\documentclass[11pt,twoside]{article}\makeatletter

\IfFileExists{xcolor.sty}%
  {\RequirePackage{xcolor}}%
  {\RequirePackage{color}}
\usepackage{colortbl}
\usepackage{wrapfig}
\usepackage{ifxetex}
\ifxetex
  \usepackage{fontspec}
  \usepackage{xunicode}
  \catcode`⃥=\active \def⃥{\textbackslash}
  \catcode`❴=\active \def❴{\{}
  \catcode`❵=\active \def❵{\}}
  \def\textJapanese{\fontspec{Noto Sans CJK JP}}
  \def\textChinese{\fontspec{Noto Sans CJK SC}}
  \def\textKorean{\fontspec{Noto Sans CJK KR}}
  \setmonofont{DejaVu Sans Mono}
  
\else
  \IfFileExists{utf8x.def}%
   {\usepackage[utf8x]{inputenc}
      \PrerenderUnicode{–}
    }%
   {\usepackage[utf8]{inputenc}}
  \usepackage[english]{babel}
  \usepackage[T1]{fontenc}
  \usepackage{float}
  \usepackage[]{ucs}
  \uc@dclc{8421}{default}{\textbackslash }
  \uc@dclc{10100}{default}{\{}
  \uc@dclc{10101}{default}{\}}
  \uc@dclc{8491}{default}{\AA{}}
  \uc@dclc{8239}{default}{\,}
  \uc@dclc{20154}{default}{ }
  \uc@dclc{10148}{default}{>}
  \def\textschwa{\rotatebox{-90}{e}}
  \def\textJapanese{}
  \def\textChinese{}
  \IfFileExists{tipa.sty}{\usepackage{tipa}}{}
\fi
\def\exampleFont{\ttfamily\small}
\DeclareTextSymbol{\textpi}{OML}{25}
\usepackage{relsize}
\RequirePackage{array}
\def\@testpach{\@chclass
 \ifnum \@lastchclass=6 \@ne \@chnum \@ne \else
  \ifnum \@lastchclass=7 5 \else
   \ifnum \@lastchclass=8 \tw@ \else
    \ifnum \@lastchclass=9 \thr@@
   \else \z@
   \ifnum \@lastchclass = 10 \else
   \edef\@nextchar{\expandafter\string\@nextchar}%
   \@chnum
   \if \@nextchar c\z@ \else
    \if \@nextchar l\@ne \else
     \if \@nextchar r\tw@ \else
   \z@ \@chclass
   \if\@nextchar |\@ne \else
    \if \@nextchar !6 \else
     \if \@nextchar @7 \else
      \if \@nextchar (8 \else
       \if \@nextchar )9 \else
  10
  \@chnum
  \if \@nextchar m\thr@@\else
   \if \@nextchar p4 \else
    \if \@nextchar b5 \else
   \z@ \@chclass \z@ \@preamerr \z@ \fi \fi \fi \fi
   \fi \fi  \fi  \fi  \fi  \fi  \fi \fi \fi \fi \fi \fi}
\gdef\arraybackslash{\let\\=\@arraycr}
\def\@textsubscript#1{{\m@th\ensuremath{_{\mbox{\fontsize\sf@size\z@#1}}}}}
\def\Panel#1#2#3#4{\multicolumn{#3}{){\columncolor{#2}}#4}{#1}}
\def\abbr{}
\def\corr{}
\def\expan{}
\def\gap{}
\def\orig{}
\def\reg{}
\def\ref{}
\def\sic{}
\def\persName{}\def\name{}
\def\placeName{}
\def\orgName{}
\def\textcal#1{{\fontspec{Lucida Calligraphy}#1}}
\def\textgothic#1{{\fontspec{Lucida Blackletter}#1}}
\def\textlarge#1{{\large #1}}
\def\textoverbar#1{\ensuremath{\overline{#1}}}
\def\textquoted#1{‘#1’}
\def\textsmall#1{{\small #1}}
\def\textsubscript#1{\@textsubscript{\selectfont#1}}
\def\textxi{\ensuremath{\xi}}
\def\titlem{\itshape}
\newenvironment{biblfree}{}{\ifvmode\par\fi }
\newenvironment{bibl}{}{}
\newenvironment{byline}{\vskip6pt\itshape\fontsize{16pt}{18pt}\selectfont}{\par }
\newenvironment{citbibl}{}{\ifvmode\par\fi }
\newenvironment{docAuthor}{\ifvmode\vskip4pt\fontsize{16pt}{18pt}\selectfont\fi\itshape}{\ifvmode\par\fi }
\newenvironment{docDate}{}{\ifvmode\par\fi }
\newenvironment{docImprint}{\vskip 6pt}{\ifvmode\par\fi }
\newenvironment{docTitle}{\vskip6pt\bfseries\fontsize{22pt}{25pt}\selectfont}{\par }
\newenvironment{msHead}{\vskip 6pt}{\par}
\newenvironment{msItem}{\vskip 6pt}{\par}
\newenvironment{rubric}{}{}
\newenvironment{titlePart}{}{\par }

\newcolumntype{L}[1]{){\raggedright\arraybackslash}p{#1}}
\newcolumntype{C}[1]{){\centering\arraybackslash}p{#1}}
\newcolumntype{R}[1]{){\raggedleft\arraybackslash}p{#1}}
\newcolumntype{P}[1]{){\arraybackslash}p{#1}}
\newcolumntype{B}[1]{){\arraybackslash}b{#1}}
\newcolumntype{M}[1]{){\arraybackslash}m{#1}}
\definecolor{label}{gray}{0.75}
\def\unusedattribute#1{\sout{\textcolor{label}{#1}}}
\DeclareRobustCommand*{\xref}{\hyper@normalise\xref@}
\def\xref@#1#2{\hyper@linkurl{#2}{#1}}
\begingroup
\catcode`\_=\active
\gdef_#1{\ensuremath{\sb{\mathrm{#1}}}}
\endgroup
\mathcode`\_=\string"8000
\catcode`\_=12\relax

\usepackage[a4paper,twoside,lmargin=1in,rmargin=1in,tmargin=1in,bmargin=1in,marginparwidth=0.75in]{geometry}
\usepackage{framed}

\definecolor{shadecolor}{gray}{0.95}
\usepackage{longtable}
\usepackage[normalem]{ulem}
\usepackage{fancyvrb}
\usepackage{fancyhdr}
\usepackage{graphicx}
\usepackage{marginnote}

\renewcommand{\@cite}[1]{#1}


\renewcommand*{\marginfont}{\itshape\footnotesize}

\def\Gin@extensions{.pdf,.png,.jpg,.mps,.tif}

  \pagestyle{fancy}

\usepackage[pdftitle={Formulation \& Evaluation of Eye Care Solution of Vasoconstrictor and Antihistaminic Drug for Conjuctivitis},
 pdfauthor={}]{hyperref}
\hyperbaseurl{}

	 \paperwidth210mm
	 \paperheight297mm
              
\def\@pnumwidth{1.55em}
\def\@tocrmarg {2.55em}
\def\@dotsep{4.5}
\setcounter{tocdepth}{3}
\clubpenalty=8000
\emergencystretch 3em
\hbadness=4000
\hyphenpenalty=400
\pretolerance=750
\tolerance=2000
\vbadness=4000
\widowpenalty=10000

