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\begin{document}


\def\RunningAuthor{Mayur R. Bhurat et al.}
\firstPage{4365}
\articleType{Review Article}
\receivedDate{27 Apr 2020}
\acceptedDate{04 Jun 2020}
\revisedDate{30 May 2020}
\journalVolume{2020, 11}
\journalIssue{3}
\journalDoi{ijrps.v11i3.2654}
\copyrightYear{2020}
\def\authorCount{4}
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\def\journalTitle{International Journal of Research in Pharmaceutical Sciences}

\title{\textbf{Mucilage: A Rich Source of Excipients Present in Plant Parts with Gold Status}}
\author{Ganesh~N.~Sharma\textsuperscript{1},  
            Mayur~R.~Bhurat\textsuperscript{*}\textsuperscript{1},  
            Upendra~B.~Gandagule\textsuperscript{1}, 
            Birendra~Shrivastava\textsuperscript{2}~\\[5pt]{\textsuperscript{1}Department of Pharmacognosy, School of Pharmaceutical Sciences, SADTM campus, Jaipur National University, Jagatpura, Jaipur, Rajasthan-302017, India}~\\{\textsuperscript{2}School of Pharmaceutical Sciences, SADTM campus, Jaipur National University, Jagatpura, Jaipur, Rajasthan-302017, India}}

\begin{abstract}
Large numbers of pharmaceutical excipients of natural origin are available nowadays. Plant materials like mucilages with a variety of pharmaceutical applications are most common. They are being used due to their abundance, safety, compatibility, cost-effectiveness and eco-friendly nature as compared to synthetic one and have various advantages over synthetic polymers. To compete with and replace artificial excipients mucilages can be modified in many ways to obtain the required form of a drug delivery system. Currently, there are a vast amount of natural pharmaceutical excipients are there, and due to its increasing demand, it has become essential to identify or explore more plant mucilage sources to fulfil the industrial need. Mucilages are polymeric mono-saccharides or mixed mono-saccharides combined with uronic acids. On hydrolysis, they yield a mixture of sugars and uronic acids, and the mucilages that are obtained from plant sources have translucent and amorphous nature. Due to presence of hydrophilic moieties in mucilages, they can easily combine with water to form a gel or a thick viscous solution, and these extracted mucilages from the plant can be processed to a certain extent and incorporated in dosage forms to achieve the specific performance of the formulation. In this review, we describe isolation, characterization, pharmaceutical application and methods of modification to develop drug delivery systems.
\end{abstract}\def\keywordstitle{Keywords}

\begin{keywords}Mucilage,\newline Characterization,\newline Isolation,\newline Modification
\end{keywords}
\twocolumn[ \maketitle {\printKwdAbsBox}]
\makeatletter{\raggedright\textsuperscript{*}Corresponding Author\par Name:\ Mayur~R.~Bhurat~\\ Phone:\ ~\\  Email:\ bhuratmayur@gmail.com
        \par}\vspace*{-11pt}\hrulefill\par{\fontsize{12}{14}\selectfont ISSN: 0975-7538}\par% 
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        \vspace*{-11pt}\hrulefill\\{\fontsize{9.12}{10.12}\selectfont Production and Hosted by}\par{IJRPS |~\href{www.ijrps.com}{www.ijrps.com}}\par%
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\section{Introduction}
Use of Mucilage in drug delivery systems and dosage forms helps in modifying the release of drug from its dosage forms, enhancement of solubility, bioavailability, patient acceptability and also ensures ease of manufacture \unskip~\citep{806850:19266426,806850:19266441}. These materials of natural origin like mucilages are cheap, safe, readily available, eco-friendly, degradable, stable \& compatible due to its natural source and capable of modification, they are seeking a lot of attention and importance in the field of delivery of drugs \unskip~\citep{806850:19266433}. These excipients of natural origin have replaced the synthetic excipients, and recently there is increased use of natural and non-toxic products. Currently, huge amounts of pharmaceutical excipients of natural origin are available and like other products of natural origin and due to its increasing demand it has become essential to identify or explore more plant mucilage sources to fulfil the industrial need. These mucilages obtained from plant sources are the hydrocolloids of Polysaccharides having sugar molecules \& uronic acids that are liked with each other. 


