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\def\RunningAuthor{Munagala Gayatri Ramya and Kothapalli Bannoth Chandra Sekhar}
\firstPage{1920}
\articleType{Original Article}
\receivedDate{10 Jan 2020}
\acceptedDate{02 Mar 2020}
\revisedDate{05 Feb 2020}
\journalVolume{2020, 11}
\journalIssue{2}
\journalDoi{ijrps.v11i2.2109}
\copyrightYear{2020}
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\title{Preparation and evaluation of matrix type gastro retentive floating atenolol tablets using sintering technique}
\author{Munagala~Gayatri~Ramya\textsuperscript{*}, 
            Kothapalli~Bannoth~Chandra~Sekhar~\\[5pt]{Jawaharlal Nehru Technological University Anantapur, Ananthapuramu 515002, Andhra Pradesh, India}}

\begin{abstract}
The aim of this investigation was to design and assess the gastric floating tablets of Atenolol using thermal sintering and investigate the effect of sintering on PEO polymer. Atenolol is an Antihypertensive with only 50 percent bioavailability due to poor absorption in lower GI tract. Gastro retentive Floating tablets were prepared to enhance the gastric retention time, to prolong the drug release. PEO which was selected as sintered polymer. Tablets were prepared by direct compression method. Formulated tablets were exposed to different temperatures (40\ensuremath{^{0}}C, 50\ensuremath{^{0}}C and 60\ensuremath{^{0}}C) at) at various time intervals( 1h ,2h ,3h and4h) in a hot air oven.  Post compression parameters were evaluated like weight variation, hardness, friability, floating lag time and total floating time. The result of the investigation indicates sintering influenced the floating time and dissolution properties. Weight variation, friability and content uniformity values were within limits. Sintering time and temperature contributes to effectiveness of polymers in extending drug release. Reduction in floating lag time and increase in total floating time as well as release of drug was delayed. All sintered formulation have no interaction was found in FTIR, DSC studies. All sintered tablets followed zero order with nonfickian diffusion mechanism. This study helps the use of thermal sintering in preparation of floating tablets.
\end{abstract}\def\keywordstitle{Keywords}

\begin{keywords}Atenolol,\newline PEO,\newline sintering,\newline time,\newline floating lag time,\newline total floating time,\newline delayed release
\end{keywords}
\twocolumn[ \maketitle {\printKwdAbsBox}]
\makeatletter{\raggedright\textsuperscript{*}Corresponding Author\par Name:\ Munagala~Gayatri~Ramya~\\ Phone:\ 9347148013~\\  Email:\ ramya\_munagala@yahoo.com
        \par}\vspace*{-11pt}\hrulefill\par{\fontsize{12}{14}\selectfont ISSN: 0975-7538}\par% 
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\section{Introduction}
Sintering is defined as generation of welded bonds between polymer particles. Controlled release dosage forms were prepared by exposing the matrix tablet to temperature near melting point range of the polymer \unskip~\citep{707819:16783034}. The temperature treatment involves the exposing the Tablet dosage form to particular temperature and the polymer forming the matrix slowly melts and the adhesive bondings are formed and leads to control the release of drug \unskip~\citep{707819:16783037}. The oral bioavailability of numerous medications are restricted due to negative physicochemical qualities or absorption in specific portion of the Body alluded as "Narrow absorption window'' \unskip~\citep{707819:16783035}. Prolonged gastric maintenance improves bioavailability; decreases medicate squander, and improve the dissolvability of drugs \unskip~\citep{707819:16783039}. GastroretentiveGastro retentive floating drug delivery helps to increment gastric living arrangement time in this way site explicit medication discharge in the upper gastrointestinal tract. Because of this prolonged gastric retention it helps to enhance drug absorption which leads better bioavailability with therapeutic efficacy \unskip~\citep{707819:16782986}. 

Atenolol was taken as a model drug. Mainly used in treatment of hypertension and angina. Atenolol elimination half life is 6 to 7 hours and is incompletely absorbed from the lower GIT \unskip~\citep{707819:16783033}. Human jejuna permeability and absorption is low \unskip~\citep{707819:16782987}. Hence, it appears that if increasing in gastro retentive floating time may improve the bioavailability of the drug.

So the investigation was planned for developing floating drug delivery system with thermal sintering method. Selected polymer was PEO. In the present investigation this polymer is selected for sintering and proposed to study sintering effect on design of gastroretentivegastro retentive floating tablets.


