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\def\citeauthor{~Arava~Vidyadhari,
              ~Guduru~Rajeswari,
              ~Dodda~Chinni~Krishna~Reddy,
              ~Gangala~Sudarsana,
              ~Gundala~Mamatha,
              ~Kuramutla~Sisindri,
              ~Podili~Swarna~Latha,
              ~Ramakkagari~Sandhya~Rani,
              ~Shaik~Shajiya~Taslim}
\def\citetitle{Formulation and Evaluation of Transdermal Film of Nitroglycerin}
\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{Arava Vidyadhari et al.}
\firstPage{37}
\articleType{Original Article et al.}
\receivedDate{01 Mar 2021}
\acceptedDate{15 Mar 2021}
\revisedDate{13 Mar 2021}
\journalVolume{1}
\journalIssue{1}
\copyrightYear{2021}
\eISSN{2583-116X}
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\def\journalTitle{Future Journal of Pharmaceuticals and Health Sciences}

\title{Formulation and Evaluation of Transdermal Film of Nitroglycerin}
\author{Arava~Vidyadhari\textsuperscript{*}\textsuperscript{1}\textsuperscript{\href{https://orcid.org/0000-0003-3815-7612}{\XeTeXLinkBox{\includegraphics[height=7pt]{orcid-logo-pharmascope.pdf}}}},  
            Guduru~Rajeswari\textsuperscript{2}\textsuperscript{\href{https://orcid.org/0000-0002-5221-7602}{\XeTeXLinkBox{\includegraphics[height=7pt]{orcid-logo-pharmascope.pdf}}}},  
            Dodda~Chinni~Krishna~Reddy\textsuperscript{3}\textsuperscript{\href{https://orcid.org/0000-0003-2834-8482}{\XeTeXLinkBox{\includegraphics[height=7pt]{orcid-logo-pharmascope.pdf}}}},  
            Gangala~Sudarsana\textsuperscript{3}\textsuperscript{\href{https://orcid.org/0000-0003-4756-5538}{\XeTeXLinkBox{\includegraphics[height=7pt]{orcid-logo-pharmascope.pdf}}}},  
            Gundala~Mamatha\textsuperscript{3}\textsuperscript{\href{https://orcid.org/0000-0003-1205-5861}{\XeTeXLinkBox{\includegraphics[height=7pt]{orcid-logo-pharmascope.pdf}}}},  
            Kuramutla~Sisindri\textsuperscript{3}\textsuperscript{\href{https://orcid.org/0000-0002-2435-6955}{\XeTeXLinkBox{\includegraphics[height=7pt]{orcid-logo-pharmascope.pdf}}}},  
            Podili~Swarna~Latha\textsuperscript{3}\textsuperscript{\href{https://orcid.org/0000-0002-6338-174X}{\XeTeXLinkBox{\includegraphics[height=7pt]{orcid-logo-pharmascope.pdf}}}},  
            Ramakkagari~Sandhya~Rani\textsuperscript{3}\textsuperscript{\href{https://orcid.org/0000-0001-9856-301X}{\XeTeXLinkBox{\includegraphics[height=7pt]{orcid-logo-pharmascope.pdf}}}}, 
            Shaik~Shajiya~Taslim\textsuperscript{2}\textsuperscript{\href{https://orcid.org/0000-0002-9079-622X}{\XeTeXLinkBox{\includegraphics[height=7pt]{orcid-logo-pharmascope.pdf}}}}~\\[5pt]{\textsuperscript{1}Department of Pharmacology, Saastra College of Pharmaceutical Education \& Research, Near Varigonda Jwalamukhi Temple, Muthukur Raod, Kakupalli, Nellore-524311, Andhra Pradesh, India}~\\{\textsuperscript{2}Department of Pharmacology, Saastra College of Pharmaceutical Education \& Research, Near Varigonda Jwalamukhi Temple, Muthukur Raod, Kakupalli, Nellore-524311, Andhra Pradesh, India}~\\{\textsuperscript{3}Saastra College of Pharmaceutical Education \& Research, Near Varigonda Jwalamukhi Temple, Muthukur Raod, Kakupalli, Nellore-524311, Andhra Pradesh, India}}

