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\def\citeauthor{~Venkata~Durga~Seshu~Priya~P,
              ~Ramesh~Babu~K,
              ~Raja~Lakshmi~S,
              ~Ramya~B,
              ~Navin~S,
              ~Harshitha~V,
              ~Chandu~Bhargav~B,
              ~Rupa~B}
\def\citetitle{Formulation and Evaluation of Ketoprofen Emulgels by Model Independent Approach}
\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{Venkata Durga Seshu Priya P et al.}
\firstPage{145}
\articleType{Original Article}
\receivedDate{03 Jun 2021}
\acceptedDate{07 Jul 2021}
\revisedDate{05 Jul 2021}
\journalVolume{1}
\journalIssue{3}
\journalDoi{fjphs.v1i3.224}
\copyrightYear{2021}
\eISSN{2583-116X}
\journalDoi{fjphs.v1i3.224}
\def\authorCount{8}
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\def\journalTitle{Future Journal of Pharmaceuticals and Health Sciences}

\title{Formulation and Evaluation of Ketoprofen Emulgels by Model Independent Approach}
\author{Venkata~Durga~Seshu~Priya~P\textsuperscript{*}\textsuperscript{1},  
            Ramesh~Babu~K\textsuperscript{2},  
            Raja~Lakshmi~S\textsuperscript{3},  
            Ramya~B\textsuperscript{3},  
            Navin~S\textsuperscript{3},  
            Harshitha~V\textsuperscript{3},  
            Chandu~Bhargav~B\textsuperscript{3}, 
            Rupa~B\textsuperscript{3}~\\[5pt]{\textsuperscript{1}Department of Pharmaceutics, Jagan's Institute of Pharmaceutical Sciences, Jangalakandriga (V), Muthukur (M), Nellore-524346, SPSR Nellore (Dist) Andhra Pradesh, India}~\\{\textsuperscript{2}Department of Pharmaceutics, Swathi College of Pharmacy, NH5, Next to Nellore Toll Plaza, Venkatachalam, Nellore-524 320, SPSR Nellore (Dist), Andhra Pradesh, India}~\\{\textsuperscript{3}Jagan's Institute of Pharmaceutical Sciences, Jangalakandriga (V), Muthukur (M), Nellore-524346, SPSR Nellore (Dist), Andhra Pradesh, India}}

\begin{abstract}
In the current study, ketoprofen emulgels were prepared using Sodium CMC, Sodium alginate and Hibiscus as gelling agents in order to overcome gastric side effects and to achieve pharmacological response. Pre formulation parameters were performed to know the compatibility of pure drug ketoprofen with polymers CMC, Na alginate, hibiscus prior to the preparation of Emulgel. It indicates that no change was observed in the peak values of the drug in the physical mixture thus providing that both the drug and polymer were said to be compatible with each other. Emulgel of ketoprofen 2.5\% w/w was prepared in 3 steps i.e., Preparation of gel, emulsion phases separately and incorporate both phases in homogenizer for a period of 45 min and stabilized it for 2 hrs. The prepared emulgels were evaluated for physical characteristics, drug content, pH, spreadability and \textit{in-vitro } permeation studies. The physical appearance of all the formulations was creamy white, consistent, homogenous and stable. The pH of the prepared emulgels was found well within the range of 6-7. Release rate kinetics of the drug was studied with \textit{in vitro } drug permeation data for all the formulations F1 to F9 and results were stated the best fit model for selected formulation F6 were found to be Zero order model with non-fickian diffusion. The formulations were compared with the reference product. The \textit{in-vitro} dissolution of F6 was nearest to the reference product F10 (f\ensuremath{_{2}} = 85.17). 
\end{abstract}\def\keywordstitle{Keywords}

\begin{keywords}Ketoprofen,\newline Emulgels,\newline Homogenizer,\newline Model Independent Approach
\end{keywords}
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\makeatletter{\raggedright{\Large$^\ast$}Corresponding Author\par Name:\ Venkata~Durga~Seshu~Priya~P~\\ Phone:\ 9959523469~\\  Email:\ seshupriya09@gmail.com
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\section{Introduction}
Ketoprofen belongs to NSAIDs that is widely used as analgesic for rheumatic disease and also for joint disorders such as any losing spondylitis, osteoarthritis. It is insoluble in water and is freely soluble in acetone, ethanol and ethylene chloride. In order to eliminate the adverse effects of NSAIDs, the development of transdermal formulations was employed. Several topical dosage forms may be utilized to deliver NSAIDs. One of the best topical dosage forms is emulgel \unskip~\cite{1143275:22575072}. The absorption of a drug into the blood requires dissolution and release of the drug thus partitioning and diffusion and finally into the aqueous epidermis is possible. By adding a chemical permeation enhancer in the formulation it will improve or increase drug partitioning into the subcutaneous. Examples are alcohols, polyalcohol's, amides, pyrrolidones, fatty acids and surfactants. A jellified emulsion (Emulgel) is prepared by mixing an emulsion i.e. water-in-oil (W/O) type or O/W along with a gelling agent. The main advantage of the emulgel is that the lipophilic drugs can be easily formulated into gels. Advantages for emulgels are increased stability, superior loading efficiency, high production with less cost \unskip~\cite{1143275:22575073}. The main constituents in emulgel preparation include water, oils mainly mineral oils as paraffin oil either used alone or mixed with Vaseline or wax, emulsifiers, gelling Agent, and permeation enhancers. The aim of the current work is to formulate ketoprofen emulgel so that GIT side effects can be eliminated and to incorporate this insoluble drug in a hydrophilic gel matrix, and to enhance the percutaneous absorption \unskip~\cite{1143275:22575075}. 
    
\section{MATERIALS AND METHODS}
Ketoprofen was received as free sample 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 are of analytical grade.

\textbf{Preformulation Studies }

\textbf{Melting point determination}

Small quantity of drug was taken in a capillary tube and it is closed at one end and the temperature at which the drug melts was recorded. The studies were performed thrice and average values were recorded \unskip~\cite{1143275:22575062}.

\textbf{Derived Properties of Powder}

Powder Flow Property of the dried powder as follows \unskip~\cite{1143275:22575059}

Angle of repose: \ensuremath{\theta } = tan\ensuremath{^{-1}} (h/r) 

Bulk density = Weight of powder/ Bulk volume

Tapped density = Weight of powder/ Tapped volume

Carr's Index (I) = (Tap ed Density -Bulk Density)/(Tapped Density)x100 

Hausner's ratio = Tapped density/ Bulk density

\textbf{Drug - Excipient Compatibility Study}

KBr was allowed to mix with drug and excipients in 1:1 ratio. FT-IR spectrum of Ketoprofen was compared with Drug and also with excipients for compatibility \unskip~\cite{1143275:22575061}.