\begin{table*}[!htbp]
\caption{\boldmath {\textbf{Composition of floating tablets with gastroretentive effect }} }
\label{tw-fa5526d2a399}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.16\linewidth-2\tabcolsep}p{\dimexpr.16\linewidth-2\tabcolsep}p{\dimexpr.16\linewidth-2\tabcolsep}p{\dimexpr.16\linewidth-2\tabcolsep}p{\dimexpr.16\linewidth-2\tabcolsep}p{\dimexpr.20\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack Ingredients & \cAlignHack AP1 & \cAlignHack AP2 & \cAlignHack AP3 & \cAlignHack AP4 & \cAlignHack AP5\\
\tblmidrule 
\cAlignHack Atenolol &
  \cAlignHack 50 &
  \cAlignHack 50 &
  \cAlignHack 50 &
  \cAlignHack 50 &
  \cAlignHack 50\\
\cAlignHack PEO (WSR coagulant) &
  \cAlignHack 50 &
  \cAlignHack 75 &
  \cAlignHack 100 &
  \cAlignHack 25 &
  \cAlignHack 37.5\\
\cAlignHack Sodium bicarbonate &
  \cAlignHack 40 &
  \cAlignHack 40 &
  \cAlignHack 40 &
  \cAlignHack 40 &
  \cAlignHack 40\\
\cAlignHack Micro crystalline cellulose &
  \cAlignHack 195 &
  \cAlignHack 165 &
  \cAlignHack 135 &
  \cAlignHack 242.5 &
  \cAlignHack 230\\
\cAlignHack Magnesium stearate &
  \cAlignHack 2.5 &
  \cAlignHack 2.5 &
  \cAlignHack 2.5 &
  \cAlignHack 2.5 &
  \cAlignHack 2.5\\
\cAlignHack Talc &
  \cAlignHack 2.5 &
  \cAlignHack 2.5 &
  \cAlignHack 2.5 &
  \cAlignHack 2.5 &
  \cAlignHack 2.5\\
\cAlignHack  &
  \cAlignHack 350 &
  \cAlignHack 350 &
  \cAlignHack 350 &
  \cAlignHack 350 &
  \cAlignHack 350\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {\textbf{Tabletting and Invitro buoyancy characteristics of unsintered tablets}} }
\label{tw-bffd2a4f4b65}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.14\linewidth-2\tabcolsep}p{\dimexpr.1548\linewidth-2\tabcolsep}p{\dimexpr.13809999999999999\linewidth-2\tabcolsep}p{\dimexpr.1271\linewidth-2\tabcolsep}p{\dimexpr.14\linewidth-2\tabcolsep}p{\dimexpr.14\linewidth-2\tabcolsep}p{\dimexpr.16\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack Formulation code & \cAlignHack Weight \mbox{}\protect\newline in \mbox{}\protect\newline (mg) & \cAlignHack Assay \mbox{}\protect\newline in \mbox{}\protect\newline (\%) & \cAlignHack Hardness \mbox{}\protect\newline in \mbox{}\protect\newline (kg/cm\ensuremath{^{2}}) & \cAlignHack Friability \mbox{}\protect\newline in \mbox{}\protect\newline (\%) & \cAlignHack Floating lag time \mbox{}\protect\newline In (sec) & \cAlignHack Total floating time \mbox{}\protect\newline in (hr)\\
\tblmidrule 
\cAlignHack AP1 &
  \cAlignHack 348.9\ensuremath{\pm}1.09 &
  \cAlignHack 98.8\ensuremath{\pm}1.98 &
  \cAlignHack 4-6 &
  \cAlignHack 0.35 &
  \cAlignHack 141 &
  \cAlignHack {\textgreater}12\\
\cAlignHack AP2 &
  \cAlignHack 350.8\ensuremath{\pm}1.87 &
  \cAlignHack 101.3\ensuremath{\pm}1.23 &
  \cAlignHack 4-6 &
  \cAlignHack 0.41 &
  \cAlignHack 137 &
  \cAlignHack {\textgreater}15\\
\cAlignHack AP3 &
  \cAlignHack 350.5\ensuremath{\pm}1.43 &
  \cAlignHack 100.1\ensuremath{\pm}1.56 &
  \cAlignHack 4-6 &
  \cAlignHack 0.38 &
  \cAlignHack 123 &
  \cAlignHack {\textgreater}17\\
\cAlignHack AP4 &
  \cAlignHack 353.1\ensuremath{\pm}1.63 &
  \cAlignHack 99.8\ensuremath{\pm}1.75 &
  \cAlignHack 4-6 &
  \cAlignHack 0.42 &
  \cAlignHack 161 &
  \cAlignHack {\textgreater}6\\
\cAlignHack AP5 &
  \cAlignHack 348.9\ensuremath{\pm}1.73 &
  \cAlignHack 100.2\ensuremath{\pm}1.02 &
  \cAlignHack 4-6 &
  \cAlignHack 0.19 &
  \cAlignHack 153 &
  \cAlignHack {\textgreater}8\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {\textbf{Tabletting and Invitro buoyancy characteristics of AP4}} }
