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\def\citeauthor{~Bijapuri~Srivastava,
              ~Sonypriya~B,
              ~Muthamsetty~Sravani,
              ~Athmakuri~Thabitharani,
              ~Kota~Lakshmi~Veda~Manasa}
\def\citetitle{\textbf{Formulation and Evaluation of Capecitabine Loaded Proniosomes}}
\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{Bijapuri Srivastava et al.}
\firstPage{34}
\articleType{Original Article}
\receivedDate{05 Mar 2022}
\acceptedDate{23 Mar 2022}
\revisedDate{22 Mar 2022}
\journalVolume{1}
\journalIssue{2}
\journalDoi{ijebr.v1i2.372}
\copyrightYear{2022}
\eISSN{2583-5254}
\journalDoi{ijebr.v1i2.372}
\def\authorCount{5}
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\def\journalTitle{International Journal of Experimental and Biomedical Research}

\title{\textbf{Formulation and Evaluation of Capecitabine Loaded Proniosomes}}
\author{Bijapuri~Srivastava\textsuperscript{*}\textsuperscript{1}\textsuperscript{\href{https://orcid.org/0000-0001-6454-5526}{\XeTeXLinkBox{\includegraphics[height=7pt]{orcid-logo-pharmascope.pdf}}}},  
            Sonypriya~B\textsuperscript{2}\textsuperscript{\href{https://orcid.org/0000-0001-9894-2212}{\XeTeXLinkBox{\includegraphics[height=7pt]{orcid-logo-pharmascope.pdf}}}},  
            Muthamsetty~Sravani\textsuperscript{2}\textsuperscript{\href{https://orcid.org/0000-0002-1869-2522}{\XeTeXLinkBox{\includegraphics[height=7pt]{orcid-logo-pharmascope.pdf}}}},  
            Athmakuri~Thabitharani\textsuperscript{2}\textsuperscript{\href{https://orcid.org/0000-0003-2287-5193}{\XeTeXLinkBox{\includegraphics[height=7pt]{orcid-logo-pharmascope.pdf}}}}, 
            Kota~Lakshmi~Veda~Manasa\textsuperscript{2}\textsuperscript{\href{https://orcid.org/0000-0002-6983-2564}{\XeTeXLinkBox{\includegraphics[height=7pt]{orcid-logo-pharmascope.pdf}}}}~\\[5pt]{\textsuperscript{1}Department of Pharmaceutics, St. Mary's Group of Institutions, Deshmukhi (Village), Pochampally (Mandal), Yadadri Bhuvanagiri (Dist), Telangana-508284, India}~\\{\textsuperscript{2}St. Mary's Group of Institutions, Deshmukhi (Village), Pochampally (Mandal), Yadadri Bhuvanagiri (Dist), Telangana-508284, India}}

\begin{abstract}
Proniosomes are amongst the many alternative warships such as transferring a dosage form itself to receptor sites. They will implicate either of those hydrophobic and hydrophilic substances. The aim as well as objective of the current research task would be to the investigate the suitability of formulate and evaluate of capecitabine proniosomes for which is an anti cancer currently indicator for the treatment of patients with metastatic breast cancer. Well all proniosomes preparations have been analyzed regarding encapsulation efficiency, drug loading, replicability, size and shape dispersion microphotography, FTIR studies and then in vitro release studies. The outcomes recommend that even in together all told to prepare noisome preparations even as emulsifier's concentration was increased an encapsulation efficiency improves. A pure drug has been found to be between 81.14\ensuremath{\pm}0.66 percent to 97.06 \ensuremath{\pm} 0.23 \% with lesser SD. The dimensions of Proniosomes was indeed did find to 0.245 \ensuremath{\pm} 0.051 mm to 0.312 \ensuremath{\pm} 0.025 mm and the Proniosomes are spherical shaped. An FTIR spectrum analyzer suggested that there has been no connection between both the opoid and also preparation preservatives. \textit{In vitro } dissolution parametric has been researched utilizing cell wall dispersion cellular. Results conclude that preparation F1 shows the better controlled release activity then the other preparation with `n' value 0.899 as well as recommending that its ovoid has been set to release besides zero order kinetics.
\end{abstract}\def\keywordstitle{Keywords}

\begin{keywords}Cholesterol,\newline Proniosomes,\newline Capecitabine,\newline Span 60
\end{keywords}
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\makeatletter{\raggedright{\Large$^\ast$}Corresponding Author\par Name:\ Bijapuri~Srivastava~\\ Phone:\ +91 9885689720~\\  Email:\ srisays2u@gmail.com
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\section{Introduction}
A proniosomes are really a multi-functional delivery mechanism due to the obvious alleviate like allocation, measurement system, transmission, as well as collection proniosomes had been researched even though alternative options to liposomes and some other carrier processes such as abducting whether polar but also non-polar or either hydrophilic and hydrophobic substances. The extra warrants as for proniosomes have been no toxicity nature, owning to none neither necessity like extra precautions as well as circumstances such as composition but also planning and preparation \unskip~\cite{1436535:25134213}. Moreover, Than it's the simple technique for such ritual and huge scale of production like proniosomes without the need for unacceptable organic solvent, notwithstanding, stabilisation is just a biggest concern inside the development of the any preparation or even proniosomes have potential benefits just like delivery systems, like cost productivity, chemically stabilisation through sales comparison to liposomes. In addition they mitigate troubles of physical properties including such condensation, discharge, sediment transport, but also agglomeration through collection \unskip~\cite{1436535:25134212}. These all potential benefits of powdered almost always considered just like Proniosomes have created those a pledging engineering products. Proniosomes were also light microscope membranous constructions. They integrate a non-ionic surfactant of di alkyl as well as polyglycerol ether category but also cholesterol tried to follow besides moisture through aqueous phase. An emulsifier's specific chemical straightforward themselves whereby the hydrophilic actually ended of a non-ionic surface active agencies. Because of preparation methods proniosomes are unilamellar either multilamellar \unskip~\cite{1436535:25134208}. A noisome has been made from an emulsifiers layer system including its water-soluble comes to an end affected outside but and inside the vesicles whereas the water repellent chain processes facial expression one another in the layer system. Thus the vesicular retains lipid soluble drug related inside the storage surrounded inside the vesicular as well as the water repellent substances have been engrained inside this layer system \unskip~\cite{1436535:25134205}.
    
\section{METHODOLOGY}
\textbf{Solubility Study}

A solubilisation of Capecitabine in 10 mg/10 ml like solute has been done with solvent system \unskip~\cite{1436535:25134206}. 

\textbf{Diffusion Study for API}

The 10 mg of API (Capecitabine) had been considered inside a glass container possessing a radius 2.5 cm including overstrength of 8 cm that it was previously disclosed with immersed osmotic pressure cellulose membrane, where it behaves just like donation storage area. A glass container has been positioned inside a flask containing 100 ml of phosphate buffered 7.4, that either functions just like receptor storage area. 

