\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[flushleft]{threeparttablex}

\usepackage{float}

\begin{document}


\def\RunningAuthor{Santhosh Raja M and Venkataramana K}
\firstPage{2657}
\articleType{Original Article}
\receivedDate{08 Apr 2020}
\acceptedDate{18 May 2020}
\revisedDate{08 May 2020}
\journalVolume{2020, 11}
\journalIssue{2}
\journalDoi{ijrps.v11i2.2280}
\copyrightYear{2020}
\def\authorCount{2}
\def\affCount{2}

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

\title{Formulation Characterization, \textit{Invitro}, \textit{Invivo} and Pharmacokinetic Evaluation of Stabilized Rosuvastatin Calcium Nanosuspension}
\author{Santhosh~Raja~M\textsuperscript{*}\textsuperscript{1}, 
            Venkataramana~K\textsuperscript{2}~\\[5pt]{\textsuperscript{1}Research Scholar, University College of Pharmaceutical Sciences, Acharya Nagarjuna University, Guntur- 522510, India}~\\{\textsuperscript{2}A.S.N. Pharmacy College, Burripalem Road, Tenali, Guntur- 522201, India}}

\begin{abstract}
Rosuvastatin calcium is a BCS class II drug which is used as hyperlipidemic. Many of the BCS class II drugs offer the disadvantage of solubility. Nanoparticle compounds present a promising solution to the insolubility of BCS class II drugs. A simple and efficient technique for the preparation of nanoparticles is a precipitation technique. Polymeric nanoparticles have been prepared by employing the nanoprecipitation method. The nanosuspensions were made by using PVP K30, HPMC K15M, Eudragit L100 in various ratios using precipitation technique. DSC tests the compatibility between the drug and different ingredients. The formed nanoparticles were evaluated for multiple testing parameters like particle size, zeta potential, drug content and dissolution testing. Among all the formulations, the nanosuspension prepared with Eudragit L 100 showed better characteristics. The dissolution test showed the drug release for 12 hours. The best formulation showed the particle size of 100.5 \ensuremath{\pm} 5.4 nm and zeta potential of -55.1 mv. The \textit{in vivo } studies on the Wistar rats showed better pharmacokinetic parameters when compared to the pure drug. Nano precipitation method was successfully employed to prepare Rosuvastatin calcium nanosuspension to improve the dissolution as well as bioavailability.
\end{abstract}\def\keywordstitle{Keywords}

\begin{keywords}bioavailability,\newline dissolution,\newline nanoparticles,\newline precipitation,\newline quasi emulsification,\newline Rosuvastatin calcium
\end{keywords}
\twocolumn[ \maketitle {\printKwdAbsBox}]
\makeatletter{\raggedright\textsuperscript{*}Corresponding Author\par Name:\ Santhosh~Raja~M~\\ Phone:\ +91-9533655477~\\  Email:\ santhosh.raja88@gmail.com
        \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}
The oral route of drug administration is the best and most convenient method of drug administration due to its ease of administration, less pronounced adverse effects and easy intake. Drug delivery by the oral route is preferred due to the ease of administration and painless approach. In recent years considerable attention has been focused on the development of new drug delivery systems \unskip~\citep{792920:18887617}. The more new drug entities developed nearly 40\% of them are hydrophobic. The preparation of nanosuspension shows an increment in the solubility and permeability. It is the most exceptional approach to increase in bioavailability. Pharmaceutical nanosuspension is defined as submicron colloidal dispersions of nano-sized drug particles stabilised by surfactants consist of the poorly water-soluble drug without any matrix material suspended in dispersion \unskip~\citep{792920:18887612,792920:18887615,792920:18887603}. In the precipitation method, the drug is dissolved in a solvent. And then the solution is mixed with a solvent to which drug is insoluble in the presence of surfactant. When a solution is added to the solvent (usually water) rapidly, it leads to rapid supersaturation of drug in the solution. This supersaturation commences formation of ultrafine amorphous or crystalline drug. This method involves nuclei formation and crystal growth which are mainly dependent on temperature. High nucleation rate and low crystal growth rate are primary requirements for preparing a stable suspension with minimum particle size \unskip~\citep{792920:18887608}. Rosuvastatin calcium is a BCS class II drug which has low solubility but high permeability \unskip~\citep{792920:18887604}. The nanosuspension approach has been performed to overcome the problem of solubility and bioavailability \unskip~\citep{792920:18887609,792920:18887614,792920:18887616}.\textbf{\space }