\label{tw-0e792518d57d}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.1449\linewidth-2\tabcolsep}p{\dimexpr.13510000000000002\linewidth-2\tabcolsep}p{\dimexpr.1667\linewidth-2\tabcolsep}p{\dimexpr.1252\linewidth-2\tabcolsep}p{\dimexpr.1281\linewidth-2\tabcolsep}p{\dimexpr.1558\linewidth-2\tabcolsep}p{\dimexpr.1442\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack Sintering temp and time & \cAlignHack Weight \mbox{}\protect\newline in \mbox{}\protect\newline (mg) & \cAlignHack Assay \mbox{}\protect\newline in \mbox{}\protect\newline (\%) & \cAlignHack Hardness \mbox{}\protect\newline in \mbox{}\protect\newline (kg/cm\ensuremath{^{2}}) & \cAlignHack Friability \mbox{}\protect\newline in \mbox{}\protect\newline (\%) & \cAlignHack Floating lag time  \mbox{}\protect\newline In (sec) & \cAlignHack Total floating time \mbox{}\protect\newline in (hr)\\
\tblmidrule 
\cAlignHack unsintered &
  \cAlignHack 348.1\ensuremath{\pm}1.33 &
  \cAlignHack 100.1\ensuremath{\pm}1.03 &
  \cAlignHack 4-6 &
  \cAlignHack 0.32 &
  \cAlignHack 161 &
  \cAlignHack {\textgreater}6\\
\cAlignHack 40\ensuremath{^{0}}C 1 hr &
  \cAlignHack 349\ensuremath{\pm}1.21 &
  \cAlignHack 99.7\ensuremath{\pm}1.99 &
  \cAlignHack 4-6 &
  \cAlignHack 0.45 &
  \cAlignHack 158 &
  \cAlignHack {\textgreater}6\\
\cAlignHack 40\ensuremath{^{0}}C 2 hr &
  \cAlignHack 350.7\ensuremath{\pm}1.64 &
  \cAlignHack 98.8\ensuremath{\pm}1.74 &
  \cAlignHack 4-6 &
  \cAlignHack 0.31 &
  \cAlignHack 154 &
  \cAlignHack {\textgreater}6\\
\cAlignHack 40\ensuremath{^{0}}C 3 hr &
  \cAlignHack 351.2\ensuremath{\pm}1.31 &
  \cAlignHack 99.5\ensuremath{\pm}1.49 &
  \cAlignHack 4-6 &
  \cAlignHack 0.19 &
  \cAlignHack 150 &
  \cAlignHack {\textgreater}6\\
\cAlignHack 40\ensuremath{^{0}}C 4 hr &
  \cAlignHack 350\ensuremath{\pm}1.07 &
  \cAlignHack 101.2\ensuremath{\pm}1.40 &
  \cAlignHack 4-6 &
  \cAlignHack 0.32 &
  \cAlignHack 144 &
  \cAlignHack {\textgreater}6\\
\cAlignHack 50\ensuremath{^{0}}C 1 hr &
  \cAlignHack 349.7\ensuremath{\pm}1.52 &
  \cAlignHack 99.1\ensuremath{\pm}1.44 &
  \cAlignHack 4-6 &
  \cAlignHack 0.43 &
  \cAlignHack 146 &
  \cAlignHack {\textgreater}8\\
\cAlignHack 50\ensuremath{^{0}}C 2 hr &
  \cAlignHack 350.9\ensuremath{\pm}1.56 &
  \cAlignHack 98.9\ensuremath{\pm}1.75 &
  \cAlignHack 4-6 &
  \cAlignHack 0.41 &
  \cAlignHack 134 &
  \cAlignHack {\textgreater}8\\
\cAlignHack 50\ensuremath{^{0}}C 3 hr &
  \cAlignHack 348.3\ensuremath{\pm}1.43 &
  \cAlignHack 100.2\ensuremath{\pm}1.95 &
  \cAlignHack 4-6 &
  \cAlignHack 0.24 &
  \cAlignHack 129 &
  \cAlignHack {\textgreater}9\\
\cAlignHack 50\ensuremath{^{0}}C 4 hr &
  \cAlignHack 350.1\ensuremath{\pm}1.84 &
  \cAlignHack 100.0\ensuremath{\pm}1.89 &
  \cAlignHack 4-6 &
  \cAlignHack 0.37 &
  \cAlignHack 117 &
  \cAlignHack {\textgreater}9\\
\cAlignHack 60\ensuremath{^{0}}C 1 hr &
  \cAlignHack 352.0\ensuremath{\pm}1.74 &
  \cAlignHack 99.8\ensuremath{\pm}1.89 &
  \cAlignHack 4-6 &
  \cAlignHack 0.45 &
  \cAlignHack 119 &
  \cAlignHack {\textgreater}9\\
\cAlignHack 60\ensuremath{^{0}}C 2 hr &
  \cAlignHack 349.6\ensuremath{\pm}1.48 &
  \cAlignHack 98.4\ensuremath{\pm}1.94 &
  \cAlignHack 4-6 &
  \cAlignHack 0.23 &
  \cAlignHack 102 &
  \cAlignHack {\textgreater}10\\
\cAlignHack 60\ensuremath{^{0}}C 3 hr &
  \cAlignHack 350.4\ensuremath{\pm}1.94 &
  \cAlignHack 101.6\ensuremath{\pm}1.84 &
  \cAlignHack 4-6 &
  \cAlignHack 0.34 &
  \cAlignHack 96 &
  \cAlignHack {\textgreater}10\\
\cAlignHack 60\ensuremath{^{0}}C 4 hr &
  \cAlignHack 350\ensuremath{\pm}1.93 &
  \cAlignHack 99..9\ensuremath{\pm}1.94 &
  \cAlignHack 4-6 &
  \cAlignHack 0.42 &
  \cAlignHack 84 &
  \cAlignHack {\textgreater}11\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}
\textbf{\space }