A whole arrangement has been resolved in a rather that now the lower part of a tube containing application programming interface API was also just impacted (1-2mm deep) that whole area of dissemination mid. A temp like receptor moderate retained at 37\ensuremath{\pm}1\ensuremath{^\circ}C and also the intermediate has been incensed there as 100rpm speed utilising magnetic stirring. 

Aliquots of 5ml survey have been forced to withdraw sporadically and with each drawdown relatively similar quantity of intermediate has been overtaken. Collected specimens had been analyzed at 303 nm in double beam UV-VIS spectrophotometrically utilising phosphate buffered 7.4 and although empty \unskip~\cite{1436535:25134210}.

\textbf{Identification of Capecitabine}

\textbf{Drug and Excipients Interaction (FTIR) Study}

A compatibility among physical mixture surfactants, cholesterol, but were identified through FTIR spectra obtained (Bruker Pvt. Ltd, Germany). Potassium bromide granules have been able to prepare through potassium bromide press. To organize granules a powder standard solution has been ground with each other in a concrete with 100 times amounts like potassium bromide \unskip~\cite{1436535:25134207}. Delicately premised flour has been invented it into steel material die. A flour has been kept pressing inside the die among polished metal anvils at such a compression of around 10t/in2. Such as sample preparation thin-film of sample fluid has been managed to make through powder form pellet. Spectra were obtained well over wavelength of 8000 cm\ensuremath{^{-1}} to 500 cm\ensuremath{^{-1}}.

\textbf{Formulation of Proniosomes}

A sludge technique is chosen gain for preparedness like proniosome nanoparticle utilizing maltodextrin as either a bearer. A fatty acid weird mix (250 \ensuremath{\mu }mol), whether neutral, positively charged, or negatively charged, as well as ac (60 mg) have been disintegrated inside a chloroform/diethyl ether mixture (1:1 v/v). A subsequent solution was then added to such a 100-ml round-bottom jar usually contains a maltodextrin bearer (maltodextrin/surfactant, 1:1). Additional chloroform/diethylether mixture was transferred to structure sludge. 

A rotary evaporator at lowest pressure has been used to evaporate solutes at 70 rpm but also temp of 60\ensuremath{^\circ}C\ensuremath{\pm}2\ensuremath{^\circ}C till the volume within jar get to be powdered as well as fast flowing item. Desiccators at room temperature overnight. An actual results proniosomal nanoparticle has been further hardened under vacuum inside at room temp up overnight. Resulting proniosome powder particles have been saved through tightly sealed cartons inside a refrigerator (4\ensuremath{^\circ}C) but were used in the preparedness like proniosome for further evaluation and study on powder properties. 

An acquired proniosome powder would be further hardened up overnight for under vacuum at room temp. Correspondingly, some other batch of proniosome has been able to prepare utilising span 60 besides able to adapt a same procedure as discussed above [Table~\ref{tw-782cc23399ed}]. An acquired powdered proniosomes substances have been saved through an airtight seal emerald colour glass vial preserved inside a fridge for any further assessment \unskip~\cite{1436535:25134211}.


\begin{table*}[!htbp]
\caption{\boldmath {Formulations of Capecitabine Loaded Proniosomes} }
\label{tw-782cc23399ed}
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\tbltoprule \rowcolor{kwdboxcolor}Formulations \mbox{}\protect\newline Code & Drug \mbox{}\protect\newline (mg) & Span 60: Cholesterol Molar ratio & Span 60  \mbox{}\protect\newline (mg) & Cholesterol (mg) & Maltodextrin \mbox{}\protect\newline (gms)\\
\tblmidrule 
F1 &
  60 &
  1:0.50 &
  430.6 &
  193 &
  1\\
F2 &
  60 &
  1:0.75 &
  430.6 &
  289 &
  1\\
F3 &
  60 &
  1:1 &
  430.6 &
  386 &
  1\\
F4 &
  60 &
  1:1.5 &
  430.6 &
  420 &
  1\\
F5 &
  60 &
  0.50:1 &
  193 &
  430.6 &
  1\\
F6 &
  60 &
  0.75:1 &
  289 &
  430.6 &
  1\\
F7 &
  60 &
  1.1 &
  386 &
  430.6 &
  1\\
F8 &
  60 &
  1.5:1 &
  420 &
  430.6 &
  1\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Angle of repose \% encapsulation and \% Drug content of formulation F1 to F8} }
\label{tw-d6699bdc1430}
\centering 
\begin{threeparttable}

\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.23960000000000004\linewidth-2\tabcolsep}p{\dimexpr.28119999999999994\linewidth-2\tabcolsep}p{\dimexpr.2292\linewidth-2\tabcolsep}p{\dimexpr.25\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack Formulation code & \cAlignHack Angle of repose(\ensuremath{\theta })*\ensuremath{\pm}SD & \cAlignHack Percentage \mbox{}\protect\newline Entrapment* \mbox{}\protect\newline \ensuremath{\pm}S.D & \cAlignHack Percentage \mbox{}\protect\newline Drug content* \mbox{}\protect\newline \ensuremath{\pm}S.D\\
\tblmidrule 
\cAlignHack F1 &
  \cAlignHack 26\ensuremath{^\circ}85'\ensuremath{\pm}0.28 &
  \cAlignHack 61.35\ensuremath{\pm}0.14 &
  \cAlignHack 97.06\ensuremath{\pm}0.23\\
\cAlignHack F2 &
  \cAlignHack 25\ensuremath{^\circ}12'\ensuremath{\pm}0.26 &
  \cAlignHack 5271, 02\ensuremath{\pm}0.54 &
  \cAlignHack 92.97\ensuremath{\pm}o.24\\
\cAlignHack F3 &
  \cAlignHack 27\ensuremath{^\circ}95'\ensuremath{\pm}0.22 &
  \cAlignHack 54.93\ensuremath{\pm}0.47 &
  \cAlignHack 94.46\ensuremath{\pm}0.41\\
\cAlignHack F4 &
  \cAlignHack 27\ensuremath{^\circ}10'\ensuremath{\pm}0.37 &
  \cAlignHack 57.36\ensuremath{\pm}0.81 &
  \cAlignHack 96.38\ensuremath{\pm}0.37\\
\cAlignHack F5 &
  \cAlignHack 25\ensuremath{^\circ}50'\ensuremath{\pm}0.51 &
  \cAlignHack 50.35\ensuremath{\pm}0.63 &
  \cAlignHack 81.14\ensuremath{\pm}0.66\\
\cAlignHack F6 &
  \cAlignHack 26\ensuremath{^\circ}32'\ensuremath{\pm}0.35 &
  \cAlignHack 43.32\ensuremath{\pm}0.71 &
  \cAlignHack 85.35\ensuremath{\pm}0.62\\
\cAlignHack F7 &
  \cAlignHack 27\ensuremath{^\circ}13'\ensuremath{\pm}0.46 &
  \cAlignHack 63.03\ensuremath{\pm}0.38 &
  \cAlignHack 90.53\ensuremath{\pm}0.46\\
\cAlignHack F8 &
  \cAlignHack 26\ensuremath{^\circ}12'\ensuremath{\pm}0.22 &
  \cAlignHack 65.43\ensuremath{\pm}0.27 &
  \cAlignHack 95.15\ensuremath{\pm}0.27\\
\tblbottomrule 
\end{tabulary}\par 
\begin{tablenotes}\footnotesize 
    