\bgroup
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\centering \makeatletter\IfFileExists{images/4b35eb6c-e9c0-4869-a4d3-72c123001952-upicture1.png}{\includegraphics{images/4b35eb6c-e9c0-4869-a4d3-72c123001952-upicture1.png}}{}
\makeatother 
\caption{\boldmath {General Isolation Method of Mucilage}}
\label{f-689dc107e2cd}
\end{figure*}
\egroup

\begin{table*}[!htbp]
\caption{\boldmath {Preliminary Confirmatory Test for Mucilage } }
\label{tw-537edc71be22}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.3784\linewidth-2\tabcolsep}p{\dimexpr.3542999999999999\linewidth-2\tabcolsep}p{\dimexpr.2673\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack Sr. No & \cAlignHack Observation & \cAlignHack Inference\\
\tblmidrule 
\textbf{Molisch's Test:} &
   &
  \\
100 mg of dried mucilage powder was taken and to that powder Molisch's reagent was added and then Conc. H\ensuremath{_{2}}SO\ensuremath{_{4}}  from the side of the test tube  &
  Violet coloured ring observed at the junction of two layers &
  Carbohydrates present\\
\textbf{Ruthenium Test:} &
   &
  \\
A Small quantity of dried mucilage powder was mounted on a slide containing ruthenium red solution and it is observed under microscope &
  Development of Pink colour observed &
  Mucilage present\\
\textbf{Iodine Test:} &
   &
  \\
100 mg of dried powder was taken and in that 1 ml of 0.2 N Iodine solution is added &
  Colourless solution obtained &
  Polysaccharides present \mbox{}\protect\newline (Starch Absent)\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}
They are polymeric mono-saccharides or mixed mono-saccharides combined with uronic acids and on their hydrolysis produce a mixture of sugars and uronic acids. The mucilages that are obtained from plant sources are translucent and amorphous. 

Due to the presence of hydrophilic moieties in mucilages, they can easily combine with water to form a gel or a thick viscous solution. Mucilages form large molecular aggregates in solution, and these mucilages are made up of complexes of polysaccharides having arabinose, galactose, rhamnose and galactouronic acid \unskip~\citep{806850:19266417}. 

Mucilages and gums have many similar properties, but the only thing in which they differ is that mucilages are metabolic products which are formed within the cell and can be produced without making injury/incision to the plant. Mucilages and their polymeric derivatives from distinct sources are extensively used in pharmaceutical dosage forms \unskip~\citep{806850:19266435}. In this context; we have deliberated various aspects of mucilages starting from their Isolation, characterization, application and Modifications of existing mucilages. 