\textbf{Methodology}

\textbf{Formulation design for Ketoprofen emulgel preparation }

The formulation code was designed based on the concentration of gelling agents: Sodium carboxyl methyl cellulose, sodium alginate, hibiscus dry powder \unskip~\cite{1143275:22575074,1143275:22575058}.

\textbf{Gel preparation}

Gel was prepared by dissolving gelling agent(s) (Na CMC, Na Alginate, hibiscus) in hot water until it attains gel consistency.

\textbf{Emulsion preparation}

The oily phase of the emulsions have been prepared by adding span 20 in light liquid paraffin and was heated up to 70\ensuremath{^{O}}C{\textendash} 80\ensuremath{^{O}}C. Aqueous phase was prepared by dissolving Ketoprofen in propylene glycol. Then Tween was added to it and heated up to 70\ensuremath{^{O}}C - 80\ensuremath{^{O}}C. Methylparaben was added to the prepared aqueous phase. Then aq. phase was allowed to mix slowly with oil phase and final volume was made with purified water.

\textbf{Emulgel preparation}

The prepared emulsion was allowed to mix with the gel and required weight was maintained with water and kept for homogenization for a period of 45 min in order to obtain Ketoprofen emulgel [Table~\ref{tw-c6b618b3b4e2}].


\begin{table*}[!htbp]
\caption{\boldmath {Formulation of ketoprofen Emulgel preparation} }
\label{tw-c6b618b3b4e2}
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\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack Ingredients (\%w/w) & \cAlignHack F1 & \cAlignHack F2 & \cAlignHack F3 & \cAlignHack F4 & \cAlignHack F5 & \cAlignHack F6 & \cAlignHack F7 & \cAlignHack F8 & \cAlignHack F9\\
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  \cAlignHack -\\
\cAlignHack Hibiscus &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack 10.0 &
  \cAlignHack 15.0 &
  \cAlignHack 20.0\\
\cAlignHack Light liquid paraffin &
  \cAlignHack 8.3 &
  \cAlignHack 8.3 &
  \cAlignHack 8.3 &
  \cAlignHack 8.3 &
  \cAlignHack 8.3 &
  \cAlignHack 8.3 &
  \cAlignHack 8.3 &
  \cAlignHack 8.3 &
  \cAlignHack 8.3\\
\cAlignHack Tween 20 &
  \cAlignHack 5.0 &
  \cAlignHack 5.0 &
  \cAlignHack 5.0 &
  \cAlignHack 5.0 &
  \cAlignHack 5.0 &
  \cAlignHack 5.0 &
  \cAlignHack 5.0 &
  \cAlignHack 5.0 &
  \cAlignHack 5.0\\
\cAlignHack Span 80 &
  \cAlignHack 5.0 &
  \cAlignHack 5.0 &
  \cAlignHack 5.0 &
  \cAlignHack 5.0 &
  \cAlignHack 5.0 &
  \cAlignHack 5.0 &
  \cAlignHack 5.0 &
  \cAlignHack 5.0 &
  \cAlignHack 5.0\\
\cAlignHack Propylene glycol &
  \cAlignHack 13.3 &
  \cAlignHack 13.3 &
  \cAlignHack 13.3 &
  \cAlignHack 13.3 &
  \cAlignHack 13.3 &
  \cAlignHack 13.3 &
  \cAlignHack 13.3 &
  \cAlignHack 13.3 &
  \cAlignHack 13.3\\
\cAlignHack Methylparaben &
  \cAlignHack 0.03 &
  \cAlignHack 0.03 &
  \cAlignHack 0.03 &
  \cAlignHack 0.03 &
  \cAlignHack 0.03 &
  \cAlignHack 0.03 &
  \cAlignHack 0.03 &
  \cAlignHack 0.03 &
  \cAlignHack 0.03\\
\cAlignHack Purified water  &
  \cAlignHack q.s &
  \cAlignHack q.s &
  \cAlignHack q.s &
  \cAlignHack q.s &
  \cAlignHack q.s &
  \cAlignHack q.s &
  \cAlignHack q.s &
  \cAlignHack q.s &
  \cAlignHack q.s\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}
\textbf{Morphological Characters of Emulgel}

\textbf{Scanning Electron Microscopy }

The surface morphology of the Emulgel was obtained by using SEM \unskip~\cite{1143275:22575071}.

\textbf{Evaluation of Ketoprofen Emulgels}

\textbf{Physical appearance}

The prepared formulations have been inspected for properties like color, homogeneity, consistency and phase separation \unskip~\cite{1143275:22575064}.

\textbf{pH }

The emulgel pH must be 5-7 to adjust to the skin conditions. pH of prepared emulgel must not be acidic or basic as it may cause irritation upon the skin \unskip~\cite{1143275:22575065}. The values were recorded in triplicate.

\textbf{Rheological studies}

The viscosity of gel during preparation and stability should be given an almost importance \unskip~\cite{1143275:22575060}. Using Falling sphere viscometer the viscosity of different formulations were measured at 25\ensuremath{^{0}}C. 

\textbf{Spreadability test}

It expresses the exposed area on which the prepared gel spreads on applying to skin. The drug efficiency depends on the spreadability values. Spreadability was given by:
\begin{eqnarray*}\style{font-family:'Times New Roman'}{\style{font-size:8px}{S\;=\;M\;\times\;L/T}} \end{eqnarray*}
Where,

M = weight to be taken, L = length of slide, T = time

The 0.5g of the sample was placed on lower plate and upper plate was placed on the top of the sample. Force was generated by adding increasing weight slowly at 1 minute interval into the pan connected to the upper plate, each sample was tested three times at constant temperature and exerted weight and the mean values of the spread surface area on lower plate were calculated \unskip~\cite{1143275:22575066}. 

\textbf{Drug content }

Ketoprofen content in emulgel was measured by taking the absorbance of the sample was measured at 261nm by using UV-Visible spectrophotometer 1700. The test was conducted in triplicate and the average \% drug content was determined \unskip~\cite{1143275:22575070}.