\item{*Average of three readings}
\end{tablenotes}
\end{threeparttable}

\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {\textit{In vitro} Drug Release Kinetic for F1 Formulation} }
\label{tw-86c5cf4260f0}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.095\linewidth-2\tabcolsep}p{\dimexpr.14829999999999998\linewidth-2\tabcolsep}p{\dimexpr.12810000000000002\linewidth-2\tabcolsep}p{\dimexpr.1886\linewidth-2\tabcolsep}p{\dimexpr.14120000000000001\linewidth-2\tabcolsep}p{\dimexpr.1459\linewidth-2\tabcolsep}p{\dimexpr.1529\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}Time in hrs & Square root of time & Log time & Cumulative percentage \mbox{}\protect\newline drug release & Cumulative percentage drug remaning & Log cumulative percentage drug release & Log cumulative percentage drug remaning\\
\tblmidrule 
1 &
  1 &
  0 &
  25.32 &
  74.68 &
  1.4034637 &
  1.873204\\
2 &
  1.414 &
  0.30103 &
  36.83 &
  63.17 &
  1.56620172 &
  1.800511\\
3 &
  1.732 &
  0.477121 &
  48.02 &
  51.98 &
  1.68142216 &
  1.715836\\
4 &
  2 &
  0.60206 &
  57.52 &
  42.48 &
  1.75981888 &
  1.628185\\
5 &
  2.236 &
  0.69897 &
  71.27 &
  28.73 &
  1.85290676 &
  1.458336\\
6 &
  2.449 &
  0.778151 &
  83.45 &
  16.55 &
  1.92142634 &
  1.218798\\
7 &
  2.645 &
  0.845098 &
  95.03 &
  4.97 &
  1.97786073 &
  0.696356\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {\textit{In vitro} Drug Release Kinetic for F2 Formulation} }
\label{tw-c987c4cac443}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.1139\linewidth-2\tabcolsep}p{\dimexpr.1341\linewidth-2\tabcolsep}p{\dimexpr.13169999999999998\linewidth-2\tabcolsep}p{\dimexpr.14120000000000001\linewidth-2\tabcolsep}p{\dimexpr.15420000000000002\linewidth-2\tabcolsep}p{\dimexpr.16259999999999998\linewidth-2\tabcolsep}p{\dimexpr.1623\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}Time in hrs & Square root of time & Log time & Cumulative percentage \mbox{}\protect\newline drug release & Cumulative percentage drug remaning & Log cumulative percentage drug release & Log cumulative percentage drug remaning\\
\tblmidrule 
1 &
  1 &
  0 &
  29.62 &
  70.38 &
  1.471585 &
  1.847449\\
2 &
  1.414 &
  0.30103 &
  42.73 &
  57.27 &
  1.630733 &
  1.757927\\
3 &
  1.732 &
  0.477121 &
  53.62 &
  46.38 &
  1.729327 &
  1.666331\\
4 &
  2 &
  0.60206 &
  62.81 &
  37.19 &
  1.798029 &
  1.570426\\
5 &
  2.236 &
  0.69897 &
  73.01 &
  26.99 &
  1.863382 &
  1.431203\\
6 &
  2.449 &
  0.778151 &
  84.07 &
  15.93 &
  1.924641 &
  1.202216\\
7 &
  2.645 &
  0.845098 &
  96.02 &
  3.98 &
  1.982362 &
  0.599883\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {\textit{In vitro} Drug Release Kinetic for F3 Formulation} }
\label{tw-d3b1bf7772a6}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.1116\linewidth-2\tabcolsep}p{\dimexpr.1293\linewidth-2\tabcolsep}p{\dimexpr.1305\linewidth-2\tabcolsep}p{\dimexpr.13410000000000004\linewidth-2\tabcolsep}p{\dimexpr.1412\linewidth-2\tabcolsep}p{\dimexpr.1933\linewidth-2\tabcolsep}p{\dimexpr.16\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}Time in hrs & Square root of time & Log time & Cumulative percentage \mbox{}\protect\newline drug release & Cumulative percentage drug remaning & Log cumulative percentage drug release & Log cumulative percentage drug remaning\\
\tblmidrule 
1 &
  1 &
  0 &
  23.51 &
  76.49 &
  1.371253 &
  1.883605\\
2 &
  1.414 &
  0.30103 &
  32.38 &
  67.62 &
  1.510277 &
  1.830075\\
3 &
  1.732 &
  0.477121 &
  42.57 &
  57.43 &
  1.629104 &
  1.759139\\
4 &
  2 &
  0.60206 &
  51.41 &
  48.59 &
  1.711048 &
  1.686547\\
5 &
  2.236 &
  0.69897 &
  60.83 &
  39.17 &
  1.784118 &
  1.592954\\
6 &
  2.449 &
  0.778151 &
  70. 4691 &
  29.09 &
  1.850707 &
  1.463744\\
7 &
  2.645 &
  0.845098 &
  82. &
  17.54 &
  1.916243 &
  1.24403\\
8 &
  2.828 &
  0.90309 &
  93.75 &
  6.25 &
  1.971971 &
  0.79588\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {\textit{In vitro} Drug Release Kinetic for F4 Formulation} }
\label{tw-471b0ba76568}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.1116\linewidth-2\tabcolsep}p{\dimexpr.11979999999999999\linewidth-2\tabcolsep}p{\dimexpr.13879999999999999\linewidth-2\tabcolsep}p{\dimexpr.14600000000000001\linewidth-2\tabcolsep}p{\dimexpr.1625\linewidth-2\tabcolsep}p{\dimexpr.1613\linewidth-2\tabcolsep}p{\dimexpr.16\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}Time in hrs & Square root of time & Log time & Cumulative percentage \mbox{}\protect\newline drug release & Cumulative percentage drug remaning & Log cumulative percentage drug release & Log cumulative percentage drug remaning\\
\tblmidrule 
1 &
  1 &
  0 &
  19.21 &
  80.79 &
  1.283527 &
  1.907358\\
2 &
  1.414 &
  0.30103 &
  31.62 &
  68.38 &
  1.499962 &
  1.834929\\
3 &
  1.732 &
  0.477121 &
  40.38 &
  59.62 &
  1.606166 &
  1.775392\\
4 &
  2 &
  0.60206 &
  49.92 &
  50.08 &
  1.698275 &
  1.699664\\
5 &
  2.236 &
  0.69897 &
  62.26 &
  37.74 &
  1.794209 &
  1.576802\\
6 &
  2.449 &
  0.778151 &
  71.43 &
  28.57 &
  1.853881 &
  1.45591\\
7 &
  2.645 &
  0.845098 &
  82.73 &
  17.27 &
  1.917663 &
  1.237292\\
8 &
  2.828 &
  0.90309 &
  93.64 &
  6.36 &
  1.971461 &
  0.803457\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {\textit{In vitro} Drug Release Kinetic for F5 Formulation} }