\begin{table*}[!htbp]
\caption{\boldmath {\textbf{Tabletting and Invitro Floating characteristics of AP5}} }
\label{tw-2e6cb3e1e5ef}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.12329999999999998\linewidth-2\tabcolsep}p{\dimexpr.15180000000000003\linewidth-2\tabcolsep}p{\dimexpr.17659999999999997\linewidth-2\tabcolsep}p{\dimexpr.1221\linewidth-2\tabcolsep}p{\dimexpr.12620000000000001\linewidth-2\tabcolsep}p{\dimexpr.14\linewidth-2\tabcolsep}p{\dimexpr.16\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack Sintering temp and time & \cAlignHack Weight in \mbox{}\protect\newline (mg) & \cAlignHack Assay in \mbox{}\protect\newline (\%) & \cAlignHack Hardness in \mbox{}\protect\newline (kg/cm\ensuremath{^{2}})  & \cAlignHack Friability in \mbox{}\protect\newline (\%) & Floating lag time in (sec) & \cAlignHack Total floating time in (hr)\\
\tblmidrule 
\cAlignHack unsintered &
  \cAlignHack 349.2\ensuremath{\pm}1.02 &
  \cAlignHack 99.12\ensuremath{\pm}1.92 &
  \cAlignHack 4-6 &
  \cAlignHack 0.21 &
  \cAlignHack 153 &
  \cAlignHack {\textgreater}8\\
\cAlignHack 40\ensuremath{^{0}}C 1 hr &
  \cAlignHack 350.1\ensuremath{\pm}1.11 &
  \cAlignHack 100.3\ensuremath{\pm}1.62 &
  \cAlignHack 4-6 &
  \cAlignHack 0.33 &
  \cAlignHack 150 &
  \cAlignHack {\textgreater}8\\
\cAlignHack 40\ensuremath{^{0}}C 2 hr &
  \cAlignHack 351.5\ensuremath{\pm}0.89 &
  \cAlignHack 100.4\ensuremath{\pm}1.34 &
  \cAlignHack 4-6 &
  \cAlignHack 0.41 &
  \cAlignHack 148 &
  \cAlignHack {\textgreater}8\\
\cAlignHack 40\ensuremath{^{0}}C 3 hr &
  \cAlignHack 352.5\ensuremath{\pm}1.45 &
  \cAlignHack 99.1\ensuremath{\pm}1.09 &
  \cAlignHack 4-6 &
  \cAlignHack 0.26 &
  \cAlignHack 142 &
  \cAlignHack {\textgreater}8\\
\cAlignHack 40\ensuremath{^{0}}C 4 hr &
  \cAlignHack 350.4\ensuremath{\pm}1.67 &
  \cAlignHack 98.6\ensuremath{\pm}1.24 &
  \cAlignHack 4-6 &
  \cAlignHack 0.32 &
  \cAlignHack 134 &
  \cAlignHack {\textgreater}8\\
\cAlignHack 50\ensuremath{^{0}}C 1 hr &
  \cAlignHack 348.7\ensuremath{\pm}1.32 &
  \cAlignHack 100.6\ensuremath{\pm}1.04 &
  \cAlignHack 4-6 &
  \cAlignHack 0.31 &
  \cAlignHack 123 &
  \cAlignHack {\textgreater}10\\
\cAlignHack 50\ensuremath{^{0}}C 2 hr &
  \cAlignHack 350.1\ensuremath{\pm}1.84 &
  \cAlignHack 99.3\ensuremath{\pm}1.71 &
  \cAlignHack 4-6 &
  \cAlignHack 0.12 &
  \cAlignHack 114 &
  \cAlignHack {\textgreater}10\\
\cAlignHack 50\ensuremath{^{0}}C 3 hr &
  \cAlignHack 351.6\ensuremath{\pm}1.31 &
  \cAlignHack 100.5\ensuremath{\pm}1.02 &
  \cAlignHack 4-6 &
  \cAlignHack 0.42 &
  \cAlignHack 102 &
  \cAlignHack {\textgreater}11\\
\cAlignHack 50\ensuremath{^{0}}C 4 hr &
  \cAlignHack 350.7\ensuremath{\pm}1.57 &
  \cAlignHack 99.9\ensuremath{\pm}1.07 &
  \cAlignHack 4-6 &
  \cAlignHack 0.27 &
  \cAlignHack 83 &
  \cAlignHack {\textgreater}12\\
\cAlignHack 60\ensuremath{^{0}}C 1 hr &
  \cAlignHack 350.9\ensuremath{\pm}1.82 &
  \cAlignHack 100.3\ensuremath{\pm}1.10 &
  \cAlignHack 4-6 &
  \cAlignHack 0.38 &
  \cAlignHack 104 &
  \cAlignHack 10\\
\cAlignHack 60\ensuremath{^{0}}C 2 hr &
  \cAlignHack 351.4\ensuremath{\pm}1.36 &
  \cAlignHack 98.3\ensuremath{\pm}1.89 &
  \cAlignHack 4-6 &
  \cAlignHack 0.31 &
  \cAlignHack 89 &
  \cAlignHack {\textgreater}11\\
\cAlignHack 60\ensuremath{^{0}}C 3 hr &
  \cAlignHack 349.5\ensuremath{\pm}1.42 &
  \cAlignHack 100.7\ensuremath{\pm}1.32 &
  \cAlignHack 4-6 &
  \cAlignHack 0.24 &
