
\journalDoi{ijrps.v11i3.2637}
\copyrightYear{2020}
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\def\journalTitle{International Journal of Research in Pharmaceutical Sciences}

\title{A review on novel excipient for tableting}
\author{Pradeep~Krishna~Baskaran, 
            Arun~Radhakrishnan\textsuperscript{*}~\\[5pt]{Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty, Nilgiris, Tamil Nadu, India}}

\begin{abstract}
Despite the fact that the standards administering direct compression method have been notable for a long time, the system has as of late become progressively settled because of the presentation of excipients explicitly intended for direct compression method. These excipients are straightforwardly compressed by their own, yet can likewise be blended in with an enormous extent of medication substance with no noteworthy decay in tablet quality. Excipients with better usefulness can be acquired by growing brand-new substance excipients, recent evaluations of already available products, and novel blends of already available products. Any novel substance excipient being created as an excipient should experience different phases of administrative endorsement planned for tending to issues of wellbeing and poisonous quality, which is an extensive and exorbitant procedure. Furthermore, the excipient should experience a period of conventional advancement, which abbreviates the market selectiveness period. Co-processing is the alternative way novel excipients are approaching to showcase without experiencing the thorough security trial of a totally new concoction. It tends to be characterized as joining at least two built up excipients by a fitting procedure. The primary point of co-preparing is to acquire an item with added esteem identified with the proportion of its usefulness/cost. Advancement of co-handled straightforwardly compressible excipient beginnings with the determination of excipients can joined, their focused on extent, choice of readiness technique to get improved item with wanted both physical and chemical substance parameters and then it closes with limiting shirking with cluster to group varieties.
\end{abstract}\def\keywordstitle{Keywords}

\begin{keywords}co-processing,\newline excipient,\newline tableting,\newline direct compression
\end{keywords}
\twocolumn[ \maketitle {\printKwdAbsBox}]
\makeatletter{\raggedright\textsuperscript{*}Corresponding Author\par Name:\ Arun~Radhakrishnan~\\ Phone:\ 7402222019~\\  Email:\ arunpharma93@gmail.com
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\section{Introduction}
Capsules and tablets are the most favored doses of pharmaceutical researchers and doctors since they can be precisely dosed and give great patient consistence, they are simple for organizations to fabricate, and they can delivered at a moderately minimal effort. This prevalence of tablets combined with an expanded comprehension of the material science of pressure and of assembling process factors have developed the production of tablets as science in its own privilege \unskip~\citep{748275:17781572}. Cellulose was biodegradable, sustainable and most ample characteristic polymer on the planet. It has exceptionally requested progressive structure beginning from the equal glucan chains framing nanosized fibrils, which are additionally composed in fibril totals \unskip~\citep{748275:17781585}. Seperating cellulose nanofibers from perceptible cellulose fiber has increased a lot of consideration because of their attributes of high surface to volume proportion and remarkable volume properties, it comprise both crystalline and shapeless locales, and furthermore the customary strategy for generation of microcrystalline cellulose (MCC), that incorporates firmly acidic conditions prompts broad hydrolysis of indistinct portions and development of short bar like MCC fibril groups with low perspective proportion. Then again, milder enzymatic hydrolysis, non nearness of hydrolysis step and the solid mechanical power have some application which present in the cellulose treatment bring about the generation of long nanoscale incompletely undefined fibrils which has been alluded as CNF \unskip~\citep{748275:17781600}. Direct compaction of powder mix is typically arranged over compaction of granules because of the basic and prudent assembling process, need of gear is exceptionally less, handling time will be diminished, and low vitality cost is required. During direct compaction there is no need of dissolvable and warmth this could influence item strength. Poor flowability, restricting properties, content consistency are a portion of the issues happens during direct compaction, it could be unraveled by improving the excipients with better useful properties \unskip~\citep{748275:17781570}.

In spite of the fact that the standards overseeing direct pressure have been outstanding for a long time, the system has as of late gotten increasingly settled because of the presentation of excipients explicitly intended for direct pressure \unskip~\citep{748275:17781589}. These excipients are straightforwardly compressible themselves, however can likewise be blended in with a huge extent of medication substance with no huge disintegration in tablet quality \unskip~\citep{748275:17781569}. Notwithstanding excipients having great stream and pressure properties, they should likewise have the accompanying qualities.