\begin{abstract}
The aim of the present study was to prepare and evaluate transdermal Films of Nitroglycerin using HPMC, Cellulose acetate phthalate, ethyl cellulose and Polypropylene glycol as a rate controlling membranes and HPMC, Cellulose acetate phthalate, ethyl cellulose as drug reservoir gels. Transdermal Films of Nitroglycerin with HPMC, Cellulose acetate phthalate, ethyl cellulose by varying the blend ratios were prepared by solvent casting method. The thickness medium range between 0.18 \ensuremath{\pm} 0.02 mm to 0.22 \ensuremath{\pm} 0.03mm whatever signifies that they're military uniform in thickness. The customized formulation NF1 acquires stability reports for one to three months and the general films were tested for drug content and \textit{In-vitro} diffusion.
\end{abstract}\def\keywordstitle{Keywords}

\begin{keywords}Nitroglycerin,\newline HPMC,\newline Ethyl Cellulose,\newline Cellulose Acetate Phthalate
\end{keywords}
\twocolumn[ \maketitle {\printKwdAbsBox}]
\makeatletter{\raggedright{\Large$^\ast$}Corresponding Author\par Name:\ Arava~Vidyadhari~\\ Phone:\ +91 6302192037~\\  Email:\ aravavidhyadhari@gmail.com
        \par}\vspace*{-13pt}\hrulefill\par\ifx\@eISSN\@empty\else{\fontsize{12}{14}\selectfont eISSN: \@eISSN\hfill pISSN: \@pISSN}\par\fi% 
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        \makeatother
        
    
\section{Introduction}
In the present study, we aimed to deliver anti angina drug nitroglycerin for developing transdermal therapeutic systems for controlled release. Hence studies have been undertaken in the present investigation on membrane moderated therapeutic systems by employing HPMC, Cellulose acetate phthalate, ethyl cellulose and Polypropylene glycol as a rate controlling membranes and HPMC, Cellulose acetate phthalate, ethyl cellulose as drug reservoir gels \unskip~\cite{1156473:22699701}. The manner of biosmiliars is certain in order to avoid of chronic disorders specified hypertension, which need longer term dosing to take care of therapeutically drug concentration. Transdermal pitch of CVS drugs throw up individual advantages as warding off hepatic first pass metabolic process, asserting constant blood level for a long per period leading to a reduction of care for frequency \unskip~\cite{1156473:22699696}.
    
\section{Materials and methods }
NItroglycerin used to be buying from Wockhardt Limited, Aurangabad. Hydroxy Propyl Methyl Cellulose, Cellulose acetate phthalate, Ethyl cellulose, Propylene glycol and dimethyl sulfoxide used to be frequent Pharmaceutics Private Limited, Mumbai and other ingredients victimised in with Analytical grade [Table~\ref{tw-63bf774506ba}].

\textbf{Methodology}

\textbf{Compatibility studies}

\textbf{IR studies }

In the preparation of drug and polymer might interact as they will be in close displace every one, which might cause the instability of drug preformulation studies \unskip~\cite{1156473:22699693}. 

\textbf{Procedure }

Beaker that included 15 ml of purified water and 3 drops of glycerin was stirred up for 15 mints. The HPMC and PVP have been added slowly at unremitting soul-stirring for 30 mints \unskip~\cite{1156473:22699687}. Add Drug \& Propylene glycol to with the above preparation it was get an aspect poured into transdermal mold \& squelch a hot air oven for 15 minutes at 50\ensuremath{^{o}}C subsequent to remove the Films restrain in desiccators [Table~\ref{tw-e5cef2506b9e}].

\textbf{Evaluation of Transdermal Films }

\textbf{Physical Appearance}

All entire formulated Films have been visually inspected for colour, flexibility, homogeneity and smoothness \unskip~\cite{1156473:22699690}.

\textbf{Thickness }

The Films was performed by screw gauge (micrometer) \unskip~\cite{1156473:22699700}.

\textbf{Weight Variation}

For each one Patch used to be weighed individually along with average weight of films used to be determined \unskip~\cite{1156473:22699695}.

\textbf{Moisture Content}

The Films (n =3) were weighed individually and kept in a desiccator containing calcium chloride at 37\ensuremath{^\circ}C for 24 hrs \unskip~\cite{1156473:22699686}. Calculate the difference between initial and final weight of films. 

\textbf{Flatness}

Then variation within the length as a result of non-uniformity in flatness was sounded \unskip~\cite{1156473:22699699}. It was planned by measuring narrowing of strips.

\textbf{Tensile Strength}

To be able to determine the stretching as a tensile strength, the polymeric patch drift in weights had been slowly added to the pan to increase the pulling work force till the patch was broken \unskip~\cite{1156473:22699691}.