\begin{table*}[!htbp]
\caption{\boldmath {Formulation of Rosuvastatin calcium nanosuspension} }
\label{tw-1f62475df058}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.145\linewidth-2\tabcolsep}p{\dimexpr.1404\linewidth-2\tabcolsep}p{\dimexpr.1704\linewidth-2\tabcolsep}p{\dimexpr.1496\linewidth-2\tabcolsep}p{\dimexpr.16\linewidth-2\tabcolsep}p{\dimexpr.2346\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}{\multirow{2}{*}{Formulation Code}} & {\multirow{2}{*}{Drug \mbox{}\protect\newline (mg)}} & \multicolumn{3}{p{\dimexpr(.48\linewidth-2\tabcolsep)}}{\cAlignHack Polymer (\%)} & {\multirow{2}{*}{Stabiliser Poloxamer  \mbox{}\protect\newline 188 (\%)}}\\
\rowcolor{kwdboxcolor} &  & PVP K 30 & HPMC K 15 M & Eudragit L 100 & \\
\tblmidrule 
R1 &
  200 &
  0.5 &
  -- &
  -- &
  0.5\\
R2 &
  200 &
  1.0 &
  -- &
  -- &
  0.5\\
R3 &
  200 &
  1.5 &
  -- &
  -- &
  0.5\\
R4 &
  200 &
  2.0 &
  -- &
  -- &
  0.5\\
R5 &
  200 &
  -- &
  0.5 &
  -- &
  0.5\\
R6 &
  200 &
  -- &
  1.0 &
  -- &
  0.5\\
R7 &
  200 &
  -- &
  1.5 &
  -- &
  0.5\\
R8 &
  200 &
  -- &
  2.0 &
  -- &
  0.5\\
R9 &
  200 &
  -- &
  -- &
  0.5 &
  0.5\\
R10 &
  200 &
  -- &
  -- &
  1.0 &
  0.5\\
R11 &
  200 &
  -- &
  -- &
  1.5 &
  0.5\\
R12 &
  200 &
  -- &
  -- &
  2.0 &
  0.5\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Release of Rosuvastatin calcium from formulations prepared with PVP K30} }
\label{tw-55a0008f742b}
\centering 
\begin{threeparttable}

\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.20\linewidth-2\tabcolsep}p{\dimexpr.20\linewidth-2\tabcolsep}p{\dimexpr.2097\linewidth-2\tabcolsep}p{\dimexpr.1903\linewidth-2\tabcolsep}p{\dimexpr.20\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}Time(h)  & \multicolumn{4}{p{\dimexpr(.80\linewidth-2\tabcolsep)}}{\cAlignHack Cumulative percent drug release* }\\
\rowcolor{kwdboxcolor} & R1 & R2 & R3 & R4\\
\tblmidrule 
0 &
  0 &
  0 &
  0 &
  0\\
1 &
  38.21 \ensuremath{\pm} 1.02 &
  31.62 \ensuremath{\pm} 1.45 &
  28.21 \ensuremath{\pm} 1.63 &
  21.41 \ensuremath{\pm} 1.95\\
2 &
  46.52 \ensuremath{\pm} 2.34 &
  34.42 \ensuremath{\pm} 2.34 &
  32.46 \ensuremath{\pm} 2.04 &
  29.45 \ensuremath{\pm} 2.58\\
3 &
  53.21 \ensuremath{\pm} 0.98 &
  43.61 \ensuremath{\pm} 1.65 &
  40.23 \ensuremath{\pm} 3.25 &
  36.54 \ensuremath{\pm} 2.31\\
4 &
  68.32 \ensuremath{\pm} 1.36 &
  54.91 \ensuremath{\pm} 0.95 &
  50.62 \ensuremath{\pm} 2.08 &
  47.29 \ensuremath{\pm} 2.57\\
5 &
  71.24 \ensuremath{\pm} 2.34 &
  62.18 \ensuremath{\pm} 1.35 &
  56.18 \ensuremath{\pm} 2.64 &
  54.64 \ensuremath{\pm} 3.02\\
6 &
  88.16 \ensuremath{\pm} 2.65 &
  78.16 \ensuremath{\pm} 2.34 &
  65.21 \ensuremath{\pm} 2.65 &
  60.47 \ensuremath{\pm} 2.95\\
7 &
  100.12 \ensuremath{\pm} 1.95 &
  89.24 \ensuremath{\pm} 1.69 &
  75.14 \ensuremath{\pm} 3.47 &
  71.24 \ensuremath{\pm} 1.64\\
8 &
   &
  98.23 \ensuremath{\pm} 3.05 &
  82.65 \ensuremath{\pm} 1.96 &
  79.54 \ensuremath{\pm} 2.46\\
9 &
   &
   &
  92.93 \ensuremath{\pm} 3.24 &
  84.21 \ensuremath{\pm} 2.19\\
10 &
   &
   &
  100.24 \ensuremath{\pm} 3.29 &
  92.64 \ensuremath{\pm} 1.54\\
11 &
   &
   &
   &
  98.87 \ensuremath{\pm} 2.84\\
12 &
   &
   &
   &
  \\
\tblbottomrule 
\end{tabulary}\par 
\begin{tablenotes}\footnotesize 
    
