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\def\citeauthor{~Bharath~Kumar~K~R~S~C,
              ~Vijay~Kumar~Voleti,
              ~Dasthagiri~Reddy~Y,
              ~Madhusudhana~Chetty~C,
              ~Poluri~Suresh,
              ~Naganjaneyulu~R}
\def\citetitle{Formulation and Evaluation of Cimetidine \textit{In-Situ} Gelling System By Factorial Design}
\def\copyrightstmt{This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial- ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.}
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\def\RunningAuthor{Bharath Kumar K R S C et al.}
\firstPage{98}
\articleType{Original Article}
\receivedDate{01 Apr 2021}
\acceptedDate{13 Apr 2021}
\revisedDate{04 Apr 2021}
\journalVolume{1}
\journalIssue{3}
\journalDoi{fjphs.v1i3.214}
\copyrightYear{2021}
\eISSN{2583-116X}
\journalDoi{fjphs.v1i3.214}
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\def\journalTitle{Future Journal of Pharmaceuticals and Health Sciences}

\title{Formulation and Evaluation of Cimetidine \textit{In-Situ} Gelling System By Factorial Design}
\author{Bharath~Kumar~K~R~S~C\textsuperscript{*}\textsuperscript{1},  
            Vijay~Kumar~Voleti\textsuperscript{1},  
            Dasthagiri~Reddy~Y\textsuperscript{1},  
            Madhusudhana~Chetty~C\textsuperscript{2},  
            Poluri~Suresh\textsuperscript{3}, 
            Naganjaneyulu~R\textsuperscript{4}~\\[5pt]{\textsuperscript{1}Department of Pharmaceutics, Santhiram College of Pharmacy, Nandyal-516 501, Kurnool (Dist), Andhra Pradesh, India}~\\{\textsuperscript{2}Santhiram College of Pharmacy, Nandyal-516 501, Kurnool (Dist), Andhra Pradesh, India}~\\{\textsuperscript{3}Department of Pharmaceutics, St.Johns College of Pharmaceutical Sciences, Yerrakota, Kurnool-518360, Andhra Pradesh, India}~\\{\textsuperscript{4}Department of Pharmacognosy, Dr K.V. Subba Reddy Institute of Pharmacy, Kurnool-518218, Andhra Pradesh, India}}

\begin{abstract}
The current papers offer the formulation, optimization, and evaluation of the starch-based \textit{in-situ} gelling system of Cimetidine. The objective of the present study was to optimize the concentration of starch and concentration of MgCl\ensuremath{_{2}} for the formulation of \textit{in-situ} gels of Cimetidine. Starch based \textit{in-situ} gels of Cimetidine were subjected to measurement of viscosity, pH, drug content, and Q\ensuremath{_{80}}. Entirely the preliminary batches were prepared by using different concentrations of sodium alginate (0.5\% - 2\%) and a constant concentration of MgCl\ensuremath{_{2}}. On source the preliminary Screening, a 3\ensuremath{^{2}} full factorial pattern set about to review the consequence containing self-sustaining variables, Put concentration Containing starch (X\ensuremath{_{1}}) and concentration containing MgCl\ensuremath{_{2}} (X\ensuremath{_{2}}) as to apprenticed probabilities like viscosity, drug content, Q\ensuremath{_{80,}} and similarity factor. The best formulation C9 exhibited optimum viscosity (316 cp), drug content (99.25\%), Q\ensuremath{_{80}} (90.15\%), and similarity factor (73.46). The best batch exhibited good water uptake (62.44\%) and there were no interactions were found during the IR study. A slow release of Cimetidine was observed and a good fit to the Korsmeyer Peppas plots was demonstrated. The correlation coefficient of the best batch is 0.9973 (Korsmeyer Peppas plots).  
\end{abstract}\def\keywordstitle{Keywords}

