\documentclass[twocolumn,twoside]{article}
\makeatletter\if@twocolumn\PassOptionsToPackage{switch}{lineno}\else\fi\makeatother

\usepackage{amsfonts,amssymb,amsbsy,latexsym,amsmath,tabulary,graphicx,times,xcolor}

%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%
% Following additional macros are required to function some 
% functions which are not available in the class used.
%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%
\usepackage{url,multirow,morefloats,floatflt,cancel,tfrupee}
\makeatletter


\AtBeginDocument{\@ifpackageloaded{textcomp}{}{\usepackage{textcomp}}}
\makeatother
\usepackage{colortbl}
\usepackage{xcolor}
\usepackage{pifont}
\usepackage[nointegrals]{wasysym}
\urlstyle{rm}
\makeatletter

%%%For Table column width calculation.
\def\mcWidth#1{\csname TY@F#1\endcsname+\tabcolsep}

%%Hacking center and right align for table
\def\cAlignHack{\rightskip\@flushglue\leftskip\@flushglue\parindent\z@\parfillskip\z@skip}
\def\rAlignHack{\rightskip\z@skip\leftskip\@flushglue \parindent\z@\parfillskip\z@skip}

%Etal definition in references
\@ifundefined{etal}{\def\etal{\textit{et~al}}}{}


%\if@twocolumn\usepackage{dblfloatfix}\fi
\usepackage{ifxetex}
\ifxetex\else\if@twocolumn\@ifpackageloaded{stfloats}{}{\usepackage{dblfloatfix}}\fi\fi

\AtBeginDocument{
\expandafter\ifx\csname eqalign\endcsname\relax
\def\eqalign#1{\null\vcenter{\def\\{\cr}\openup\jot\m@th
  \ialign{\strut$\displaystyle{##}$\hfil&$\displaystyle{{}##}$\hfil
      \crcr#1\crcr}}\,}
\fi
}

%For fixing hardfail when unicode letters appear inside table with endfloat
\AtBeginDocument{%
  \@ifpackageloaded{endfloat}%
   {\renewcommand\efloat@iwrite[1]{\immediate\expandafter\protected@write\csname efloat@post#1\endcsname{}}}{\newif\ifefloat@tables}%
}%

\def\BreakURLText#1{\@tfor\brk@tempa:=#1\do{\brk@tempa\hskip0pt}}
\let\lt=<
\let\gt=>
\def\processVert{\ifmmode|\else\textbar\fi}
\let\processvert\processVert

\@ifundefined{subparagraph}{
\def\subparagraph{\@startsection{paragraph}{5}{2\parindent}{0ex plus 0.1ex minus 0.1ex}%
{0ex}{\normalfont\small\itshape}}%
}{}

% These are now gobbled, so won't appear in the PDF.
\newcommand\role[1]{\unskip}
\newcommand\aucollab[1]{\unskip}
  
\@ifundefined{tsGraphicsScaleX}{\gdef\tsGraphicsScaleX{1}}{}
\@ifundefined{tsGraphicsScaleY}{\gdef\tsGraphicsScaleY{.9}}{}
% To automatically resize figures to fit inside the text area
\def\checkGraphicsWidth{\ifdim\Gin@nat@width>\linewidth
	\tsGraphicsScaleX\linewidth\else\Gin@nat@width\fi}

\def\checkGraphicsHeight{\ifdim\Gin@nat@height>.9\textheight
	\tsGraphicsScaleY\textheight\else\Gin@nat@height\fi}

\def\fixFloatSize#1{}%\@ifundefined{processdelayedfloats}{\setbox0=\hbox{\includegraphics{#1}}\ifnum\wd0<\columnwidth\relax\renewenvironment{figure*}{\begin{figure}}{\end{figure}}\fi}{}}
\let\ts@includegraphics\includegraphics

\def\inlinegraphic[#1]#2{{\edef\@tempa{#1}\edef\baseline@shift{\ifx\@tempa\@empty0\else#1\fi}\edef\tempZ{\the\numexpr(\numexpr(\baseline@shift*\f@size/100))}\protect\raisebox{\tempZ pt}{\ts@includegraphics{#2}}}}

%\renewcommand{\includegraphics}[1]{\ts@includegraphics[width=\checkGraphicsWidth]{#1}}
\AtBeginDocument{\def\includegraphics{\@ifnextchar[{\ts@includegraphics}{\ts@includegraphics[width=\checkGraphicsWidth,height=\checkGraphicsHeight,keepaspectratio]}}}

\DeclareMathAlphabet{\mathpzc}{OT1}{pzc}{m}{it}

\def\URL#1#2{\@ifundefined{href}{#2}{\href{#1}{#2}}}

%%For url break
\def\UrlOrds{\do\*\do\-\do\~\do\'\do\"\do\-}%
\g@addto@macro{\UrlBreaks}{\UrlOrds}



\edef\fntEncoding{\f@encoding}
\def\EUoneEnc{EU1}
\makeatother
\def\floatpagefraction{0.8} 
\def\dblfloatpagefraction{0.8}
\def\style#1#2{#2}
\def\xxxguillemotleft{\fontencoding{T1}\selectfont\guillemotleft}
\def\xxxguillemotright{\fontencoding{T1}\selectfont\guillemotright}

\newif\ifmultipleabstract\multipleabstractfalse%
\newenvironment{typesetAbstractGroup}{}{}%