\textbf{Folding Endurance}

This was determined by repeatedly folding one film at the same place till it broke. The number of times the film could be folded at the same place without breaking gave the value of folding endurance \unskip~\cite{1156473:22699692}.

\textbf{Water Vapour Transmission Rate}

The film was fixed over the brim of a glass vial, containing 3 g of fused calcium chloride as desiccant, with an adhesive tape. The vial was weighed and kept in desiccators containing saturated solution of potassium chloride to provide relative humidity of 84\%. The vial was taken out and weighed at every 24 hrs interval for a period of 72 hrs. \unskip~\cite{1156473:22699689}.

\textbf{Drug Content }

The Films at 1cm2 were cut and added to a beaker containing 100ml of Phosphate buffered solution of pH 7.4. The medium was stirred with a Teflon coated magnetic bead for 5hrs \unskip~\cite{1156473:22699690}.

\textit{\textbf{In vitro}} \textbf{ drug Permeation studies}

\textit{In vitro} release studies can be performed in a modified Franz diffusion cell over a period of time 12 hours. At specific time intervals, aliquots of samples containing the released drug are taken from the acceptor compartment and are quantified using a suitable method of determination \unskip~\cite{1156473:22699697}.

\textbf{Release Order Kinetics }

The data obtained of the \textit{in vitro } dissolution studies acquire kinetic track record analysis \unskip~\cite{1156473:22699694}. 

Zero-order kinetics: \textit{Q \ensuremath{_{t}} = Q \ensuremath{_{o}}+K\ensuremath{_{o}} t}

First-order kinetics: \textit{ Q\ensuremath{_{t}} = log Q\ensuremath{_{o\ }} + K\ensuremath{_{1}}t}/2.303

Higuchi model: \textit{Q\ensuremath{_{t}} = K\ensuremath{_{H\ }} \ensuremath{\cdot}t\ensuremath{^{1/2}}; }Korsmeyer-Peppas release model: \textit{Mt / }\textit{M\ensuremath{_{\infty}}} \textit{ = K \ensuremath{\cdot} t \ensuremath{^{n}}}

\textbf{Stability Conditions}

Stability study of Nitroglycerin transdermal films was carried out at tracking temperatures for 40\ensuremath{^{o}}C/75\% RH one and three months the parameters estimated \textit{In-vitro} diffusion \unskip~\cite{1156473:22699688}.
    
\section{RESULTS AND DISCUSSION}
\textbf{Compatibility Studies}

The spectrum of the pure Nitroglycerin sample recorded by FTIR is shown in Figures~\ref{f-4504f482adb5}, \ref{f-0c9292c9c58d}, \ref{f-2b62ed559b38}, \ref{f-daea0d0983e2} and~\ref{f-be0391cc2ae2}. 

\textbf{Evaluation of Nitroglycerin Transdermal Films}

\textbf{Physicochemical }

The planned out formulations of Films used to be thin, flexible, elastic, smooth and transparent/ translucent [Table~\ref{tw-ff49f12c5d91}]. 

\textbf{Thickness }

The variability between 0.18 \ensuremath{\pm} 0.02 mm to 0.22 \ensuremath{\pm} 0.03mm which signifies homogenous in thickness [Table~\ref{tw-ff49f12c5d91}]. 