\item{*Indicates the average of 6 samples}
\end{tablenotes}
\end{threeparttable}

\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Release of Rosuvastatin calcium from formulations prepared with HPMC K 15 M} }
\label{tw-75cff0e46804}
\centering 
\begin{threeparttable}

\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.2014\linewidth-2\tabcolsep}p{\dimexpr.1986\linewidth-2\tabcolsep}p{\dimexpr.20\linewidth-2\tabcolsep}p{\dimexpr.20\linewidth-2\tabcolsep}p{\dimexpr.20\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}Time(h) & \multicolumn{4}{p{\dimexpr(.7986\linewidth-2\tabcolsep)}}{\cAlignHack Cumulative percent drug release*}\\
\rowcolor{kwdboxcolor} & R5 & R6 & R7 & R8\\
\tblmidrule 
0 &
  0 &
  0 &
  0 &
  0\\
1 &
  35.41 \ensuremath{\pm} 1.29 &
  26.51 \ensuremath{\pm} 2.51 &
  24.15 \ensuremath{\pm} 1.48 &
  20.57 \ensuremath{\pm} 1.51\\
2 &
  47.24 \ensuremath{\pm} 2.64 &
  35.67 \ensuremath{\pm} 1.93 &
  31.24 \ensuremath{\pm} 2.54 &
  28.46 \ensuremath{\pm} 2.31\\
3 &
  53.91 \ensuremath{\pm} 2.56 &
  42.51 \ensuremath{\pm} 1.54 &
  39.67 \ensuremath{\pm} 2.51 &
  33.47 \ensuremath{\pm} 2.54\\
4 &
  67.14 \ensuremath{\pm} 1.42 &
  53.27 \ensuremath{\pm} 2.41 &
  48.62 \ensuremath{\pm} 1.42 &
  45.21 \ensuremath{\pm} 1.63\\
5 &
  73.24 \ensuremath{\pm} 1.54 &
  65.21 \ensuremath{\pm} 2.52 &
  55.71 \ensuremath{\pm} 1.74 &
  52.47 \ensuremath{\pm} 1.89\\
6 &
  84.38 \ensuremath{\pm} 2.17 &
  72.59 \ensuremath{\pm} 1.95 &
  61.24 \ensuremath{\pm} 1.56 &
  58.49 \ensuremath{\pm} 2.51\\
7 &
  92.16 \ensuremath{\pm} 2.24 &
  80.61 \ensuremath{\pm} 1.64 &
  72.91 \ensuremath{\pm} 1.48 &
  64.48 \ensuremath{\pm} 2.18\\
8 &
  98.51 \ensuremath{\pm} 1.68 &
  92.34 \ensuremath{\pm} 1.57 &
  80.54 \ensuremath{\pm} 2.24 &
  69.58 \ensuremath{\pm} 1.64\\
9 &
   &
  97.21 \ensuremath{\pm} 2.64 &
  88.47 \ensuremath{\pm} 2.51 &
  71.54 \ensuremath{\pm} 1.58\\
10 &
   &
   &
  98.24 \ensuremath{\pm} 2.09 &
  78.11 \ensuremath{\pm} 2.64\\
11 &
   &
   &
   &
  86.11 \ensuremath{\pm} 1.82\\
12 &
   &
   &
   &
  96.41 \ensuremath{\pm} 2.61\\
\tblbottomrule 
\end{tabulary}\par 
\begin{tablenotes}\footnotesize 
    