\textbf{New Excipient used in tablets}

\textbf{Direct compression excipients}

Molecule size disseminations that are comparable for most dynamic medication substances, subsequently keeping away from isolation during handling; a high mass thickness; Cluster to-bunch standard should be replicable. These characteristics are the major basic for direct pressure usefulness. The rest of the characteristics are needful for each excipients, in that they ought to likewise be: truly and artificially steady when in proximity with dampness, warmth and air; synthetically latent; that is, don't quicken the corruption of dynamic fixings or different excipients; good with bundling segments; accessible around the world, and ideally from more than one provider.

\textbf{Pros and Cons on direct compression}

\textbf{Pros}

Need less unit activities contrasted and wet granulation (Lesser preparing time and low vitality utilization). Less stability problems for actives that are delicate to warmth or dampness. For specific mixes, quicker dissolution rates might be produced from tablets arranged by direct pressure contrasted and wet granulation; for instance, norfloxacin. Less excipients might be required in an direct compression formula.

\textbf{Cons}

Problems with isolation {\textendash} these can be diminished by coordinating the molecule size and thickness of drug product with excipients. All in all, the drug content is restricted to roughly 30\% or around 50 mg. May not be appropriate for substances having a less mass thickness on the grounds that after pressure the tablets created might be excessively thin. Not appropriate for inadequately poor flowing drug. Static charges may create on the medication particles or excipients during blending, which may prompt binding of substances delivering bad blending \unskip~\citep{748275:17781593}.

\textbf{Ludipress}

The term Ludipress is a co-prepared item comprising of three segments: a filler, a cover and a disintegrant. The accurate convergences of its components are expressed underneath: 93.4\% of a-lactose monohydrate, 3.2\% of polyvinylpyrrolidone and 3.4\% of crospovidone. Ludipress has incredible flowability in light of the fact that the components comprises of circular molecules along with countless little gems with smooth surfaces. Great tablets can be set up at minimum pressure powers and when Ludipress was contrasted and six other lactose-based excipients, in addition to agglomerated lactose and anhydrous b structure, it results the second good presentation as far as physical quality. Introductory examinations demonstrated the requirement for a glidant to be consolidated inside a definition in light of the development of rubbing upon pressure \unskip~\citep{748275:17781586,748275:17781578}. Of the two glidants utilized, 2\% stearyl fumarate demonstrated the good advancement in friability, squashing quality and crumbling period contrasted and magnesium stearate, which seemed to increment the friability and the breaking down period. By and large, the breaking down period of plans consisting Ludipress is any larger than those consisting lactose, because of the nearness of PVP. This constraint can be overwhelmed by the expansion of microcrystalline cellulose (MCC) in the recipe, advancing crumbling by a slender and wicking activity. On the other hand, tests have demonstrated that amazing disintegrants, for example, sodium starch glycolate. \unskip~\citep{748275:17781594}. Some direct compression excipients are given in upcoming Table~\ref{tw-6f60ac8f75b6}