\textit{\textbf{In-vitro}} \textbf{ drug permeation study}

The test was performed by using Franz diffusion cell. Egg membrane was isolated and used for the study. The egg membrane was clamped between donor and receptor compartment. The receptor compartment was filled with 100ml of 7.4pH phosphate buffer maintained at room temperature and stirred by using magnetic stirrer \unskip~\cite{1143275:22575075}. Pre weighed (1.0g) emulgel was taken on the egg membrane. The sample (5ml) was collected for an interval of every one hour and analyzed for drug content by UV-Visible Spectrophotometer 1700 at 261nm after appropriate dilutions. 

\textbf{Kinetic Treatment}

The data obtained from \textit{in vitro }dissolution studies acquire kinetic track record analysis \unskip~\cite{1143275:22575069}.

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 / M\ensuremath{_{\infty}} = K \ensuremath{\cdot} t \ensuremath{^{n}}}

\textbf{Comparison of diffusion profiles}

\textbf{Model independent approach }

According to US FDA guidance for dissolution data equivalence, model independent approach is acceptable. This involves the use of similarity (f\ensuremath{_{2}}) and dissimilar factor (f\ensuremath{_{1}}) which provides simple means to compare the dissolution data \unskip~\cite{1143275:22575068,1143275:22575063}.

\textbf{Similarity factor (f\ensuremath{_{2}})}

The similarity factor f\ensuremath{_{2}} was defined as a logarithmic reciprocal square root transformation of the sum of squared error and is a measurement of the similarity in the percent (\%) dissolution between the two curves. It was calculated data according to the following equation:

$\style{font-family:'Times New Roman'}{\style{font-size:8px}{f_2\;=\;50\;\times\;\log\;\{\lbrack1+\;(1/n)\;\sum t=1\;n\;(Rt\;-\;Tt)2\rbrack^{-0.5}\;\times100\}}} $

Where, 

n = No. of full time points

Rt = Reference profile at the time point t

Tt = Test profile at the same point

The method is more adequate to compare the dissolution profiles when more than three or four dissolution time points are available and can be applied if average difference between Rt and Tt is {\textgreater}100.

\textbf{Dissimilarity factor (f\ensuremath{_{1}})}

It is also called as Difference factor. It describes the relative percentage error between two dissolution profiles. The percent error is zero when the test and reference profiles are identical and increases the proportionality with the dissimilarity between the two profiles.

$\style{font-family:'Times New Roman'}{\style{font-size:8px}{f_1\;=\;\{\lbrack\sum t=1\;n\;(Rt-Tt)\rbrack\;/\;\sum t=1\;n\;Rt\rbrack\}\;\times100}} $
    
\section{RESULTS \& DISCUSSION}
\textbf{Characterization of API }

The melting point of the ketoprofen was determined by capillary tube method and was found to be 98\ensuremath{^{o}}C \ensuremath{\pm} 0.56\ensuremath{^{o}}C. From the below results, it was concluded that the API, Ketoprofen exhibited Poor flow property [Table~\ref{tw-3caea17a16af}].