\begin{keywords}In-situ,\newline Gelling System,\newline Starch,\newline Cimetidine,\newline Factorial Design
\end{keywords}
\twocolumn[ \maketitle {\printKwdAbsBox}]
\makeatletter{\raggedright{\Large$^\ast$}Corresponding Author\par Name:\ Bharath~Kumar~K~R~S~C~\\ Phone:\ 8019450185~\\  Email:\ krsc.mpharm1@gmail.com
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\section{Introduction}
\textit{The in-situ} gel-forming drug delivery may be a variety of mucoadhesive drug delivery systems. These gels are liquescent at temperature but submit to gelation in swap body fluids in pH \unskip~\cite{1064055:21907474}. May have a safety feature worldly belongings of room temperature dependant plus cation elicited gelation. This gelation comes to the water level of the double-helical circle zones adopted by aggregation of the double-helical losses to form a multidimensional mesh by complexation along with cations and hydrogen bonding \unskip~\cite{1064055:21907473}. Cimetidine, the antiulcer agent was selected as the drug which explains an H2 receptor antagonist, any patients with gastroesophageal reflux who're being treated with proton pump inhibitors would possibly produce acid in the night. 
    
\section{Materials and Methods}
Cimetidine was received as freely given sampling from Glaxosmithkline, Mumbai, Sodium citrate, starch, Magnesium chloride used to be acquired from SD fine chemicals Ltd., Mumbai. All abundant chemical as well as chemical agent utilized in this study in with analytical grade. 

\textbf{Starch based \textit{in-situ} gelling system of Cimetidine}

\textbf{Infrared studies}

The Starch based \textit{In-situ} gels of cimedtidine and other excipients was recorded using Fourier transform infrared spectrophotometer (FTIR 4100 Jasco Japan). Sample preparation was done by mixing the drug with potassium bromide (1:300), triturating it in a glass mortar. A transparent pellet of the mixture was formed and placed in the sample holder and scanned over a frequency range of 4000-400cm-\ensuremath{^{1}}. The spectrum obtained was compared with the reported standard \unskip~\cite{1064055:21907468}.

\textbf{Method of Preparation}

Starch was dissolved in ultrapure water involving sodium citrate and heat to 50\ensuremath{^{o}}C, after chilling below those 35\ensuremath{^{o}}C Suitable quantities of magnesium chloride used to be added. Cimetidine was liquefied in 0.1N HCl solution used to be additional slowly into the more than starch solution consequent to soul-stirring as to a magnetic stirrer there has been proper as well as homogeneous dispersal of the drug. Application formulations were confined to a bath sonicator for 15 minutes and after that total the sort-out solutions in pH 1.2 buffer. In batches, C1-C12 the concentration of the starch was 0.5-2 \%, and also the put concentration containing MgCl\ensuremath{_{2}} and sodium citrate stand by at 0.1\% and 0.25\% respectively. In CC1 to CC9 takes out 1, 1.5 along with 2\% of starch as X\ensuremath{_{1}} variable and takes out 0.075, 0.1 in addition to 0.125\% of MgCl\ensuremath{_{2\ }} as X\ensuremath{_{2}} varying while concentrate sodium citrates stay constant \unskip~\cite{1064055:21907466}. \textit{}

\textbf{Optimization by using 3\ensuremath{^{2}} full factorial designs}

The report the consequence of independent variables, i.e. Con. of starch (X\ensuremath{_{1}}) and the con. of MgCl\ensuremath{_{2}} (X\ensuremath{_{2}}) on dependent variables \unskip~\cite{1064055:21907470}.

$\style{font-family:'Times New Roman'}{\style{font-size:8px}{Y\;=\;b_0\;+\;b_1X_1+b_2X_2\;+\;b_{12}X_1X_2\;+\;b_{11}X_1^{2}\;+\;b_{22}X_2^{2}}} $

Where Y is the dependent variable, b\ensuremath{_{0}} is the arithmetic mean response of the nine runs, and b\ensuremath{_{1}} is the estimated coefficient for the factor X\ensuremath{_{1}}. The main effects (X\ensuremath{_{1}} and X\ensuremath{_{2}}) represent the average result of changing one factor at a time. The polynomial terms (X\ensuremath{_{1}}\ensuremath{^{2}} and X\ensuremath{_{2}}\ensuremath{^{2}}) are included to investigate non-linearity. The results depicted in Table~\ref{tw-d847ef3f5b86}  stand for that each one of the dependent probabilities will be strongly dependent on the chosen independent probabilities as the variety show a large variation among the CC1 to CC9 (Table~\ref{tw-d847ef3f5b86}).  