\renewcommand\section{\@startsection {section}{1}{\z@}%
     {-1.75ex \@plus -0.5ex \@minus -.2ex}%
     {0.5ex \@plus .2ex}%
     {\reset@font\Large\bfseries}}
\renewcommand\subsection{\@startsection{subsection}{2}{\z@}%
     {-1.75ex\@plus -0.5ex \@minus- .2ex}%
     {0.5ex \@plus .2ex}%
     {\reset@font\Large}}
\renewcommand\subsubsection{\@startsection{subsubsection}{3}{\z@}%
     {-1.5ex\@plus -0.35ex \@minus -.2ex}%
     {0.5ex \@plus .2ex}%
     {\reset@font\large}}
\renewcommand\paragraph{\@startsection{paragraph}{4}{\z@}%
     {-1ex \@plus-0.35ex \@minus -0.2ex}%
     {0.5ex \@plus .2ex}%
     {\reset@font\normalsize}}
\renewcommand\subparagraph{\@startsection{subparagraph}{5}{\parindent}%
     {1.5ex \@plus1ex \@minus .2ex}%
     {-1em}%
     {\reset@font\normalsize\bfseries}}


\def\l@section#1#2{\addpenalty{\@secpenalty} \addvspace{1.0em plus 1pt}
 \@tempdima 1.5em \begingroup
 \parindent \z@ \rightskip \@pnumwidth 
 \parfillskip -\@pnumwidth 
 \bfseries \leavevmode #1\hfil \hbox to\@pnumwidth{\hss #2}\par
 \endgroup}
\def\l@subsection{\@dottedtocline{2}{1.5em}{2.3em}}
\def\l@subsubsection{\@dottedtocline{3}{3.8em}{3.2em}}
\def\l@paragraph{\@dottedtocline{4}{7.0em}{4.1em}}
\def\l@subparagraph{\@dottedtocline{5}{10em}{5em}}
\@ifundefined{c@section}{\newcounter{section}}{}
\@ifundefined{c@chapter}{\newcounter{chapter}}{}
\newif\if@mainmatter 
\@mainmattertrue
\def\chaptername{Chapter}
\def\frontmatter{%
  \pagenumbering{roman}
  \def\thechapter{\@roman\c@chapter}
  \def\theHchapter{\roman{chapter}}
  \def\thesection{\@roman\c@section}
  \def\theHsection{\roman{section}}
  \def\@chapapp{}%
}
\def\mainmatter{%
  \cleardoublepage
  \def\thechapter{\@arabic\c@chapter}
  \setcounter{chapter}{0}
  \setcounter{section}{0}
  \pagenumbering{arabic}
  \setcounter{secnumdepth}{6}
  \def\@chapapp{\chaptername}%
  \def\theHchapter{\arabic{chapter}}
  \def\thesection{\@arabic\c@section}
  \def\theHsection{\arabic{section}}
}
\def\backmatter{%
  \cleardoublepage
  \setcounter{chapter}{0}
  \setcounter{section}{0}
  \setcounter{secnumdepth}{2}
  \def\@chapapp{\appendixname}%
  \def\thechapter{\@Alph\c@chapter}
  \def\theHchapter{\Alph{chapter}}
  \appendix
}
\newenvironment{bibitemlist}[1]{%
   \list{\@biblabel{\@arabic\c@enumiv}}%
       {\settowidth\labelwidth{\@biblabel{#1}}%
        \leftmargin\labelwidth
        \advance\leftmargin\labelsep
        \@openbib@code
        \usecounter{enumiv}%
        \let\p@enumiv\@empty
        \renewcommand\theenumiv{\@arabic\c@enumiv}%
	}%
  \sloppy
  \clubpenalty4000
  \@clubpenalty \clubpenalty
  \widowpenalty4000%
  \sfcode`\.\@m}%
  {\def\@noitemerr
    {\@latex@warning{Empty `bibitemlist' environment}}%
    \endlist}

\def\tableofcontents{\section*{\contentsname}\@starttoc{toc}}
\parskip0pt
\parindent1em
\def\Panel#1#2#3#4{\multicolumn{#3}{){\columncolor{#2}}#4}{#1}}
\newenvironment{reflist}{%
  \begin{raggedright}\begin{list}{}
  {%
   \setlength{\topsep}{0pt}%
   \setlength{\rightmargin}{0.25in}%
   \setlength{\itemsep}{0pt}%
   \setlength{\itemindent}{0pt}%
   \setlength{\parskip}{0pt}%
   \setlength{\parsep}{2pt}%
   \def\makelabel##1{\itshape ##1}}%
  }
  {\end{list}\end{raggedright}}
\newenvironment{sansreflist}{%
  \begin{raggedright}\begin{list}{}
  {%
   \setlength{\topsep}{0pt}%
   \setlength{\rightmargin}{0.25in}%
   \setlength{\itemindent}{0pt}%
   \setlength{\parskip}{0pt}%
   \setlength{\itemsep}{0pt}%
   \setlength{\parsep}{2pt}%
   \def\makelabel##1{\upshape ##1}}%
  }
  {\end{list}\end{raggedright}}
\newenvironment{specHead}[2]%
 {\vspace{20pt}\hrule\vspace{10pt}%
  \phantomsection\label{#1}\markright{#2}%

  \pdfbookmark[2]{#2}{#1}%
  \hspace{-0.75in}{\bfseries\fontsize{16pt}{18pt}\selectfont#2}%
  }{}
      \def\TheFullDate{2015-05-15 (revised: 15 May 2015)}
\def\TheID{\makeatother }
\def\TheDate{2015-05-15}
\title{Formulation \& Evaluation of Eye Care Solution of Vasoconstrictor and Antihistaminic Drug for Conjuctivitis}
\author{}\makeatletter 
\makeatletter
\newcommand*{\cleartoleftpage}{%
  \clearpage
    \if@twoside
    \ifodd\c@page
      \hbox{}\newpage
      \if@twocolumn
        \hbox{}\newpage
      \fi
    \fi
  \fi
}
\makeatother
\makeatletter
\thispagestyle{empty}
\markright{\@title}\markboth{\@title}{\@author}
\renewcommand\small{\@setfontsize\small{9pt}{11pt}\abovedisplayskip 8.5\p@ plus3\p@ minus4\p@
\belowdisplayskip \abovedisplayskip
\abovedisplayshortskip \z@ plus2\p@
\belowdisplayshortskip 4\p@ plus2\p@ minus2\p@
\def\@listi{\leftmargin\leftmargini
               \topsep 2\p@ plus1\p@ minus1\p@
               \parsep 2\p@ plus\p@ minus\p@
               \itemsep 1pt}
}
\makeatother
\fvset{frame=single,numberblanklines=false,xleftmargin=5mm,xrightmargin=5mm}
\fancyhf{} 
\setlength{\headheight}{14pt}
\fancyhead[LE]{\bfseries\leftmark} 
\fancyhead[RO]{\bfseries\rightmark} 
\fancyfoot[RO]{}
\fancyfoot[CO]{\thepage}
\fancyfoot[LO]{\TheID}
\fancyfoot[LE]{}
\fancyfoot[CE]{\thepage}
\fancyfoot[RE]{\TheID}
\hypersetup{citebordercolor=0.75 0.75 0.75,linkbordercolor=0.75 0.75 0.75,urlbordercolor=0.75 0.75 0.75,bookmarksnumbered=true}
\fancypagestyle{plain}{\fancyhead{}\renewcommand{\headrulewidth}{0pt}}