\begin{table*}[!htbp]
\caption{\boldmath {API Characteristics} }
\label{tw-3caea17a16af}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.13300000000000002\linewidth-2\tabcolsep}p{\dimexpr.29669999999999998\linewidth-2\tabcolsep}p{\dimexpr.57029999999999994\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}S No & Characteristics & Results\\
\tblmidrule 
1. &
  Description &
  White or almost white crystalline, odorless, bitter powder\\
2. &
  Melting Point &
  98\ensuremath{^{o}}C \ensuremath{\pm} 0.56\ensuremath{^{o}}C\\
3. &
  Bulk Density &
  0.434 \ensuremath{\pm} 0.47 gm/mL\\
4. &
  Tapped Density &
  0.625 \ensuremath{\pm} 0.11gm/mL\\
5. &
  Carr's Index &
  30.56 \ensuremath{\pm} 0.29\%\\
6. &
  Hausner's Ratio &
  1.44 \ensuremath{\pm} 0.21\\
7. &
  Angle of Repose &
  39.63\ensuremath{\pm} 0.32\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Wave numbers obtained for drug along with excipients} }
\label{tw-db694ef62169}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.1821\linewidth-2\tabcolsep}p{\dimexpr.1379\linewidth-2\tabcolsep}p{\dimexpr.13649999999999999\linewidth-2\tabcolsep}p{\dimexpr.1835\linewidth-2\tabcolsep}p{\dimexpr.1807\linewidth-2\tabcolsep}p{\dimexpr.1793\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack Functional Group & \cAlignHack Literature \mbox{}\protect\newline Value & \cAlignHack Pure Drug & \cAlignHack Drug \& Sodium CMC & \cAlignHack Drug \& Sodium alginate & \cAlignHack Drug \& Hibiscus\\
\tblmidrule 
\cAlignHack N-H Stretching &
  \cAlignHack 3000-3700 &
  \cAlignHack 3425.69 &
  \cAlignHack 3211.29 &
  \cAlignHack 3576.72 &
  \cAlignHack 3578.88\\
\cAlignHack C-H Stretching &
  \cAlignHack 1700-3300 &
  \cAlignHack 1790.49 &
  \cAlignHack 1787.96 &
  \cAlignHack 1790.69 &
  \cAlignHack 1730.21\\
\cAlignHack C=N Stretching &
  \cAlignHack 1400-1700 &
  \cAlignHack 1582.35 &
  \cAlignHack 1584.81 &
  \cAlignHack 1583.02 &
  \cAlignHack 1435\\
\cAlignHack O-H Stretching &
  \cAlignHack 1100-2400 &
  \cAlignHack 1536.94 &
  \cAlignHack 1514.68 &
  \cAlignHack 1256.32 &
  \cAlignHack 1147.69\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Physical Characteristics of Ketoprofen Emulgels} }
\label{tw-772af8f38f3a}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.22990000000000002\linewidth-2\tabcolsep}p{\dimexpr.2149\linewidth-2\tabcolsep}p{\dimexpr.2015\linewidth-2\tabcolsep}p{\dimexpr.16019999999999996\linewidth-2\tabcolsep}p{\dimexpr.19349999999999998\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack Formulation code & \cAlignHack Color & \cAlignHack Homogeneity & \cAlignHack Consistency & \cAlignHack Phase Separation\\
\tblmidrule 
\cAlignHack F1 &
  \cAlignHack Creamy white &
  \cAlignHack Homogenous &
  \cAlignHack Smooth &
  \cAlignHack No\\
\cAlignHack F2 &
  \cAlignHack Creamy white &
  \cAlignHack Homogenous &
  \cAlignHack Smooth &
  \cAlignHack No\\
\cAlignHack F3 &
  \cAlignHack Creamy white &
  \cAlignHack Homogenous &
  \cAlignHack Smooth &
  \cAlignHack No\\
\cAlignHack F4 &
  \cAlignHack Creamy white &
  \cAlignHack Homogenous &
  \cAlignHack Smooth &
  \cAlignHack No\\
\cAlignHack F5 &
  \cAlignHack Creamy white &
  \cAlignHack Homogenous &
  \cAlignHack Smooth &
  \cAlignHack No\\
\cAlignHack F6 &
  \cAlignHack Creamy white &
  \cAlignHack Homogenous &
  \cAlignHack Smooth &
  \cAlignHack No\\
\cAlignHack F7 &
  \cAlignHack Off Creamy white &
  \cAlignHack Homogenous &
  \cAlignHack Smooth &
  \cAlignHack No\\
\cAlignHack F8 &
  \cAlignHack Off Creamy white &
  \cAlignHack Homogenous &
  \cAlignHack Smooth &
  \cAlignHack No\\
\cAlignHack F9 &
  \cAlignHack Off Creamy white &
  \cAlignHack Homogenous &
  \cAlignHack Smooth &
  \cAlignHack No\\
\cAlignHack F10 (Marketed gel) &
  \cAlignHack Creamy white &
  \cAlignHack Homogenous &
  \cAlignHack Smooth &
  \cAlignHack No\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Evaluation Parameters of Ketoprofen Emulgels} }
\label{tw-b6113f143f65}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.24980000000000004\linewidth-2\tabcolsep}p{\dimexpr.18499999999999996\linewidth-2\tabcolsep}p{\dimexpr.1652\linewidth-2\tabcolsep}p{\dimexpr.20\linewidth-2\tabcolsep}p{\dimexpr.20\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack Formulation code & \cAlignHack Spreadability (cm/sec)* & \cAlignHack Viscosity (cp) & \cAlignHack Drug Content (\%) & \cAlignHack pH\\
\tblmidrule 
\cAlignHack F1 &
  \cAlignHack 12.144\ensuremath{\pm}0.21 &
  \cAlignHack 3695\ensuremath{\pm}2.34  &
  \cAlignHack 98.41\ensuremath{\pm}0.55 &
  \cAlignHack 6.6\ensuremath{\pm}0.26\\
\cAlignHack F2 &
  \cAlignHack 38.204\ensuremath{\pm}0.52 &
  \cAlignHack 4115\ensuremath{\pm}3.21  &
  \cAlignHack 99.15\ensuremath{\pm}0.54 &
  \cAlignHack 6.7\ensuremath{\pm}0.60\\
\cAlignHack F3 &
  \cAlignHack 29.282\ensuremath{\pm}0.18 &
  \cAlignHack 4130\ensuremath{\pm}4.87  &
  \cAlignHack 98.02\ensuremath{\pm}0.65 &
  \cAlignHack 6.7\ensuremath{\pm}0.15\\
\cAlignHack F4 &
  \cAlignHack 41.902\ensuremath{\pm}0.14 &
  \cAlignHack 4120\ensuremath{\pm}3.46  &
  \cAlignHack 98.83\ensuremath{\pm}0.18 &
  \cAlignHack 6.4\ensuremath{\pm}0.42\\
\cAlignHack F5 &
  \cAlignHack 43.162\ensuremath{\pm}0.26 &
  \cAlignHack 4150\ensuremath{\pm}2.57  &
  \cAlignHack 97.54\ensuremath{\pm}0.46 &
  \cAlignHack 6.5\ensuremath{\pm}0.15\\
\cAlignHack F6 &
  \cAlignHack 43.432\ensuremath{\pm}0.50 &
  \cAlignHack 4560\ensuremath{\pm}3.46  &
  \cAlignHack 99.47\ensuremath{\pm}0.48 &
  \cAlignHack 6.5\ensuremath{\pm}0.25\\
\cAlignHack F7 &
  \cAlignHack 29.540\ensuremath{\pm}0.48 &
  \cAlignHack 4475\ensuremath{\pm}6.13  &
  \cAlignHack 98.74\ensuremath{\pm}0.75 &
  \cAlignHack 6.3\ensuremath{\pm}0.12\\
\cAlignHack F8 &
  \cAlignHack 28.663\ensuremath{\pm}0.42 &
  \cAlignHack 4286\ensuremath{\pm}4.32  &
  \cAlignHack 99.90\ensuremath{\pm}0.58 &
  \cAlignHack 6.2\ensuremath{\pm}0.23\\
\cAlignHack F9 &