\begin{table*}[!htbp]
\caption{\boldmath {Direct compression excipients} }
\label{tw-6f60ac8f75b6}
\def\arraystretch{1.1}
\ignorespaces 
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\begin{tabulary}{\linewidth}{p{\dimexpr.16620000000000005\linewidth-2\tabcolsep}p{\dimexpr.8338\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}Excipient & Description\\
\tblmidrule 
Microcrystalline cellulose (MCC) &
  MCC is a refined, halfway depolymerized cellulose, which is set up by using a-cellulose contains mineral acids, creating groups of needle shaped microcrystals. This excipient appears to be a white, crystalline powder made out of agglomerated permeable particles \unskip~\citep{748275:17781589}\\
Starch 1500 &
  Local starches have great pressure qualities, yet their poor stream properties and high ointment affectability makes them less appropriate for use in direct pressure. They are especially helpful because of their great authoritative and disintegrant properties. All things considered, Starch 1500 keeps on being generally viewed as the following decision excipient after lactose and microcrystalline cellulose \unskip~\citep{748275:17781589}\\
Dicalcium phosphate dehydrate &
  The expansion of an ointment is fundamental as non-greased up tablets prepared with dicalcium phosphate are hard to launch from bites the dust. One of the primary points of interest of utilizing dicalcium phosphate as a filler or folio is that antacid ointments, for example, magnesium stearate have for all intents and purposes no impact on its coupling properties \unskip~\citep{748275:17781589}\\
Lactose &
  Lactose is broadly utilized as a filler or diluent in tablets and a few levels are monetarily accessible with varying physical properties Different sorts utilized for direct pressure are agglomerated lactose delivered by liquid bed drying, anhydrous a-lactose and anhydrous b-lactose. Anhydrous a-lactose has the critical downside of moderately moderate breaking down. Hydrous lactose monohydrate isn't legitimately compressible and is in this way utilized in wet granulation details. \unskip~\citep{748275:17781597}\\
Sarbitol &
  There are four unique sorts (a, b, g, and d) just as a nebulous structure exist. The g structure is the steady and with good compaction properties. In any case, need larger than different excipients, for example, lactose, for crumbling and disintegration to occur.The tableting characteristics of sorbitol are needy upon molecule structure, molecule size appropriation and mass thickness \unskip~\citep{748275:17781598}\\
Mannitol &
  mannitol is non-hygroscopic, it is conceivable to utilize it with dampness delicate medications. What's more, not at all like sorbitol, the digestion of mannitol doesn't produce increments in blood sugar levels, making it a feasible filler for the plan of diabetic medications. \unskip~\citep{748275:17781602}\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Various particle properties affecting excipient functions} }
\label{tw-8b7344cab05d}
\def\arraystretch{1.1}
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\tbltoprule \rowcolor{kwdboxcolor}Particle properties & Excipient functions\\
\tblmidrule 
Particle size enlarging &
  Compressibility and flowability\\
Surface roughness &
  Separating efficiency and flowability\\
limited distribution of particle size &
  Separating efficiency\\
Expansion of particle porosity &
  Solubility and Compressibility \\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Examples of marketed coprocessed excipients} }
\label{tw-221d9b36f2a2}
\def\arraystretch{1.1}
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\tbltoprule \rowcolor{kwdboxcolor}Coprocessed excipients & Marketed name  & Advantage \\
\tblmidrule 
Lactose 25\% cellulose  &
  Cellactose  &
  Highly compressible and production cost is low\\
MCC, silicon dioxide &
  Prosolv &
  Good flow, diminished affectability to wet granulation, least friability, Greater tablet hardness.\\
MCC, guar gum  &
  Avicel CE-15 &
  Low dirt, low tooth packing, least pallor, improved in general satisfactoriness\\
Sucrose, 3\% Dextrin &
  Diopac  &
  Directly compressible\\
Microcrystalline cellulose, lactose &
  Microcelac  &
  Fit for developing high dose, little tablets with inadequately flowable active\\
Calcium carbonate sorbitol  &
  Merck &
  Regulated particle-size distribution\\
15\% native corn starch, 85\% lactose monohydrate &
  Starlac  &
  Better flowability.\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Co-processing of excipients using spray drier} }
\label{tw-50b579626314}
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\tbltoprule \rowcolor{kwdboxcolor}Co-processed Excipients & Frequently Selected Ratio & Applications and dosage form & Note\\
\tblmidrule 
MCC \mbox{}\protect\newline Calcium carbonate &
  65:35-50:50 &
  In this Direct compression method was used to prepare vitamin tablets, used as pharmaceutical excipients &
  Low cost produce less lubricant sensitivity \unskip~\citep{748275:17781581}\\
MCC \mbox{}\protect\newline Calcium carbonate &
  75:25-85:15 &
  Multiple compaction steps process has been used to produce solid dosage form, used as an excipient &
  Better recompactability than the co-processed products containing less MCC: calcium carbonate ratio \unskip~\citep{748275:17781567}\\
Calcium carbonate \mbox{}\protect\newline MCC &
  80:20-85:15 &
  Vitamin caplets &
  Cost effective, \mbox{}\protect\newline Enhances weight variability of tablet, improves flow property \unskip~\citep{748275:17781574}\\
MCC Mannitol &
  75:25-95:5 &
  Direct compression method was used to prepare the tablets, used as pharmaceutical excipient &
  Improved similarity, lubricant sensitivity \unskip~\citep{748275:17781579}\\
MCC Mannitol (wet cake) &
  75:25-90:10 &
  Dry granulation or direct compression method was used to prepare the binders for the formulation of tablet &
  Better   recompactability \mbox{}\protect\newline \unskip~\citep{748275:17781583}\\
MCC \mbox{}\protect\newline Colloidal silicon dioxide \mbox{}\protect\newline Crospovidone \mbox{}\protect\newline Mannitol \mbox{}\protect\newline Fructose &
  - &
  Fast tablet disintegration &
  Better dilution capacity. Create compacts that are strong with reduced friability \unskip~\citep{748275:17781576}\\
Mannitol \mbox{}\protect\newline Calcium silicate &
  1:20-20:1 &
  Orally disintegrating tablets (ODT) \mbox{}\protect\newline Hiding the taste of   ODT of memantine \mbox{}\protect\newline hydrochloride &
  To prevent the interaction of calcium with API and processing equipments, it has been coated with carbohydrate. \mbox{}\protect\newline highly increased flow behavior. \mbox{}\protect\newline Generate tablets that results better \mbox{}\protect\newline mechanical power while conserving fast disintegration behavior \unskip~\citep{748275:17781577,748275:17781603}\\
MCC \mbox{}\protect\newline HPMC \mbox{}\protect\newline Crospovidone &
  Crospovidone \mbox{}\protect\newline (about 10 \%)  \mbox{}\protect\newline HPMC \mbox{}\protect\newline (2 to 5 \%) \mbox{}\protect\newline MCC \mbox{}\protect\newline (85 to 93 \%) \mbox{}\protect\newline  &
  Directly compressed tablets &
  Results improved flowability, excellent \mbox{}\protect\newline compactability, improved loading of API and blendability \unskip~\citep{748275:17781565}\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}
\textbf{Different variables driving the search for new excipients are}