\begin{table*}[!htbp]
\caption{\boldmath {Ingredients of Transdermal Films} }
\label{tw-63bf774506ba}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.4545000000000001\linewidth-2\tabcolsep}p{\dimexpr.09120000000000005\linewidth-2\tabcolsep}p{\dimexpr.10670000000000003\linewidth-2\tabcolsep}p{\dimexpr.08469999999999999\linewidth-2\tabcolsep}p{\dimexpr.09249999999999998\linewidth-2\tabcolsep}p{\dimexpr.08110000000000001\linewidth-2\tabcolsep}p{\dimexpr.08930000000000001\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}Ingredients & \cAlignHack NF1 & \cAlignHack NF2 & \cAlignHack NF3 & \cAlignHack NF4 & \cAlignHack NF5 & \cAlignHack NF6\\
\tblmidrule 
Nitroglycerin (mg) &
  \cAlignHack 100 &
  \cAlignHack 100 &
  \cAlignHack 100 &
  \cAlignHack 100 &
  \cAlignHack 100 &
  \cAlignHack 100\\
Hydroxy Propyl Methyl Cellulose \mbox{}\protect\newline (mg) &
  \cAlignHack 400 &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack 100 &
  \cAlignHack 100 &
  \cAlignHack -\\
Cellulose acetate phthalate (mg) &
  \cAlignHack - &
  \cAlignHack 400 &
  \cAlignHack - &
  \cAlignHack 200 &
  \cAlignHack - &
  \cAlignHack 100\\
Ethyl cellulose (mg) &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack 400 &
  \cAlignHack - &
  \cAlignHack 200 &
  \cAlignHack 200\\
Propylene glycol (w/v) &
  \cAlignHack 40 \% &
  \cAlignHack 40 \% &
  \cAlignHack 40 \% &
  \cAlignHack 40 \% &
  \cAlignHack 40 \% &
  \cAlignHack 40 \%\\
Alcohol (ml) &
  \cAlignHack 10 &
  \cAlignHack 10 &
  \cAlignHack 10 &
  \cAlignHack 10 &
  \cAlignHack 10 &
  \cAlignHack 10\\
Dimethylsulfoxide  &
  \cAlignHack 20\% &
  \cAlignHack 20\% &
  \cAlignHack 20\% &
  \cAlignHack 40\% &
  \cAlignHack 40\% &
  \cAlignHack 40\%\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Evaluation of Transdermal Films} }
\label{tw-ff49f12c5d91}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.1567\linewidth-2\tabcolsep}p{\dimexpr.1515\linewidth-2\tabcolsep}p{\dimexpr.1375\linewidth-2\tabcolsep}p{\dimexpr.131\linewidth-2\tabcolsep}p{\dimexpr.131\linewidth-2\tabcolsep}p{\dimexpr.1375\linewidth-2\tabcolsep}p{\dimexpr.1548\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack Parameters  & \cAlignHack NF1 & \cAlignHack NF2 & \cAlignHack NF3 & \cAlignHack NF4 & \cAlignHack NF5 & \cAlignHack NF6 \\
\tblmidrule 
\cAlignHack Physical Appearance &
  \cAlignHack Satisfactory &
  \cAlignHack Satisfactory  &
  \cAlignHack Satisfactory  &
  \cAlignHack Satisfactory  &
  \cAlignHack Satisfactory  &
  \cAlignHack Satisfactory \\
\cAlignHack Thickness (mm) &
  \cAlignHack 0.20 \ensuremath{\pm} 0.04  &
  \cAlignHack 0.18 \ensuremath{\pm} 0.02  &
  \cAlignHack 0.19 \ensuremath{\pm} 0.03  &
  \cAlignHack 0.22 \ensuremath{\pm} 0.03  &
  \cAlignHack 0.20 \ensuremath{\pm} 0.04  &
  \cAlignHack 0.21 \ensuremath{\pm} 0.05\\
\cAlignHack Weight variation (mg) &
  \cAlignHack 210 \ensuremath{\pm} 1.19  &
  \cAlignHack 170 \ensuremath{\pm} 2.20  &
  \cAlignHack 150 \ensuremath{\pm} 2.2  &
  \cAlignHack 221 \ensuremath{\pm} 2.6  &
  \cAlignHack 202 \ensuremath{\pm} 5.0  &
  \cAlignHack 187 \ensuremath{\pm} 2.2\\
\cAlignHack Moisture content &
  \cAlignHack 3.113 \ensuremath{\pm} 0.04  &
  \cAlignHack 3.321 \ensuremath{\pm} 0.31  &
  \cAlignHack 3.354 \ensuremath{\pm} 0.02  &
  \cAlignHack 3.131 \ensuremath{\pm} 0.03  &
  \cAlignHack 2.432 \ensuremath{\pm} 0.01  &
  \cAlignHack 3.114 \ensuremath{\pm} 0.23\\
\cAlignHack Flatness (I) &
  \cAlignHack 98\%  &
  \cAlignHack 98\%  &
  \cAlignHack 98\%  &
  \cAlignHack 98\%  &
  \cAlignHack 98\%  &
  \cAlignHack 98\%\\
\cAlignHack Tensile strength \mbox{}\protect\newline (Nm\ensuremath{^{-2}}) &