\label{tw-dce34ec522d1}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.1116\linewidth-2\tabcolsep}p{\dimexpr.13170000000000002\linewidth-2\tabcolsep}p{\dimexpr.1198\linewidth-2\tabcolsep}p{\dimexpr.14950000000000001\linewidth-2\tabcolsep}p{\dimexpr.16490000000000002\linewidth-2\tabcolsep}p{\dimexpr.1625\linewidth-2\tabcolsep}p{\dimexpr.16\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}Time in hrs & Square root of time & Log time & Cumulative percentage \mbox{}\protect\newline drug release & Cumulative percentage drug remaning & Log cumulative percentage drug release & Log cumulative percentage drug remaning\\
\tblmidrule 
1 &
  1 &
  0 &
  18.63 &
  71.26 &
  1.270213 &
  1.910464\\
2 &
  1.414 &
  0.30103 &
  28.74 &
  60.7 &
  1.458487 &
  1.852846\\
3 &
  1.732 &
  0.477121 &
  39.30 &
  51.09 &
  1.594393 &
  1.783189\\
4 &
  2 &
  0.60206 &
  48.91 &
  42.5 &
  1.689398 &
  1.708336\\
5 &
  2.236 &
  0.69897 &
  57.5 &
  34.39 &
  1.759668 &
  1.628389\\
6 &
  2.449 &
  0.778151 &
  65.61 &
  26.29 &
  1.81697 &
  1.536432\\
7 &
  2.645 &
  0.845098 &
  73.71 &
  18.18 &
  1.867526 &
  1.419791\\
8 &
  2.828 &
  0.90309 &
  81.82 &
  9.42 &
  1.912859 &
  1.259594\\
9 &
  3 &
  0.954243 &
  90.58 &
  81.37 &
  1.957032 &
  0.974051\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {\textit{In vitro} Drug Release Kinetic for F6 Formulation} }
\label{tw-040382b080d2}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.1293\linewidth-2\tabcolsep}p{\dimexpr.13409999999999997\linewidth-2\tabcolsep}p{\dimexpr.1246\linewidth-2\tabcolsep}p{\dimexpr.1495\linewidth-2\tabcolsep}p{\dimexpr.1341\linewidth-2\tabcolsep}p{\dimexpr.1601\linewidth-2\tabcolsep}p{\dimexpr.1683\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}Time in hrs & Square root of time & Log time & Cumulative percentage \mbox{}\protect\newline drug release & Cumulative percentage drug remaning & Log cumulative percentage drug release & Log cumulative percentage drug remaning\\
\tblmidrule 
1 &
  1 &
  0 &
  17.73 &
  82.27 &
  1.248709 &
  1.9152\\
2 &
  1.414 &
  0.30103 &
  25.36 &
  74.64 &
  1.404149 &
  1.87297\\
3 &
  1.732 &
  0.477121 &
  33.64 &
  66.36 &
  1.526856 &
  1.82191\\
4 &
  2 &
  0.60206 &
  41.92 &
  58.08 &
  1.622421 &
  1.76403\\
5 &
  2.236 &
  0.69897 &
  50.293 &
  49.707 &
  1.701508 &
  1.69642\\
6 &
  2.449 &
  0.778151 &
  58.62 &
  41.38 &
  1.768046 &
  1.61679\\
7 &
  2.645 &
  0.845098 &
  66.91 &
  33.09 &
  1.825491 &
  1.5197\\
8 &
  2.828 &
  0.90309 &
  77.63 &
  22.37 &
  1.89003 &
  1.34967\\
9 &
  3 &
  0.954243 &
  83.06 &
  16.94 &
  1.919392 &
  1.22891\\
10 &
  3.162 &
  1 &
  92.65 &
  7.35 &
  1.966845 &
  0.86629\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {\textit{In vitro} Drug Release Kinetic for F7 Formulation} }
\label{tw-f1d5c0449219}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.1068\linewidth-2\tabcolsep}p{\dimexpr.16599999999999998\linewidth-2\tabcolsep}p{\dimexpr.1271\linewidth-2\tabcolsep}p{\dimexpr.13169999999999998\linewidth-2\tabcolsep}p{\dimexpr.153\linewidth-2\tabcolsep}p{\dimexpr.1554\linewidth-2\tabcolsep}p{\dimexpr.16\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}Time in hrs & Square root of time & Log time & Cumulative percentage drug release & Cumulative percentage drug remaning & Log cumulative percentage drug release & Log cumulative percentage drug remaning\\
\tblmidrule 
1 &
  1 &
  0 &
  23.63 &
  76.37 &
  1.373464 &
  1.882923\\
2 &
  1.414 &
  0.30103 &
  32.84 &
  67.16 &
  1.516403 &
  1.827111\\
3 &
  1.732 &
  0.477121 &
  39.29 &
  60.71 &
  1.594282 &
  1.78326\\
4 &
  2 &
  0.60206 &
  47.21 &
  52.79 &
  1.674034 &
  1.722552\\
5 &
  2.236 &
  0.69897 &
  56.05 &
  43.95 &
  1.748576 &
  1.642959\\
6 &
  2.449 &
  0.778151 &
  65.02 &
  34.98 &
  1.813047 &
  1.54382\\
7 &
  2.645 &
  0.845098 &
  74.26 &
  25.74 &
  1.870755 &
  1.410609\\
8 &
  2.828 &
  0.90309 &
  83.01 &
  16.99 &
  1.91913 &
  1.230193\\
9 &
  3 &
  0.954243 &
  92.47 &
  7.53 &
  1.966001 &
  0.876795\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {\textit{In vitro} Drug Release Kinetic for F8 Formulation} }
\label{tw-ec56430e2904}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.1341\linewidth-2\tabcolsep}p{\dimexpr.1459\linewidth-2\tabcolsep}p{\dimexpr.14\linewidth-2\tabcolsep}p{\dimexpr.14\linewidth-2\tabcolsep}p{\dimexpr.14\linewidth-2\tabcolsep}p{\dimexpr.1459\linewidth-2\tabcolsep}p{\dimexpr.1541\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}Time in hrs & Square root of time & Log time & Cumulative percentage \mbox{}\protect\newline drug release & Cumulative percentage drug remaning & Log cumulative percentage drug release & Log cumulative percentage drug remaning\\
\tblmidrule 
1 &
  1 &
  0 &
  22.82 &
  77.18 &
  1.358316 &
  1.8875\\
2 &
  1.414 &
  0.30103 &
  32.47 &
  67.53 &
  1.511482 &
  1.8295\\
3 &
  1.732 &
  0.477121 &
  42.61 &
  57.39 &
  1.629512 &
  1.75884\\
4 &
  2 &
  0.60206 &
  53.04 &
  46.96 &
  1.724604 &
  1.67173\\
5 &
  2.236 &
  0.69897 &
  64.07 &
  35.93 &
  1.806655 &
  1.55546\\
6 &
  2.449 &
  0.778151 &
  73.92 &
  26.08 &
  1.868762 &
  1.41631\\
7 &
  2.645 &
  0.845098 &
  82.05 &
  17.95 &
  1.914079 &
  1.25406\\
8 &
  2.828 &
  0.90309 &
  95.53 &
  4.47 &
  1.98014 &
  0.65031\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Pharmacokinetic Parameters for Formulation F1 to F8} }