  \cAlignHack 73 &
  \cAlignHack {\textgreater}12\\
\cAlignHack 60\ensuremath{^{0}}C 4 hr &
  \cAlignHack 350.6\ensuremath{\pm}1.37 &
  \cAlignHack 99.6\ensuremath{\pm}1.06 &
  \cAlignHack 4-6 &
  \cAlignHack 0.32 &
  \cAlignHack 66 &
  \cAlignHack {\textgreater}12\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {\textbf{Coefficient of Correlation values and release of the kinetics of AP4}} }
\label{tw-c0f573a6f486}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.188\linewidth-2\tabcolsep}p{\dimexpr.16119999999999997\linewidth-2\tabcolsep}p{\dimexpr.14\linewidth-2\tabcolsep}p{\dimexpr.1529\linewidth-2\tabcolsep}p{\dimexpr.15780000000000001\linewidth-2\tabcolsep}p{\dimexpr.04269999999999999\linewidth-2\tabcolsep}p{\dimexpr.15739999999999997\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}Sintering  & \cAlignHack Zero order & \cAlignHack First order & \cAlignHack Higuchi model & \multicolumn{3}{p{\dimexpr(.3579\linewidth-2\tabcolsep)}}{\cAlignHack Peppas model}\\
\rowcolor{kwdboxcolor}temp and time &
  \cAlignHack r &
  \cAlignHack r &
  \cAlignHack r &
  \multicolumn{2}{p{\dimexpr(.2005\linewidth-2\tabcolsep)}}{\cAlignHack r} &
  \cAlignHack n\\
\tblmidrule 
\cAlignHack unsintered &
  \cAlignHack 0.9547 &
  \cAlignHack 0.7328 &
  \cAlignHack 0.8829 &
  \multicolumn{2}{p{\dimexpr(.2005\linewidth-2\tabcolsep)}}{\cAlignHack 0.9715} &
  \cAlignHack 0.550\\
\cAlignHack 40\ensuremath{^{0}}C 1 hr &
  \cAlignHack 0.9668 &
  \cAlignHack 0.7994 &
  \cAlignHack 0.9400 &
  \multicolumn{2}{p{\dimexpr(.2005\linewidth-2\tabcolsep)}}{\cAlignHack 0.9929} &
  \cAlignHack 0.628\\
\cAlignHack 40\ensuremath{^{0}}C 2 hr &
  \cAlignHack 0.9619 &
  \cAlignHack 0.7433 &
  \cAlignHack 0.9502 &
  \multicolumn{2}{p{\dimexpr(.2005\linewidth-2\tabcolsep)}}{\cAlignHack 0.9929} &
  \cAlignHack 0.627\\
\cAlignHack 40\ensuremath{^{0}}C 3 hr &
  \cAlignHack 0.9573 &
  \cAlignHack 0.8563 &
  \cAlignHack 0.9372 &
  \multicolumn{2}{p{\dimexpr(.2005\linewidth-2\tabcolsep)}}{\cAlignHack 0.9762} &
  \cAlignHack 0.640\\
\cAlignHack 40\ensuremath{^{0}}C 4 hr &
  \cAlignHack 0.9865 &
  \cAlignHack 0.6932 &
  \cAlignHack 0.8723 &
  \multicolumn{2}{p{\dimexpr(.2005\linewidth-2\tabcolsep)}}{\cAlignHack 0.9637} &
  \cAlignHack 0.709\\
\cAlignHack 50\ensuremath{^{0}}C 1 hr &
  \cAlignHack 0.9769 &
  \cAlignHack 0.6783 &
  \cAlignHack 0.8605 &
  \multicolumn{2}{p{\dimexpr(.2005\linewidth-2\tabcolsep)}}{\cAlignHack 0.9700} &
  \cAlignHack 0.578\\
\cAlignHack 50\ensuremath{^{0}}C 2 hr &
  \cAlignHack 0.9831 &
  \cAlignHack 0.7694 &
  \cAlignHack 0.8247 &
  \multicolumn{2}{p{\dimexpr(.2005\linewidth-2\tabcolsep)}}{\cAlignHack 0.9413} &
  \cAlignHack 0.618\\
\cAlignHack 50\ensuremath{^{0}}C 3 hr &
  \cAlignHack 0.9866 &
  \cAlignHack 0.6737 &
  \cAlignHack 0.8477 &
  \multicolumn{2}{p{\dimexpr(.2005\linewidth-2\tabcolsep)}}{\cAlignHack 0.9571} &
  \cAlignHack 0.615\\
\cAlignHack 50\ensuremath{^{0}}C 4 hr &
  \cAlignHack 0.9842 &
  \cAlignHack 0.7840 &
  \cAlignHack 0.8508 &
  \multicolumn{2}{p{\dimexpr(.2005\linewidth-2\tabcolsep)}}{\cAlignHack 0.9665} &
  \cAlignHack 0.595\\
\cAlignHack 60\ensuremath{^{0}}C 1 hr &
  \cAlignHack 0.9791 &
  \cAlignHack 0.7376 &
  \cAlignHack 0.8168 &
  \multicolumn{2}{p{\dimexpr(.2005\linewidth-2\tabcolsep)}}{\cAlignHack 0.9495} &
  \cAlignHack 0.566\\
\cAlignHack 60\ensuremath{^{0}}C 2 hr &
  \cAlignHack 0.9695 &
  \cAlignHack 0.8711 &