  \cAlignHack 11.12 \ensuremath{\pm} 1.11 &
  \cAlignHack 12.14 \ensuremath{\pm} 1.31  &
  \cAlignHack 11.89 \ensuremath{\pm} 1.57  &
  \cAlignHack 12.12 \ensuremath{\pm} 1.31  &
  \cAlignHack 12.23 \ensuremath{\pm} 1.78  &
  \cAlignHack 10.21 \ensuremath{\pm} 3.00\\
\cAlignHack Folding endurance (F) &
  \cAlignHack 170.1 \ensuremath{\pm} 3.10  &
  \cAlignHack 150 \ensuremath{\pm} 2.34  &
  \cAlignHack 160 \ensuremath{\pm} 1.10  &
  \cAlignHack 134 \ensuremath{\pm} 5.3  &
  \cAlignHack 143.2 \ensuremath{\pm} 4.5  &
  \cAlignHack 100 \ensuremath{\pm} 2.43\\
\cAlignHack WVTR (g/m\ensuremath{^{2}}) &
  \cAlignHack 3.110 \ensuremath{\pm} 0.24  &
  \cAlignHack 3.232 \ensuremath{\pm} 0.32  &
  \cAlignHack 3.121 \ensuremath{\pm} 0.14  &
  \cAlignHack 2.189 \ensuremath{\pm} 0.04  &
  \cAlignHack 2.51 \ensuremath{\pm} 0.34  &
  \cAlignHack 2.01 \ensuremath{\pm} 0.21\\
\cAlignHack Drug Content (\%) &
  \cAlignHack 98.2 \ensuremath{\pm} 0.2  &
  \cAlignHack 97.1 \ensuremath{\pm} 0.1  &
  \cAlignHack 96.9 \ensuremath{\pm} 0.2  &
  \cAlignHack 97.8 \ensuremath{\pm} 0.3  &
  \cAlignHack 96.3 \ensuremath{\pm} 0.2  &
  \cAlignHack 97.2 \ensuremath{\pm} 0.3\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Cumulative \% drug releases of Nitroglycerin Transdermal Films} }
\label{tw-59b07591e1a9}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.1387\linewidth-2\tabcolsep}p{\dimexpr.1413\linewidth-2\tabcolsep}p{\dimexpr.14\linewidth-2\tabcolsep}p{\dimexpr.14\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 Time \mbox{}\protect\newline (Mints) & \multicolumn{6}{p{\dimexpr(.8613\linewidth-2\tabcolsep)}}{\cAlignHack  \% of Drug release}\\
\rowcolor{kwdboxcolor}\cAlignHack  & \cAlignHack NF1 & \cAlignHack NF2 & \cAlignHack NF3 & \cAlignHack NF4 & \cAlignHack NF5 & \cAlignHack NF6\\
\tblmidrule 
\cAlignHack 5 &
  \cAlignHack 1.54 &
  \cAlignHack 4.06 &
  \cAlignHack 5.96 &
  \cAlignHack 11.68 &
  \cAlignHack 5.58 &
  \cAlignHack 13.14\\
\cAlignHack 10 &
  \cAlignHack 9.62 &
  \cAlignHack 10.96 &
  \cAlignHack 11.24 &
  \cAlignHack 22.36 &
  \cAlignHack 19.42 &
  \cAlignHack 26.98\\
\cAlignHack 15 &
  \cAlignHack 15.96 &
  \cAlignHack 21.46 &
  \cAlignHack 23.59 &
  \cAlignHack 34.64 &
  \cAlignHack 28.32 &
  \cAlignHack 33.16\\
\cAlignHack 20 &
  \cAlignHack 20.68 &
  \cAlignHack 31.58 &
  \cAlignHack 44.64 &
  \cAlignHack 49.32 &
  \cAlignHack 33.16 &
  \cAlignHack 43.94\\
\cAlignHack 25 &
  \cAlignHack 31.58 &
  \cAlignHack 45.42 &
  \cAlignHack 59.32 &
  \cAlignHack 53.16 &
  \cAlignHack 47.06 &
  \cAlignHack 56.31\\
\cAlignHack 30 &
  \cAlignHack 45.42 &
  \cAlignHack 57.06 &
  \cAlignHack 60.90 &
  \cAlignHack 65.32 &
  \cAlignHack 57.08 &
  \cAlignHack 68.64\\
\cAlignHack 35 &
  \cAlignHack 57.06 &
  \cAlignHack 64.80 &
  \cAlignHack 74.80 &
  \cAlignHack 78.64 &
  \cAlignHack 79.42 &
  \cAlignHack 70.98\\
\cAlignHack 40 &
  \cAlignHack 80.90 &
  \cAlignHack 82.48 &
  \cAlignHack 81.00 &
  \cAlignHack 84.90 &
  \cAlignHack 82.64 &
  \cAlignHack 81.10\\
\cAlignHack 45 &
  \cAlignHack 97.34 &
  \cAlignHack 83.22 &
  \cAlignHack 92.12 &
  \cAlignHack 95.86 &
  \cAlignHack 91.26 &
  \cAlignHack 93.56\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Release kinetics of Nitroglycerin Transdermal Films NF1-NF6} }