\item{*Indicates the average of 6 samples}
\end{tablenotes}
\end{threeparttable}

\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Release of Rosuvastatin calcium from formulations prepared with Eudragit L 100} }
\label{tw-ad61010b50ab}
\centering 
\begin{threeparttable}

\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.2208\linewidth-2\tabcolsep}p{\dimexpr.1792\linewidth-2\tabcolsep}p{\dimexpr.20\linewidth-2\tabcolsep}p{\dimexpr.20\linewidth-2\tabcolsep}p{\dimexpr.20\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}Time(h) & \multicolumn{4}{p{\dimexpr(.7792\linewidth-2\tabcolsep)}}{\cAlignHack Cumulative percent drug release*}\\
\rowcolor{kwdboxcolor} & R9 & R10 & R11 & R12\\
\tblmidrule 
0 &
  0 &
  0 &
  0 &
  0\\
1 &
  39.14 \ensuremath{\pm} 1.56 &
  28.41 \ensuremath{\pm} 1.42 &
  27.41 \ensuremath{\pm} 2.51 &
  19.48 \ensuremath{\pm} 1.67\\
2 &
  46.37 \ensuremath{\pm} 2.41 &
  33.49 \ensuremath{\pm} 2.51 &
  31.59 \ensuremath{\pm} 2.64 &
  26.59 \ensuremath{\pm} 1.84\\
3 &
  53.51 \ensuremath{\pm} 2.34 &
  42.71 \ensuremath{\pm} 1.27 &
  40.05 \ensuremath{\pm} 2.45 &
  32.45 \ensuremath{\pm} 2.51\\
4 &
  67.96 \ensuremath{\pm} 2.51 &
  55.42 \ensuremath{\pm} 2.51 &
  49.11 \ensuremath{\pm} 1.95 &
  45.54 \ensuremath{\pm} 2.67\\
5 &
  73.24 \ensuremath{\pm} 1.23 &
  64.21 \ensuremath{\pm} 2.61 &
  56.03 \ensuremath{\pm} 1.64 &
  51.26 \ensuremath{\pm} 2.34\\
6 &
  87.16 \ensuremath{\pm} 2.15 &
  81.24 \ensuremath{\pm} 1.65 &
  61.07 \ensuremath{\pm} 1.42 &
  57.96 \ensuremath{\pm} 2.31\\
7 &
  100.01 \ensuremath{\pm} 1.96 &
  93.61 \ensuremath{\pm} 2.54 &
  73.11 \ensuremath{\pm} 2.65 &
  63.24 \ensuremath{\pm} 1.56\\
8 &
   &
  99.21 \ensuremath{\pm} 2.81 &
  81.63 \ensuremath{\pm} 1.68 &
  70.28 \ensuremath{\pm} 1.75\\
9 &
   &
   &
  89.62 \ensuremath{\pm} 1.45 &
  77.45 \ensuremath{\pm} 2.64\\
10 &
   &
   &
  98.41 \ensuremath{\pm} 2.08 &
  84.29 \ensuremath{\pm} 2.34\\
11 &
   &
   &
   &
  92.67 \ensuremath{\pm} 2.69\\
12 &
   &
   &
   &
  99.53 \ensuremath{\pm} 2.09\\
\tblbottomrule 
\end{tabulary}\par 
\begin{tablenotes}\footnotesize 
    