  \cAlignHack 0.7958 &
  \multicolumn{2}{p{\dimexpr(.2005\linewidth-2\tabcolsep)}}{\cAlignHack 0.9481} &
  \cAlignHack 0.559\\
\cAlignHack 60\ensuremath{^{0}}C 3 hr &
  \cAlignHack 0.9700 &
  \cAlignHack 0.8417 &
  \cAlignHack 0.7979 &
  \multicolumn{2}{p{\dimexpr(.2005\linewidth-2\tabcolsep)}}{\cAlignHack 0.9498} &
  \cAlignHack 0.562\\
\cAlignHack 60\ensuremath{^{0}}C 4 hr &
  \cAlignHack 0.9838 &
  \cAlignHack 0.9232 &
  \cAlignHack 0.8254 &
  \multicolumn{2}{p{\dimexpr(.2005\linewidth-2\tabcolsep)}}{\cAlignHack 0.9589} &
  \cAlignHack 0.597\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {\textbf{Coefficient of Correlation values and release of the kinetics of AP5}} }
\label{tw-f7cf4de67eb7}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.1871\linewidth-2\tabcolsep}p{\dimexpr.1329\linewidth-2\tabcolsep}p{\dimexpr.16\linewidth-2\tabcolsep}p{\dimexpr.17380000000000003\linewidth-2\tabcolsep}p{\dimexpr.18080000000000002\linewidth-2\tabcolsep}p{\dimexpr.1654\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}Sintering & \cAlignHack Zero order & \cAlignHack First order & \cAlignHack Higuchi model & \multicolumn{2}{p{\dimexpr(.34620000000000005\linewidth-2\tabcolsep)}}{\cAlignHack Peppas}\\
\rowcolor{kwdboxcolor}temp and time &
  \cAlignHack r &
  \cAlignHack r &
  \cAlignHack r &
  \cAlignHack r &
  \cAlignHack n\\
\tblmidrule 
\cAlignHack unsintered &
  \cAlignHack 0.9773 &
  \cAlignHack 0.7939 &
  \cAlignHack 0.8976 &
  \cAlignHack 0.9883 &
  \cAlignHack 0.583\\
\cAlignHack 40\ensuremath{^{0}}C 1 hr &
  \cAlignHack 0.9734 &
  \cAlignHack 0.6756 &
  \cAlignHack 0.8428 &
  \cAlignHack 0.9652 &
  \cAlignHack 0.552\\
\cAlignHack 40\ensuremath{^{0}}C 2 hr &
  \cAlignHack 0.9804 &
  \cAlignHack 0.6981 &
  \cAlignHack 0.8436 &
  \cAlignHack 0.9695 &
  \cAlignHack 0.586\\
\cAlignHack 40\ensuremath{^{0}}C 3 hr &
  \cAlignHack 0.9764 &
  \cAlignHack 0.6666 &
  \cAlignHack 0.8122 &
  \cAlignHack 0.9476 &
  \cAlignHack 0.565\\
\cAlignHack 40\ensuremath{^{0}}C 4 hr &
  \cAlignHack 0.9621 &
  \cAlignHack 0.7043 &
  \cAlignHack 0.7570 &
  \cAlignHack 0.9222 &
  \cAlignHack 0.608\\
\cAlignHack 50\ensuremath{^{0}}C 1 hr &
  \cAlignHack 0.9711 &
  \cAlignHack 0.9260 &
  \cAlignHack 0.8696 &
  \cAlignHack 0.9662 &
  \cAlignHack 0.525\\
\cAlignHack 50\ensuremath{^{0}}C 2 hr &
  \cAlignHack 0.9647 &
  \cAlignHack 0.9312 &
  \cAlignHack 0.8136 &
  \cAlignHack 0.9222 &
  \cAlignHack 0.470\\
\cAlignHack 50\ensuremath{^{0}}C 3 hr &
  \cAlignHack 0.9723 &
  \cAlignHack 0.9636 &
  \cAlignHack 0.8556 &
  \cAlignHack 0.9682 &
  \cAlignHack 0.524\\
\cAlignHack 50\ensuremath{^{0}}C 4 hr &
  \cAlignHack 0.9651 &
  \cAlignHack 0.9684 &
  \cAlignHack 0.8626 &
  \cAlignHack 0.9701 &
  \cAlignHack 0.500\\
\cAlignHack 60\ensuremath{^{0}}C 1 hr &
  \cAlignHack 0.9713 &
  \cAlignHack 0.9075 &
  \cAlignHack 0.7907 &
  \cAlignHack 0.9279 &
  \cAlignHack 0.529\\
\cAlignHack 60\ensuremath{^{0}}C 2 hr &
  \cAlignHack 0.9762 &
  \cAlignHack 0.9327 &
  \cAlignHack 0.8384 &
  \cAlignHack 0.9722 &
  \cAlignHack 0.574\\
\cAlignHack 60\ensuremath{^{0}}C 3 hr &
  \cAlignHack 0.9727 &
  \cAlignHack 0.9779 &
  \cAlignHack 0.8714 &
  \cAlignHack 0.9766 &
  \cAlignHack 0.530\\
\cAlignHack 60\ensuremath{^{0}}C 4 hr &
  \cAlignHack 0.9865 &
  \cAlignHack 0.9795 &
  \cAlignHack 0.8484 &
  \cAlignHack 0.9735 &
  \cAlignHack 0.608\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