\label{tw-9c6f8b825d13}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.18269999999999996\linewidth-2\tabcolsep}p{\dimexpr.07680000000000002\linewidth-2\tabcolsep}p{\dimexpr.07209999999999999\linewidth-2\tabcolsep}p{\dimexpr.07700000000000003\linewidth-2\tabcolsep}p{\dimexpr.0617\linewidth-2\tabcolsep}p{\dimexpr.06370000000000003\linewidth-2\tabcolsep}p{\dimexpr.0632\linewidth-2\tabcolsep}p{\dimexpr.06499999999999998\linewidth-2\tabcolsep}p{\dimexpr.06110000000000001\linewidth-2\tabcolsep}p{\dimexpr.07900000000000002\linewidth-2\tabcolsep}p{\dimexpr.074899999999999975\linewidth-2\tabcolsep}p{\dimexpr.06789999999999997\linewidth-2\tabcolsep}p{\dimexpr.05490000000000001\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack Model & \multicolumn{2}{p{\dimexpr(.1489\linewidth-2\tabcolsep)}}{\cAlignHack NF1} & \multicolumn{2}{p{\dimexpr(.13870000000000003\linewidth-2\tabcolsep)}}{\cAlignHack NF2} & \multicolumn{2}{p{\dimexpr(.12690000000000003\linewidth-2\tabcolsep)}}{\cAlignHack NF3} & \multicolumn{2}{p{\dimexpr(.1261\linewidth-2\tabcolsep)}}{\cAlignHack NF4} & \multicolumn{2}{p{\dimexpr(.1539\linewidth-2\tabcolsep)}}{\cAlignHack NF5} & \multicolumn{2}{p{\dimexpr(.12279999999999998\linewidth-2\tabcolsep)}}{\cAlignHack NF6}\\
\rowcolor{kwdboxcolor}\cAlignHack  & \cAlignHack r\ensuremath{^{2}} & \cAlignHack m & \cAlignHack r\ensuremath{^{2}} & \cAlignHack m & \cAlignHack r\ensuremath{^{2}} & \cAlignHack m & \cAlignHack r\ensuremath{^{2}} & \cAlignHack m & \cAlignHack r\ensuremath{^{2}} & \cAlignHack m & \cAlignHack r\ensuremath{^{2}} & \cAlignHack m\\
\tblmidrule 
\cAlignHack Zero order &
  \cAlignHack 0.655 &
  \cAlignHack 69.4 &
  \cAlignHack 0.655 &
  \cAlignHack 69.4 &
  \cAlignHack 0.939 &
  \cAlignHack 1123 &
  \cAlignHack 0.007 &
  \cAlignHack 15.93 &
  \cAlignHack 0.202 &
  \cAlignHack 72.88 &
  \cAlignHack 0.928 &
  \cAlignHack 1414\\
\cAlignHack First order  &
  \cAlignHack 0.494 &
  \cAlignHack 0.061 &
  \cAlignHack 0.494 &
  \cAlignHack 0.061 &
  \cAlignHack 0.540 &
  \cAlignHack 0.067 &
  \cAlignHack 0.257 &
  \cAlignHack 0.038 &
  \cAlignHack 0.352 &
  \cAlignHack 0.044 &
  \cAlignHack 0.438 &
  \cAlignHack 0.062\\
\cAlignHack Higuchi's Matrix &
  \cAlignHack 0.516 &
  \cAlignHack 4508 &
  \cAlignHack 0.516 &
  \cAlignHack 4508 &
  \cAlignHack 0.767 &
  \cAlignHack 7420 &
  \cAlignHack 0.023 &
  \cAlignHack 212.0 &
  \cAlignHack 0.189 &
  \cAlignHack 515.5 &
  \cAlignHack 0.803 &
  \cAlignHack 9618\\
\cAlignHack Korsmeyer- Peppar &
  \cAlignHack 0.835 &
  \cAlignHack 2.354 &
  \cAlignHack 0.835 &
  \cAlignHack 2.354 &
  \cAlignHack 0.884 &
  \cAlignHack 2.545 &
  \cAlignHack 0.572 &
  \cAlignHack 1.709 &
  \cAlignHack 0.663 &
  \cAlignHack 1.813 &
  \cAlignHack 0.806 &
  \cAlignHack 2.517\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Stability studies of the optimized formulation NF1} }
\label{tw-e5cef2506b9e}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.2298\linewidth-2\tabcolsep}p{\dimexpr.2186\linewidth-2\tabcolsep}p{\dimexpr.27020000000000003\linewidth-2\tabcolsep}p{\dimexpr.2814\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack Time in (Mints)  & \multicolumn{3}{p{\dimexpr(.7702000000000001\linewidth-2\tabcolsep)}}{\cAlignHack Cumulative \% Drug Release }\\
\rowcolor{kwdboxcolor}\cAlignHack  & \cAlignHack Standard  & \cAlignHack After 1 Month  & \cAlignHack After 3 Month \\
\tblmidrule 
\cAlignHack 5 &
  \cAlignHack 1.54 &
  \cAlignHack 1.59 &
  \cAlignHack 2.59\\
\cAlignHack 10 &
  \cAlignHack 9.62 &
  \cAlignHack 9.79 &
  \cAlignHack 10.79\\
\cAlignHack 15 &
  \cAlignHack 15.96 &
  \cAlignHack 16.00 &
  \cAlignHack 17.00\\
\cAlignHack 20 &
  \cAlignHack 20.68 &
  \cAlignHack 22.68 &
  \cAlignHack 23.68\\
\cAlignHack 25 &
  \cAlignHack 31.58 &
  \cAlignHack 33.58 &
  \cAlignHack 34.58\\
\cAlignHack 30 &
  \cAlignHack 45.42 &
  \cAlignHack 46.42 &
  \cAlignHack 47.42\\
\cAlignHack 35 &