\date{}
\usepackage{authblk}

\providecommand{\keywords}[1]
{
\footnotesize
  \textbf{\textit{Index terms---}} #1
}

\usepackage{graphicx,xcolor}
\definecolor{GJBlue}{HTML}{273B81}
\definecolor{GJLightBlue}{HTML}{0A9DD9}
\definecolor{GJMediumGrey}{HTML}{6D6E70}
\definecolor{GJLightGrey}{HTML}{929497} 

\renewenvironment{abstract}{%
   \setlength{\parindent}{0pt}\raggedright
   \textcolor{GJMediumGrey}{\rule{\textwidth}{2pt}}
   \vskip16pt
   \textcolor{GJBlue}{\large\bfseries\abstractname\space}
}{%   
   \vskip8pt
   \textcolor{GJMediumGrey}{\rule{\textwidth}{2pt}}
   \vskip16pt
}

\usepackage[absolute,overlay]{textpos}

\makeatother 
      \usepackage{lineno}
      \linenumbers
      
\begin{document}

             \author[1]{Mehul B.  Vyas}

             \author[2]{Dhaval  Patel}

             \author[3]{Dr. Samir  K.Shah}

             \affil[1]{  SARDAR PATEL COLLEGE OF PHARMACY, GUJARAT TECHNOLOGICAL UNIVERSITY}

\renewcommand\Authands{ and }

\date{\small \em Received: 6 April 2015 Accepted: 1 May 2015 Published: 15 May 2015}

\maketitle


\begin{abstract}
        


The purpose of present research work was to formulate and evaluate eye care solution of Naphazoline hydrochloride (Vasoconstrictor) and Pheniramine maleate (Antihistaminic) drug for allergic conjunctivitis. The optimum values of responses for viscous eye care solution formulation was found to be 97.6 cps viscosity, 1759 cps mucoadhesion index and 96.67 % CDR for naphazoline hydrochloride and 93.34% CDR for pheniramine maleate. These could be obtained at lower levels of NaCMC and higher level of HPMCE4M (0.25/0.6%w/w respectively).These viscous eye care solution showed acceptable physicochemical properties. The optimized formulation was found to be stable in one month study and providing prolonged release of the drug over an 8 hr period. Irritation study on rabbit eye revealed that it was non-irritant. All the rabbits? eyes were normal by the end of 5 hour without any redness. There were no other adverse affects on the eyes throughout 8 hours study. This proves that optimized formulations of viscous eye care solution were very effective against common allergic conditions.

\end{abstract}


\keywords{naphazoline hydrochloride, Pheniramine maleate, HPMC E4M, conjunctivitis.}

\begin{textblock*}{18cm}(1cm,1cm) % {block width} (coords) 
\textcolor{GJBlue}{\LARGE Global Journals \LaTeX\ JournalKaleidoscope\texttrademark}
\end{textblock*}

\begin{textblock*}{18cm}(1.4cm,1.5cm) % {block width} (coords) 
\textcolor{GJBlue}{\footnotesize \\ Artificial Intelligence formulated this projection for compatibility purposes from the original article published at Global Journals. However, this technology is currently in beta. \emph{Therefore, kindly ignore odd layouts, missed formulae, text, tables, or figures.}}
\end{textblock*}