%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%

\usepackage[authoryear]{natbib}



\newif\ifnokeywords\nokeywordsfalse

\makeatletter\input{size10-pointfive.clo}\makeatother%
\definecolor{kwdboxcolor}{RGB}{242,242,242}
\usepackage[hidelinks,colorlinks=true,allcolors=blue]{hyperref}
\linespread{1}                 
\def\floatpagefraction{0.8}

\usepackage[paperheight=11.69in,paperwidth=8.26in,top=1in,bottom=1in,left=1in,right=.75in,headsep=24pt]{geometry}

\usepackage{multirow-custom}

\makeatletter

\def\hlinewd#1{%
  \noalign{\ifnum0=`}\fi\hrule \@height #1%
  \futurelet\reserved@a\@xhline}
\def\tbltoprule{\hlinewd{1pt}\\[-14pt]}
\def\tblbottomrule{\noalign{\vspace*{6pt}}\hline\noalign{\vspace*{2pt}}}
\def\tblmidrule{\hline\noalign{\vspace*{2pt}}}



\let\@articleType\@empty
\let\@journalDoi\@empty
\let\@journalVolume\@empty
\let\@journalIssue\@empty
\let\@crossMarkLink\@empty
\let\@receivedDate\@empty
\let\@acceptedDate\@empty
\let\@revisedDate\@empty
\let\@publishedDate\@empty
\let\@copyrightYear\@empty
\let\@firstPage\@empty
\def\articleType#1{\gdef\@articleType{#1}}
\def\journalDoi#1{\gdef\@journalDoi{#1}}
\def\crossMarkLink#1{\gdef\@crossMarkLink{#1}}
\def\receivedDate#1{\gdef\@receivedDate{#1}}
\def\acceptedDate#1{\gdef\@acceptedDate{#1}}
\def\revisedDate#1{\gdef\@revisedDate{#1}}
\def\publishedDate#1{\gdef\@publishedDate{#1}}
\def\copyrightYear#1{\gdef\@copyrightYear{#1}}
\def\journalVolume#1{\gdef\@journalVolume{#1}}
\def\journalIssue#1{\gdef\@journalIssue{#1}}
\def\firstPage#1{\gdef\@firstPage{#1}}
\let\@issuelogo\@empty%
\let\@issuelogoex\@empty%
\def\issuelogo#1{\gdef\@issuelogo{#1}}
\def\issuelogoex#1{\gdef\@issuelogoex{#1}}


\def\author#1{%
  \gdef\@author{%
    \hskip-\dimexpr(\tabcolsep)\hskip5pt%
    \parbox{\dimexpr\textwidth-1pt}%
    {\fontsize{11}{13}\selectfont\raggedright #1}%
  }%
}


\usepackage{pharmascope-abs}
\usepackage{caption}
\usepackage{lastpage}
\usepackage{fancyhdr}
\usepackage[noindentafter,explicit]{titlesec}
\usepackage{fontspec}

\setmainfont[%
BoldFont=cambriab.ttf,%
ItalicFont=CAMBRIAI.TTF,%
BoldItalicFont=CAMBRIAZ.TTF]{Cambria.ttf}
\lefthyphenmin = 3

\def\title#1{%
  \gdef\@title{%
      \vspace*{-40pt}%
       \ifx\@articleType\@empty\else{\fontsize{10}{12}\scshape\selectfont\hspace{8pt}\@articleType\hfill\mbox{}\par\vspace{2pt}}\fi%
       \minipage{\linewidth}
         \hrulefill\\[-0.7pt]%%{\includegraphics[width=75pt,height=50pt]{ijrps_logo.png}}\hfill
         \mbox{~}\hspace{5pt}\parbox{.1\linewidth}{\IfFileExists{images/\@issuelogo.\@issuelogoex}{\includegraphics[width=79pt,height=61pt]{images/\@issuelogo.\@issuelogoex}}{\includegraphics[width=75pt,height=50pt]{ijrps_logo.png}}}\hfill
         \fcolorbox{kwdboxcolor}{kwdboxcolor}{\parbox{.792\linewidth}{%
          \begin{center}\fontsize{17}{17}\selectfont\scshape\vskip-7pt International Journal of Research in Pharmaceutical Sciences\hfill\end{center}%
          \vspace*{-10pt}\hspace*{4pt}{\fontsize{8}{9}\selectfont Published by JK Welfare \& Pharmascope Foundation\hfill  Journal Home Page: \href{www.ijrps.com}{\color{blue}\underline{\smash{www.ijrps.com}}}}\hspace*{4pt}\mbox{}}}%
       \par\vspace*{-1pt}\rule{\linewidth}{1.3pt}%
       \endminipage%
    \par\vspace*{9.2pt}\parbox{.98\linewidth}{\linespread{.9}\raggedright\fontsize{14}{17}\selectfont #1}%
    \vspace*{-8pt}%
  }
}


\setlength{\parindent}{0pt}
\setlength{\parskip}{0.4pc plus 1pt minus 1pt}

\def\abbrvJournalTitle{Int. J. Res. Pharm. Sci.}

\fancypagestyle{headings}{%
  \renewcommand{\headrulewidth}{0pt}%
  \renewcommand{\footrulewidth}{0.3pt}
  \fancyhf{}%
  \fancyhead[R]{%
    \fontsize{9.12}{11}\selectfont\RunningAuthor,\ \abbrvJournalTitle,\ \ifx\@journalVolume\@empty X\else\@journalVolume\fi%
    \ifx\@journalIssue\@empty\else(\@journalIssue)\fi%
    ,\ \ifx\@firstPage\@empty 1\else\@firstPage\fi-\pageref*{LastPage}%
  }%
  \fancyfoot[LO,RE]{\fontsize{9.12}{11}\selectfont\textcopyright\ International Journal of Research in Pharmaceutical Sciences}%
  \fancyfoot[RO,LE]{\fontsize{9.12}{11}\selectfont\thepage}
}\pagestyle{headings}