\item{*Indicates the average of 6 samples}
\end{tablenotes}
\end{threeparttable}

\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Release characteristics of Rosuvastatin calcium nanosuspension} }
\label{tw-331c20af3333}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.1681\linewidth-2\tabcolsep}p{\dimexpr.1634\linewidth-2\tabcolsep}p{\dimexpr.15079999999999998\linewidth-2\tabcolsep}p{\dimexpr.1635\linewidth-2\tabcolsep}p{\dimexpr.1727\linewidth-2\tabcolsep}p{\dimexpr.1815\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}Formulation  & \multicolumn{4}{p{\dimexpr(.6503999999999999\linewidth-2\tabcolsep)}}{\cAlignHack Correlation coefficient values ( R2) } & Diffusion exponent \\
\rowcolor{kwdboxcolor}code  &
  Zero Order & First Order & Higuchi's Model & Peppas Model & (n) value of Peppas \\
\tblmidrule 
R1 &
  0.9319 &
  0.9471 &
  0.9843 &
  0.9594 &
  0.47\\
R2 &
  0.9620 &
  0.7977 &
  0.9770 &
  0.9711 &
  0.55\\
R3 &
  0.9738 &
  0.9216 &
  0.9775 &
  0.9807 &
  0.59\\
R4 &
  0.9824 &
  0.9545 &
  0.9703 &
  0.9912 &
  0.67\\
R5 &
  0.9331 &
  0.8627 &
  0.9979 &
  0.9963 &
  0.51\\
R6 &
  0.9482 &
  0.8926 &
  0.9946 &
  0.9984 &
  0.56\\
R7 &
  0.9666 &
  0.7807 &
  0.9847 &
  0.9954 &
  0.59\\
R8 &
  0.9764 &
  0.8729 &
  0.9818 &
  0.9948 &
  0.63\\
R9 &
  0.9407 &
  0.9550 &
  0.9841 &
  0.9661 &
  0.49\\
R10 &
  0.9728 &
  0.8907 &
  0.9622 &
  0.9641 &
  0.59\\
R11 &
  0.9799 &
  0.7780 &
  0.9641 &
  0.9760 &
  0.60\\
R12 &
  0.9878 &
  0.9056 &
  0.9665 &
  0.9906 &
  0.67\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Evaluation parameters for Rosuvstatin calcium nanosuspension} }
\label{tw-57352e74e39f}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.25\linewidth-2\tabcolsep}p{\dimexpr.25\linewidth-2\tabcolsep}p{\dimexpr.2742\linewidth-2\tabcolsep}p{\dimexpr.2258\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}Formulation  & Particle size (nm) & Zeta Potential & \% Drug entrapped\\
\tblmidrule 
R1 &
  321-341 &
  11.4\ensuremath{\pm}3 &
  87.41\\
R2 &
  332-353 &
  13.1\ensuremath{\pm}2 &
  84.52\\
R3 &
  385-415 &
  13.2\ensuremath{\pm}2 &
  83.24\\
R4 &
  275-281 &
  12.5\ensuremath{\pm}3 &
  85.21\\
R5 &
  167-183 &
  40.2\ensuremath{\pm}2 &
  80.51\\
R6 &
  158-161 &
  42.2\ensuremath{\pm}3 &
  82.49\\
R7 &
  201-215 &
  44.2\ensuremath{\pm}1 &
  82.34\\
R8 &
  124-135 &
  45.2\ensuremath{\pm}3 &
  81.24\\
R9 &
  108-119 &
  48.2\ensuremath{\pm}1 &
  90.24\\
R10 &
  125-134 &
  46.2\ensuremath{\pm}3 &
  90.91\\
R11 &
  95-109 &
  50.4\ensuremath{\pm}1 &
  93.27\\
R12 &
  91-103 &
  56.1\ensuremath{\pm}2 &
  94.21\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Pharmacokinetic parameters of R12 and Pure Rosuvastatin} }
\label{tw-867623087bf2}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.2448\linewidth-2\tabcolsep}p{\dimexpr.2552\linewidth-2\tabcolsep}p{\dimexpr.25\linewidth-2\tabcolsep}p{\dimexpr.25\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}Parameter & Unit & Value R12 & Pure Drug\\
\tblmidrule 
t1/2 &
  h &
  5.07 &
  2.89\\
Tmax &
  h &
  2 &
  4\\
Cmax &
  ng/ml &
  58.13 &
  31.24\\
AUC 0-t &
  ng/ml*h &
  368.445 &
  192.170\\
AUC 0-\ensuremath{\infty} &
  ng/ml*h &
  381.492 &
  193.213\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

    
\section{Materials and Methods}
\textbf{Materials}

Rosuvastatin calcium is a gift sample from J.B. Chemical and Pharmaceuticals Ltd, Mumbai, PVP K30, HPMC K15 M were procured from Loba chem. Pvt Ltd, Mumbai, Eudragit L 100 is a gift sample from Evonik Industries, Mumbai, Poloxamer 188 is purchased from BASF, Mumbai, and all other ingredients used were of analytical grade.