\textbf{Evaluations}

\textbf{pH }

It is used to be sounded in starch primarily gels of Cimetidine, employing a digital pH meter \unskip~\cite{1064055:21907469}.

\textbf{Viscosity }

The \textit{in-situ} gel formulations were determined by using Brookfield viscometer \unskip~\cite{1064055:21907472}.

\textbf{Drug content}

Prepared starch-based \textit{in-situ}  gels of drug assayed spectrophotometrically for the drug content at the maximum wavelength with proper dilution of formulations taking suitable solvent as blank. Taking accurately weighted 50mg of prepared gel mixed in a beaker containing 100ml phosphate buffer pH 7.4 and stirred it at 75 rpm for 2 hrs \unskip~\cite{1064055:21907467}. Filtered it taken supernant filtrate and observed at 622 nm using UV spectroscopy and calculate drug content using the following formula.

$\style{font-family:'Times New Roman'}{\style{font-size:8px}{\%\;Drug\;Content=\frac{Practical\;Drug\;Content}{Theoretical\;Drug\;content}\times100}} $

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

The CC1 to CC9 formulations of starch based \textit{in-situ} gels of Cimetidine \unskip~\cite{1064055:21907463}  were carried out. The average values of Q\ensuremath{_{80}}.  

\textbf{Comparison containing dissolution profiles}

Finding out the similarity factor (f\ensuremath{_{2}}) of CC1 to CC9 formulations of \textit{in-situ} gels of Cimetidine \unskip~\cite{1064055:21907464}.

\textbf{Kinetics modelling of dissolution profiles}

All the formulations of Cimetidine gels batches CC1 to CC9 were studied for their release mechanism and determined which was the perfect model for all the formulations and also determined the release mechanism for the selected batch CC5. The correlation coefficient beliefs with kinetic models \unskip~\cite{1064055:21907462}. 

\textbf{Water Uptake }

The study for the selected formulation of Cimetidine gels \unskip~\cite{1064055:21907471}. \textbf{\space }

\textbf{Stability study }

The starch based \textit{in-situ} formulation containing Cimetidine used to be approximate three months \unskip~\cite{1064055:21907465}.


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\label{f-a1ea674adcfc}
\end{figure*}
\egroup

\bgroup
\fixFloatSize{images/d024681e-e544-4680-bde1-b881117682ac-upicture2.png}
\begin{figure*}[!htbp]
\centering \makeatletter\IfFileExists{images/d024681e-e544-4680-bde1-b881117682ac-upicture2.png}{\includegraphics{images/d024681e-e544-4680-bde1-b881117682ac-upicture2.png}}{}
\makeatother 
\caption{\boldmath {FTIR image of Starch}}
\label{f-e89a97280bdd}
\end{figure*}
\egroup

\bgroup
\fixFloatSize{images/e28e5bdf-4e5e-4ede-94fa-e240cd21a079-upicture3.png}
\begin{figure*}[!htbp]
\centering \makeatletter\IfFileExists{images/e28e5bdf-4e5e-4ede-94fa-e240cd21a079-upicture3.png}{\includegraphics{images/e28e5bdf-4e5e-4ede-94fa-e240cd21a079-upicture3.png}}{}
\makeatother 
\caption{\boldmath {FTIR Spectrum for the physical mixture of drug + polymer + excipients}}
\label{f-93bafbb44c46}
\end{figure*}
\egroup

\begin{table*}[!htbp]
\caption{\boldmath {Preliminary trial batches of \textit{in-situ} gels of Cimetidine } }
\label{tw-c9e42963df87}
\centering 
\begin{threeparttable}