                                                         
\fancypagestyle{plain}{%
  \renewcommand{\headrulewidth}{0pt}%
  \renewcommand{\footrulewidth}{0.3pt}%
  \fancyhf{}%
  \fancyhead[R]{%
    \fontsize{9.12}{11}\selectfont\RunningAuthor,\ \abbrvJournalTitle,\ \ifx\@journalVolume\@empty X\else\@journalVolume\fi%
    \ifx\@journalIssue\@empty\else(\@journalIssue)\fi%
    ,\ \ifx\@firstPage\@empty 1\else\@firstPage\fi-\pageref*{LastPage}%
  }%
  \fancyfoot[LO,RE]{\fontsize{9.12}{11}\selectfont\textcopyright\ International Journal of Research in Pharmaceutical Sciences}%
  \fancyfoot[RO,LE]{\fontsize{9.12}{11}\selectfont\thepage}
  \ifx\@firstPage\@empty\else\setcounter{page}{\@firstPage}\fi
}


\def\NormalBaseline{\def\baselinestretch{1.1}}
\usepackage{textcase}
\setcounter{secnumdepth}{0}

\titleformat{\section}[block]{\bfseries\boldmath\NormalBaseline\filright\fontsize{10.5}{13}\selectfont}
{\thesection}
{6pt}
{\MakeTextUppercase{#1}}
[]
\titleformat{\subsection}[block]{\bfseries\boldmath\NormalBaseline\filright\fontsize{10.5}{12}\selectfont}
{\thesubsection}
{6pt}
{#1}
[]
\titleformat{\subsubsection}[block]{\NormalBaseline\filright\fontsize{10.5}{12}\selectfont}
{\thesubsubsection}
{6pt}
{#1}
[]
\titleformat{\paragraph}[block]{\NormalBaseline\filright\fontsize{10.5}{10}\selectfont}
{\theparagraph}
{6pt}
{#1}
[]
\titleformat{\subparagraph}[block]{\NormalBaseline\filright\fontsize{10.5}{12}\selectfont}
{\thesubparagraph}
{6pt}
{#1}
[]

\titlespacing{\section}{0pt}{.5\baselineskip}{.5\baselineskip}  
\titlespacing{\subsection}{0pt}{.5\baselineskip}{.5\baselineskip}  
\titlespacing{\subsubsection}{0pt}{.5\baselineskip}{.5\baselineskip}  
\titlespacing{\paragraph}{0pt}{.5\baselineskip}{.5\baselineskip}  
\titlespacing{\subparagraph}{0pt}{.5\baselineskip}{.5\baselineskip}

\captionsetup[figure]{skip=1.4pt,font=bf,labelsep=colon,justification=raggedright,singlelinecheck=false}
\captionsetup[table]{skip=1.4pt,font=bf,labelsep=colon,justification=raggedright,singlelinecheck=false}

\def\bibyear#1{#1}
%\def\bibjtitle#1{#1}   %%Publisher request
\def\bibauand{}
\setlength\bibsep{3pt}
\setlength\bibhang{8pt}

\makeatother
\date{}


\usepackage{float}

\begin{document}


\def\RunningAuthor{Amit B Patil et al.}
\firstPage{1807}
\articleType{Original Article}
\receivedDate{04.09.2019}
\acceptedDate{15.12.2019}
\revisedDate{07.12.2019}
\journalVolume{2020, 11}
\journalIssue{2}
\journalDoi{ijrps.v11i2.2084}
\copyrightYear{2020}
\def\authorCount{4}
\def\affCount{2}

\def\journalTitle{International Journal of Research in Pharmaceutical Sciences}

\title{Formulation, Characterisation and Evaluation of the Ethosuximide Oral Immediate Release Tablets}
\author{Naga~Sujan~M\textsuperscript{1},  
            Kunal~K~Mehta\textsuperscript{1},  
            Amit~B~Patil\textsuperscript{*}\textsuperscript{1}, 
            Anusha~Vajhala\textsuperscript{2}~\\[5pt]{\textsuperscript{1} Department of Pharmaceutics, JSS College of Pharmacy, Mysuru-570015, Karnataka, India}~\\{\textsuperscript{2}Malla Reddy College of Pharmacy, Dhulapally - 500014, Hyderbad, India}}