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

Atenolol was obtained from yarrow chem products (Ghatkopar, Mumbai).PEO obtained from the yarrow chem products (Ghatkopar ,MumbaiGhatkopar, Mumbai). All other reagents and chemicals were of analytical grade.

\textbf{Drug excipients compatibility study}

Similarity contemplates were done understand the potential associations among drug and inactive ingredients. Physical blends of active ingredient and inactive ingredients in the proportion 1: 1 ratio were set up for examination the similarity. Drug polymer similarity ponders were done using FTIR spectroscopy. The IR spectra's were recorded in the middle of 500{\textendash}4000 cm\ensuremath{^{\ensuremath{-}1}}\unskip~\citep{707819:16782990}.


\bgroup
\fixFloatSize{images/e6f94173-f630-423a-85c6-a42060cd92d5-upicture1.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/e6f94173-f630-423a-85c6-a42060cd92d5-upicture1.png}{\includegraphics{images/e6f94173-f630-423a-85c6-a42060cd92d5-upicture1.png}}{}
\makeatother 
\caption{\boldmath {Calibration curve }}
\label{f-43dc0bbb873a}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/394e7184-3dab-465d-a956-489e85ebd3e0-upicture2.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/394e7184-3dab-465d-a956-489e85ebd3e0-upicture2.png}{\includegraphics{images/394e7184-3dab-465d-a956-489e85ebd3e0-upicture2.png}}{}
\makeatother 
\caption{\boldmath {Drug release profile of AP4 }}
\label{f-10100ac52a72}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/f6357775-34bf-455a-b06a-abf750a63933-upicture3.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/f6357775-34bf-455a-b06a-abf750a63933-upicture3.png}{\includegraphics{images/f6357775-34bf-455a-b06a-abf750a63933-upicture3.png}}{}
\makeatother 
\caption{\boldmath {Drug release profile of AP5}}
\label{f-b5e2150af09a}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/01a555e2-667a-45b1-944e-3e8f89422b06-upicture4.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/01a555e2-667a-45b1-944e-3e8f89422b06-upicture4.png}{\includegraphics{images/01a555e2-667a-45b1-944e-3e8f89422b06-upicture4.png}}{}
\makeatother 
\caption{\boldmath {FTIR of drug}}
\label{f-41ec3402ab7c}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/2e7b38e4-f426-4a81-aebe-0ed2a873cb34-upicture5.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/2e7b38e4-f426-4a81-aebe-0ed2a873cb34-upicture5.png}{\includegraphics{images/2e7b38e4-f426-4a81-aebe-0ed2a873cb34-upicture5.png}}{}
\makeatother 
\caption{\boldmath {FTIR of Mixture}}
\label{f-35b1ec0486a7}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/02c36bc5-ec76-496b-ae31-5a905f2fa4a6-upicture6.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/02c36bc5-ec76-496b-ae31-5a905f2fa4a6-upicture6.png}{\includegraphics{images/02c36bc5-ec76-496b-ae31-5a905f2fa4a6-upicture6.png}}{}
\makeatother 
\caption{\boldmath {DSC of Pure drug}}
\label{f-a6212575235e}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/dbbc92f7-2728-4c20-9e69-fe9d64169c5e-upicture7.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/dbbc92f7-2728-4c20-9e69-fe9d64169c5e-upicture7.png}{\includegraphics{images/dbbc92f7-2728-4c20-9e69-fe9d64169c5e-upicture7.png}}{}
\makeatother 
\caption{\boldmath {DSC of Mixture}}
\label{f-95025ae81d6c}
\end{figure}
\egroup
\textbf{Methods}

\textbf{Calibration curve}

Standard stock solution of atenolol done in methanol to a concentration of 100 mg/ml. Working Standard solutions were prepared from the stock standard solution by diluting with 0.1N Hydrochloric acid .Calibration graph was constructed in the range 5, 10,15,20,25 \ensuremath{\mu}g/ml. The absorption peak maxima found at 225 nm (Figure~\ref{f-43dc0bbb873a}). 

\textbf{Preparation of tablets}

 Floating tablets of Atenolol were setup by direct compression method using PEO polymer. All excipients were weighed according to formulae (Table~\ref{tw-fa5526d2a399}) and passed through sieve number 40 \# and geometrically mixed for 5 min and then lubricated using Magnesium stearate and talc for 3 min in a poly bag. Compressed tablets were exposed to 40\ensuremath{^{0}}C , 50\ensuremath{^{0}}C and 60\ensuremath{^{0}}C for 4 different period of 1h, 2h, 3h and 4h in a hot air oven. After exposing to different temperatures remove the tablets and allowed to cool at room temperature. 

\textbf{Evaluation of tablets}

Tablets had been evaluated for uniformity of weight, assay, hardness, in  vitro buoyancy and dissolution studies.

\textbf{Content uniformity of drug}

Ten tablets were powdered and precisely weighed powder which is equivalent to 50 mg was transferred to a 100 ml of volumetric flask to this add 0.1N HCl Solution and mixed carefully. Solution was make up to the volume 100 ml and filtered. 1ml was transferred and make up to 100 ml volume with 0.1 N HCl. Absorbance of the resulting solution was measured at 225nm using UV Visible Spectrophotometer. Estimation of Atenolol in tablet formulation was obtained from linearity equation of Calibration curve \unskip~\citep{707819:16783036}.

\textbf{Invitro buoyancy studies}

 Tablets were put into a 900 ml beaker containing 0.1N HCl . Floating lag time and total floating time was determined \unskip~\citep{707819:16782989}. 

\textbf{Invitro dissolution studies}

The drug release of all tablet batches were done indone in 900ml of 0.1 N HCl medium using USP Type II apparatus. RPM  was maintained at 50 by maintaining the temperature at 37\ensuremath{\pm}0.5\ensuremath{^{0}}C. The absorbance of the samples was conducted at different time intervals at 225 nm \unskip~\citep{707819:16782991}.

\textbf{Kinetics study}

The drug release mechanism was assessed from floating tablets in the following models: Zero order \ensuremath{M}= \ensuremath{M}\ensuremath{_{0}} \ensuremath{-} \ensuremath{K}\ensuremath{_{0}}\ensuremath{t}; First order: Log\ensuremath{C} = Log\ensuremath{C}\ensuremath{_{0}} \ensuremath{-} \ensuremath{K}\ensuremath{t}/2.303; Higuchi model : \ensuremath{Q} = \ensuremath{k}\ensuremath{t}\ensuremath{^{1/2}}; Korsemeyer : \ensuremath{M}\ensuremath{_{\ensuremath{t}}}/\ensuremath{M}\ensuremath{_{\ensuremath{\infty\ }}} = \ensuremath{k}\ensuremath{t}\ensuremath{^{\ensuremath{n}}} ; where \ensuremath{M}, \ensuremath{C}, and \ensuremath{Q} are the drug release amount at time \ensuremath{t}, \ensuremath{M}\ensuremath{_{0}}, and \ensuremath{C}\ensuremath{_{0}} are gross drug release, and \ensuremath{K}\ensuremath{_{0}}, \ensuremath{K}, and \ensuremath{k} are rate constant. Korsemeyer's model: \ensuremath{M}\ensuremath{_{\ensuremath{t}}}/\ensuremath{M}\ensuremath{_{\ensuremath{\infty\ }\ }}is the fractional amount of drug release at time \ensuremath{t}, \ensuremath{k} is a constant, \ensuremath{n} value is kinetic constant, which is denotes transport mechanism. The value of \ensuremath{n} for a cylinder is \textless\ \ensuremath{n} \textless\ 1.0 for Anomalous transport (Nonfickian diffusion), 1.0 indicates Case-II transport, {\textgreater}1.0 shows Super Case-II transport \unskip~\citep{707819:16783038}.