\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.1503\linewidth-2\tabcolsep}p{\dimexpr.15170000000000002\linewidth-2\tabcolsep}p{\dimexpr.10600000000000001\linewidth-2\tabcolsep}p{\dimexpr.14909999999999998\linewidth-2\tabcolsep}p{\dimexpr.1572\linewidth-2\tabcolsep}p{\dimexpr.28569999999999997\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack Batch No. & \cAlignHack Conc. of \mbox{}\protect\newline starch (\%) & \cAlignHack pH & \cAlignHack Viscosity \mbox{}\protect\newline (cp) & \cAlignHack Drug content \mbox{}\protect\newline (\%)  & \cAlignHack Characteristic of \mbox{}\protect\newline \textit{in-situ} gels \\
\tblmidrule 
\cAlignHack C1 &
  \cAlignHack 0.5 &
  \cAlignHack 7.6 &
  \cAlignHack 156 &
  \cAlignHack 81.20 &
  \multicolumn{1}{p{\dimexpr(.28569999999999997\linewidth-2\tabcolsep)}}{\multirow{3}{\linewidth}{\cAlignHack The gel is not formed decently less drug content}}\\
\cAlignHack C2 &
  \cAlignHack 0.5 &
  \cAlignHack 7.6 &
  \cAlignHack 155 &
  \cAlignHack 84.32 &
  \\
\cAlignHack C3 &
  \cAlignHack 0.5 &
  \cAlignHack 7.7 &
  \cAlignHack 151 &
  \cAlignHack 85.45 &
  \\
\cAlignHack C4 &
  \cAlignHack 1 &
  \cAlignHack 7.3 &
  \cAlignHack 229 &
  \cAlignHack 89.98 &
  \multicolumn{1}{p{\dimexpr(.28569999999999997\linewidth-2\tabcolsep)}}{\multirow{3}{\linewidth}{\cAlignHack Gel formation \& drug content are slightly better}}\\
\cAlignHack C5 &
  \cAlignHack 1 &
  \cAlignHack 7.4 &
  \cAlignHack 228 &
  \cAlignHack 92.76 &
  \\
\cAlignHack C6 &
  \cAlignHack 1 &
  \cAlignHack 7.5 &
  \cAlignHack 226 &
  \cAlignHack 91.89 &
  \\
\cAlignHack C7 &
  \cAlignHack 1.5 &
  \cAlignHack 7.2 &
  \cAlignHack 315 &
  \cAlignHack 97.98 &
  \multicolumn{1}{p{\dimexpr(.28569999999999997\linewidth-2\tabcolsep)}}{\multirow{3}{\linewidth}{\cAlignHack Easy formation of Gel \& Good drug content}}\\
\cAlignHack C8 &
  \cAlignHack 1.5 &
  \cAlignHack 7.1 &
  \cAlignHack 318 &
  \cAlignHack 98.98 &
  \\
\cAlignHack C9 &
  \cAlignHack 1.5 &
  \cAlignHack 7.1 &
  \cAlignHack 316 &
  \cAlignHack 99.25 &
  \\
\cAlignHack C10 &
  \cAlignHack 2 &
  \cAlignHack 6.8 &
  \cAlignHack 399 &
  \cAlignHack 95.56 &
  \multicolumn{1}{p{\dimexpr(.28569999999999997\linewidth-2\tabcolsep)}}{\multirow{3}{\linewidth}{\cAlignHack Gel formation \& good drug content}}\\
\cAlignHack C11 &
  \cAlignHack 2 &
  \cAlignHack 6.7 &
  \cAlignHack 399 &
  \cAlignHack 96.11 &
  \\
\cAlignHack C12 &
  \cAlignHack 2 &
  \cAlignHack 6.6 &
  \cAlignHack 399 &
  \cAlignHack 94.12 &
  \\
\tblbottomrule 
\end{tabulary}\par 
\begin{tablenotes}\footnotesize 
    
\item{Note: The entire batches have been sort out using MgCl\ensuremath{_{2}} 0.01\%.}
\end{tablenotes}
\end{threeparttable}