\begin{table*}[!htbp]
\caption{\boldmath {Pharmaceutical applications of plant} }
\label{tw-4bff725332cf}
\def\arraystretch{1.1}
\ignorespaces 
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\begin{tabulary}{\linewidth}{p{\dimexpr.0701\linewidth-2\tabcolsep}p{\dimexpr.1964\linewidth-2\tabcolsep}p{\dimexpr.14620000000000001\linewidth-2\tabcolsep}p{\dimexpr.58730000000000004\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack Sr. No  & \cAlignHack Botanical Name  & \cAlignHack Family  & \cAlignHack Pharmaceical Applications \\
\tblmidrule 
\cAlignHack 1 &
  \cAlignHack Abelmoschus esculentus  &
  \cAlignHack Malvaceae  &
  Binding agent \& as a sustained release in tablet formulations \unskip~\citep{806850:19266442}\\
\cAlignHack 2 &
  \cAlignHack Aloe species  &
  \cAlignHack Liliaceae  &
  Gel forming \&sustained release agent \unskip~\citep{806850:19266449}\\
\cAlignHack 3 &
  \cAlignHack Lepidum sativum  &
  \cAlignHack Cruciferae  \mbox{}\protect\newline  &
  Suspending agent, emulsifier \& as a \mbox{}\protect\newline controlled release in tablet formulations \unskip~\citep{806850:19266430}\\
\cAlignHack 4 &
  \cAlignHack Ocimum canum  &
  \cAlignHack Labiatae  &
  Suspending agent \& Emulsifier \unskip~\citep{806850:19266432}\\
\cAlignHack 5 &
  \cAlignHack Trigonella foenum graecum  &
  \cAlignHack Leguminoseae  \mbox{}\protect\newline  &
  Binding \& Gel forming agent, Binder \& disintegrant in tablet formulations and also as an emollient \& \mbox{}\protect\newline Demulcent \unskip~\citep{806850:19266444}\\
\cAlignHack 6 &
  \cAlignHack Hibiscus esculentus Linn  &
  \cAlignHack Malvaceae  \mbox{}\protect\newline  &
  Emulsifier, Suspending and Sustaining agent \unskip~\citep{806850:19266438}\\
\cAlignHack 7 &
  \cAlignHack Hibiscus rosasinensis Linn  &
  \cAlignHack Malvaceae  \mbox{}\protect\newline  &
  Suspending agent \& as a sustaining \mbox{}\protect\newline Agent \unskip~\citep{806850:19266420}\\
\cAlignHack 8. &
  \cAlignHack Plantago psyllium and Plantago ovata  &
  \cAlignHack Plantaginaceae  \mbox{}\protect\newline  &
  Binding, emulsifying, sustaining agent \mbox{}\protect\newline  and also as a lubricant \unskip~\citep{806850:19266415}\\
\cAlignHack 9. &
  \cAlignHack Ocimum gratissimum Linn  &
  \cAlignHack Labiatae  &
  Binder \& Suspending agent \unskip~\citep{806850:19266431}\\
\cAlignHack 10 &
  \cAlignHack Asparagus racemosus  &
  \cAlignHack Aapocynaceae  \mbox{}\protect\newline  &
  Binder and sustaining agent in \mbox{}\protect\newline Tablet formulations \unskip~\citep{806850:19266439}\\
\cAlignHack 11 &
  \cAlignHack Opuntiaficus-indica  &
  \cAlignHack Cactaceae  &
  Gel forming agent \unskip~\citep{806850:19266423}\\
\cAlignHack 12 &
  \cAlignHack Anacardium occidentale  &
  \cAlignHack Anacardiaceae  &
  Gel forming agent \unskip~\citep{806850:19266442}\\
\cAlignHack 13 &
  \cAlignHack Cassia sophera  &
  \cAlignHack Fabaceae  &
  Binding agent \unskip~\citep{806850:19266439}\\
\cAlignHack 14 &
  \cAlignHack Chlorophytum borivilianum  &
  \cAlignHack Asparagaceae  &
  Suspending agent\& binding agent \unskip~\citep{806850:19266448}\\
\cAlignHack 15 &
  \cAlignHack Delonixregia  &
  \cAlignHack Fabaceae  &
  Binding agent \unskip~\citep{806850:19266455}\\
\cAlignHack 16 &
  \cAlignHack Vignamungo  &
  \cAlignHack Fabaceae  &
  Binding agent \unskip~\citep{806850:19266434}\\
\cAlignHack 17 &
  \cAlignHack Cissuspopulnea  &
  \cAlignHack Vitaceae  &
  Binding agent \unskip~\citep{806850:19266418}\\
\cAlignHack 18 &
  \cAlignHack Caesalpiniap &
  \cAlignHack Fabaceae  &
  Granulating \& Binding agent \unskip~\citep{806850:19266416}\\
 &
  \cAlignHack ulcherrima &
   &
  \\
\cAlignHack 19 &
  \cAlignHack Cassia angustifolia  &
  \cAlignHack Fabaceae  &
  Granulating \& Binding agent \unskip~\citep{806850:19266427}\\
\cAlignHack 20 &
  \cAlignHack Zizyphus jujubalamk  &
  \cAlignHack Rhamnaceae  &
  Binding agent \unskip~\citep{806850:19266421}\\
\cAlignHack 21 &
  \cAlignHack Prosopisjuliflora  &
  \cAlignHack Mimosaceae  &
  Binding agent \unskip~\citep{806850:19266429}\\
\cAlignHack 22 &
  \cAlignHack Cassia auriculata  &
  \cAlignHack Fabaceae  &
  Binding agent \unskip~\citep{806850:19266414}\\
\cAlignHack 23 &
  \cAlignHack Cassia fistula  &
  \cAlignHack Cassia fistula  &
  Binding agent \unskip~\citep{806850:19266446}\\
\cAlignHack 24 &
  \cAlignHack Dilleniaindica  &
  \cAlignHack Dilleniaceae  &
  Gel forming agent \unskip~\citep{806850:19266428}\\
\cAlignHack 25 &
  \cAlignHack Alyssum halocarpus  &
  \cAlignHack Brassicaceae  &
  Viscosity enhancer \unskip~\citep{806850:19266440}\\
\cAlignHack 26 &
  \cAlignHack Coriolushirsutus  &
  \cAlignHack Polyporaceae  &
  Base for gel preparation \unskip~\citep{806850:19266413}\\
\cAlignHack 27 &
  \cAlignHack Chlorophytum &
  \cAlignHack Asparagaceae  &
  Suspending agent \unskip~\citep{806850:19266452}\\
 &
  borivilianum  &
   &
  \\
\cAlignHack 28 &
  \cAlignHack Hibiscus rosasinensis  &
  \cAlignHack Malvaceae  &
  Super-disintegrant \unskip~\citep{806850:19266419}\\
\cAlignHack 29 &
  \cAlignHack Mimosa pudica  &
  \cAlignHack Fabaceae  &
  Bioadhesive polymer \unskip~\citep{806850:19266422}\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

    
\section{\textbf{ISOLATION OF MUCILAGE}}
Various methods of isolation of mucilages depending on the presence of mucilage in a particular plant part such as stem, leaves, fruit, seeds, tubers etc. The techniques used for isolation from leaves, i.e. the drying process was not performed whereas, for extraction of mucilage from other plant parts, the stem drying process is essential. In the case of the method used for isolation from the fruit of a plant, they are made to be directly crushed in a mixer without drying. 