\label{tw-aea4b0bdb2e8}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.16\linewidth-2\tabcolsep}p{\dimexpr.16\linewidth-2\tabcolsep}p{\dimexpr.1697\linewidth-2\tabcolsep}p{\dimexpr.2361\linewidth-2\tabcolsep}p{\dimexpr.1544\linewidth-2\tabcolsep}p{\dimexpr.11979999999999999\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}Formulation code & Zero order \mbox{}\protect\newline (R\ensuremath{^{2}}) & First order \mbox{}\protect\newline (R\ensuremath{^{2}}) & Higuchi model \mbox{}\protect\newline (R\ensuremath{^{2}}) & \multicolumn{2}{p{\dimexpr(.27419999999999998\linewidth-2\tabcolsep)}}{\cAlignHack Korsmeyer-Peppas model}\\
\rowcolor{kwdboxcolor} &  &  &  & (R\ensuremath{^{2}}) & N\\
\tblmidrule 
F1 &
  0.9932 &
  0.8951 &
  0.9508 &
  0.9889 &
  0.899\\
F2 &
  0.9642 &
  0.8427 &
  0.9843 &
  0.9932 &
  0.794\\
F3 &
  0.9853 &
  0.8582 &
  0.9587 &
  0.9832 &
  0.768\\
F4 &
  0.9923 &
  0.8763 &
  0.9517 &
  0.9948 &
  0.876\\
F5 &
  0.9865 &
  0.9311 &
  0.9687 &
  0.9985 &
  0.895\\
F6 &
  0.9832 &
  0.7731 &
  0.9623 &
  0.9881 &
  0.817\\
F7 &
  0.9807 &
  0.8851 &
  0.9649 &
  0.9786 &
  0.892\\
F8 &
  0.9869 &
  0.8341 &
  0.9611 &
  0.989 &
  0.793\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Stability Study for Formulation F1 in Different Condition} }
\label{tw-9017c416b2a5}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.1554\linewidth-2\tabcolsep}p{\dimexpr.1389\linewidth-2\tabcolsep}p{\dimexpr.1257\linewidth-2\tabcolsep}p{\dimexpr.14\linewidth-2\tabcolsep}p{\dimexpr.14\linewidth-2\tabcolsep}p{\dimexpr.14120000000000001\linewidth-2\tabcolsep}p{\dimexpr.15879999999999999\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}Time period & \multicolumn{2}{p{\dimexpr(.2646\linewidth-2\tabcolsep)}}{\cAlignHack 4\ensuremath{^\circ}C \ensuremath{\pm} 1\ensuremath{^\circ}C } & \multicolumn{2}{p{\dimexpr(.28\linewidth-2\tabcolsep)}}{\cAlignHack 25\ensuremath{^\circ}C \ensuremath{\pm} 5\ensuremath{^\circ}C } & \multicolumn{2}{p{\dimexpr(.30\linewidth-2\tabcolsep)}}{\cAlignHack 30\ensuremath{^\circ}C \ensuremath{\pm} 2\ensuremath{^\circ}C and \mbox{}\protect\newline 60\% RH \ensuremath{\pm} 5\% RH}\\
\rowcolor{kwdboxcolor} & \% Drug content & Sterility of Product & \% Drug Content & Sterility of \mbox{}\protect\newline product & \% Drug content & Sterility of \mbox{}\protect\newline product\\
\tblmidrule 
15 Days &
  97.06\ensuremath{\pm}0.23 &
  Sterile &
  97.06\ensuremath{\pm}0.23 &
  Sterile &
  97.06\ensuremath{\pm}0.23 &
  Sterile\\
30 Days &
  97.03\ensuremath{\pm}0.35 &
  Sterile &
  97.01\ensuremath{\pm}0.72 &
  Sterile &
  97.94\ensuremath{\pm}0.73 &
  Sterile\\
60 Days &
  96.01\ensuremath{\pm}0.42 &
  Sterile &
  97.05\ensuremath{\pm}0.41 &
  Sterile &
  96.63\ensuremath{\pm}0.73 &
  Sterile\\
90 Days &
  96.07\ensuremath{\pm}0.84 &
  Sterile &
  96.03\ensuremath{\pm}0.67 &
  Sterile &
  96.01\ensuremath{\pm}0.64 &
  Sterile\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {\textit{In vitro} Studies of Formulation F1 Stored at Refrigeration Condition} }
\label{tw-19f84d86df95}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.1867\linewidth-2\tabcolsep}p{\dimexpr.2133\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 in hrs & \multicolumn{4}{p{\dimexpr(.8133\linewidth-2\tabcolsep)}}{\cAlignHack Cumulative Percentage Drug Release}\\
\rowcolor{kwdboxcolor} & 15 Days & 30 Days & 60 Days & 90 Days\\
\tblmidrule 
1 &
  25.32 &
  25.34 &
  24.54 &
  24.42\\
2 &
  36.83 &
  36.54 &
  35.83 &
  35.83\\
3 &
  48.02 &
  48.75 &
  47.65 &
  47.65\\
4 &
  57.52 &
  57.34 &
  57.56 &
  57.75\\
5 &
  71.27 &
  70.53 &
  69.27 &
  68.27\\
6 &
  83.45 &
  82.23 &
  81.45 &
  80.45\\
7 &
  95.03 &
  94.54 &
  95.23 &
  94.03\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {\textit{In vitro} Studies of Formulation F1 Stored at Room Temperature} }
\label{tw-59e7c3cb694d}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.1867\linewidth-2\tabcolsep}p{\dimexpr.2133\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 in hrs & \multicolumn{4}{p{\dimexpr(.8133\linewidth-2\tabcolsep)}}{\cAlignHack Cumulative Percentage Drug Release}\\
\rowcolor{kwdboxcolor} & 15 Days & 30 Days & 60 Days & 90 Days\\
\tblmidrule 
1 &
  25.32 &
  24.92 &
  24.86 &
  23.21\\
2 &
  36.83 &
  35.34 &
  35.87 &
  36.93\\
3 &
  48.02 &
  47.44 &
   47.54 &
  46.32\\
4 &
  57.52 &
  56.65 &
  56.67 &
  55.71\\
5 &
  71.27 &
  70.45 &
  70.87 &
  69.63\\
6 &
  83.45 &
  82.63 &
  82.97 &
  81.01\\
7 &
  95.03 &
  94.42 &
  94.75 &
  93.31\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {\textit{In vitro} Studies of Formulation F1 Stored at Accelerated Condition} }
\label{tw-45189a340f75}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.21160000000000004\linewidth-2\tabcolsep}p{\dimexpr.1884\linewidth-2\tabcolsep}p{\dimexpr.1884\linewidth-2\tabcolsep}p{\dimexpr.2116\linewidth-2\tabcolsep}p{\dimexpr.20\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}Time in hrs & \multicolumn{4}{p{\dimexpr(.7884\linewidth-2\tabcolsep)}}{\cAlignHack Cumulative percentage drug release}\\
\rowcolor{kwdboxcolor} & 15 Days & 30 Days & 60 Days & 90 Days\\
\tblmidrule 
1 &
  25.32 &
  24.64 &
  23.11 &
  22.21\\
2 &
  36.83 &
  35.23 &
  34.44 &
  33.43\\
3 &
  48.02 &
  47.32 &
  46.26 &
  45.32\\
4 &
  57.52 &
  56.53 &
  55.24 &
  54.13\\
5 &
  71.27 &
  70.14 &
  69.35 &
  68.36\\
6 &
  83.45 &
  82.32 &
  81.42 &
  80.24\\
7 &
  95.03 &
  94.47 &
  93.52 &
  92.41\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\bgroup