\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {3\ensuremath{^{2}} Full factorial design layouts of \textit{in-situ} gels of Cimetidine } }
\label{tw-19aa84b37256}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.06650000000000002\linewidth-2\tabcolsep}p{\dimexpr.185\linewidth-2\tabcolsep}p{\dimexpr.12100000000000001\linewidth-2\tabcolsep}p{\dimexpr.11759999999999996\linewidth-2\tabcolsep}p{\dimexpr.14579999999999998\linewidth-2\tabcolsep}p{\dimexpr.1887\linewidth-2\tabcolsep}p{\dimexpr.1754\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}Batch No. & \multicolumn{2}{p{\dimexpr(.306\linewidth-2\tabcolsep)}}{Variables levels in coded form } & Viscosity  \mbox{}\protect\newline (cp)  & Drug content (\%)  & \% Drug release \mbox{}\protect\newline  (Q\ensuremath{_{80}})  & Similarity factor (F\ensuremath{_{2}})\\
\rowcolor{kwdboxcolor} & \cAlignHack X\ensuremath{_{1}} & \cAlignHack X\ensuremath{_{2}} &  &  &  & \\
\tblmidrule 
CC1 &
  \cAlignHack -0 &
  \cAlignHack -2 &
  226 &
  87.99 &
  99.32 &
  31.21\\
CC2 &
  \cAlignHack -1 &
  \cAlignHack 0 &
  249 &
  89.56 &
  96.34 &
  32.46\\
CC3 &
  \cAlignHack -0 &
  \cAlignHack +2 &
  247 &
  92.73 &
  98.63 &
  45.46\\
CC4 &
  \cAlignHack 0 &
  \cAlignHack -2 &
  288 &
  97.32 &
  98.15 &
  51.72\\
CC5 &
  \cAlignHack 0 &
  \cAlignHack 0 &
  317 &
  98.54 &
  91.26 &
  73.71\\
CC6 &
  \cAlignHack 0 &
  \cAlignHack +2 &
  347 &
  96.73 &
  86.32 &
  72.89\\
CC7 &
  \cAlignHack +2 &
  \cAlignHack -2 &
  386 &
  93.32 &
  82.64 &
  66.32\\
CC8 &
  \cAlignHack +2 &
  \cAlignHack 0 &
  389 &
  95.89 &
  78.58 &
  68.52\\
CC9 &
  \cAlignHack +2 &
  \cAlignHack +2 &
  400 &
  93.82 &
  90.15 &
  73.46\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Cumulative \% drug release of \textit{in-situ} gels of Cimetidine } }
\label{tw-b34ab0b6bff3}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.12899999999999999\linewidth-2\tabcolsep}p{\dimexpr.08260000000000002\linewidth-2\tabcolsep}p{\dimexpr.0884\linewidth-2\tabcolsep}p{\dimexpr.10\linewidth-2\tabcolsep}p{\dimexpr.10\linewidth-2\tabcolsep}p{\dimexpr.10\linewidth-2\tabcolsep}p{\dimexpr.10\linewidth-2\tabcolsep}p{\dimexpr.10\linewidth-2\tabcolsep}p{\dimexpr.10\linewidth-2\tabcolsep}p{\dimexpr.10\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack Time in hr.  & \multicolumn{9}{p{\dimexpr(.871\linewidth-2\tabcolsep)}}{\cAlignHack Cumulative \% drug release}\\
\rowcolor{kwdboxcolor}\cAlignHack  & \cAlignHack CC1 & \cAlignHack CC2 & \cAlignHack CC3 & \cAlignHack CC4 & \cAlignHack CC5 & \cAlignHack CC6 & \cAlignHack CC7 & \cAlignHack CC8 & \cAlignHack CC9\\
\tblmidrule 
\cAlignHack 1 &
  \cAlignHack 50.43 &
  \cAlignHack 46.76 &
  \cAlignHack 41.84 &
  \cAlignHack 27.01 &
  \cAlignHack 19.92 &
  \cAlignHack 17.95 &
  \cAlignHack 16.92 &
  \cAlignHack 13.14 &
  \cAlignHack 12.48\\
\cAlignHack 2 &
  \cAlignHack 68.21 &
  \cAlignHack 65.67 &
  \cAlignHack 56.88 &
  \cAlignHack 45.39 &
  \cAlignHack 31.35 &
  \cAlignHack 28.03 &
  \cAlignHack 27.71 &
  \cAlignHack 23.92 &
  \cAlignHack 19.88\\
\cAlignHack 3 &
  \cAlignHack 88.85 &
  \cAlignHack 84.20 &
  \cAlignHack 75.14 &
  \cAlignHack 62.82 &
  \cAlignHack 43.47 &
  \cAlignHack 39.12 &
  \cAlignHack 38.51 &
  \cAlignHack 33.26 &