\bgroup
\fixFloatSize{images/4348ec67-7cf5-4e86-91f6-856a3434967a-upicture1.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/4348ec67-7cf5-4e86-91f6-856a3434967a-upicture1.png}{\includegraphics{images/4348ec67-7cf5-4e86-91f6-856a3434967a-upicture1.png}}{}
\makeatother 
\caption{\boldmath {ATR Spectrum of Rosuvastatin calcium and along with excipients. [*A = Pure Rosuvastatin, B =combination of Rosuvastatin along with excipients]}}
\label{f-66f89f522261}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/28bfeccb-d7b7-4ed0-b1bc-c8099f84344c-upicture2.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/28bfeccb-d7b7-4ed0-b1bc-c8099f84344c-upicture2.png}{\includegraphics{images/28bfeccb-d7b7-4ed0-b1bc-c8099f84344c-upicture2.png}}{}
\makeatother 
\caption{\boldmath {DSC Thermogram of Rosuvastatin Calcium and along with excipients [*A = Pure Rosuvastatin, B =combination of Rosuvastatin along with excipients]}}
\label{f-701e7aa47df8}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/9a634c26-c035-4fbd-bcbd-bae745101a22-upicture3.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/9a634c26-c035-4fbd-bcbd-bae745101a22-upicture3.png}{\includegraphics{images/9a634c26-c035-4fbd-bcbd-bae745101a22-upicture3.png}}{}
\makeatother 
\caption{\boldmath {Drugrelease plot of Rosuvastatin calcium from formulations prepared with PVP K30}}
\label{f-26d33eec319d}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/ec232684-0237-452b-8455-82a8fa500a60-upicture4.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/ec232684-0237-452b-8455-82a8fa500a60-upicture4.png}{\includegraphics{images/ec232684-0237-452b-8455-82a8fa500a60-upicture4.png}}{}
\makeatother 
\caption{\boldmath {Drug release plot of Rosuvastatin calcium from formulations prepared with HPMC K 15 M}}
\label{f-8627767d65ab}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/ecce43d2-74cd-4d50-9940-38bbae45094d-upicture5.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/ecce43d2-74cd-4d50-9940-38bbae45094d-upicture5.png}{\includegraphics{images/ecce43d2-74cd-4d50-9940-38bbae45094d-upicture5.png}}{}
\makeatother 
\caption{\boldmath {Drug release plot of Rosuvastatin calcium from formulations prepared with Eudragit L 100}}
\label{f-5cb4050925fb}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/b0f979dd-c2d2-4fcd-a695-5f54ed77265e-upicture6.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/b0f979dd-c2d2-4fcd-a695-5f54ed77265e-upicture6.png}{\includegraphics{images/b0f979dd-c2d2-4fcd-a695-5f54ed77265e-upicture6.png}}{}
\makeatother 
\caption{\boldmath {SEM image of Rosuvastatin calcium nanosuspension(R12)}}
\label{f-bced1e352666}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/bdc06bb1-3a81-4986-93cd-430e2ea70503-upicture7.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/bdc06bb1-3a81-4986-93cd-430e2ea70503-upicture7.png}{\includegraphics{images/bdc06bb1-3a81-4986-93cd-430e2ea70503-upicture7.png}}{}
\makeatother 
\caption{\boldmath {Zeta Potential graph of Rosuvastatin Nanosuspension(R12)}}
\label{f-99b1b04cfb54}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/4fc6f135-85ef-4899-a789-8919e8e0fd28-upicture8.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/4fc6f135-85ef-4899-a789-8919e8e0fd28-upicture8.png}{\includegraphics{images/4fc6f135-85ef-4899-a789-8919e8e0fd28-upicture8.png}}{}
\makeatother 
\caption{\boldmath {Comparative pharmacokinetic evaluation of Rosuvastatin calcium nanosuspension along with pure drug}}
\label{f-373b70d68bf3}
\end{figure}
\egroup
\textbf{Methods }

\textbf{Formulation of Rosuvastatin calcium nanosuspension}

Polymeric nanoparticles have been prepared by employing nanoprecipitation technique \unskip~\citep{792920:18887609,792920:18887607}. Polymers in specific ratios as mentioned in the formulation Table~\ref{tw-1f62475df058} are dissolved in 15 ml of PEG 200 with the help of vortex mixer for 5 minutes to form a diffusion phase. To the above diffusion phase accurately weighed drug 10 mg is added and see that the drug was dissolved entirely in it. The aqueous phase is prepared by dissolving Poloxomer 188 (0.5\% solution) in water which is a non-solvent. The diffusive (PEG) phase is slowly injected into the aqueous phase (35 ml) under stirring at 1000 RPM. After 30 min of stirring the mixture is homogenised under high-speed homogeniser for 30 min at 7000 RPM. The resultant suspension is preserved and used as such for further study.