\begin{abstract}
 The present study is aimed to formulate, characterization, and evaluate oral immediate-release tablets of Ethosuximide. It is employed as an anti-epileptic agent used in the treatment of epilepsy, in all the age groups who were \ensuremath{\geq } 1 year. The dosage form is formulated by directly compressing the blend and granulating the powder blend by wet granulation methods. The optimized formulation is achieved by the trial and error method by changing the concentration of lactose monohydrate and di-basic calcium phosphate dehydrate as diluents, sodium starch glycolate as Super-dis-integrant, rice Starch as an intra-granular binder, hydroxypropyl cellulose as binder talc as a lubricant. Evaluation parameters such as micromeritic properties, disintegration time along with \textit{in-vitro } drug release studies were performed for characterizing the dosage form. \textit{In-vitro} drug release studies were carried out using 0.1 N HCl as dissolution media with 75 rpm and temperature of 37\ensuremath{^{0}}C \ensuremath{\pm} 5\ensuremath{^{0}}C by employing USP apparatus II (Paddle type). Estimation of the \% drug release of the tablet was carried out using the UV method. The prepared formulation and the marketed formulation were tested for the \textit{in-vitro} drug release profile and the prepared formulation was compared with the marketed formulation. All the evaluated result was found to be within the specifications. Therefore, from the obtained evaluation results F6 trail was selected as the best formulation.
\end{abstract}\def\keywordstitle{Keywords}

\begin{keywords}Anti-epileptic drug,\newline Epilepsy,\newline Immediate Release,\newline In-vitro dissolution studies,\newline disintegration
\end{keywords}
\twocolumn[ \maketitle {\printKwdAbsBox}]
\makeatletter{\raggedright\textsuperscript{*}Corresponding Author\par Name:\ Amit~B~Patil~\\ Phone:\ +917975787977~\\  Email:\ amitbpatil@jssuni.edu.in
        \par}\vspace*{-11pt}\hrulefill\par{\fontsize{12}{14}\selectfont ISSN: 0975-7538}\par% 
        \textsc{DOI:}\ \href{https://doi.org/10.26452/\@journalDoi}{\textcolor{blue}{\underline{\smash{https://doi.org/10.26452/\@journalDoi}}}}\par%
        \vspace*{-11pt}\hrulefill\\{\fontsize{9.12}{10.12}\selectfont Production and Hosted by}\par{IJRPS |~\href{www.ijrps.com}{www.ijrps.com}}\par%
        \vspace*{-2pt}{\fontsize{9.12}{10.12}\selectfont\textcopyright\ \@copyrightYear\ $|$ All rights reserved.}\par%
        \vspace*{-11pt}\rule{\linewidth}{1.2pt}
        \makeatother
        
    
\section{Introduction}
 Epilepsy can be characterized as a neurological disorder with a tendency for recurring, unprovoked seizures \unskip~\citep{667901:15753858}. A seizure is an alteration in individuals' consciousness and behavior due to abrupt disturbances in the electric impulses in the brain \unskip~\citep{667901:15753859}. Epilepsy may occur due to an imbalance between inhibitory and excitatory processes in neurons or ensues abnormal and overweening cortical neuronal activity inside the brain \unskip~\citep{667901:15753860}. The seizures may range from short and sensible to lengthy rip snorting shaking, uncontrollable twitching, losing consciousness, muscle stiffness, unresponsive, sudden loss of muscle tone \unskip~\citep{667901:15753861,667901:15753862}.

Around 50 million of the world's population are suffering from epilepsy and most of them are from a developing country \unskip~\citep{667901:15753863}. An approximate population of ten (10) million in India are epileptic and many of them aren't able to receive proper treatment due to a multitude of reasons such as poverty, cultural beliefs, and lack of knowledge, treatment gap, stigma and shortage of healthcare professionals \unskip~\citep{667901:15753864,667901:15753865}.

The Immediate-release formulations are known for their rapid onset of action and hence are intended in the usage of treating diseases or disorders which require such action. Examples of such cases were angina, pulmonary arterial hypertension, vasoconstriction and pain \unskip~\citep{667901:15753867}. It also possess a broad spectrum of advantages such as enhanced oral bioavailability because of the pre-gastric absorption, convenience in administration to nauseous patients, geriatrics, and expansion in business \unskip~\citep{667901:15753868}.

Numerous formulations come under conventional immediate release which includes fast disintegrating tablets, effervescent tablets and granules, fast dissolving films \unskip~\citep{667901:15753869}. Trending technology employed in the manufacturing of fast-dispersing dosage forms a multitude of equipment such as modified tableting systems, floss or shear form technology \unskip~\citep{667901:15753870}.
    
\section{Materials and Methods}
Ethosuximide was purchased from the TCI chemicals and all the other excipients like lactose monohydrate, sodium starch glycolate, dibasic calcium phosphate dehydrate, hydroxypropyl cellulose, rice starch, talc were procured from Loba chemicals.

\textbf{Pre-formulation Studies}

\textbf{Identification of Active Pharmaceutical Ingredient}

\textbf{Preparation of standard curve for API\ensuremath{^{}}}

The drug was weighed accurately to 100mg and dissolved and the solution obtained was diluted with water to 100ml in a volumetric flask.

The above solution was the primary stock solution, having a concentration of 1000\ensuremath{\mu}g/ml. From this solution, accurately pipette out 1ml into 10ml volumetric flask, having 100\ensuremath{\mu}g/ml of concentration which was the secondary stock solution.

From secondary stock solution pipette out 1, 2, 3, 4, and 5ml into individual 10ml volumetric flask and water was used to make up the volume to 10ml. All the obtained samples were measured at 264nm and the data is mentioned in Table~\ref{tw-624560e2612f} and the calibration curve obtained by the values is mentioned in Figure~\ref{f-e766b610e341},\unskip~\citep{667901:15753871}.

\textbf{Solubility profile}

100mg of the active pharmaceutical ingredient was taken in four different solvents of volume 100ml each for the solubility analysis and observed for clarity of the solution. The solvents used were water, ethanol, ether, and chloroform and dimethyl sulfoxide.