\fixFloatSize{images/eb8f6557-6e68-405b-8c6d-e65611a952c1-upicture1.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/eb8f6557-6e68-405b-8c6d-e65611a952c1-upicture1.png}{\includegraphics{images/eb8f6557-6e68-405b-8c6d-e65611a952c1-upicture1.png}}{}
\makeatother 
\caption{\boldmath {FTIR Spectrum of Capecitabine}}
\label{f-de69c283e587}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/dfe29eb8-8f4e-408a-8680-8b5d574f8388-upicture2.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/dfe29eb8-8f4e-408a-8680-8b5d574f8388-upicture2.png}{\includegraphics{images/dfe29eb8-8f4e-408a-8680-8b5d574f8388-upicture2.png}}{}
\makeatother 
\caption{\boldmath {FTIR Spectrum of Cholesterol}}
\label{f-dd7c9637e3cb}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/1c53dd1b-df3a-4a76-bd38-eef3bb397ff6-upicture3.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/1c53dd1b-df3a-4a76-bd38-eef3bb397ff6-upicture3.png}{\includegraphics{images/1c53dd1b-df3a-4a76-bd38-eef3bb397ff6-upicture3.png}}{}
\makeatother 
\caption{\boldmath {FTIR Spectrum of Span - 60}}
\label{f-b35a3e33b672}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/5c0f8a12-7362-48a3-a176-a01c1e2385a1-upicture4.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/5c0f8a12-7362-48a3-a176-a01c1e2385a1-upicture4.png}{\includegraphics{images/5c0f8a12-7362-48a3-a176-a01c1e2385a1-upicture4.png}}{}
\makeatother 
\caption{\boldmath {FTIR Spectrum of Capecitabine + Cholesterol}}
\label{f-9d506fc5322a}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/a753e64f-ce87-4f8d-bbff-20d7da6245f7-upicture5.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/a753e64f-ce87-4f8d-bbff-20d7da6245f7-upicture5.png}{\includegraphics{images/a753e64f-ce87-4f8d-bbff-20d7da6245f7-upicture5.png}}{}
\makeatother 
\caption{\boldmath {FTIR Spectrum of Capecitabine + Span {\textendash} 60}}
\label{f-5711b22f1943}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/9008aa70-c623-4a72-8010-7e9b53ab2901-upicture6.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/9008aa70-c623-4a72-8010-7e9b53ab2901-upicture6.png}{\includegraphics{images/9008aa70-c623-4a72-8010-7e9b53ab2901-upicture6.png}}{}
\makeatother 
\caption{\boldmath {FTIR Spectrum of Capecitabine + Cholesterol + Span {\textendash} 60}}
\label{f-1341f5c428ae}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/777f6512-2e5f-4ec8-860f-c5a08062def4-upicture7.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/777f6512-2e5f-4ec8-860f-c5a08062def4-upicture7.png}{\includegraphics{images/777f6512-2e5f-4ec8-860f-c5a08062def4-upicture7.png}}{}
\makeatother 
\caption{\boldmath {SEM Image of Formulation F1}}
\label{f-b2e799407c69}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/fee93b39-8964-42a5-afaa-a333ba710c83-upicture8.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/fee93b39-8964-42a5-afaa-a333ba710c83-upicture8.png}{\includegraphics{images/fee93b39-8964-42a5-afaa-a333ba710c83-upicture8.png}}{}
\makeatother 
\caption{\boldmath {Zero Order Kinetic for F1 Formulation}}
\label{f-251ff857cc71}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/39d230b7-142c-41ff-8695-b2b3857688a6-upicture9.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/39d230b7-142c-41ff-8695-b2b3857688a6-upicture9.png}{\includegraphics{images/39d230b7-142c-41ff-8695-b2b3857688a6-upicture9.png}}{}
\makeatother 
\caption{\boldmath {First Order Kinetic for F1 Formulation}}
\label{f-8495265149b7}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/90d7ce5d-0113-409d-9485-9f5caa20102a-upicture10.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/90d7ce5d-0113-409d-9485-9f5caa20102a-upicture10.png}{\includegraphics{images/90d7ce5d-0113-409d-9485-9f5caa20102a-upicture10.png}}{}
\makeatother 
\caption{\boldmath {Higuchi Kinetic Model for F1 Formulation}}
\label{f-f1a105eab311}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/cbb17cd9-1081-47f4-9b2f-c0720c19af91-upicture11.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/cbb17cd9-1081-47f4-9b2f-c0720c19af91-upicture11.png}{\includegraphics{images/cbb17cd9-1081-47f4-9b2f-c0720c19af91-upicture11.png}}{}
\makeatother 
\caption{\boldmath {Korsmeyer-Peppas Model Modulefor F1 Formulation}}
\label{f-193c702baae1}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/2ab2371a-69eb-445f-97d8-3809a93ebe61-upicture12.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/2ab2371a-69eb-445f-97d8-3809a93ebe61-upicture12.png}{\includegraphics{images/2ab2371a-69eb-445f-97d8-3809a93ebe61-upicture12.png}}{}
\makeatother 
\caption{\boldmath {\textit{In vitro} Studies of Formulation F1 Stored at Refrigeration Condition}}
\label{f-7838c550b24c}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/04e24233-ce18-4989-8e81-1ebb19b2de64-upicture13.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/04e24233-ce18-4989-8e81-1ebb19b2de64-upicture13.png}{\includegraphics{images/04e24233-ce18-4989-8e81-1ebb19b2de64-upicture13.png}}{}
\makeatother 
\caption{\boldmath {\textit{In vitro} Studies of Formulation F1 Stored at Room Temperature}}
\label{f-f6b7867a9553}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/e7bbf8a7-db09-409a-80b6-47536b63e0a2-upicture14.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/e7bbf8a7-db09-409a-80b6-47536b63e0a2-upicture14.png}{\includegraphics{images/e7bbf8a7-db09-409a-80b6-47536b63e0a2-upicture14.png}}{}
\makeatother 
\caption{\boldmath {\textit{In vitro} Studies of Formulation F6 Stored at Accelerated Condition}}
\label{f-b2c2a8476555}
\end{figure}
\egroup
\textbf{Characterization of Proniosome}