  \cAlignHack 57.06 &
  \cAlignHack 58.06 &
  \cAlignHack 59.06\\
\cAlignHack 40 &
  \cAlignHack 80.90 &
  \cAlignHack 81.90 &
  \cAlignHack 82.90\\
\cAlignHack 45 &
  \cAlignHack 97.34 &
  \cAlignHack 97.37 &
  \cAlignHack 98.37\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Stability studies of the Drug Content of optimized formulation NF1} }
\label{tw-6d63dbf68d6b}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.33\linewidth-2\tabcolsep}p{\dimexpr.2807\linewidth-2\tabcolsep}p{\dimexpr.3893\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack Drug Content (\%)  & \cAlignHack After 1 Month  & \cAlignHack After 3 Month \\
\tblmidrule 
\cAlignHack 98.2 \ensuremath{\pm} 0.2  &
  \cAlignHack 98.3 \ensuremath{\pm} 0.1  &
  \cAlignHack 99.5 \ensuremath{\pm} 0.3 \\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\bgroup
\fixFloatSize{images/777ba180-590a-4101-9f4b-1051c5c1033f-upicture1.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/777ba180-590a-4101-9f4b-1051c5c1033f-upicture1.png}{\includegraphics{images/777ba180-590a-4101-9f4b-1051c5c1033f-upicture1.png}}{}
\makeatother 
\caption{\boldmath {FTIR Spectrum of Nitroglycerin}}
\label{f-4504f482adb5}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/d4df1ccc-ef06-46a2-a0de-aaf61ec01099-upicture2.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/d4df1ccc-ef06-46a2-a0de-aaf61ec01099-upicture2.png}{\includegraphics{images/d4df1ccc-ef06-46a2-a0de-aaf61ec01099-upicture2.png}}{}
\makeatother 
\caption{\boldmath {FTIR Spectrum of Hydroxy Propyl Methyl Cellulose}}
\label{f-0c9292c9c58d}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/ce1991b4-338f-46fd-ad96-9fa3167bfa3e-upicture3.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/ce1991b4-338f-46fd-ad96-9fa3167bfa3e-upicture3.png}{\includegraphics{images/ce1991b4-338f-46fd-ad96-9fa3167bfa3e-upicture3.png}}{}
\makeatother 
\caption{\boldmath {FTIR Spectrum of Cellulose acetate phthalate}}
\label{f-2b62ed559b38}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/378d8206-925e-4e22-8165-458e660bf097-upicture4.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/378d8206-925e-4e22-8165-458e660bf097-upicture4.png}{\includegraphics{images/378d8206-925e-4e22-8165-458e660bf097-upicture4.png}}{}
\makeatother 
\caption{\boldmath {FTIR Spectrum of Ethylcellulose}}
\label{f-daea0d0983e2}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/7196ca11-5435-4165-b9ed-60a42e6a98f4-upicture5.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/7196ca11-5435-4165-b9ed-60a42e6a98f4-upicture5.png}{\includegraphics{images/7196ca11-5435-4165-b9ed-60a42e6a98f4-upicture5.png}}{}
\makeatother 
\caption{\boldmath {FTIR Spectrum of Mixture of compounds}}
\label{f-be0391cc2ae2}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/5ff14fbe-3a31-4dd6-ab4f-0a700323567e-upicture6.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/5ff14fbe-3a31-4dd6-ab4f-0a700323567e-upicture6.png}{\includegraphics{images/5ff14fbe-3a31-4dd6-ab4f-0a700323567e-upicture6.png}}{}
\makeatother 
\caption{\boldmath {\textit{In Vitro} diffusion Studies Nitroglycerin Transdermal Films}}
\label{f-7e4f059f7fac}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/f8b36105-4a3c-41fc-b47a-6aa0ba77facf-upicture7.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/f8b36105-4a3c-41fc-b47a-6aa0ba77facf-upicture7.png}{\includegraphics[width=.83\linewidth]{images/f8b36105-4a3c-41fc-b47a-6aa0ba77facf-upicture7.png}}{}
\makeatother 
\caption{\boldmath {Stability studies of Optimized Formulation of NF1}}
\label{f-df27893a7422}
\end{figure}
\egroup
\textbf{Weight Variation}