\textbf{Preformulation studies of blend}

Preformulation studies for the blend are carried out and the results of the study are mentioned in the Table~\ref{tw-e6a782609bd8} ,\unskip~\citep{667901:15753872}.


\begin{table}[!htbp]
\caption{\boldmath {Standard Calibration curve of Ethosuximide} }
\label{tw-624560e2612f}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{LL}
\tbltoprule \rowcolor{kwdboxcolor}Concentration (\ensuremath{\mu}g/ml) & Absorbance\\
\tblmidrule 
10 &
  0.238\\
20 &
  0.378\\
30 &
  0.523\\
40 &
  0.647\\
50 &
  0.723\\
\tblbottomrule 
\end{tabulary}\par 
\end{table}

\bgroup
\fixFloatSize{images/ac5a76c6-7baf-441f-bd02-072ce8be71dd-upicture1.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/ac5a76c6-7baf-441f-bd02-072ce8be71dd-upicture1.png}{\includegraphics{images/ac5a76c6-7baf-441f-bd02-072ce8be71dd-upicture1.png}}{}
\makeatother 
\caption{\boldmath {Calibration Curve of Ethosuximide}}
\label{f-e766b610e341}
\end{figure}
\egroup
\textbf{Bulk Density\ensuremath{^{}}}

To calculate bulk density, granules were weighed initially and transferred to graduated measuring cylinder and the occupied volume of the granules were noted. By substituting these values as in the formula mentioned below,
\begin{eqnarray*}Bulk\;density\;=\frac{Mass}{Apparent\;volume\;(V0)} \end{eqnarray*}
 It was expressed in grams per milli liters or kilograms per cubic meter.

\textbf{Tapped density}

To calculate tapped density, granules were weighed and calculated by tapping the measuring cylinder with granules that remained unaffected after tapping. 
\begin{eqnarray*}Tapped\;density=\frac{Mass}{Tapped\;volume\;(Vt)} \end{eqnarray*}

\begin{table*}[!htbp]
\caption{\boldmath {Preformulation studies of Blend} }
\label{tw-e6a782609bd8}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{LLLLL}
\tbltoprule \rowcolor{kwdboxcolor}Formulation Batch & Bulk density \mbox{}\protect\newline (gm/ml) & Tapped density \mbox{}\protect\newline (gm/ml) & Carr's Index \% & Hausner's ratio\\
\tblmidrule 
F1 &
  0.332 &
  0.346 &
  33.43 &
  1.04\\
F2 &
  0.467 &
  0.734 &
  17.42 &
  1.57\\
F3 &
  0.563 &
  0.732 &
  16.43 &
  1.30\\
F4 &
  0.537 &
  0.683 &
  17.74 &
  1.27\\
F5 &
  0.585 &
  0.724 &
  18.92 &
  1.23\\
F6 &
  0.571 &
  0.687 &
  18.38 &
  1.20\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Sieve Analysis} }
\label{tw-ffa9aead9bad}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.1958\linewidth-2\tabcolsep}p{\dimexpr.1554\linewidth-2\tabcolsep}p{\dimexpr.16110000000000003\linewidth-2\tabcolsep}p{\dimexpr.168\linewidth-2\tabcolsep}p{\dimexpr.1658\linewidth-2\tabcolsep}p{\dimexpr.1539\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\multicolumn{6}{p{\dimexpr(1\linewidth-2\tabcolsep)}}{\cAlignHack \% cumulative retained}\\
\rowcolor{kwdboxcolor}Sieve no & F2 & F3 & F4 & F5 & F6\\
\tblmidrule 
\#20 &
  12.93 &
  7.14 &
  11.52 &
  13.46 &
  9.76\\
\#40 &
  34.73 &
  17.98 &
  31.76 &
  18.34 &
  27.16\\
\#60 &
  42.81 &
  31.36 &
  35.78 &
  17.38 &
  31.52\\
\#80 &
  53.47 &
  44.87 &
  40.34 &
  29.58 &
  44.35\\
\#120 &
  64.32 &
  57.33 &
  49.97 &
  42.31 &
  57.27\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}
\textbf{Carr's Compressibility Index}

Carr's Index of granules was calculated through the application of the formula.
\begin{eqnarray*}Carr's\;compressibility\;Index\;(\%)\;=\left[\frac{V0-vt}{V0}\right]\times100 \end{eqnarray*}
\textbf{Hausner's Ratio}

Hausner ratio can be obtained as  
\begin{eqnarray*}Hausner's\;ratio=\frac{Tapped\;density}{Bulk\;density} \end{eqnarray*}
\textbf{Sieve analysis}

The set of sieves were placed on a vibrating sifter with the largest sieve size on top. 5gms of granules were accurately weighed and were passed through the set of sieves for a set time. Upon completion, the material was collected from each individual sieve and weighed and the percent cumulative weight retained was determined and the data obtained is mentioned in the Table~\ref{tw-ffa9aead9bad}.