  \cAlignHack 29.76\\
\cAlignHack 4 &
  \cAlignHack 98.14 &
  \cAlignHack 98.00 &
  \cAlignHack 93.13 &
  \cAlignHack 78.38 &
  \cAlignHack 54.73 &
  \cAlignHack 50.52 &
  \cAlignHack 47.11 &
  \cAlignHack 43.36 &
  \cAlignHack 38.56\\
\cAlignHack 5 &
  \cAlignHack 99.05 &
  \cAlignHack 98.00 &
  \cAlignHack 97.73 &
  \cAlignHack 94.60 &
  \cAlignHack 65.86 &
  \cAlignHack 62.29 &
  \cAlignHack 59.62 &
  \cAlignHack 52.32 &
  \cAlignHack 49.43\\
\cAlignHack 6 &
  \cAlignHack 98.07 &
  \cAlignHack 98.00 &
  \cAlignHack 97.73 &
  \cAlignHack 97.03 &
  \cAlignHack 76.33 &
  \cAlignHack 73.07 &
  \cAlignHack 69.62 &
  \cAlignHack 63.70 &
  \cAlignHack 58.34\\
\cAlignHack 7 &
  \cAlignHack 99.05 &
  \cAlignHack 98.00 &
  \cAlignHack 97.73 &
  \cAlignHack 97.03 &
  \cAlignHack 83.36 &
  \cAlignHack 82.61 &
  \cAlignHack 78.35 &
  \cAlignHack 74.85 &
  \cAlignHack 69.97\\
\cAlignHack 8 &
  \cAlignHack 98.07 &
  \cAlignHack 98.00 &
  \cAlignHack 97.73 &
  \cAlignHack 97.03 &
  \cAlignHack 90.18 &
  \cAlignHack 85.03 &
  \cAlignHack 81.04 &
  \cAlignHack 77.48 &
  \cAlignHack 74.70\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Regression analysis of \textit{in-situ} gel of Cimetidine } }
\label{tw-3626261b3699}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.2361\linewidth-2\tabcolsep}p{\dimexpr.0723\linewidth-2\tabcolsep}p{\dimexpr.0879\linewidth-2\tabcolsep}p{\dimexpr.08370000000000001\linewidth-2\tabcolsep}p{\dimexpr.0993\linewidth-2\tabcolsep}p{\dimexpr.0992\linewidth-2\tabcolsep}p{\dimexpr.08879999999999999\linewidth-2\tabcolsep}p{\dimexpr.2327\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack Parameters & \cAlignHack B0 & \cAlignHack B1 & \cAlignHack B2 & \cAlignHack B11 & \cAlignHack B22 & \cAlignHack B12 & \cAlignHack Multiple Regression\\
\tblmidrule 
\cAlignHack Viscosity &
  \cAlignHack 314.25 &
  \cAlignHack 86.7 &
  \cAlignHack 17 &
  \cAlignHack -4 &
  \cAlignHack -3.6 &
  \cAlignHack 2 &
  \cAlignHack 0.887\\
\cAlignHack Drug content (\%) &
  \cAlignHack 88.53 &
  \cAlignHack 2.40 &
  \cAlignHack 0.37 &
  \cAlignHack -0.18 &
  \cAlignHack -5.5 &
  \cAlignHack -1.83 &
  \cAlignHack 0.898\\
\cAlignHack Q80 (\%) &
  \cAlignHack 91.67 &
  \cAlignHack -11.26 &
  \cAlignHack -2.28 &
  \cAlignHack -1.37 &
  \cAlignHack -3.8 &
  \cAlignHack 0.65 &
  \cAlignHack 0.981\\
\cAlignHack Similarity factor (f2) &
  \cAlignHack 75.82 &
  \cAlignHack 9.12 &
  \cAlignHack 0.50 &
  \cAlignHack -3.26 &
  \cAlignHack -20.7 &
  \cAlignHack -3.71 &
  \cAlignHack 0.972\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Release kinetics of \textit{in-situ} gels} }
\label{tw-d847ef3f5b86}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.215\linewidth-2\tabcolsep}p{\dimexpr.185\linewidth-2\tabcolsep}p{\dimexpr.1768\linewidth-2\tabcolsep}p{\dimexpr.16669999999999998\linewidth-2\tabcolsep}p{\dimexpr.2565\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack Batch no. & \cAlignHack  & \multicolumn{2}{p{\dimexpr(.34349999999999994\linewidth-2\tabcolsep)}}{\cAlignHack Regression} &
  \\
\rowcolor{kwdboxcolor}\cAlignHack  & \cAlignHack Zero-order  & \cAlignHack First order  & \cAlignHack Higuchi  & \cAlignHack Krosmeyer peppas\\
\tblmidrule 
\cAlignHack CC1 &
  \cAlignHack 0.8172 &
  \cAlignHack 0.5212 &