\textbf{Differential scanning calorimetry}

Samples were measured and hermetically sealed in flat bottomed aluminium pans. These samples were heated over a range of 30 {\textendash} 250\ensuremath{^{0}}C at a constant rate of 5\ensuremath{^{0}}C per minute in nitrogen atmosphere and recorded at a constant speed of 10mm per minute \unskip~\citep{707819:16782988}.
    
\section{Results and Discussion}
Both ``Un  sintered and warm sintered tablets'' were tested for hardness in kg/cm\ensuremath{^{2}}, \% weight variation, \% friability, \% drug content , invitro buoyancy and invitro dissolution studies. Tablets hardness were in a range 4-6 kg/cm\ensuremath{^{2}}.Estimated drug content was within 98.3\% - 101.6 \%. Friability test was found to be less than 0.5\%. The percentage variation of weight was within the limits of \ensuremath{\pm}5\%. (Tables~\ref{tw-bffd2a4f4b65}, \ref{tw-0e792518d57d} and~\ref{tw-2e6cb3e1e5ef}). In vitro floating test of un  sintered and sintered tablets were within the range of 66 to 161 sec. It was observed that floating lag time was reduced due to concentration of polymer. After sintering floating time was decreased with the increase in sintering temperature may be due to decreasing porosity. Un  sintered and sintered tablets Total time of floating were within range of 6-17 h. Total Floating time was increased with the increase in sintering temperature may be because of strong bonding between the particles formed. So if sintering time was increased it improves Invitro buoyancy. Dissolution profile of AP1, AP2 and AP3 un  sintered tablets retarted the drug release up to 12, 15 and 17 h respectively. From the dissolution data it was noted that dissolution profile was not altered for formulation of AP 4 and AP5 when it was exposed to 40\ensuremath{^{0}}C. The formulation AP4 tablets kept at 50\ensuremath{^{0}}C for 1, 2, 3 and 4h and the drug release is more than 97\%. AP4 tablets exposed to 60\ensuremath{^{0}}C for 1,2,3,and 4h drug released more than 97\%. Formulation AP5 with out without sintering condition the drug released up to 8h and the tablets of AP5 formulation at 50\ensuremath{^{0}}C for 1h,2h,3h and 4h retarded the drug up to 10h,10h , 11h and 12h respectively and at 60\ensuremath{^{0}}C for 1h,2h.3h and 4 h prolonged the drug release up to 10h,11h,12h and 13h. It is evident from the data that if temperature and time of exposure increases the retarding power of polymer was increased. Dissolution profile of the formulation are given in Figures~\ref{f-10100ac52a72} and~\ref{f-b5e2150af09a}. 

Results of kinetic models for AP4 and AP5 are given in Tables~\ref{tw-c0f573a6f486} and~\ref{tw-f7cf4de67eb7}. In case of AP4 follows the zero order with Non {\textendash} fickian diffusion. Whereas sintered formulation of AP5 follows zero order with nonfickian anomalous diffusion. Sintered formulation AP5 at 50\ensuremath{^{0}}C for 1h, 2h, and 3h follows zero order with nonfickian anomalous diffusion. At 60\ensuremath{^{0}}C exposed for 1h, 2h, 3h and 4h follows zero order with non fickian anomalous diffusion.

The formulation AP5 sintered at temperature 50\ensuremath{^{0}}C for 4h was selected as an optimized because low polymer concentration compared to AP1 to AP3 and after sintering at low polymer concentration drug release was retarded up to 12h. 

\textbf{FTIR Studies}

The results of spectral analysis showed the major peaks for atenolol shows C-H stretch at 2959\ensuremath{^{-1}} , C=N stretch at 1633\ensuremath{^{-1}} , N-H bend at 1514\ensuremath{^{-1}}, C-O stretch at 1237 cm\ensuremath{^{-1}}. Since there have been no major changes in the absorption peaks drug polymer interactions were ruled out. Spectrum were shown in Figures~\ref{f-41ec3402ab7c} and~\ref{f-35b1ec0486a7}.

\textbf{DSC}

 DSC of pure atenolol showed endothermic melting peak at 155.56\ensuremath{^{0}}C. Based on thermogram there is no polymeric change in the drug due to sintering Figures~\ref{f-a6212575235e} and~\ref{f-95025ae81d6c}.
    
\section{Conclusions}
With less polymer concentration desired dissolution was obtained by applying thermal sintering. Not only that it cancan that it be concluded  that floating character was improved with temperature exposure length. Drug release retarding was maintained well when exposed to sintering temperature. Hence sintering method can be used for the formulation of gastric floating tablets of atenolol with PEO.
    

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