\textbf{Evaluation of Tablets}

Following Evaluation tests were performed for the formulations \unskip~\citep{667901:15753870}.\ensuremath{^{}}


\begin{table}[!htbp]
\caption{\boldmath {Weight variation and thickness of the tablets} }
\label{tw-00b080943af7}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{LLL}
\tbltoprule \rowcolor{kwdboxcolor}Batch no & Weight variation & Thickness\\
\tblmidrule 
F2 &
  Pass &
  5.93 \ensuremath{\pm} 0.10\\
F3 &
  Pass &
  6.17 \ensuremath{\pm} 0.10\\
F4 &
  Pass &
  5.61 \ensuremath{\pm} 0.10\\
F5 &
  Pass &
  5.73 \ensuremath{\pm} 0.10\\
F6 &
  Pass &
  5.69 \ensuremath{\pm} 0.10\\
\tblbottomrule 
\end{tabulary}\par 
\end{table}
\textbf{Formulation development}

The active and inactive ingredients were weighed and sifted through \#20 sieve. The ingredients like sodium starch glycolate and rice starch were sifted through \#40 sieve. After sifting, whole ingredients were mixed for 15mins.

F1 was directly compressed by adding the required excipients such as lactose monohydrate as both filler and binder, talc as a lubricant.

Hydroxypropyl cellulose was taken in distilled water, used as a binder for wet granulation and used for the formulation of F2 to F6 by changing the concentrations of hydroxypropyl cellulose, sodium starch glycolate, rice starch, lactose monohydrate.

\textbf{Hardness test}

Hardness was the mainly required element to maintain the friability stand against mechanical shocks during the period of manufacturing, packing, and shipping. The hardness tester was used to check the hardness. Three tablets from every batch were used for the evaluation and the results obtained are mentioned in Table~\ref{tw-5e845c419cf9}.

The unit used to measure the hardness was K\ensuremath{_{p.}}

\textbf{Thickness}

Vernier calliper's instrument was used to measure the thickness and diameter. The values were expressed in mm. The test was carried out for all formulations and data is mentioned in Table~\ref{tw-00b080943af7}.


\begin{table*}[!htbp]
\caption{\boldmath {Hardness of the tablets} }
\label{tw-5e845c419cf9}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.2638\linewidth-2\tabcolsep}p{\dimexpr.2535\linewidth-2\tabcolsep}p{\dimexpr.2656\linewidth-2\tabcolsep}p{\dimexpr.2171\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}Formulation & Maximum hardness (N) & Optimum hardness (N) & Friability (\%w/w)\\
\tblmidrule 
F2 &
  80 &
  60-80 &
  0.02\\
F3 &
  90 &
  75-90 &
  0.01\\
F4 &
  175 &
  155-175 &
  0.04\\
F5 &
  188 &
  176-188 &
  0.03\\
F6 &
  190 &
  175-190 &
  0.01\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Disintegration Time of the Formulations} }
\label{tw-61bdddbff7f4}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.32300000000000004\linewidth-2\tabcolsep}p{\dimexpr.337\linewidth-2\tabcolsep}p{\dimexpr.34\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}Formulation & Medium & Disintegration time (minutes)\\
\tblmidrule 
F2 &
  \multicolumn{1}{p{\dimexpr(.337\linewidth-2\tabcolsep)}}{\multirow{5}{\linewidth}{Purified water with the temperature maintained at 37\ensuremath{\pm}0.5 0C}} &
  7-8\\
F3 &
   &
  7-9\\
F4 &
   &
  5-6\\
F5 &
   &
  7-9\\
F6 &
   &
  6-8\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}
\textbf{Weight variation test and content uniformity}

20 tablets from each batch were randomly selected and weighed to calculate the weight variation, content uniformity and standard deviation of the tablets and the results are mentioned in Table~\ref{tw-00b080943af7}. The content uniformity is calculated by UV method and the results are mentioned in the Table~\ref{tw-8006de2c438b}.

\textbf{Friability test}

Initially, 20 tablets were selected randomly and weighed. These tablets were transferred into the Friabulator disk. The RPM of the disk was set to 25 and the disk was allowed to rotate for 4 minutes. The tablets were collected after the completion of rotations and were weighed. The initial weight and final weight were incorporated in the below formula and the results obtained are mentioned in Table~\ref{tw-5e845c419cf9}.

           \%friability =
\begin{eqnarray*}\left[\frac{Initial\;weight-final\;weight}{final\;weight}\right]\times100 \end{eqnarray*}

\begin{table}[!htbp]
\caption{\boldmath {Content Uniformity} }
\label{tw-8006de2c438b}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{LL}
\tbltoprule \rowcolor{kwdboxcolor}Formulation & Drug Content (\%)\\
\tblmidrule 
F2 &
  96.89\\
F3 &
  97.34\\
F4 &
  98.18\\
F5 &
  98.53\\
F6 &
  98.79\\
\tblbottomrule 
\end{tabulary}\par 
\end{table}