  \cAlignHack 24.634\ensuremath{\pm}0.15 &
  \cAlignHack 4395\ensuremath{\pm}4.13  &
  \cAlignHack 98.35\ensuremath{\pm}0.67 &
  \cAlignHack 6.3\ensuremath{\pm}0.21\\
\cAlignHack F10 (Marketed gel) &
  \cAlignHack 33.32\ensuremath{\pm}0.19 &
  \cAlignHack 4054\ensuremath{\pm}2.36  &
  \cAlignHack 96.24\ensuremath{\pm}0.75 &
  \cAlignHack 6.4\ensuremath{\pm}0.24\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {\textit{In-Vitro} Drug permeation Data of Ketoprofen Emulgels using Sodium CMC as Gelling agent (F1 {\textendash} F3)} }
\label{tw-b114d3e4ee9b}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.1685\linewidth-2\tabcolsep}p{\dimexpr.19169999999999998\linewidth-2\tabcolsep}p{\dimexpr.1784\linewidth-2\tabcolsep}p{\dimexpr.21\linewidth-2\tabcolsep}p{\dimexpr.2514\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack Time (hrs)  & \multicolumn{4}{p{\dimexpr(.8315\linewidth-2\tabcolsep)}}{\cAlignHack \% Cumulative Drug Release }\\
\rowcolor{kwdboxcolor}\cAlignHack  & \cAlignHack F1  & \cAlignHack F2  & \cAlignHack F3  & \cAlignHack F10 (Marketed gel) \\
\tblmidrule 
\cAlignHack 0  &
  \cAlignHack 0  &
  \cAlignHack 0  &
  \cAlignHack 0  &
  \cAlignHack 0 \\
\cAlignHack 1  &
  \cAlignHack 19.22\ensuremath{\pm}0.02  &
  \cAlignHack 37.31\ensuremath{\pm}0.01  &
  \cAlignHack 30.61\ensuremath{\pm}0.0001  &
  \cAlignHack 19.23\ensuremath{\pm}0.07 \\
\cAlignHack 2  &
  \cAlignHack 34.32\ensuremath{\pm}0.04  &
  \cAlignHack 38.13\ensuremath{\pm}0.03  &
  \cAlignHack 39.34\ensuremath{\pm}0.24  &
  \cAlignHack 32.89\ensuremath{\pm}0.29 \\
\cAlignHack 3  &
  \cAlignHack 48.26\ensuremath{\pm}0.46  &
  \cAlignHack 41.34\ensuremath{\pm}0.25  &
  \cAlignHack 43.86\ensuremath{\pm}0.16  &
  \cAlignHack 47.98\ensuremath{\pm}0.37 \\
\cAlignHack 4  &
  \cAlignHack 61\ensuremath{\pm}0.0.17  &
  \cAlignHack 44.29\ensuremath{\pm}0.49  &
  \cAlignHack 50.16\ensuremath{\pm}0.19  &
  \cAlignHack 62.34\ensuremath{\pm}0.59 \\
\cAlignHack 5  &
  \cAlignHack 81.26\ensuremath{\pm}0.24  &
  \cAlignHack 75.56\ensuremath{\pm}0.47  &
  \cAlignHack 58.78\ensuremath{\pm}0.39  &
  \cAlignHack 70.36\ensuremath{\pm}0.74 \\
\cAlignHack 6  &
  \cAlignHack 92.34\ensuremath{\pm}0.16  &
  \cAlignHack 82.46\ensuremath{\pm}0.55  &
  \cAlignHack 72.61\ensuremath{\pm}0.32  &
  \cAlignHack 87.56\ensuremath{\pm}0.82 \\
\cAlignHack 7  &
  \cAlignHack 94.26\ensuremath{\pm}0.18  &
  \cAlignHack 94.61\ensuremath{\pm}0.85  &
  \cAlignHack 85.54\ensuremath{\pm}0.68  &
  \cAlignHack 90.81\ensuremath{\pm}1.15 \\
\cAlignHack 8  &
  \cAlignHack 96.21\ensuremath{\pm}0.20  &
  \cAlignHack 94.54\ensuremath{\pm}1.12  &
  \cAlignHack 93.34\ensuremath{\pm}0.86  &
  \cAlignHack 93.45\ensuremath{\pm}0.56 \\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {In-Vitro Drug permeation Data of Ketoprofen Emulgels using Sodium alginate as Gelling agent (F4 {\textendash} F6)} }
\label{tw-d7affbb6aa33}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.17009999999999998\linewidth-2\tabcolsep}p{\dimexpr.18180000000000003\linewidth-2\tabcolsep}p{\dimexpr.1818\linewidth-2\tabcolsep}p{\dimexpr.2016\linewidth-2\tabcolsep}p{\dimexpr.2647\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack Time (hrs)  & \multicolumn{4}{p{\dimexpr(.8299\linewidth-2\tabcolsep)}}{\cAlignHack \% Cumulative Drug Release }\\
\rowcolor{kwdboxcolor}\cAlignHack  & \cAlignHack F4  & \cAlignHack F5  & \cAlignHack F6  & \cAlignHack F10 (Marketed gel) \\
\tblmidrule 
\cAlignHack 0  &
  \cAlignHack 0  &
  \cAlignHack 0  &
  \cAlignHack 0  &
  \cAlignHack 0 \\
\cAlignHack 1  &
  \cAlignHack 38.25\ensuremath{\pm}0.02  &
  \cAlignHack 55.15\ensuremath{\pm}0.01  &
  \cAlignHack 32.13\ensuremath{\pm}0.01  &
  \cAlignHack 19.23\ensuremath{\pm}0.07 \\
\cAlignHack 2  &
  \cAlignHack 35.24\ensuremath{\pm}0.04  &
  \cAlignHack 56.25\ensuremath{\pm}0.03  &
  \cAlignHack 36.34\ensuremath{\pm}0.24  &
  \cAlignHack 32.89\ensuremath{\pm}0.29 \\
\cAlignHack 3  &
  \cAlignHack 55.48\ensuremath{\pm}0.46  &
  \cAlignHack 72.36\ensuremath{\pm}0.25  &
  \cAlignHack 45.24\ensuremath{\pm}0.16  &
  \cAlignHack 47.98\ensuremath{\pm}0.37 \\
\cAlignHack 4  &
  \cAlignHack 64.87\ensuremath{\pm}0.17  &
  \cAlignHack 81.98\ensuremath{\pm}0.49  &
  \cAlignHack 57.17\ensuremath{\pm}0.19  &
  \cAlignHack 62.34\ensuremath{\pm}0.59 \\
\cAlignHack 5  &
  \cAlignHack 83.36\ensuremath{\pm}0.64  &
  \cAlignHack 91.54\ensuremath{\pm}0.47  &
  \cAlignHack 73.15\ensuremath{\pm}0.39  &
  \cAlignHack 70.36\ensuremath{\pm}0.74 \\
\cAlignHack 6  &
  \cAlignHack 98.15\ensuremath{\pm}0.16  &
  \cAlignHack 94.15\ensuremath{\pm}0.55  &
  \cAlignHack 84.17\ensuremath{\pm}0.32  &
  \cAlignHack 87.56\ensuremath{\pm}0.82 \\
\cAlignHack 7  &
  \cAlignHack 98.45\ensuremath{\pm}0.18  &
  \cAlignHack 95.23\ensuremath{\pm}0.85  &
  \cAlignHack 97.57\ensuremath{\pm}0.68  &
  \cAlignHack 90.81\ensuremath{\pm}1.15 \\
\cAlignHack 8  &
  \cAlignHack 98.56\ensuremath{\pm}0.20  &
  \cAlignHack 97.26\ensuremath{\pm}1.12  &
  \cAlignHack 98.58\ensuremath{\pm}0.86  &
  \cAlignHack 93.45\ensuremath{\pm}0.56 \\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {\textit{In-Vitro} Drug permeation Data of Ketoprofen Emulgels using Hibiscus as Gelling agent (F7 {\textendash} F9)} }
\label{tw-cc7cc331bd62}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.1884\linewidth-2\tabcolsep}p{\dimexpr.1934\linewidth-2\tabcolsep}p{\dimexpr.20\linewidth-2\tabcolsep}p{\dimexpr.1568\linewidth-2\tabcolsep}p{\dimexpr.2614\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack Time (hrs) & \multicolumn{4}{p{\dimexpr(.8116\linewidth-2\tabcolsep)}}{\cAlignHack \% Cumulative Drug Release }\\
\rowcolor{kwdboxcolor}\cAlignHack  & \cAlignHack F7  & \cAlignHack F8  & \cAlignHack F9  & \cAlignHack F10 (Marketed gel) \\
\tblmidrule 
\cAlignHack 0  &
  \cAlignHack 0  &
  \cAlignHack 0  &
  \cAlignHack 0  &
  \cAlignHack 0 \\
\cAlignHack 1  &
  \cAlignHack 51.48\ensuremath{\pm}0.005  &