\let\tabcellsep& 	 	 		 
\section[{I. Introduction}]{I. Introduction}\par
ustained and controlled delivery of drugs to the ocular tissues continue to remain a major objective for formulation scientists and engineers in light of the emergence of more potent drugs and biological response modifications with limited biological half-lives. In ophthalmic drug delivery, in the front of the eye, the major hurdles of optimum drug bioavailability include rapid turnover, lacrimal drainage, reflex blinking and drug dilution by tears. Another physiological constraint is the limited permeability of cornea resulting into low absorption of ophthalmic drugs. A major portion of the administered dose drains into the nasolacrimal duct and thus can cause unwanted systemic side effects. Additionally, the rapid elimination of the drug through the punctum results in a short duration of the therapeutic effect resulting in a frequent dosing regimen.\par
A significant challenge for the formulation is to circumvent these protective barriers of the eye without causing permanent damage to the tissue. Due to these physiological and anatomical barriers, only a very small fraction of the drug, usually 1-5\% or even less of the instilled dose, is effectively absorbed. Frequent instillations of eye care solution are necessary to maintain a therapeutic drug level in the tear film or at the site of action. The frequent use of ophthalmic solutions may induce toxic side effects and cellular damage at the ocular surface. Moreover, once-a-day or twice-a-day formulations would like to improve patient compliance. 
\section[{a) Materials}]{a) Materials}\par
Naphazoline hydrochloride, Pheniramine maleate, HPMC E4M, NaCMC, Benzalkonium chloride, Sodium chloride, NaoH. 
\section[{II. Methods}]{II. Methods}\par
To prepare viscous eye care solution, different concentrations of HPMC E4M and NaCMC as per 3 \hyperref[b1]{2} factorial design were used. In order to obtain clear viscous solutions, accurately weighed HPMC E4M and NaCMC were dispersed and thoroughly hydrated in about 30 ml of the required amount of WFI. The dispersion was vigorously stirred and heated to 80-90°C, until the solution became clear. Then add weighed quantity of Sodium Chloride, Disodium Edetate, Disodium Hydrogen Phosphate, Sodium Hydroxide and at last add weighed quantity of drugs and Benzalkonium Chloride in about 40-50\% of the required amount of WFI. Add this mixture to the dispersion of polymers while stirring. Adequate WFI was then added to obtain the required volume. The viscous solutions prepared with the excipients were sterilized at 121°C in autoclave for 20 min. Afterward, aqueous solutions were sterilized by filtration through 0.22 ?m sterile filter. The same formulation was prepared into simulated tear fluid in place of WFI. 
\section[{III. Experimental Design}]{III. Experimental Design}\par
Experimental designs are frequently used to establish an empirical relationship in terms of a mathematical model between dependent variables, and a number of factors or independent variables. To study all the possible combinations of all factors at all levels, a S Volume XV Issue II Version IYear 2 015 ( D D D D ) B\par
two factor, three level full factorial design was constructed and conducted in a fully randomized order. The experimental design consists of total 9 experiments. The concentration of HPMC E4M (X 1 ) and concentration of NaCMC (X 2 ) was selected as formulation (independent) variables. The factor levels were chosen from the knowledge obtained from the preliminary studies. All other formulation and process variables were kept invariant throughout the study. Table \hyperref[tab_1]{2} Summarizes the 9 experimental runs studied and their factor combinations and translation of the coded levels to the experimental units employed during the study. The viscosity (Y 1 ), Mucoadhesion index (Y 2 ), cumulative percentage drug released after 8 hrs. (Y 3 ) were studied as response variables (dependent variables).Design-Expert software (V.8.0.7.1, Stat-Ease Inc.) was used for the generation of the mathematical models.  iv. Osmolarity The osmolarity of optimized sterilized viscous eye care solution was determined with a vapor pressure osmometer at room temperature. 
\section[{v. Mucoadhesion Tes}]{v. Mucoadhesion Tes}\par
Mucin dispersion method was used to measure mucoadhesion index. Mucin Dispersion (MUC): MUC (15\%w/v) was prepared by dispersing required amount of Mucin powder -into phosphate buffer (pH 7.4 ) and kept on magnetic stirrer at 600 rpm for 24 hrs for complete hydration and measured it viscosity (?m). To study the mucoadhesive interaction, 5 ml of polymer dispersion (?p) and 15 ml of MUC was mixed and determined its viscosity (?t) at 37°±1°C at shear rates D of 12.5, 25, 50, and 100 s -1 . An interaction between polymer and mucin should be seen as a synergistic effect in the rheological properties, which means that the rheological response of the Polymer/MUC mixture should be larger than the sum of the rheological responses of the single components polymer and mucin. Therefore, it is essential to rheologically characterise the single components as well as the polymer/MUC mixture.Trial No. Coded Factor X 1 Conc.of HPMC E4M (\%w/v) X 2 Conc. Of NaCMC (\%w/v) F1 1 1 F2 1 0 F3 1 -1 F4 0 1 F5 0 0 F6 0 -1 F7 -1 1 F8 -1 0 F9 -1 -1\par
vi. Sterilization Study Membrane filter of 0.2-?m porosity was used for sterilization by filtration in ?m aseptic area. The suitability of both methods of sterilization in the present study was tested by determining drug content of representative eye solution formulation of (aqueous based) before and after subjecting to sterilization by the respective method. Aqueous base solutions were prepared with 1 \% drug and other excipients filled in vials and sealed. These vials were autoclaved for 20 minutes. In some other vials, solutions were filled by filtration through 0.2?m Millex, Millipore filter. 
\section[{vii. Sterility testing}]{vii. Sterility testing}\par
The sterility testing of the viscous eye care solution was performed for the aerobic, anaerobic bacteria and fungi by using alternative thioglycolate medium (ATGM) and soyabean casein digest medium (SBCD). The positive control (growth promotion), negative control (sterlity) test was also conducted. Bacillus subtilis was used as a test organism in the case of aerobic bacteria test. Bacterio desvulgatus was used as a test organism in case of anaerobic bacteria test and candida albicans in fungi test. Incubation was carried in all cases and growth was checked. All the samples were inoculated separately in to ATGM and SBCD media and incubated at 35°C and 20-25°C, respectively for 7 days. Similarly unsterilized samples of films were also inoculated separately in to ATGM and SBCD media and incubated at 35°C and 20-25°C, respectively for 7 days. A control evaluation was also carried out.\par
viii. Antimicrobial Test The test was performed according to USP. Cultures of bacteria [Escherichia coli (ATCC 4352), Pseudomonas aeruginosa (ATCC 9027), Staphylococcus aureus (ATCC 6538)] and fungi [Aspergillus niger (ATCC 16404) and Candida albicans (ATCC 10231)] were grown on solid agar media and soyabean casein digest media respectively. The test microorganism cultures were diluted with sterile WFI to obtain 10 -6 CFU/ml as per USP. All the cultures were transferred into 5 test tubes containing 10ml prepared eye drops(solution) and 0.1\% prepared cultures in each. Initial counts were noted. These solutions were poured into petri plate containing Soya bean Casein Digest Agar Medium for bacterial cultures and Sabouraud Glucose Agar Medium for fungi. Keep them into incubator at 32.5±2.5ºC and 22.5±2.5ºC for bacteria and fungi respectively. Record the numbers of colony of microorganism at 7 th , 14 th and 28 th day. Check the criteria for preservative effectiveness for their acceptable range.\par
ix. Invitro Diffusion study The Franz diffusion cell was used for studying the in vitro release of the viscous eye care solution(drops). A cellulose acetate membrane (Dialysis membrane with 25 mm diameter) was adapted to the terminal portion of the cylindrical donor compartment. 2.5 mL viscous eye drops containing drug, sufficient for establishing sink conditions for the assay was placed into the donor compartment. The receptor compartment contained 15 mL of Phosphate buffer solution of pH 7.4 maintained at 37°C under mild agitation using a magnetic stirrer. At specific time intervals, aliquots of 3mL will be withdrawn and immediately restored with the same volume of fresh phosphate buffer. The amount of drug released was assessed by measuring the absorbance at 261.6 nm and 272.4nm for Naphazoline and Pheniramine respectively using UV spectrophotometers. In order to analyze the drug release mechanism, in vitro release data was fitted into a zero-order, first order, Higuchi, And Korsmeyerpeppas model.\par
x To assess the drug and formulation stability, stability studies was done according to ICH guidelines. Optimized formulation was kept in the stability chamber at specified temperature and humidity (40°±10°C and 75\%RH) for one month. The chemical stability of the formulation was assessed by the estimation of the percentage drug remaining in the formulation and physical stability was evaluated by monitoring any change in pH, viscosity and appearance.\par
Volume XV Issue II Version I  
\section[{Result and Discussion}]{Result and Discussion}\par
Development of first order derivative spectroscopy method for simultaneous determination of NH and PM:-Selection of wavelength for simultaneous estimation of NH and PM :-      
\begin{quote}
Figure 1\end{quote}

\begin{quote}
Figure 11 Figure 12\end{quote}
 
\section[{a) pH}]{a) pH}\par
The pH values for all formulations were shown in Table \hyperref[tab_4]{4}. The pH was within acceptable range (6.8 to 7.4) and would not cause any irritation upon administration of the formulation. 
\section[{b) Refractive index}]{b) Refractive index}\par
Refractive index of tear fluid is 1.340 to 1.360. (Hussein et al.2009) It is recommended that eye care solution should have refractive index values not higher than 1.476. Table \hyperref[tab_4]{4} depicts that Naphazoline hydrochloride and Pheniramine maleate viscous eye care solution had refractive index values ranging from 1.443 to 1.334 which are within the recommended values. Data reflected that no visual problem may cause in patient after administration of formulation. 
\section[{c) Viscosity}]{c) Viscosity}\par
The longer contact time and effectiveness of the formulation in the eye is probably dependent not only on its mucoadhesive properties, but also on its viscosity and bulk rheological properties. Viscosity data of all the batches are shown in figures. Viscosity study in phosphate buffer 7.4 pH and in simulated tear fluid was carried out. From the rheograms shown in Fig.  {\ref 14} \& 15 medium remain same. From the data, it was found that batches F1, F4 and F7 shows very high viscosity due to highest concentration of NaCMC; was not selected as they were too viscous to instill properly into the eye. While, batches F6, F8 and F9 shows low viscosity due to lowest concentrations 0.5\% HPMC, was not selected as aim of this study was to increase the viscosity of the formulations developed for residence time in ocular globe. Batches F3, F5 and F7 showed satisfactory viscosity. Each batch showed non-newtonian (dilatant) flow behaviour without any hysteresis. Non-newtonian solutions offer less resistance to movement of the eyelids over the globe and, therefore, are expected to be more comfortable in the eye than Newtonian solutions. By using the viscolysers like HPMC and NaCMC, viscosity of the prepared eye care solution was increased which gives longer contact time to the ocular globe. Therefore frequency of the instillation is decreased, which improves patient compliance. This increasing shear rate mimic ocular shear rates and respectively was found that viscosity in both the associated with normal blinking which is extremely wide, ranging from 0.03-28500S -1 .    \hyperref[tab_7]{7} and as per USP there should be 1 log reduction after 7 days, 3 log reductions after 14 days and no growth in population as compare to 14 th day after 28 days. In case of fungi, as per USP, there should be no growth/inhibition for AET. Optimized batch was obeyed the similar pattern of reduction in population as per standard limit and complies with the results.    
\section[{Figure 14}]{Figure 14}
\begin{quote}
Figure 15\end{quote}