\textbf{Measurement of Angle of Repose}

An angle of repose of dry Proniosomes powder has been evaluated through funnel method. A proniosomes powder has been started pouring it into a funnel which has been fixed at such a posture such that the access point orifice of a funnel is 10 cm over an stage dark surface \unskip~\cite{1436535:25134201}. A powder started flowing bottom out from funnel to structure a cone upon that surface, as well as the angle of repose then was calculated besides measuring the peak of a concave and also the radius from its bottom. Angle of repose has been calculated by using the following formula:\textbf{\space }

\ensuremath{\theta } = tan\ensuremath{^{-1}} (h/r)

Where,

h = height of pile

r = radius

\textbf{Drug Content}

The weighed quantity of capecitabine proniosomes similar to 100 mg of drug of it was disintegrated through 100ml of water. All these solution has been filtrated and thus further solubilised to make a conc. of 10 \ensuremath{\mu}g/ml solution. Absorption of solution providers has been evaluated at 303 nm to use double beam UV- visible spectrometer against distilled water as blank but also measured for such proportion of drug present in a sample \unskip~\cite{1436535:25134202}.

\textbf{Entrapment efficiency}

The entrapment efficiency \unskip~\cite{1436535:25134203}  could be estimated through using following formulae.

$\style{font-family:'Times New Roman'}{\style{font-size:8px}{\%\;Entrapment\;efficiency=\frac{Actual\;drug\;loaded}{Theoritical\;drug\;loaded}\times100}} $

\textbf{Scanning Electron Microscopy}

Size of the particles proniosomes is indeed a component of primary importance. A surface morphology as well as size distribution like proniosomes has been analyzed besides SEM. The double sided tape that it was attached through aluminium stubs and indeed the proniosomal powder has been distributed through it \unskip~\cite{1436535:25134214}. An aluminium stub has been positioned inside a vacuum chamber of scanning electron microscopy SEM (XL 30 ESEM with EDAX, Philips, Netherlands). 

\textit{\textbf{In vitro}} \textbf{ Release Studies}

A discharge of Capecitabine from proniosomal preparations have been ascertained utilising membrane diffusion technical. A proniosomal composition similar to 10 mg of LP has been transformed to proniosomal suspension and brought inside a glass container possessing a radius 2.5 cm with just an over strength like 8 cm that it was previously disclosed with soaked osmosis cellulose membrane, where it behaves as donation storage area, a glass container has been positioned inside beakers 100 ml of saline buffer ph 7.4, that either functions just like receptor storage area. A whole arrangement has been corrected in a rather way that now the lower part of a beaker containing suspension just was impacted (1-2mm deep) a surface of dispersion moderate. A heat of receptor moderate preserved there as 37\ensuremath{\pm}1\ensuremath{^\circ}C and also the moderate has been agitated at 100 rpm speed utilising magnetic stirring \unskip~\cite{1436535:25134215}. 

Aliquots like 5ml specimen have been discharged periodically and then after each drawdown same amount of moderate has been supplanted. Collected specimens have been examined at 303 nm with double bean UV-Vis spectrophotometrically utilizing saline buffer 7.4 even though featureless.

\textbf{Release Kinetics}

To analyze potential mechanisms of release of drug from the prepared Proniosomes, the discharge data obtained were analyzed mathematical model according to the following systems \unskip~\cite{1436535:25134204}.

Zero-order- Q=Ko t

First-order- Log Q= Log Qo-K1 t/2.303

Higuchi- Qt = KH t \ensuremath{\frac12}  

Korsmeyer - Peppas- Qt/Q\ensuremath{\alpha } = K tn

Where,

Q is the amount of drug release at a time (t) and K is the rate constant.

\textbf{Stability Studies}

A stability studies for finest proniosomes preparation were done according to ICH guidelines for three months. Constructed proniosomes have been divided to three groups. Each group has been managed to keep at refrigeration (4\ensuremath{^\circ}\ensuremath{\pm}2\text{\textordmasculine}C). A second category has been incubated at room temperature (25\ensuremath{^\circ}\ensuremath{\pm}2\ensuremath{^\circ}C). A third category has been managed to keep at 40\ensuremath{\pm}2\text{\textordmasculine}C and 60\ensuremath{\pm}5\% RH. Each month 1 ml of preparation has been forced to withdraw as well as evaluated for drug content \unskip~\cite{1436535:25134209}. A release of drug research for preparation F1 had also been conducted before and after three months there as varying temperatures.
    
\section{RESULTS AND DISCUSSION}
\textbf{Preformulation Studies}

\textbf{Solubility Study}

Solubilisation like Capecitabine through 10 mg/10 ml of solutes has been done and so it confirms that this is openly water{\textendash}soluble, ethanol proniosomes Methanol, but practically insoluble in acetone.

\textbf{Identification of Capecitabine}

The IR Spectrum of Capecitabine was found to be similar to the standard spectrum of Capecitabine. The spectrum of Capecitabine shows the following functional groups at their frequencies.