  \cAlignHack 43.82\ensuremath{\pm}0.07  &
  \cAlignHack 33.53\ensuremath{\pm}0.01  &
  \cAlignHack 19.23\ensuremath{\pm}0.07 \\
\cAlignHack 2  &
  \cAlignHack 56.36\ensuremath{\pm}0.21  &
  \cAlignHack 44.86\ensuremath{\pm}0.54  &
  \cAlignHack 42.84\ensuremath{\pm}0.47  &
  \cAlignHack 32.89\ensuremath{\pm}0.29 \\
\cAlignHack 3  &
  \cAlignHack 60.86\ensuremath{\pm}0.34  &
  \cAlignHack 55.66\ensuremath{\pm}0.51  &
  \cAlignHack 47.32\ensuremath{\pm}0.15  &
  \cAlignHack 47.98\ensuremath{\pm}0.37 \\
\cAlignHack 4  &
  \cAlignHack 65.62\ensuremath{\pm}0.46  &
  \cAlignHack 62.06\ensuremath{\pm}0.47  &
  \cAlignHack 48.68\ensuremath{\pm}0.25  &
  \cAlignHack 62.34\ensuremath{\pm}0.59 \\
\cAlignHack 5  &
  \cAlignHack 79.39\ensuremath{\pm}0.47  &
  \cAlignHack 73.66\ensuremath{\pm}0.54  &
  \cAlignHack 55.36\ensuremath{\pm}0.17  &
  \cAlignHack 70.36\ensuremath{\pm}0.74 \\
\cAlignHack 6  &
  \cAlignHack 95.15\ensuremath{\pm}0.85  &
  \cAlignHack 89.55\ensuremath{\pm}0.24  &
  \cAlignHack 87.01\ensuremath{\pm}0.75  &
  \cAlignHack 87.56\ensuremath{\pm}0.82 \\
\cAlignHack 7  &
  \cAlignHack 95.54\ensuremath{\pm}1.14  &
  \cAlignHack 93.92\ensuremath{\pm}0.01  &
  \cAlignHack 95.58\ensuremath{\pm}0.48  &
  \cAlignHack 90.81\ensuremath{\pm}1.15 \\
\cAlignHack 8  &
  \cAlignHack 96.52\ensuremath{\pm}1.21  &
  \cAlignHack 95.97\ensuremath{\pm}0.48  &
  \cAlignHack 97.24\ensuremath{\pm}0.14  &
  \cAlignHack 93.45\ensuremath{\pm}0.56 \\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {\textit{In-Vitro} Drug permeation kinetics Data of Ketoprofen Emulgels} }
\label{tw-8330805860b3}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.14869999999999997\linewidth-2\tabcolsep}p{\dimexpr.09620000000000001\linewidth-2\tabcolsep}p{\dimexpr.0713\linewidth-2\tabcolsep}p{\dimexpr.10809999999999999\linewidth-2\tabcolsep}p{\dimexpr.0658\linewidth-2\tabcolsep}p{\dimexpr.12110000000000003\linewidth-2\tabcolsep}p{\dimexpr.0952\linewidth-2\tabcolsep}p{\dimexpr.10629999999999999\linewidth-2\tabcolsep}p{\dimexpr.1873\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack Formulation Code & \multicolumn{2}{p{\dimexpr(.1675\linewidth-2\tabcolsep)}}{\cAlignHack Zero order} & \multicolumn{2}{p{\dimexpr(.1739\linewidth-2\tabcolsep)}}{\cAlignHack First order} & \cAlignHack Order of release & \cAlignHack Higuchi & \cAlignHack Peppas & \cAlignHack Mechanism of Diffusion\\
\rowcolor{kwdboxcolor}\cAlignHack  & \cAlignHack r\ensuremath{^{2}} & \cAlignHack ko & \cAlignHack r\ensuremath{^{2}} & \cAlignHack K1 & \cAlignHack  & \cAlignHack r\ensuremath{^{2}} & \cAlignHack n & \cAlignHack \\
\tblmidrule 
\cAlignHack F1 &
  \cAlignHack 0.963 &
  \cAlignHack 12.86 &
  \cAlignHack 0.952 &
  \cAlignHack 0.403 &
  \cAlignHack Zero order &
  \cAlignHack 0.943 &
  \cAlignHack 0.748 &
  \cAlignHack Non fickian diffusion \\
\cAlignHack F2 &
  \cAlignHack 0.920 &
  \cAlignHack 11.18 &
  \cAlignHack 0.901 &
  \cAlignHack 0.345 &
  \cAlignHack Zero order  &
  \cAlignHack 0.906 &
  \cAlignHack 0.984 &
  \cAlignHack Case-II transport \\
\cAlignHack F3 &
  \cAlignHack 0.957 &
  \cAlignHack 10.3 &
  \cAlignHack 0.872 &
  \cAlignHack 0.283 &
  \cAlignHack Zero order  &
  \cAlignHack 0.951 &
  \cAlignHack 0.728 &
  \cAlignHack Non fickian diffusion \\
\cAlignHack F4 &
  \cAlignHack 0.897 &
  \cAlignHack 11.36 &
  \cAlignHack 0.839 &
  \cAlignHack 0.575 &
  \cAlignHack Zero order  &
  \cAlignHack 0.967 &
  \cAlignHack 0.654 &
  \cAlignHack Non fickian diffusion \\
\cAlignHack F5 &
  \cAlignHack 0.934 &
  \cAlignHack 11.04 &
  \cAlignHack 0.875 &
  \cAlignHack 0.471 &
  \cAlignHack Zero order  &
  \cAlignHack 0.977 &
  \cAlignHack 0.862 &
  \cAlignHack Case-II transport \\
\cAlignHack F6 &
  \cAlignHack 0.967 &
  \cAlignHack 11.88 &
  \cAlignHack 0.847 &
  \cAlignHack 0.492 &
  \cAlignHack Zero order  &
  \cAlignHack 0.955 &
  \cAlignHack 0.668 &
  \cAlignHack Non fickian diffusion \\
\cAlignHack F7 &
  \cAlignHack 0.933 &
  \cAlignHack 10.17 &
  \cAlignHack 0.908 &
  \cAlignHack 0.365 &
  \cAlignHack Zero order  &
  \cAlignHack 0.965 &
  \cAlignHack 0.567 &
  \cAlignHack Non fickian diffusion \\
\cAlignHack F8 &
  \cAlignHack 0.906 &
  \cAlignHack 10.18 &
  \cAlignHack 0.86 &
  \cAlignHack 0.423 &
  \cAlignHack Zero order  &
  \cAlignHack 0.967 &
  \cAlignHack 0.684 &
  \cAlignHack Non fickian diffusion \\
\cAlignHack F9 &
  \cAlignHack 0.951 &
  \cAlignHack 11.43 &
  \cAlignHack 0.89 &
  \cAlignHack 0.462 &
  \cAlignHack Zero order  &
  \cAlignHack 0.962 &
  \cAlignHack 0.756 &
  \cAlignHack Non fickian diffusion \\
\cAlignHack F10 \mbox{}\protect\newline (Marketed Gel) &
  \cAlignHack 0.944 &
  \cAlignHack 11.99 &
  \cAlignHack 0.922 &
  \cAlignHack 0.345 &
  \cAlignHack Zero order  &
  \cAlignHack 0.957 &
  \cAlignHack 0.796 &
  \cAlignHack Non fickian diffusion \\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {f\ensuremath{_{1}} and f\ensuremath{_{2}} values for Ketoprofen Emulgel formulations} }
\label{tw-838ea745a9b0}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.3425\linewidth-2\tabcolsep}p{\dimexpr.31750000000000004\linewidth-2\tabcolsep}p{\dimexpr.34\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack Formulation code & \cAlignHack f1 & \cAlignHack f2\\
\tblmidrule 
\cAlignHack F1 &
  \cAlignHack 3.71 &
  \cAlignHack 60.53\\
\cAlignHack F2 &
  \cAlignHack 3.94 &
  \cAlignHack 56.56\\
\cAlignHack F3 &
  \cAlignHack 4.76 &
  \cAlignHack 57.32\\
\cAlignHack F4 &
  \cAlignHack 3.42 &
  \cAlignHack 60.21\\
\cAlignHack F5 &
  \cAlignHack 4.01 &
  \cAlignHack 57.54\\
\cAlignHack F6 &
  \cAlignHack 2.05 &
  \cAlignHack 70.58\\
\cAlignHack F7 &
  \cAlignHack 3.56 &
  \cAlignHack 58.52\\
\cAlignHack F8 &
  \cAlignHack 4.07 &
  \cAlignHack 51.56\\
\cAlignHack F9 &
  \cAlignHack 3.57 &
  \cAlignHack 59.23\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}
\textbf{Drug - Excipient compatibility studies}