Although there are differences in the methods followed in which chemicals are utilized for isolation. The standard chemicals used for isolation are Petroleum ether, acetone, ethanol etc. \unskip~\citep{806850:19266447}

In the flow chart (Figure~\ref{f-689dc107e2cd}), the general isolation method for mucilage was described. But now a day's using some advanced techniques yield of mucilage was increased. In 2011 Biren Shah, et al. used a microwave-assisted extraction technique used for isolation of okra mucilage. Microwave-assisted extraction performed at the intensity of 160W for 40 minutes duration of heating increased 11.55\% yield of mucilage when compared to the conventional heating method for 1 hour \unskip~\citep{806850:19266454}. Hence, mucilage can be extracted from various plants using the method mentioned in Figure~\ref{f-689dc107e2cd}.

\textbf{Characterization of Mucilage}

Preliminary confirmatory test for Mucilage is given in Table~\ref{tw-537edc71be22}. \unskip~\citep{806850:19266425}

\textbf{Chemical Characterization}

Various identification tests were performed to confirm the presence of amino acids, tannins, saponins, phenols, flavonoids, terpenes, glycosides, steroids, alkaloids, oils and fats

\textbf{Structural Characterization}

Mucilages contain sugar (Polysaccharides), so by using various chromatographic methods like TLC, HLPC \& HPTLC presence of sugars can be confirmed and FTIR, Mass and NMR Spectroscopic can be used for structural elucidation.

\textbf{Physicochemical Properties}

Various physicochemical properties can be determined by using parameters such as hygroscopic nature, shape, texture, touch, colour, odour, taste, pH, solubility, swelling index, LOD, percentage yield, total ash, Acid insoluble ash, melting point, Moisture content, true density, bulk density, angle of repose and surface tension and presence of various microbes and pathogens can be determined by various microbial assays. Mucilages are vicious \& produce thick gel-like mass in solution and to decide its commercial use and industrial application rheological properties of excipients are evaluated.

\textbf{Impurity determination}

To determine or detect the impurities present various analytical techniques can be used.

\textbf{Toxicity}

For determination of acute toxicity of mucilage Fix dose method (OECD Guideline No. 425) can be used. \unskip~\citep{806850:19266451,806850:19266436}

\textbf{Pharmaceutical Applications of mucilages}

Application of some plant mucilages are summarized given in Table~\ref{tw-4bff725332cf}.

\textbf{Modification of existing mucilage}

Mucilages are the biodegradable materials used in drug delivery systems, and they have some disadvantages like thickening, decrease in viscosity on prolonged storage, uncontrolled hydration rate \& microbial growth, to overcome these disadvantages and problems it requires some modification. \unskip~\citep{806850:19266424}. 

These modifications methods involve:

\textbf{Carboxymethylation/carbomoyethylaion}

Modification can be done by replacing some free hydroxylgroupswhich enhances the water/aqueous solubility of mucilage and clarity of the solution. \unskip~\citep{806850:19266437}

\textbf{Cross linking or grafting}

Cross linking or grafting of vinyl monomers on polysaccharides using Physical \& chemical Methods producing a promising material which can be used in drug delivery systems.
  
  \begin{enumerate}
  \item \relax \textbf{Physical methods:} Modification by physical means can be done by exposing mucilages/polymerstomicrowave, Ultra Violet, gamma radiations, dry heat and saturated steam. \unskip~\citep{806850:19266445,806850:19266443}
  \item \relax \textbf{Chemical Methods: }Modification by chemical means include treating/heating mucilage/polymer with compounds like aldehydes, epichlorhydrin, borax or glutaraldehyde. \unskip~\citep{806850:19266450}
  \end{enumerate}
  
    
\section{Conclusion}
There are large numbers of mucilage's available, having various applications in pharmaceutical preparations are reviewed and discussed. Natural excipients are preferable as not only they are fulfilling their role but also providing health benefits by overcoming the risks associated with synthetic excipients. More research efforts should be provided on natural excipients to innovate non-toxic, biocompatible, cost-effective, eco-friendly suitable for the development of dosage forms.
\section*{Acknowledgement}We are very thankful to Jaipur national university for providing all the necessary facilities.

\textbf{Funding Source}

Nil

\textbf{Conflict of interest}

Nil
    

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