\begin{quote}
Figure 17 Figure 18 Figure 19\end{quote}
 
\section[{f) Osmolarity}]{f) Osmolarity}\par
The Osmolarity of the ophthalmic preparation should be in the range of 310-350 mOsmol/kg to avoid irritation. Osmolarity of optimized batches was found to be in the range and shows 325 mOsmol/kg which was within the acceptable tonicity range of the eye to avoid ocular irritation. V. 
\section[{g) Animal Study}]{g) Animal Study} 
\section[{Conclusion}]{Conclusion}\par
Thus, on the basis of all the studies we can conclude that the batch having naphazoline hydrochloride and pheniramine maleate along with 0.59 \% of HPMC E4M in the combination with 0.26 \% NaCMC viscous solution may be considered as a promising for ophthalmic drug delivery.If the aforementioned formulation will scaled-up to manufacturing level, it will be used for potential sustained release effect for the allergic conjuctivitis. \begin{figure}[htbp]
\noindent\textbf{}\includegraphics[]{image-2.png}
\caption{\label{fig_0}}\end{figure}
 \begin{figure}[htbp]
\noindent\textbf{243}\includegraphics[]{image-3.png}
\caption{\label{fig_1}Figure 2 Figure 4 yFigure 3 y}\end{figure}
 \begin{figure}[htbp]
\noindent\textbf{5}\includegraphics[]{image-4.png}
\caption{\label{fig_2}Figure 5 :}\end{figure}
 \begin{figure}[htbp]
\noindent\textbf{7}\includegraphics[]{image-5.png}
\caption{\label{fig_3}Figure 7 :}\end{figure}
 \begin{figure}[htbp]
\noindent\textbf{13}\includegraphics[]{image-6.png}
\caption{\label{fig_4}Figure 13}\end{figure}
 \begin{figure}[htbp]
\noindent\textbf{}\includegraphics[]{image-7.png}
\caption{\label{fig_5}}\end{figure}
 \begin{figure}[htbp]
\noindent\textbf{5}\includegraphics[]{image-8.png}
\caption{\label{fig_6}5 )}\end{figure}
 \begin{figure}[htbp]
\noindent\textbf{20}\includegraphics[]{image-9.png}
\caption{\label{fig_7}Figure 20}\end{figure}
 \begin{figure}[htbp]
\noindent\textbf{10}\includegraphics[]{image-10.png}
\caption{\label{fig_8}4 12 x 10 3}\end{figure}
 \begin{figure}[htbp]
\noindent\textbf{}\includegraphics[]{image-11.png}
\caption{\label{fig_9}}\end{figure}
 \begin{figure}[htbp]
\noindent\textbf{1} \par 
\begin{longtable}{P{0.45\textwidth}P{0.22999999999999998\textwidth}P{0.13333333333333333\textwidth}P{0.03666666666666667\textwidth}}
Independent Variables\tabcellsep \tabcellsep Levels\tabcellsep \\
\tabcellsep Low\tabcellsep Medium\tabcellsep High\\
X 1 = Concentration of HPMC E4M (\% W/V)\tabcellsep 0.5\tabcellsep 0.55\tabcellsep 0.6\\
X 2 = Concentration of NaCMC (\% W/V)\tabcellsep 0.25\tabcellsep 0.4\tabcellsep 0.5\\
Transformed values\tabcellsep -1\tabcellsep 0\tabcellsep 1\\
\tabcellsep \tabcellsep Y 1 = Viscosity(cps)\tabcellsep \\
Dependent variables\tabcellsep \multicolumn{2}{l}{Y 2 = Mucoadhesive Index}\tabcellsep \\
\tabcellsep \multicolumn{3}{l}{Y 3 = Drug Release in 8 hr(\%CDR)}\end{longtable} \par
 
\caption{\label{tab_0}Table 1 :}\end{figure}
 \begin{figure}[htbp]
\noindent\textbf{2} \par 
\begin{longtable}{P{0.85\textwidth}}
a) Evaluation Parameters\\
i. Clarity\\
Clarity test was done by visual inspection of\\
each container and by measuring the refractive index\\
using refractometer at 25°c.\\
ii. PH\\
PH of prepared viscous eye care solution was\\
measured with pH meter.\\
iii. Viscosity\\
Viscosity of batches F1-F9 by Brookfield\\
viscometer at different RPM. By plotting graph of RPM\\
vs. viscosity, flow pattern was checked.\end{longtable} \par
 
\caption{\label{tab_1}Table 2 :}\end{figure}
 \begin{figure}[htbp]
\noindent\textbf{3} \par 
\begin{longtable}{P{0.85\textwidth}}
Name of components\end{longtable} \par
 
\caption{\label{tab_3}Table 3 :}\end{figure}
 \begin{figure}[htbp]
\noindent\textbf{4} \par 
\begin{longtable}{P{0.06015384615384615\textwidth}P{0.25369230769230766\textwidth}P{0.2353846153846154\textwidth}P{0.3007692307692308\textwidth}}
Batch\tabcellsep Clarity\tabcellsep pH (n= 3)\tabcellsep Refractive Index\\
F1\tabcellsep Slightly translucent\tabcellsep 7.40±0.02\tabcellsep 1.469±0.001\\
F2\tabcellsep Clear\tabcellsep 7.40±0.01\tabcellsep 1.431±0.001\\
F3\tabcellsep Clear\tabcellsep 7.41±0.01\tabcellsep 1.356±0.001\\
F4\tabcellsep Slightly translucent\tabcellsep 7.40±0.01\tabcellsep 1.465±0.002\\
F5\tabcellsep Clear\tabcellsep 7.40±0.03\tabcellsep 1.358±0.002\\
F6\tabcellsep Clear\tabcellsep 7.40±0.01\tabcellsep 1.341±0.001\\
F7\tabcellsep Slightly translucent\tabcellsep 7.41±0.01\tabcellsep 1.471±0.001\\
F8\tabcellsep Clear\tabcellsep 7.41±0.02\tabcellsep 1.341±0.002\\
F9\tabcellsep Clear\tabcellsep 7.40±0.01\tabcellsep 1.334±0.001\end{longtable} \par
 
\caption{\label{tab_4}Table 4 :}\end{figure}
 \begin{figure}[htbp]
\noindent\textbf{5} \par 
\begin{longtable}{P{0.6900369003690037\textwidth}P{0.043911439114391146\textwidth}P{0.07214022140221402\textwidth}P{0.043911439114391146\textwidth}}
Batch\tabcellsep Media\tabcellsep \tabcellsep Result\\
\tabcellsep ATGM\tabcellsep SBCD\tabcellsep \\
F*\tabcellsep Clear\tabcellsep Clear\tabcellsep Complies\\
\multicolumn{3}{l}{ATGM-Alternative Thio glycolate media; SBCD -Soya bean casein digest media}\tabcellsep \\
\multicolumn{2}{l}{e) Antimicrobial efficacy testing (AET)}\tabcellsep shown in Table\tabcellsep \\
\multicolumn{2}{l}{The microbial count for bacteria (Escherichia coli,}\tabcellsep \tabcellsep \\
\multicolumn{2}{l}{Pseudomonas aeruginosa, Staphylococcus aureus) is}\tabcellsep \tabcellsep \end{longtable} \par
 