The developing prominence of the direct compression technique and an interest for a perfect filler{\textendash}binder that can substitute at least two excipients. Tableting equipments speeding up abilities, which needs excipients to keep up great compressibility and less weight variety even at reduced abide period. Weaknesses of existing excipients, for example, compaction loss of MCC upon wet granulation, greater moisture sensitivity, and bad die filling because of agglomeration \unskip~\citep{748275:17781568}. The absence of excipients that is required for particular patients, for example, hypertension, diabetes patients, and sorbitol and lactose affectability. The capacity to regulate the dissolvability, penetrability, or security of medication particles. The developing execution desires for excipients to address issues, for example, breaking down, disintegration, and bioavailability. The continues usage of solid dosage forms, a thin pipeline of new compound excipients, and an expanding inclination for the direct compression technique makes a way  for the improvement of greater-usefulness excipients \unskip~\citep{748275:17781596}.

\textbf{Origin of novel excipients}

Excipients with increased usefulness can be acquired by growing new compound excipients, new evaluations of alive compounds, and new mixes of alive compounds \unskip~\citep{748275:17781596}. Any novel compound excipient existence created as an excipient must experience different phases of administrative endorsement planned for tending to issues of security and poisonous quality, which is an extensive and expensive procedure. Some of the particle properties affecting excipient functions are given in Table~\ref{tw-8b7344cab05d}\unskip~\citep{748275:17781563}. Likewise, the excipient must experience a period of common improvement, which abbreviates the retail selectiveness time \unskip~\citep{748275:17781588}. Growing new evaluations of already available excipients (physical and chemical) has been the best procedure for the advancement of new excipients in recent years \unskip~\citep{748275:17781566}. A procedure that has been upheld by the presentation of good execution evaluations of excipients, for example, crospovidone, pregelatinized starch, croscarmellose, \unskip~\citep{748275:17781573}. Some of the examples of marketed co processed excipients are given in Table~\ref{tw-221d9b36f2a2}.