  \cAlignHack 0.9388 &
  \cAlignHack 0.8212\\
\cAlignHack CC2 &
  \cAlignHack 0.8588 &
  \cAlignHack 0.6112 &
  \cAlignHack 0.9735 &
  \cAlignHack 0.8411\\
\cAlignHack CC3 &
  \cAlignHack 0.9222 &
  \cAlignHack 0.6112 &
  \cAlignHack 0.9883 &
  \cAlignHack 0.8538\\
\cAlignHack CC4 &
  \cAlignHack 0.9968 &
  \cAlignHack 0.8282 &
  \cAlignHack 0.8625 &
  \cAlignHack 0.9865\\
\cAlignHack CC5 &
  \cAlignHack 0.9842 &
  \cAlignHack 0.9934 &
  \cAlignHack 0.9977 &
  \cAlignHack 0.9864\\
\cAlignHack CC6 &
  \cAlignHack 0.8987 &
  \cAlignHack 0.8789 &
  \cAlignHack 0.9884 &
  \cAlignHack 0.9836\\
\cAlignHack CC7 &
  \cAlignHack 0.8988 &
  \cAlignHack 0.8714 &
  \cAlignHack 0.8931 &
  \cAlignHack 0.9868\\
\cAlignHack CC8 &
  \cAlignHack 0.9841 &
  \cAlignHack 0.8765 &
  \cAlignHack 0.8868 &
  \cAlignHack 0.9817\\
\cAlignHack CC9 &
  \cAlignHack 0.9872 &
  \cAlignHack 0.8976 &
  \cAlignHack 0.9728 &
  \cAlignHack 0.9716\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Water uptake study of Cimetidine gel batch C5} }
\label{tw-0442c2a6ffae}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.16700000000000003\linewidth-2\tabcolsep}p{\dimexpr.333\linewidth-2\tabcolsep}p{\dimexpr.25\linewidth-2\tabcolsep}p{\dimexpr.25\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack Time in min. & \cAlignHack Weight after Decantation (gm) & \cAlignHack Difference in weight \mbox{}\protect\newline (gm) & \cAlignHack Percentage water uptake (\%)\\
\tblmidrule 
\cAlignHack 30 &
  \cAlignHack 55.45 &
  \cAlignHack 0.30 &
  \cAlignHack 4.2\\
\cAlignHack 60 &
  \cAlignHack 55.74 &
  \cAlignHack 0.59 &
  \cAlignHack 7.02\\
\cAlignHack 90 &
  \cAlignHack 56.25 &
  \cAlignHack 2.10 &
  \cAlignHack 21.13\\
\cAlignHack 150 &
  \cAlignHack 57.32 &
  \cAlignHack 3.17 &
  \cAlignHack 31.96\\
\cAlignHack 180 &
  \cAlignHack 57.69 &
  \cAlignHack 3.53 &
  \cAlignHack 35.66\\
\cAlignHack 240 &
  \cAlignHack 58.54 &
  \cAlignHack 4.38 &
  \cAlignHack 44.22\\
\cAlignHack 270 &
  \cAlignHack 58.92 &
  \cAlignHack 4.77 &
  \cAlignHack 48.10\\
\cAlignHack 360 &
  \cAlignHack 60.05 &
  \cAlignHack 5.90 &
  \cAlignHack 59.56\\
\cAlignHack 390 &
  \cAlignHack 60.62 &
  \cAlignHack 6.46 &
  \cAlignHack 65.23\\
\cAlignHack 450 &
  \cAlignHack 61.17 &
  \cAlignHack 7.01 &
  \cAlignHack 70.78\\
\cAlignHack 480 &
  \cAlignHack 61.33 &
  \cAlignHack 7.18 &
  \cAlignHack 72.45\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Stability of Cimetidine gel for best formulation C5} }
\label{tw-cc394362be44}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.3806\linewidth-2\tabcolsep}p{\dimexpr.10899999999999995\linewidth-2\tabcolsep}p{\dimexpr.2397\linewidth-2\tabcolsep}p{\dimexpr.2707\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack The period for sampling & \cAlignHack pH & \cAlignHack Viscosity (cp) & \cAlignHack Drug content (\%)\\
\tblmidrule 
\cAlignHack Initial &
  \cAlignHack 7.1 &
  \cAlignHack 316 &
  \cAlignHack 99.25\\
\cAlignHack One month &
  \cAlignHack 7.1 &
  \cAlignHack 316 &
  \cAlignHack 99.25\\
\cAlignHack Two month &
  \cAlignHack 7.2 &
  \cAlignHack 317 &
  \cAlignHack 99.26\\
\cAlignHack Three month &
  \cAlignHack 7.2 &
  \cAlignHack 317 &
  \cAlignHack 99.27\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