\caption{\label{tab_5}Table 5 :}\end{figure}
 \begin{figure}[htbp]
\noindent\textbf{6} \par 
\begin{longtable}{P{0.25437956204379564\textwidth}P{0.05583941605839416\textwidth}P{0.1240875912408759\textwidth}P{0.0062043795620437955\textwidth}P{0.0062043795620437955\textwidth}P{0.1364963503649635\textwidth}P{0.012408759124087591\textwidth}P{0.14270072992700727\textwidth}P{0.0062043795620437955\textwidth}P{0.09927007299270073\textwidth}P{0.0062043795620437955\textwidth}}
Culture\tabcellsep Batch\tabcellsep \multicolumn{2}{l}{Initial}\tabcellsep \tabcellsep \multicolumn{2}{l}{7 th day}\tabcellsep \multicolumn{2}{l}{14 th day}\tabcellsep \multicolumn{2}{l}{28 th day}\\
Candida albicans\tabcellsep F*\tabcellsep \multicolumn{2}{l}{15 x 10}\tabcellsep 6\tabcellsep 85 x 10\tabcellsep 5\tabcellsep 46 x 10\tabcellsep 4\tabcellsep 33 x 10\tabcellsep 3\\
Aspergillus Nniger\tabcellsep F*\tabcellsep 9 x 10\tabcellsep \multicolumn{2}{l}{6}\tabcellsep 34 x 10\tabcellsep 5\tabcellsep 52 x 10\tabcellsep \tabcellsep \end{longtable} \par
 
\caption{\label{tab_6}Table 6 :}\end{figure}
 \begin{figure}[htbp]
\noindent\textbf{7} \par 
\begin{longtable}{P{0.31875\textwidth}P{0.053125\textwidth}P{0.13522727272727272\textwidth}P{0.014488636363636362\textwidth}P{0.14005681818181817\textwidth}P{0.014488636363636362\textwidth}P{0.08693181818181818\textwidth}P{0.08693181818181818\textwidth}}
Culture\tabcellsep Batch\tabcellsep Initial\tabcellsep \tabcellsep \multicolumn{2}{l}{7 th day}\tabcellsep 14 th day\tabcellsep 28 th day\\
Escherichia Coli\tabcellsep F*\tabcellsep 25 x 10\tabcellsep 5\tabcellsep 18 x 10\tabcellsep 4\tabcellsep 300\tabcellsep 253\\
Pseudomonas aeruginosa\tabcellsep F*\tabcellsep 19 x 10\tabcellsep 5\tabcellsep 11 x 10\tabcellsep 4\tabcellsep 287\tabcellsep 218\\
Staphylococcus aureus\tabcellsep F*\tabcellsep 22 x 10\tabcellsep 5\tabcellsep 13 x 10\tabcellsep 4\tabcellsep 240\tabcellsep 198\end{longtable} \par
 
\caption{\label{tab_7}Table 7 :}\end{figure}
 \begin{figure}[htbp]
\noindent\textbf{8} \par 
\begin{longtable}{P{0.31166666666666665\textwidth}P{0.035416666666666666\textwidth}P{0.035416666666666666\textwidth}P{0.09208333333333334\textwidth}P{0.035416666666666666\textwidth}P{0.035416666666666666\textwidth}P{0.035416666666666666\textwidth}P{0.035416666666666666\textwidth}P{0.035416666666666666\textwidth}P{0.09208333333333334\textwidth}P{0.035416666666666666\textwidth}P{0.035416666666666666\textwidth}P{0.035416666666666666\textwidth}}
FORMULATION\tabcellsep \tabcellsep \tabcellsep \multicolumn{2}{l}{RABBIT A}\tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \multicolumn{2}{l}{RABBIT B}\tabcellsep \tabcellsep \\
TIME (HR.)\tabcellsep 1\tabcellsep 2\tabcellsep 3\tabcellsep 4\tabcellsep 5\tabcellsep 6\tabcellsep 1\tabcellsep 2\tabcellsep 3\tabcellsep 4\tabcellsep 5\tabcellsep 6\\
F*\tabcellsep N\tabcellsep N\tabcellsep N\tabcellsep N\tabcellsep N\tabcellsep N\tabcellsep -\tabcellsep -\tabcellsep -\tabcellsep -\tabcellsep -\tabcellsep -\\
CONTROL\tabcellsep N\tabcellsep N\tabcellsep N\tabcellsep N\tabcellsep N\tabcellsep N\tabcellsep -\tabcellsep -\tabcellsep -\tabcellsep -\tabcellsep -\tabcellsep -\\
OPCON A\tabcellsep -\tabcellsep -\tabcellsep -\tabcellsep -\tabcellsep -\tabcellsep -\tabcellsep N\tabcellsep N\tabcellsep N\tabcellsep N\tabcellsep N\tabcellsep N\\
CONTROL\tabcellsep -\tabcellsep -\tabcellsep -\tabcellsep -\tabcellsep -\tabcellsep -\tabcellsep N\tabcellsep N\tabcellsep N\tabcellsep N\tabcellsep N\tabcellsep N\end{longtable} \par
  {\small\itshape [Note: S-Severe itching / irritation, M-Mild itching / irritation, N-No itching / irritation Stability]} 
\caption{\label{tab_8}Table 8 :}\end{figure}
 \begin{figure}[htbp]
\noindent\textbf{9} \par 
\begin{longtable}{P{0.1913612565445026\textwidth}P{0.10680628272251308\textwidth}P{0.1824607329842932\textwidth}P{0.1824607329842932\textwidth}P{0.1869109947643979\textwidth}}
Days\tabcellsep pH*\tabcellsep Assay of NH (\% w/v)*\tabcellsep Assay of PM (\% w/v)*\tabcellsep Assay of BKC (\% w/v)*\\
15\tabcellsep 7.4 ± 0.02\tabcellsep 99.60±0.54\tabcellsep 99.34±0.34\tabcellsep 99.79±0.64\\
30\tabcellsep 7.41 ± 0.01\tabcellsep 99.41±0.83\tabcellsep 98.76±0.43\tabcellsep 99.58±0.90\\
\multicolumn{3}{l}{*Value Expressed as Mean ± SD (n=3)}\tabcellsep \tabcellsep \end{longtable} \par
 