Preformulation parameters were carried out for studying the compatibility of pure drug ketoprofen with polymers CMC, Na alginate, hibiscus prior to the preparation of Emulgel [Tables~\ref{tw-c6b618b3b4e2}, \ref{tw-3caea17a16af}, \ref{tw-db694ef62169} and~\ref{tw-772af8f38f3a}]. It indicates that there was no change in the peak values of the drug in the physical mixture thus providing that drug and polymer were compatible with each other [Table~\ref{tw-db694ef62169}].


\bgroup
\fixFloatSize{images/a9fef215-fe88-4b6c-a325-d664783769c4-upicture1.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/a9fef215-fe88-4b6c-a325-d664783769c4-upicture1.png}{\includegraphics{images/a9fef215-fe88-4b6c-a325-d664783769c4-upicture1.png}}{}
\makeatother 
\caption{\boldmath {FTIR Spectra of Ketoprofen}}
\label{f-74dfb8d85658}
\end{figure}
\egroup
As there was no interaction between the drug and other excipients, the excipients were found to be compatible with the drug.


\bgroup
\fixFloatSize{images/dcea94d9-d284-441f-af76-483e5e0c1884-upicture2.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/dcea94d9-d284-441f-af76-483e5e0c1884-upicture2.png}{\includegraphics{images/dcea94d9-d284-441f-af76-483e5e0c1884-upicture2.png}}{}
\makeatother 
\caption{\boldmath {FTIR Spectra of Ketoprofen and Sodium CMC}}
\label{f-9647750aa6fe}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/3d6df58b-ee17-4c7c-ac1e-34a78657385d-upicture3.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/3d6df58b-ee17-4c7c-ac1e-34a78657385d-upicture3.png}{\includegraphics{images/3d6df58b-ee17-4c7c-ac1e-34a78657385d-upicture3.png}}{}
\makeatother 
\caption{\boldmath {FTIR Spectra of Ketoprofen and Sodium alginate}}
\label{f-e046f980e797}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/3829570d-1c23-48d5-9071-5919dafe70e8-upicture4.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/3829570d-1c23-48d5-9071-5919dafe70e8-upicture4.png}{\includegraphics{images/3829570d-1c23-48d5-9071-5919dafe70e8-upicture4.png}}{}
\makeatother 
\caption{\boldmath {FTIR Spectra of Ketoprofen and Hibiscus}}
\label{f-90d331f69330}
\end{figure}
\egroup
From the FTIR spectra of drug [Figures~\ref{f-74dfb8d85658}, \ref{f-9647750aa6fe}, \ref{f-e046f980e797} and~\ref{f-90d331f69330}], it was found that Ketoprofen gave principle peaks at wave numbers 3425.69 Cm\ensuremath{^{-1}}, 1790.49 Cm\ensuremath{^{-1}}, 1582.35 Cm\ensuremath{^{-1}}, 1536.94 Cm\ensuremath{^{-1}}. Principal peaks were present in drug and excipients physical mixture. This indicates that there was no interaction between the drug and excipients. From the results obtained for Drug- excipients compatibility study, it was found that the drug was compatible with the other excipients under evaluation. So that chosen excipients can be used in the formulation trails.

\textbf{Scanning electron microscope studies}

The surface morphology of the Emulgel was obtained by using SEM of best formulation F6 [Table~\ref{tw-b6113f143f65}, Figure~\ref{f-d38bd5af0dd0}].