\textbf{Evaluation of Rosuvastatin Nanosuspension}

\textbf{Attenuated total reflectance studies}

The pure Rosuvastatin Calcium powder was taken, and the ATR spectrum was recorded in Bruker instrument. It was compared with that of reference, and the ATR spectrum of final formulation was made to identify the compatibility issues between the drug and selected excipients.

\textbf{Differential Scanning Calorimetry}

DSC scan of about 5mg; using an automatic thermal analyser system performed accurately weighed Rosuvastatin Calcium and tablet containing the same amount of drug. The entire samples were run at a scanning rate of 10{\textdegree}C/min from 25-250{\textdegree}C. The DSC was conducted for the final formulation to identify the compatibility issues \unskip~\citep{792920:18887613}. 

\textit{\textbf{Invitro}} \textbf{ dissolution studies}

Drug release from the nanosuspension formulations was studied using eight-station dissolution test apparatus (Electro lab TDT 08L) employing a USP II type paddle stirrer at a speed of 50 rpm and 37 \ensuremath{\pm} 1\ensuremath{^{0}}c. The dissolution medium consisted of phosphate buffer of pH 6.8 (900ml). The drug release forms various nanosuspension formulations at different time intervals were measured from the developed method by U.V. visible spectrophotometer (Systronics 2202), which was validated. The dissolution experiments were conducted in triplicate. The dissolution data were fitted into various release kinetics like zero order, first order, Higuchi and Peppas models to describe multiple release patterns \unskip~\citep{792920:18887606,792920:18887605,792920:18887610}.

\textbf{Particle size analysis}

Total formulations of the drug were exposed to Scanning Electron Microscopy (SEM) for particle size determination, and particle size had been determined \& recorded \unskip~\citep{792920:18887611}.

\textbf{Zeta potential}

Zeta potential is a measure of the charge on the electrical double layer of the nanoparticle, which indicates the various stability concerns. Zeta potential measurements have been conducted at a temperature of 25\ensuremath{^\circ}C along with an electric field strength of 23 V/m, using Zetasizer (Malvern).

\textbf{Percentage Entrapment efficiency}

The \% entrapment is determined by taking around 2ml formulation into Nessler's cylinder tube (10 ml) and centrifuged at 2000-3000 RPM for 4 hrs. The supernatant layer formed after centrifugation is filtered using Whatman filter paper (No:41). This filtered content is diluted using Phosphate buffer (6.8 pH) up to 10ml. The resultant solution for drug content was analysed at specific lambda max of the drug utilising U.V. visible spectrophotometer (Systronics 2202) for already developed method. These were repeated for three times, and the result was recorded. \% E.E. was calculated basing on formula$\%\;EE=\;\frac{Total\;drug\;content-Free\;drug}{Total\;drug\;used}\times100 $

\textbf{Pharmacokinetic evaluation}

Based on the drug release pattern and other \textit{in-vitro} examinations among all the formulations, the best formulation is selected for \textit{in vivo} studies to estimate various pharmacokinetic parameters. The institutional animal ethics committee approved all the procedures. Wistar albino rats were selected for the study. The animals were acclimatised for 20 days fasted overnight before the experiment but had free access to water. The blood samples (approximately 500 \ensuremath{\mu }L) were collected from retro-orbital plexus of the anesthetised rat into prelabelled heparinised Eppendorf tubes. Plasma concentration of drug in rats (n=6) following p.o., administration (1 mg/Kg b.wt) are determined, and the strength of the drug is determined according to the validated and developed method. 
    
\section{Results and Discussion}
\textbf{Attenuated total reflectance studies}

ATR spectrums of Pure Rosuvastatin calcium and the final formulation are shown in Figure~\ref{f-66f89f522261}. From these, it is clear that there are no major shifts in the functional groups indicating the compatibility of the selected polymers with the drug.

*A = Pure Rosuvastatin, B = combination of Rosuvastatin along with excipients

\textbf{Differential Scanning Calorimetry}

DSC scans of pure drug Rosuvastatin calcium as in Figure~\ref{f-701e7aa47df8}, indicating the melting point at 149.2\ensuremath{^{0}}C and the final formulation also shows a characteristic peak at 150.2\ensuremath{^{0}}C showing no major shift in peaks indicating the compatibility of the polymers.