\caption{\label{tab_9}Table 9 :}\end{figure}
 			\footnote{© 2015 Global Journals Inc. (US)} 			\footnote{Formulation \& Evaluation of Eye Care Solution of Vasoconstrictor and Antihistaminic Drug for Conjuctivitis} 			\footnote{© 2015 Global Journals Inc. (US) Year 2 015} 		 		\backmatter  			  				\begin{bibitemlist}{1}
\bibitem[ Ophthalmol. Vis. Sci ()]{b13}\label{b13} 	 		\textit{},  	 	 		\textit{Ophthalmol. Vis. Sci}  		2003. 44 p. .  	 
\bibitem[Unlu and Ludwig ()]{b33}\label{b33} 	 		‘A comparative rheological study on carbopol viscous solutions and evaluation of their suitability as the ophthalmic vehicle and artificial tears’.  		 			N Unlu 		,  		 			A Ludwig 		.  	 	 		\textit{Pharma Act}  		1992. 67  (1)  p. .  	 
\bibitem[Sharma ()]{b17}\label{b17} 	 		‘A novel approach sustained ocular drug delivery: In-situ Gel’.  		 			Hitesh Sharma 		.  	 	 		\textit{International Journal of Research in Pharmacy and Life Science}  		2013. 1  (2)  p. .  	 
\bibitem[Mayol and Quaglia ()]{b58}\label{b58} 	 		‘A novel poloxamers/ hyaluronic acid in situ forming hydrogel for drug delivery: rheological, mucoadhesive and in vitro release properties’.  		 			L Mayol 		,  		 			F Quaglia 		.  	 	 		\textit{European Journal of Pharm and Biopharms}  		2008. 70 p. .  	 
\bibitem[Lopez ()]{b34}\label{b34} 	 		‘A poloxamer/chitosan in situ forming gel with prolonged retention time for ocular delivery’.  		 			Vianna Lopez 		.  	 	 		\textit{European Journal of Pharmaceutics and Biopharmaceutics}  		2010. 75 p. .  	 
\bibitem[Shetty and Charyulu ()]{b60}\label{b60} 	 		‘A study on stability and in-vivo drug release of naphazoline and antazoline in situ gelling systems for ocular delivery’.  		 			G N Shetty 		,  		 			R N Charyulu 		.  	 	 		\textit{Int J of Pharm Bio Sci}  		2013. 4  (1)  p. .  	 
\bibitem[Mark]{b23}\label{b23} 	 		\textit{Allergic conjunctivitis: update on pathophysiology and prospects for future treatment},  		 			Santa J Mark 		,  		 			BA 		.  		 	 
\bibitem[Rathore and Nima ()]{b21}\label{b21} 	 		‘An insight into ophthalmic drug delivery system’.  		 			K S Rathore 		,  		 			R K Nima 		.  	 	 		\textit{International Journal of Pharmaceutical Science and Drug Research}  		2009. 47 p. .  	 
\bibitem[Rathore ()]{b2}\label{b2} 	 		‘An overview and advancement in ocular drug delivery systems’.  		 			Rathore 		.  	 	 		\textit{International Journal of Pharmaceutical Science \& Research}  		2010. 46 p. .  	 
\bibitem[Eva and Del Amo ()]{b3}\label{b3} 	 		‘Current and future ophthalmic drug delivery systems, A Shift to the posterior segment’.  		 			M Eva 		,  		 			Atourtti Del Amo 		.  	 	 		\textit{Drug Discovery Today}  		2008. 13 p. .  	 
\bibitem[Mark and Babizhayev ()]{b18}\label{b18} 	 		‘Current ocular drug delivery challenges for N-acetyloxcarnosine: novel patented routes and modes of delivery, design for enhancement of therapeutic activity and drug delivery relationships’.  		 			A Mark 		,  		 			Babizhayev 		.  	 	 		\textit{Drug Delivery \& Formulation}  		2009. 18 p. .  	 	 (Recent Patents on) 
\bibitem[Bisca ()]{b0}\label{b0} 	 		‘Current therapy of allergic conjunctivitis’.  		 			M Bisca 		.  	 	 		\textit{Current Therapeutic Research}  		1997. 58 p. .  	 
\bibitem[Jansook and Stefánsson ()]{b53}\label{b53} 	 		‘Cyclodextrin solubilization of carbonic anhydrase inhibitor drugs: formulation of dorzolamide eye drop microparticle suspension’.  		 			P Jansook 		,  		 			E Stefánsson 		.  	 	 		\textit{European Journal of Pharmaceutics and Biopharmaceutics}  		2010. 76 p. .  	 
\bibitem[Patel and Shastri ()]{b48}\label{b48} 	 		‘Development and evaluation of pH triggered in-situ ophthalmic gel formulation of ofloxacin’.  		 			P B Patel 		,  		 			D H Shastri 		.  	 	 		\textit{American Journal of Pharmtech Research}  		2011. 1 p. .  	 
\bibitem[Moya-Ortega ()]{b6}\label{b6} 	 		‘Dexamethasone eye drops containing alpha cyclodextrin-based nanogels’.  		 			Maria D Moya-Ortega 		.  	 	 		\textit{International Journal of Pharmaceutics}  		2013.  (44)  p. .  	 
\bibitem[Kulkarni and Sandeep ()]{b49}\label{b49} 	 		‘Effect of a single drop of latanoprost ophthalmic gel on intra ocular pressure in the treatment of glaucoma’.  		 			S V Kulkarni 		,  		 			H N Sandeep 		.  	 	 		\textit{International Journal of Pharmaceutical Sciences}  		2010. 2 p. .  	 
\bibitem[Jingcai ()]{b41}\label{b41} 	 		\textit{Eye preparation for treating medicine, US Patents 03132242},  		 			Forming Jingcai 		.  		2004.  	 
\bibitem[Kaur ()]{b39}\label{b39} 	 		‘Formulation and evaluation of ophthalmic preparations of acetazolamide’.  		 			I P Kaur 		.  	 	 		\textit{International Journal of Pharmaceutics}  		2000. 199 p. .  	 
\bibitem[Sibelbozdag ()]{b36}\label{b36} 	 		‘Formulation and Invitro evaluation of cysteamine hydrochloride viscous solution for treatment of corneal cystinosis’.  		 			Koraygum Sibelbozdag 		.  	 	 		\textit{European Journal of Pharmaceutics and Biopharmaceutics}  		2008. 70 p. .  	 
\bibitem[Sibelbozdag ()]{b47}\label{b47} 	 		‘Formulation and Invitro evaluation of cysteamine hydrochloride viscous solution for treatment of corneal cystinosis’.  		 			Koraygum Sibelbozdag 		.  	 	 		\textit{European Journal of Pharmaceutics and Biopharmaceutics}  		2008. 70 p. .  	 
\bibitem[Sibelbozdag ()]{b51}\label{b51} 	 		‘Formulation and Invitro evaluation of cysteamine hydrochloride viscous solution for treatment of corneal cystinosis’.  		 			Koraygumu Sibelbozdag 		.  	 	 		\textit{European Journal of Pharmaceutics and Biopharmaceutics}  		2008. 70 p. .  	 
\bibitem[Raymond et al. ()]{b29}\label{b29} 	 		\textit{Handbook of Pharmaceutical Excipients},  		 			C Raymond 		,  		 			Rowa 		,  		 			C Siân 		,  		 			Owen 		.  		2006. The Pharmaceutical Press. p. .  	 	 (6 th edn) 
\bibitem[Raymond et al. ()]{b31}\label{b31} 	 		\textit{Handbook of Pharmaceutical Excipients},  		 			C Raymond 		,  		 			Rowa 		,  		 			C Siân 		,  		 			Owen 		.  		2006. The Pharmaceutical Press. p. .  	 	 (6 th edn) 
\bibitem[Raymond et al. ()]{b32}\label{b32} 	 		\textit{Handbook of Pharmaceutical Excipients},  		 			C Raymond 		,  		 			Rowa 		,  		 			C Siân 		,  		 			Owen 		.  		2006. The Pharmaceutical Press. p. .  	 	 (6 th edn) 