    
\section{Results and Discussion}
\textbf{IR study}

The infrared spectrophotometer studies were carried CC5 of Cimetidine gel. IR spectrum for the pure drug, starch, physical mixture  there was no strong interaction the functional groups of API with the Additives are shown in Figures~\ref{f-a1ea674adcfc}, \ref{f-e89a97280bdd} and~\ref{f-93bafbb44c46}  respectively. 

\textbf{Preliminary trials }

The formulations of C1 to C12 were preset out to review the consequence of polymer put concentration on spectacular viscosity, drug content, pH, and the physical properties of the gel in pH 1.2 buffer. The con. of starch used to be varying from 0.5, 1, 1.5, and 2 \% [Table~\ref{tw-c9e42963df87}]. 

\textbf{3\ensuremath{^{2}} full factorial design} \textbf{\space }

In the present study, a 3\ensuremath{^{2}} full factorial design was employed to study the effect of independent variables, i.e. con. of starch (X\ensuremath{_{1}}) and the con. of MgCl\ensuremath{_{2}} (X\ensuremath{_{2}}) on dependent variables [Table~\ref{tw-19aa84b37256}]. The selected independent probabilities show a large variation among the CC1 to CC9. Fitted equations touching on the responses i.e. viscosity, drug content Q\ensuremath{_{80,}} and similarity factor to the transforming factor are shown in Table~\ref{tw-3626261b3699}.  The viscosity of solutions varied from 226 cp to 400 cp which was measured at 150 rpm [Table~\ref{tw-19aa84b37256}]. 

\textbf{Factorial for drug content\ensuremath{_{}}\textit{}}

The drug content varying delight in 87.99\% to 98.54\% in batches CC1 to CC9 \textit{in-situ} formulations of Cimetidine and displayed to more excellence multiple regression as 0.898 [Tables~\ref{tw-3626261b3699} and~\ref{tw-19aa84b37256}]. 

\textbf{The factorial equation for Q\ensuremath{_{80}}}

The drug let loose at eight hours in all the batches CC1-CC9 varied from 78.58\% to 99.32\% (Table~\ref{tw-b34ab0b6bff3}) and showed good multiple regression as 0.981 (Table~\ref{tw-3626261b3699}).

\textbf{The factorial trial equation for similarity factor}

The similarity factor of CC1 to CC9 formulation varying from 31.21 to 73.71 [Table~\ref{tw-19aa84b37256}] and displayed a very good coefficient of 0.972 [Table~\ref{tw-3626261b3699}]. 

\textbf{Water uptake study }

The water uptake studies depend on TGA used to be the best formulation C5 [Table~\ref{tw-0442c2a6ffae}].

\textbf{Stability Study}

Short-term stability of \textit{in-situ} gel going from Cimetidine revealed which no alterations started at three months at normal room temperature and humidity condition [Table~\ref{tw-cc394362be44}].
    
\section{Conclusion }
The overall \textit{in-situ }gel formulation displayed well viscosity, drug content, and release order this report review which oral of misty solutions involving starch leads to the formation of \textit{in-situ} gel, such formulation will be homogenously unfrozen once administered orally become gel on the vocalization site. The results of a 3\ensuremath{^{2}} full factorial design conspicuous therefore the rarefaction going from starch based MgCl\ensuremath{_{2}} considerably wonder affected sensational dependent probabilities.

\textbf{Conflict of Interest}

The authors attest that they have no conflict of interest in this study.

\textbf{Funding support}

No financial support for the current study.
    

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