*A = Pure Rosuvastatin, B = combination of Rosuvastatin along with excipients

\textit{\textbf{Invitro}} \textbf{ dissolution studies}

The drug release from various formulations is shown in Tables~\ref{tw-55a0008f742b}, \ref{tw-75cff0e46804} and~\ref{tw-ad61010b50ab}, Figures~\ref{f-26d33eec319d}, \ref{f-8627767d65ab} and~\ref{f-5cb4050925fb}, and the drug release characteristics are shown in Table~\ref{tw-331c20af3333}. The drug release profiles showed different values, the formulations prepared with varying concentrations, i.e. 0.5\%, 1\%, 1.5\% and 2 \% of PVP K30, i.e. R1, R2, R3, R4 showed per cent drug release of 100.12 \ensuremath{\pm} 1.95, 98.23 \ensuremath{\pm} 3.05, 100.24 \ensuremath{\pm} 3.29, 98.87 \ensuremath{\pm} 2.84 at the end of 7\ensuremath{^{th}}, 8\ensuremath{^{th}}, 10\ensuremath{^{th}} 11\ensuremath{^{th}} hour respectively. In contrast, the formulations prepared with HPMC K 15 M, i.e. R5, R6, R7 and R8 showed the per cent drug release of 98.51 \ensuremath{\pm} 1.68, 97.21 \ensuremath{\pm} 2.64, 98.24 \ensuremath{\pm} 2.09, 96.41 \ensuremath{\pm} 2.61 at the end of 8\ensuremath{^{th}}, 9\ensuremath{^{th}},10\ensuremath{^{th}} and 12\ensuremath{^{th}} hour respectively. Similarly, the formulations prepared with Eudragit L 100, i.e. R9, R10, R11 and R12 showed per cent drug release of 100.01 \ensuremath{\pm} 2.04, 99.21 \ensuremath{\pm} 2.73, 98.41 \ensuremath{\pm} 2.04, 99.53 \ensuremath{\pm} 1.98 at the end of 8\ensuremath{^{th}}, 9\ensuremath{^{th}}, 10\ensuremath{^{th}} and 12\ensuremath{^{th}} hour respectively. Based on the above release pattern, the R12 the formulation prepared with 2 \% of Eudragit L 100 showed release pattern according to the prescribed limits.

The complete dissolution data is fitted into various kinetic models to describe the release mechanisms. The zero-order kinetic model shows the correlation coefficient r\ensuremath{^{2}} values in the range of 0.9319 to 0.9878, indicating the drug release mechanism followed zero-order kinetics. The first order r\ensuremath{^{2}} lies in the range of 0.7977 to 0.9550, indicating that the drug release followed zero-order kinetics. The r\ensuremath{^{2}} values of the Higuchi model range from 0.9622 to 0.9979, indicating the drug release mechanism is diffusion. The n value of Peppas kinetics showed the majority lies in the range of 0.5 {\textendash} 1 indicating the non-fickian form of diffusion. Based on above all parameters, the R12 was selected as the best formulation and proceeded for further studies. 

\textbf{Particle size}

All the formulations prepared were in the nanoparticles range and the best formulation i.e. R12 showed particle size of 91-103 nm (Figure~\ref{f-bced1e352666}, Table~\ref{tw-57352e74e39f}), satisfactory zetapotential of 56.1\ensuremath{\pm}2 mv (Figure~\ref{f-99b1b04cfb54}) and percentage drug entrapped was 94.21.

\textbf{Pharmacokinetic evaluation}

Based on results obtained (Figure~\ref{f-373b70d68bf3} and Table~\ref{tw-867623087bf2}), the Rosuvastatin calcium nanosuspension R12 showed better pharmacokinetic parameters when compared to pure drug.
    
\section{Conclusions}
Nanosuspension of Rosuvastatin calcium was successfully prepared by using emulsification method. Among all the polymers, the R12 (Eudragit RL100 at 2.0\%concnetration) showed better release pattern and satisfactory zeta and particle size. The prepared formulations showed significant dissolution and other evaluation characteristics. Hence the Rosuvastatin nanosuspension can be conveniently used as an oral drug delivery system. 
    
\section{  Acknowledgement}
None

\textbf{Funding Support}

None

\textbf{Conflict of Interest}

The authors declare no conflict of interest.
    

\bibliographystyle{pharmascope_apa-custom}

\bibliography{\jobname}
\end{document}