The variability between 150 \ensuremath{\pm} 2.2mg to 221 \ensuremath{\pm} 2.6mg, Whichever signifies that assorted batches patch weights were similar [Table~\ref{tw-ff49f12c5d91}]. 

\textbf{Moisture Content}

The variability between 2.432 \ensuremath{\pm} 0.01 \% to 3.354 \ensuremath{\pm} 0.02 \% [Table~\ref{tw-ff49f12c5d91}].

\textbf{Flatness}

The flatness report displayed to that each one the formulation indicating 98\% flatness [Table~\ref{tw-ff49f12c5d91}].

\textbf{Tensile Strength}

The NF1 to NF6 shows the 11.12 \ensuremath{\pm} 1.11 to 12.23 \ensuremath{\pm}1.31 shows the comprehensive viscosity [Table~\ref{tw-ff49f12c5d91}].

\textbf{Folding Endurance}

The NF1 to NF6 shows the 100 \ensuremath{\pm} 2.43 to 170.1 \ensuremath{\pm} 3.10 [Table~\ref{tw-ff49f12c5d91}]. 

\textbf{Water Vapour Transmission Rate}

The WVTR in NF1 to NF6 shows the 2.01 \ensuremath{\pm} 0.21 to 3.232 \ensuremath{\pm} 0.32 [Table~\ref{tw-ff49f12c5d91}]. 

\textbf{Drug Content }

The total amount of drug is present in the Films was found to be 98.2 \ensuremath{\pm} 0.2 to  96.3 \ensuremath{\pm} 0.2 \% [Table~\ref{tw-6d63dbf68d6b}].

\textit{\textbf{In-vitro }} \textbf{Drug Permeation studies}

NF1 presented preeminent 97.34 \% of drug release [Figure~\ref{f-7e4f059f7fac}  and Table~\ref{tw-59b07591e1a9}].

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

The \textit{in vitro} drug diffusion data acquired was suited to various analytical models [Table~\ref{tw-9c6f8b825d13}].

\textbf{Stability Study }

The NF1 was subjected to stability studies for 1 to 3 months and the films were tested for Drug content \& \textit{In-vitro} diffusion [Table~\ref{tw-e5cef2506b9e}  and Figures~\ref{f-7e4f059f7fac} and~\ref{f-df27893a7422}].
    
\section{CONCLUSION}
Finally, I~over for which drug release during the films of Nitroglycerin obeys First order kinetics. Customized formulation NF1 obtained stability reports for 1 to 3 months and also the films were proven for drug content as well as \textit{In-vitro} diffusion. The finding of fact of the current effect revealed that the problems of Nitroglycerin on oral like dissolution rate limited absorption and gastric unwanted effects can be sweep over by using Nitroglycerin locally in the form of transdermal films.
    
\section{Acknowledgement}
I would like to thank Dr. G. H. Srinivaasa Rao Sir (Founder and Manager), Saastra College of Pharmaceutical Education \& Research, Near Varigonda Jwalamuhi Temple, Muthukur Raod, Kakupalli, Nellore-524311, Andhra Pradesh, India.

\textbf{Funding Support}

The authors declare that they have no funding support for this study.

\textbf{Conflict of Interest}

The authors declare that there is no conflict of interest.
    

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