\textbf{Coprocessing of excipients}

The genuine procedure of building up a coprocessed excipient includes the accompanying advances: Recognizing the gathering of excipients to be coprocessed via cautiously concentrating the material attributes and functionality reqirements. Choosing the extents of different excipients. Surveying the molecule size needed for coprocessing. This is particularly significant when one of the segments is prepared in a dispersed phase. Post-processing the molecule size of the last relies upon its initial molecule size. Choosing a reasonable procedure of drying, for example, shower or flashdrying. Advancing the procedure (on the grounds that even this can add to usefulness varieties) \unskip~\citep{748275:17781563}. Co-processing is used as a technique for the novel excipients are approaching to market without experiencing the thorough safety trial of a totally new chemical  \unskip~\citep{748275:17781563}. It may be characterized as at least two built up excipients by a fitting procedure \unskip~\citep{748275:17781582}. The primary point of co-processing is to get product with added esteem identified with the proportion of its usefulness/cost. Advancement of co-processed directly compressible adjuvant beginnings with the choice of the excipients to be joined, their focused on extent, choice of arrangement technique to get improved item with wanted physical and chemical parameters and it closes with limiting prevention with batch-to-batch varieties. An excipient of sensible cost must be joined with the ideal measure of a useful material so as to acquire incorporated item, with prevalent usefulness than the basic blend of segments. Co-processing is fascinating on the grounds that the items are truly adjusted in a unique manner without modifying the chemical structure. A fixed and homogenous circulation for the segments is accomplished by inserting them inside minigranules. Isolation is reduced by bond of the actives on the permeable particles making process approval and in process control simple and dependable \unskip~\citep{748275:17781587}

\textbf{Pros and Cons of co-processed excipients}

Improved compressibility, Eg; co-processed MCC and colloidal silicon dioxide \unskip~\citep{748275:17781584}. Better dilution capacity, Eg; co-processed 􀀁-lactose and sorbitol \unskip~\citep{748275:17781564}. Lower fill weight variety through direct pressure, Eg; MCC and co-processed calcium carbonate \unskip~\citep{748275:17781574}. Decreased oil affectability, Model co-handled MCC and calcium carbonate \unskip~\citep{748275:17781581}. better API loading and mixing, Eg; hydroxy propyl methyl cellulose (HPMC), co-processed MCC and crospovidone \unskip~\citep{748275:17781565}. Multifunctional excipients created by means of co-processing can assist lessen the quantity of excipients in the stock. Worth expansion to strong measurement shapes as far as better organoleptic characteristics for eg; Avicel CE-15. Co-preparing of excipients can assist in planning customized excipients. Decrease being developed timetables and procedure approval endeavors. Co-processing excipients due to non-obvious advantages carry the chance of patenting the dosage form \unskip~\citep{748275:17781590}. Co-processing of excipients using spray drier is given in the upcoming Table~\ref{tw-50b579626314}

\textbf{Polymers used in pharmaceutical dosage form}

\textbf{Water-Soluble synthetic polymers}

Poly (acrylic acid) cosmetic, pharmaceuticals, immobilization of cationic drugs, base for Carbopol polymers. Poly (ethylene oxide) Coagulant, hairy, extremely high particle up to two or three millions, swelling agent. Poly (ethylene glycol) Mw 1000), plasticizer, base for suppositories. 

\textbf{Biodegradable Polymers in-soluble in water }

Polymers for protein delivery, Lactide-co-glycolide.

\textbf{Polymers based on starch }

Starch Glidant {\textendash} used as diluents and disintegrants in capsules and tablets, also used as tablet binder. Sodium starch glycolate act as a super disintegrant for both capsules and tablets in oral delivery.

\textbf{Rubber and Plastics}

Polyurethane Transdermal fix assistance (delicate, agreeable, medium dampness transference), blood elevation, unnaturalheart, and vascular unions, froth in biomedical and commercial items. Silicones Pacifier, therapeutic agents, inserts, restorative evaluation cement for transdermal delivery. Polycarbonate type for biomedical and pharmaceutical items. Polychloroprene Septum for infusion, uncloggers for injections, and nozzle parts. Polyisobutylene Weight delicate binders for transdermal delivery \unskip~\citep{748275:17781591,748275:17781571}. An appropriate thought of exterior and mass characteristics will help for structuring of polymers for different drug delivery approaches. Biodegradable polymers discovered across the board utilized in drug delivery and may be degraded to nontoxic monomers interior part of  the body.. Hydrogels that have the tendency to react to an assortment of  biological and physio-chemical boosts withstand huge ability for structure of closed-loop drug-delivery systems \unskip~\citep{748275:17781592}.