\begin{table*}[!htbp]
\caption{\boldmath {In-vitro Release Profile} }
\label{tw-ba8ef75a0a89}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.21320000000000004\linewidth-2\tabcolsep}p{\dimexpr.06759999999999999\linewidth-2\tabcolsep}p{\dimexpr.1386\linewidth-2\tabcolsep}p{\dimexpr.10209999999999999\linewidth-2\tabcolsep}p{\dimexpr.0992\linewidth-2\tabcolsep}p{\dimexpr.08470000000000002\linewidth-2\tabcolsep}p{\dimexpr.0984\linewidth-2\tabcolsep}p{\dimexpr.10160000000000002\linewidth-2\tabcolsep}p{\dimexpr.09459999999999999\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}{\multirow{2}{*}{Dissolution  \mbox{}\protect\newline Media}} & {\multirow{2}{*}{Sl. \mbox{}\protect\newline No}} & {\multirow{2}{*}{Time  \mbox{}\protect\newline (hrs)}} & \multicolumn{6}{p{\dimexpr(.5806\linewidth-2\tabcolsep)}}{\cAlignHack \% Drug release}\\
\rowcolor{kwdboxcolor} &  &  & RLD & F2 & F3 & F4 & F5 & F6\\
\tblmidrule 
\multicolumn{1}{p{\dimexpr(.21320000000000004\linewidth-2\tabcolsep)}}{\multirow{8}{\linewidth}{0.1 N Hcl}} &
  1 &
  2 &
  27.1 &
  16.9 &
  19.3 &
  21.3 &
  23.7 &
  25.3\\
 &
  2 &
  4 &
  40.5 &
  24.5 &
  25.7 &
  36.7 &
  35.9 &
  39.4\\
 &
  3 &
  6 &
  56.7 &
  43.6 &
  44.8 &
  45.8 &
  47.3 &
  54.7\\
 &
  4 &
  8 &
  69.7 &
  52.3 &
  53.4 &
  61.2 &
  65.4 &
  68.3\\
 &
  5 &
  10 &
  79.3 &
  65.7 &
  65.7 &
  70.9 &
  76.9 &
  78.6\\
 &
  6 &
  12 &
  89.4 &
  76.8 &
  71.7 &
  77.1 &
  82.7 &
  87.9\\
 &
  7 &
  14 &
  95.73 &
  79.4 &
  82.3 &
  81.8 &
  91.5 &
  94.8\\
 &
  8 &
  16 &
  98.71 &
  87.3 &
  85.1 &
  92.5 &
  94.6 &
  97.8\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\bgroup
\fixFloatSize{images/f294a08e-0dc7-47bc-9c9e-5463819a29cf-upicture2.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/f294a08e-0dc7-47bc-9c9e-5463819a29cf-upicture2.png}{\includegraphics{images/f294a08e-0dc7-47bc-9c9e-5463819a29cf-upicture2.png}}{}
\makeatother 
\caption{\boldmath {In-vitro drug release studies}}
\label{f-021902baf22f}
\end{figure}
\egroup

\begin{table*}[!htbp]
\caption{\boldmath {Criteria for selection of Optimized Formulation} }
\label{tw-9847996c3339}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{LLLLLLLL}
\tbltoprule \rowcolor{kwdboxcolor}Sl.NO & Time(hrs) & RLD (R) & Optimized Formulation F6 (T) & /R-T/ & /R-T/2 & f2 value & f1 value\\
\tblmidrule 
1. &
  2 &
  22.1 &
  21.2 &
  0.60 &
  0.36 &
  \multicolumn{1}{p{\dimexpr(\mcWidth{7})}}{\multirow{8}{\linewidth}{89}} &
  \multicolumn{1}{p{\dimexpr(\mcWidth{8})}}{\multirow{8}{\linewidth}{1.779}}\\
2. &
  4 &
  39.2 &
  38.5 &
  0.70 &
  0.49 &
   &
  \\
3. &
  6 &
  51.7 &
  49.5 &
  2.20 &
  4.84 &
   &
  \\
4. &
  8 &
  69.4 &
  68.2 &
  1.20 &
  1.44 &
   &
  \\
5. &
  10 &
  76.9 &
  75.6 &
  1.30 &
  1.69 &
   &
  \\
6. &
  12 &
  84.7 &
  83.5 &
  1.20 &
  1.44 &
   &
  \\
7. &
  14 &
  93.05 &
  92.8 &
  0.25 &
  0.0625 &
   &
  \\
8. &
  16 &
  99.6 &
  97.5 &
  2.1 &
  4.41 &
   &
  \\
\multicolumn{2}{p{\dimexpr(\mcWidth{1}+\mcWidth{2})}}{Total} &
  536.65 &
  526.8 &
  9.55 &
  14.73 &
  \multicolumn{2}{p{\dimexpr(\mcWidth{7}+\mcWidth{8})}}{}\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}
\textbf{Stability Studies}


\begin{table*}[!htbp]
\caption{\boldmath {Stability data for the optimized formulation (F6)} }
\label{tw-99e0979f9a07}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.20269999999999996\linewidth-2\tabcolsep}p{\dimexpr.1565\linewidth-2\tabcolsep}p{\dimexpr.1589\linewidth-2\tabcolsep}p{\dimexpr.16570000000000004\linewidth-2\tabcolsep}p{\dimexpr.1577\linewidth-2\tabcolsep}p{\dimexpr.15849999999999998\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}{\multirow{2}{*}{Tests}} & {\multirow{2}{*}{Initial Values}} & \multicolumn{2}{p{\dimexpr(.3246000000000001\linewidth-2\tabcolsep)}}{\cAlignHack 25 C/60\% RH} & \multicolumn{2}{p{\dimexpr(.31619999999999997\linewidth-2\tabcolsep)}}{\cAlignHack 40 C/75\% RH}\\
\rowcolor{kwdboxcolor} &  & 1 month & 3 months & 1 month & 3 months\\
\tblmidrule 
Appearance &
  \multicolumn{5}{p{\dimexpr(.7972999999999999\linewidth-2\tabcolsep)}}{\cAlignHack White-colored circular tablets with scoreline}\\
Thickness (mm) &
  5.69+\_0.10 &
  5.69+\_0.10 &
  5.69+\_0.10 &
  5.69+\_0.10 &
  5.69+\_0.10\\
Hardness (N) &
  175-190 &
  176-190 &
  178-190 &
  176-190 &
  175-185\\
Disintegration Time  &
  6-8 minutes &
  6-8 minutes &
  6-8 minutes &
  7-9 minutes &
  8-9 minutes\\
Dissolution Studies (0.1 N HCl) &
  In 16 hours = 98.5 &
  In 16 hours = 96.9 &
  In 16 hours = 94.3 &
  In 16 hours = 93.6 &
  In 16 hours = 91.7\\
Water Assay Not less than 90.0\% w/w to 110.0\% of Ethosuximide 250 mg per Tablet &
  100.25 &
  98.90 &
  98.72 &
  97.5 &
  99.58\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}
 \textbf{Disintegration test}