FTIR spectrum of capecitabine, cholesterol, span 60 and proniosomes formulations. FTIR spectrum of capecitabine showed characteristics absorption bands in the IR region, 3735.48cm-1 (O-H(stretch, free)); 3171.36cm-1 (N-H stretch); 1338.58cm-1 (CH\ensuremath{_{3}} bend); 885.16cm-1 (C-H bend). Span 60 in pure form shows the presence of hydroxyl absorption at 3416 cm-1, strong aromatic CH=CH stretching at 2920cm-1 and a strong C=O of carboxylic ester is notice at 1739cm-1. Cholesterol shows the presence of hydroxyl absorption at 3423cm-1, strong aromatic CH=CH stretching at 2868.62 cm-1 and a strong C=O of carboxylic ester at 1710.43cm-1. Similarly cholesterol as expected shows the presence of hydroxyl absorption at 3392.20 cm{\textendash}1. The FTIR spectrum of proniosomes formulation shows C=O stretch at 1739.20 cm-1; C-H bend at 835.17 cm-1; CH\ensuremath{_{3}} bend at 1377.45 cm-1; O-H (stretch, free) at 3408.45 cm-1 [Figure~\ref{f-de69c283e587}, Figure~\ref{f-dd7c9637e3cb}, Figure~\ref{f-b35a3e33b672}, Figure~\ref{f-9d506fc5322a}, Figure~\ref{f-5711b22f1943} \& Figure~\ref{f-1341f5c428ae}].

\textbf{Angle of Repose}

The angle of repose of dry proniosomes powder was measured by funnel method [Table~\ref{tw-d6699bdc1430}]. The angle of repose of dry proniosomes was between 25\ensuremath{^\circ}12'\ensuremath{\pm}0.26 to 27\ensuremath{^\circ}95'\ensuremath{\pm}0.22. 

\textbf{Entrapment Efficiency}

The entrapment efficiency of proniosomes prepared at varied concentration of surfactants (Span 60) the drug entrapped was range between of 43.32\ensuremath{\pm}0.71 to 65.43\ensuremath{\pm}0.27. The entrapment efficiency increases with increasing surfactant concentration [Table~\ref{tw-d6699bdc1430}].

\textbf{Drug Content}

Drug content was determined for all proniosomal formulations [Table~\ref{tw-d6699bdc1430}]. Average of three determinations was considered. The drug content was found to be in the range of 81.14\ensuremath{\pm}0.66 \% to 97.06\ensuremath{\pm}0.23 \%.

\textbf{Scanning Electron Microscopy}

SEM photographs of pro niosomes preparations F1 showed that such pro niosomes have been spherical shapes [Figure~\ref{f-b2e799407c69}]. A release of drug through the vesicles depends forward concentration levels like span 60.

\textit{\textbf{In vitro}} \textbf{ Drug Release Studies}

The various capecitabine proniosomal formulations prepared were subjected to \textit{in vitro } drug release studies and dissolution kinetic profiles [Figure~\ref{f-251ff857cc71}, Figure~\ref{f-8495265149b7}, Figure~\ref{f-f1a105eab311} \& Figure~\ref{f-193c702baae1}]. The percentage drug release from proniosomal formulations F1 are 95.03, at 7 hrs, F2 are 96.02 at 7 hrs, F3 are 93.75 at 8 hrs, F4 are 93.64 at 8 hrs, F5 are 90.58 at 9 hrs, F6 are 92.65 at 10 hrs, F7 are 92.47 at 9 hrs and F8 are 95.53 at 8 hours. In all formulation, 17 \% to 30\% of drug is released in the first hours, due to initial bursting of improper proniosomes in the formulations [Table~\ref{tw-86c5cf4260f0}, Table~\ref{tw-c987c4cac443}, Table~\ref{tw-d3b1bf7772a6}, Table~\ref{tw-471b0ba76568}, Table~\ref{tw-dce34ec522d1}, Table~\ref{tw-040382b080d2}, Table~\ref{tw-f1d5c0449219} and Table~\ref{tw-ec56430e2904}]. However, after 3 hours, the release was steady because the stable proniosomes retain the drug and the release was extended up to 12 hours with sustained action. The proniosomes formulations F1 shows better controlled released compared to other formulations.

The kinetic models selected were Zero order, First order, Higuchi Matrix, and Korsemayer Peppas. The regression coefficient values for all these models were shown in tables 70. In all the cases the best fit model was found to be peppas with `n' value between 0.768 to 0.895. The `n' value of formulation F1 was 0.899and suggesting that the drug was released by Zero order kinetics [Table~\ref{tw-aea4b0bdb2e8}].

\textbf{Stability Studies}

Stability studies are done for best formulation (F1) as per ICH guideline in 3 different storage conditions for 3 months [Table~\ref{tw-9017c416b2a5}]. The formulation is analyzed for the drug content, in vitro drug release studies and sterility studies [Table~\ref{tw-19f84d86df95}, Figure~\ref{f-7838c550b24c}]. After 3 months studies it revolves that there is no change in sterility of formulation, but slightly change in \% of drug content and \textit{In vitro} drug release studies but it was in accepted limit [Table~\ref{tw-59e7c3cb694d}, Table~\ref{tw-45189a340f75}, Figure~\ref{f-f6b7867a9553}, Figure~\ref{f-b2c2a8476555}].
    
\section{CONCLUSION}
Pro niosomes preparations could be comfortably able to prepare through thin film filtration technique utilising non ionic emulsifiers (span 60), but also saturated fat there as various concentration all of the pro niosomes powder particles have been discovered to just be quick passing with repose angle inside the range like 25\ensuremath{^\circ}12\textcent \ensuremath{\pm}0.26to 27\ensuremath{^\circ}95\textcent \ensuremath{\pm}0.22 through funnel technique entrapment efficiency of pro niosomes preparations tends to increase as for enhances an accumulation like span 60. Drug content among all pro niosomes preparations were all in range of 81.14\ensuremath{\pm}0.66 \% to 97.06\ensuremath{\pm}0.23 \% with low standard variance and also the outcomes have been repeatable. The typical vesicular shape of pro niosomes of all of the portions has been evaluated inside variety of 0.271\ensuremath{\pm}0.024 \ensuremath{\mu}m to 0.312\ensuremath{\pm}0.025\ensuremath{\mu}m. SEM photographs of pro niosomes preparations F1 showed that such pro niosomes have been spherical shapes. A release of drug through the vesicles depends forward concentration levels like span 60. It's indeed primarily due to a impact of phase transformation temp. Throughout all composition the simplest fit model has been noticed to also be peppas with `n' value among 0.768 to 0.895. A preparation F1 shows the better controlled released action then all the other preparation with `n' value 0.899 but also recommending that such drug has been set to release besides zero order kinetics.
    
\section{ACKNOWLEDGEMENT}
I would like to thank Principal sir (Dr. Kamal Hassan), St. Mary's Group of Institutions, Deshmukhi (Village), Pochampally (Mandal), Yadadri Bhuvanagiri(Dist), Telangana-508284, India.

\textbf{Conflict of Interest}

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

\textbf{Funding Support}

The authors declare that there is no financial support for the current study.
    
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