\textbf{Futures in polymer drug delivery}

The majority of availablility in polymer drug delivery rest on responsive delivery systems, which makes possible to deliver drugs via implantable products because of a intentional amount of blood or to deliver a drug correctly to a determined on location. A great portion of the development of novel substances in controlled drug delivery is focusing on the positioning and usage of these reactive polymers with explicitly programmed microscopic and macroscopic chemical and structural features. Example: Copolymers with alluring hydrophobic and hydrophilic connections. Square or unite copolymers. Complexation systems reacts through hydrogen or ionic bonding. Star polymers or dendrimers as nanoparticles for holding of catalysts, medicaments, peptides, or another organic specialists. \unskip~\citep{748275:17781595,748275:17781601}

\textbf{Natural polymers}

A polymer is an enormous atom (macromolecules) made out of rehashing structural units. These subunits are ordinarily associated by covalent chemical bonds. The two synthetic and natural polymers are accessible yet the utilization of natural polymers for pharmaceutical implementation is appealing in light of the fact that they are practical, promptly accessible and non-toxic. They are fit for chemical modification, conceivably biodegradable and with hardly any special cases, likewise biocompatible \unskip~\citep{748275:17781599}.

\textbf{Need of herbal polymers}

Biodegradable means naturally occurring polymers delivered by every single living organism. They show no antagonistic impacts on the environment or individual. Biocompatible and non-dangerous {\textendash} chemically, almost these plant materials are carbohydrates in nature and made out of rehashing monosaccharide units. Thus they are non-poisonous. Financial - They are less expensive and their creation cost is not exactly synthetic substance. secured and without side effects. Simple accessibility {\textendash} In numerous nations, they are created because of their application in several industries \unskip~\citep{748275:17781570}.

\textbf{Disadvantages of herbal polymers}

Microbial adulteration {\textendash} throughout creation, they are presented to outside condition and consequently, there are odds of microbialadulteration. Group to clump variety {\textendash} synthetic production is restrained methodology with exact amounts of components while generation of natural polymers is subject to condition and different physical components. The unconstrained pace of hydration{\textemdash}Because of contrasts in the assortment of natural products at various occasions, just as contrasts in locale, species, and atmosphere terms the level of concoction components available in a given products might differ \unskip~\citep{748275:17781570} . Slow Procedure {\textendash} As the generation rate is relies on the environment and numerous different components, it can't be changed. So natural polymers have a moderate pace of creation. There are odds of Heavy metal contamination often connected with herbal excipients \unskip~\citep{748275:17781580}.
    
\section{Conclusions}
The excipient industry, which has to a great extent been an expansion of the food industry, has taken up the novel utilization of molecule designing and material sciences to make ready for another classification of functional excipients called coprocessed excipients. The achievement of any pharmaceutical excipient relies upon quality, wellbeing, and usefulness. Despite the fact that the initial two parameters have stayed steady, huge enhancements in usefulness open the entryway for the expanded utilization of coprocessed excipients. The benefits of these excipients are various, however further scientific exploration is required to comprehend the components basic their exhibition. The primary hindrance to the development of this region of excipients is the avoidance of their monographs in pharmacopeias, which debilitates pharmaceutical producers to utilize them. Polymers play a vital role in the drug delivery. Thus, the choice of polymer assumes a significant role in drug delivery. In any case, while choosing polymers care must be taken with respect to its poisonous quality, drug compatibility and degradation pattern. By this survey, we can say that natural polymers can be acceptable substitute for the synthetic polymers and a significant number of the reactions of the manufactured polymers can be overwhelmed by utilizing natural polymers.

\textbf{Funding Support}

None.

\textbf{Conflict of Interest}

None.
    

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