3 tablets from each formulation were collected and placed separately in disintegration apparatus filled with distilled water. The complete disintegration time of the tablet was noted and mentioned in Table~\ref{tw-61bdddbff7f4}.

\textit{\textbf{In-vitro}} \textbf{ drug release test}

The vessels in the paddle apparatus were filled completely with 0.1N HCl and each tablet was placed in each vessel, maintaining temperature at 37 \ensuremath{\pm} 0.5\ensuremath{^{o}}C temperature and the rpm at 75. The samples were collected at 2, 4, 6, 8, 10, 12, 14 and 16 hours and analysed by UV spectroscopy at 264 nm against the respective dissolution medium as blank. The results are mentioned in the Table~\ref{tw-ba8ef75a0a89} and the criteria for selection of optimized formulation are mentioned in Table~\ref{tw-9847996c3339}. The percentage drug release of all the formulations along with the marketed formulation which is taken as reference is noted and the graph drawn by plotting the points is mentioned in the Figure~\ref{f-021902baf22f}.  

\textbf{Stability studies of optimized formulation}

The shelf life of optimized formulation was performed with accelerating storage conditions such as relative humidity and temperature which can result in decomposition or a degradation reaction of active moiety if the formulation was not stable and results in a decrease in active moiety over time. Samples of the final formulation were packed in a High-Density Polyethylene bottle with screw capping with some desiccants in it for 90 days at 25 \ensuremath{\pm} 2 \ensuremath{^{0}}C and 60 \ensuremath{\pm} 5\% RH and 40 \ensuremath{\pm} 2 \ensuremath{^{0}}C and 75 \ensuremath{\pm} 5\% RH. The Samples were obtained and analysed and the results are mentioned in the Table~\ref{tw-99e0979f9a07}, \unskip~\citep{667901:15753874}. 
    
\section{Results and Discussion}
 The solubility of the drug was examined and it has been found that the calibration curve values fall under 200-800\textbf{\space }\ensuremath{\mu}g/ml in water. Among all the trails that have been done, the F1 (direct compression) was found to be not falling under the satisfying results, hence F1 has not been studied further.

Formulations from F2 to F4 showed satisfactory results and meets all the requirements but the dissolution profile was not satisfactory when compared to the marketed formulation. Formulation F5 and F6 showed promising dissolution results when compared to the marketed formulation. The dissolution results of F6 were almost similar to the marketed formulation and has better disintegration time when compared to that of the F5 and also has less surface area. 

\textbf{Summary}

The present research was aimed to prepare oral disintegrating tablets of Ethosuximide which is an anti-epileptic drug. A total of six formulations has been prepared by trial and error method using various concentrations of excipients such as lactose monohydrate and dibasic calcium phosphate dehydrate as diluents, sodium starch glycolate as Super-disintegrant, rice Starch as an intragranular binder, hydroxypropyl cellulose as binder talc as lubricant with an average tablet weight of 400 mg were developed.

Formulation F1 was formulated from the direct compression method and formulation F2 to F6 was formulated from the wet granulation method. The prepared immediate-release tablets were evaluated for post-compression evaluation studies like thickness, hardness, weight variation, friability, drug content uniformity, in-vitro dissolution studies. F6 formulation showed good evaluation studies and a good drug release. Finally, the dissolution profile of optimized sample F6 was matched with the RLD (innovator sample) obtained from the market. From the dissolution profile, f1 \& f2 value was calculated and from that value optimize trial F6 was selected. The stability of the formulation (F6) was conducted by ``Accelerated stability testing'' by packing the tablets in an HDPE bottle with screw capping with some desiccants in it for 90 days at 25 \ensuremath{\pm} 2 C and 60 \ensuremath{\pm} 5\% RH and 40 \ensuremath{\pm} 2 C and 75 \ensuremath{\pm} 5\% RH and sample were obtained and analysed.
    
\section{\textbf{\space }Conclusions}
In formulation F1 the flow characterization was not an acceptable range for compression due to which specified weight was not achieved. Formulation F2 to F4 showed good flow property but the \textit{in-vitro} dissolution studies were found to be slow when compared with the innovator sample. Formulation F5 showed good flow property and the drug release was also found satisfactory but the surface area of tablets was more compared to RLD hence a formulation F6 was planned to reduce the tablet weight by reducing the tablet filler which doesn't impact the formulation. Formulation F6 showed good flow property and the dissolution profile was found satisfactory when compared with the innovator sample and the occupancy was also matching with the RLD.
    

\bibliographystyle{pharmascope_apa-custom}

\bibliography{\jobname}
\end{document}