\bgroup
\fixFloatSize{images/bc05cc91-a7b5-42bf-92bf-188ea26c892b-upicture5.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/bc05cc91-a7b5-42bf-92bf-188ea26c892b-upicture5.png}{\includegraphics{images/bc05cc91-a7b5-42bf-92bf-188ea26c892b-upicture5.png}}{}
\makeatother 
\caption{\boldmath {SEM of Best formulation (F6)}}
\label{f-d38bd5af0dd0}
\end{figure}
\egroup
\textit{\textbf{In-vitro}} \textbf{ Evaluation studies of Ketoprofen Emulgels}

\textbf{Physical Characteristics of Ketoprofen Formulations }

The formulated emulgels (F1-F9) were characterized for clarity, color, Consistency and phase separation tests [Table~\ref{tw-772af8f38f3a}]. 

\textbf{pH }

All the formulations were evaluated for the pH and all the values were found [Table~\ref{tw-b6113f143f65}] well within the range of 6-7. 

\textbf{Spreadability studies}

The formulated ketoprofen emulgels (F1-F9) were evaluated for determining spreadability by using spreadability apparatus and the results [Table~\ref{tw-b6113f143f65}].

\textbf{Rheological parameters}

The formulated ketoprofen emulgels (F1-F9) were evaluated for determining viscosity by using falling sphere viscometer apparatus [Table~\ref{tw-b6113f143f65}]. Amongst the formulations, formulations with Sodium alginate showed increased viscosity that indicates Sodium alginate as the better gelling agent in low concentration compared to other batches.

\textbf{Drug content }

The formulated ketoprofen emulgels (F1-F9) were evaluated for determining Drug content was found to be in the range 96.24\%-99.90\% [Table~\ref{tw-b6113f143f65}].

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

The \textit{in vitro} drug release studies were carried out for all the formulations and Figures represents the drug release from sodium CMC, Sodium alginate and Hibiscus. The study was carried out in order to examine the effect of gelling agent reaction (concentration \& ratio) on the emulgels i.e. sodium CMC, Sodium alginate and Hibiscus were selected and formulations were prepared and their individual drug release parameters were evaluated. Based on the drug release comparison studies with the marketed gel, it was observed that maximum drug release from the emulgels from all formulations were higher when compared with that of the marketed gel. To give similar type of drug release in case of other gelling agents based emulgel preparations, they required high concentration of polymer than Sodium alginate [Tables~\ref{tw-b114d3e4ee9b}, \ref{tw-d7affbb6aa33} and~\ref{tw-cc7cc331bd62}]. Thus the F6 formulation having Sodium alginate was considered as the better formulation when compared to others [Figures~\ref{f-00fd500e87ad}, \ref{f-729a8df4a331} and~\ref{f-9de388aede33}].


\bgroup
\fixFloatSize{images/f90e0f2f-a093-4882-9f4e-9132053eaff0-upicture6.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/f90e0f2f-a093-4882-9f4e-9132053eaff0-upicture6.png}{\includegraphics{images/f90e0f2f-a093-4882-9f4e-9132053eaff0-upicture6.png}}{}
\makeatother 
\caption{\boldmath {\textit{In-Vitro} Drug permeation Data of Ketoprofen Emulgels using Sodium CMC as Gelling agent (F1 {\textendash} F3)}}
\label{f-00fd500e87ad}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/6b359aa6-997f-4d67-b5c3-ef3297a70c2c-upicture7.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/6b359aa6-997f-4d67-b5c3-ef3297a70c2c-upicture7.png}{\includegraphics{images/6b359aa6-997f-4d67-b5c3-ef3297a70c2c-upicture7.png}}{}
\makeatother 
\caption{\boldmath {\textit{In-Vitro }Drug permeation Data of Ketoprofen Emulgels using Sodium alginate as Gelling agent (F4 {\textendash} F6)}}
\label{f-729a8df4a331}
\end{figure}
\egroup

\bgroup
\fixFloatSize{images/0f660089-97ac-4e9d-b4fd-d21011321f42-upicture8.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/0f660089-97ac-4e9d-b4fd-d21011321f42-upicture8.png}{\includegraphics{images/0f660089-97ac-4e9d-b4fd-d21011321f42-upicture8.png}}{}
\makeatother 
\caption{\boldmath {\textit{In-Vitro} Drug permeation Data of Ketoprofen Emulgels using Hibiscus as Gelling agent (F7 {\textendash} F9)}}
\label{f-9de388aede33}
\end{figure}
\egroup
\textbf{Drug release mechanism and kinetics}

It was determined by zero order and first order kinetics, Higuchi's model, and Peppas models. All the formulations followed zero order kinetics. Most of the emulgel formulations showed high r\ensuremath{^{2}} values for Higuchi's model as their r\ensuremath{^{2}} values were above 0.9. The high regression value of Higuchi model ensured that the release of drug from emulgels followed diffusion mechanism. From peppas studies, it was observed that all the formulations except F2 and F5 followed Non-fickian diffusion while they followed case - II transport mechanism [Table~\ref{tw-8330805860b3}].

\textbf{Calculation of similarity (f\ensuremath{_{2}}) and dissimilarity factors (f\ensuremath{_{1}}) for best formulations}

Hence it was sure that the diffusion profile of F6 was similar to that of the marketed diffusion profile [Table~\ref{tw-838ea745a9b0}].
    
\section{CONCLUSION}
From the current study of Ketoprofen Emulgels proved it as better topical administration and the release was comparable with that the marketed gel. It was observed that the release of the drugs from its emulsified Sodium alginate gel formulation can be ranked in the given descending order: F6 {\textgreater} F5 {\textgreater} F6 where, the F6 formulation showed highest drug release after 8h. It was confirmed from the results that Sodium alginate containing Ketoprofen emulgels followed zero order release and the optimized formulation F6 followed zero order kinetics with Non-fickian mechanism of diffusion. The calculated f\ensuremath{_{1}} and f\ensuremath{_{2}} values were within the limits. f\ensuremath{_{2}} values of F6 formulation was higher when compared to the others.
    
\section{ACKNOWLEDGEMENT}
The authors are thankful to the Secretary \& Correspondent (Mr. Madhu Sudhan Reddy Sir) \& Principal (Dr. P. Venkatesh Sir) of Jagan's Institute of Pharmaceutical Sciences, Jangalakandriga (V), Muthukur (M) Nellore-524 346, SPSR Nellore (Dist) Andhra Pradesh for providing the necessary facilities to carry out this work.

\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.
\section*{Acknowledgements}
    

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