\bibitem[Joossand and Chirmule ()]{b20}\label{b20} 	 		‘Immunity to adenovirus and adeno-associated viral vectors: implications for gene therapy’.  		 			K Joossand 		,  		 			N Chirmule 		.  	 	 		\textit{Gene Therapy}  		2003. 10 p. .  	 
\bibitem[Kyyronen ()]{b46}\label{b46} 	 		‘Improved ocular: systemic absorption ratio of timolol by viscous vehicle and phenylephrine’.  		 			Krisriino Kyyronen 		,  		 			Arrourrri 		.  	 	 		\textit{Investigative Ophthalmology \& Visual Science}  		1990. 15 p. .  	 
\bibitem[Attwood ()]{b38}\label{b38} 	 		‘In-situ gelling xyloglucan formulations for sustained release ocular delivery of pilocarpine hydrochloride’.  		 			D Attwood 		.  	 	 		\textit{International Journal of Pharmaceutics}  		2001. p. 229.  	 
\bibitem[Sankara ()]{b61}\label{b61} 	 		‘In-vivo evaluation of dexamethasone sodium phosphate nanoparticles for post cataract treatment’.  		 			V Sankara 		.  	 	 		\textit{Pharmacologyonline}  		2009. 8 p. .  	 
\bibitem[Ya and Lehmussaari ()]{b1}\label{b1} 	 		‘Industrial perspective in ocular drug delivery’.  		 			Ali Ya 		,  		 			K Lehmussaari 		.  	 	 		\textit{Advanced Drug Delivery Reviews}  		2006. 58 p. .  	 
\bibitem[Santvliet and Ludwig ()]{b27}\label{b27} 	 		‘Influence of the physico-chemical properties of ophthalmic viscolysers on the weight of drops dispensed from a flexible dropper bottle’.  		 			Van Santvliet 		,  		 			A K Ludwig 		.  	 	 		\textit{European Journal of Pharmaceutical Sciences}  		1999. 95 p. .  	 
\bibitem[Bourges and Behar-Cohen ()]{b14}\label{b14} 	 		‘Intraocular implants for extended drug delivery: therapeutic applications’.  		 			J L Bourges 		,  		 			F Behar-Cohen 		.  	 	 		\textit{Adv. Drug Delivery Review}  		2006. 58 p. .  	 
\bibitem[Farnes ()]{b44}\label{b44} 	 		\textit{Ketorolac tromethamine compositions for treating ocular pain},  		 			Farnes 		.  		 US Patents 12/396.  		2009. 131.  	 
\bibitem[Hathout and Mansour ()]{b9}\label{b9} 	 		‘Liposomes as an ocular delivery system for acetazolamide: in-vitro and in vivo studies’.  		 			R M Hathout 		,  		 			S Mansour 		.  	 	 		\textit{Aaps Pharm scitech}  		2007. 8  (1) .  	 
\bibitem[Hutterer ()]{b42}\label{b42} 	 		\textit{Method and composition for treatment of skin conditions, US Patents PCT},  		 			Jeffrey Hutterer 		.  		US2005/010269,2005.  	 
\bibitem[Mj and Kohli ()]{b7}\label{b7} 	 		‘Microemulsion as potential drug delivery system’.  		 			Ansari Mj 		,  		 			Kohli 		.  	 	 		\textit{Pdaj. Pharma Science Techno}  		2008. 62 p. .  	 
\bibitem[Soumendra Sahoo and Al ()]{b28}\label{b28} 	 		‘Mucoadhesive nanopolymer -a novel drug carrier for topical ocular drug delivery’.  		 			Soumendra Sahoo 		,  		 			Al 		.  	 	 		\textit{European Journal of Scientific Research}  		2010. 46 p. .  	 
\bibitem[Hussein and Salama ()]{b50}\label{b50} 	 		‘Nanoemulsion as a potential ophthalmic delivery system for dorzolamide hydrochloride’.  		 			O A Hussein 		,  		 			H A Salama 		.  	 	 		\textit{AAPS Pharmscitech}  		2009. 10 p. .  	 
\bibitem[Kassem and Abdelrahman ()]{b8}\label{b8} 	 		‘Nanosuspension as an ophthalmic delivery system for certain glucocorticoid drugs’.  		 			M A Kassem 		,  		 			A A Abdelrahman 		.  	 	 		\textit{Int. J. Pharm}  		2007. 340 p. .  	 
\bibitem[Bourges and Gautier]{b12}\label{b12} 	 		\textit{Ocular drug delivery targeting the retina and retinal pigment epithelium using polylactide nanoparticles},  		 			J L Bourges 		,  		 			S E Gautier 		.  		 	 	 (Invest) 
\bibitem[Dm and Mishima ()]{b4}\label{b4} 	 		‘Ocular pharmacokinetics’.  		 			Maurice Dm 		,  		 			S P Mishima 		.  	 	 		\textit{Handbook Of Experimental Pharmacology}  		1984. Berlin-Heidelberg Publication. p. .  	 	 (15th Edition) 
\bibitem[Denick and Hu ()]{b43}\label{b43} 	 		\textit{Ophthalmic compositions including glycerin and propylene glycol, US Patents US 08/794},  		 			John Denick 		,  		 			Zhenze Hu 		.  		1998. 690.  	 
\bibitem[Bourlais and Acar ()]{b55}\label{b55} 	 		‘Ophthalmic drug delivery systems recent advances’.  		 			C L Bourlais 		,  		 			L Acar 		.  	 	 		\textit{Progress In Retinal And Eye Research}  		1998. 17 p. .  	 
\bibitem[Gulsenand and Chauhan ()]{b16}\label{b16} 	 		‘Ophthalmic drug delivery through contact lenses’.  		 			D Gulsenand 		,  		 			A Chauhan 		.  	 	 		\textit{Invest Ophthalmol Vis Science}  		2004. 45 p. .  	 
\bibitem[Olejnik and Wendel ()]{b45}\label{b45} 	 		\textit{Ophthalmic formulation, US Patents US 081329},  		 			Orest Olejnik 		,  		 			Fred W Wendel 		.  		1997. 808.  	 
\bibitem[Jack ()]{b37}\label{b37} 	 		‘Pheniramine maleate/naphazoline hydrochloride ophthalmic solution and olopatadine hydrochloride ophthalmic solution in the conjunctival allergen challenge model’.  		 			V G Jack 		.  	 	 		\textit{Clinical Therapeutics}  		2005. p. 27.  	 
\bibitem[Vandammeand and Brobeck ()]{b10}\label{b10} 	 		‘Poly (amidoamine) dendrimers as ophthalmic vehicles for ocular delivery of pilocarpine nitrate and tropicamide’.  		 			T F Vandammeand 		,  		 			L Brobeck 		.  	 	 		\textit{J. Control Release}  		2007. 4 p. .  	 
\bibitem[Sigrid ()]{b52}\label{b52} 	 		‘Polyacrylic acid/ polyvinylpyrrolidone bipolymeric systems.i. Rheological and mucoadhesive properties of formulations potentially useful for the treatment of dry-eye-syndrome’.  		 			Matthias O Sigrid 		,  		 			K 		.  	 	 		\textit{European Journal of Pharmaceutics and Biopharmaceutics}  		1999. 47 p. .  	 
\bibitem[Gaudana and Saih ()]{b5}\label{b5} 	 		‘Recent perspectives in ocular drug delivery-expert review’.  		 			Ripal Gaudana 		,  		 			And Saih 		,  		 			A 		.  	 	 		\textit{Pharmaceutical Research}  		2009. 26 p. .  	 
\bibitem[Colo and Zambito ()]{b57}\label{b57} 	 		‘Selected polysaccharide at comparison for their mucoadhesiveness and effect on precorneal resident of different drugs in rabbit model’.  		 			G D Colo 		,  		 			Y Zambito 		.  	 	 		\textit{Drug. Dev. and Ind. Pharmacy}  		2009. 35 p. .  	 
\bibitem[Kulkarni ()]{b54}\label{b54} 	 		‘Solubility enhancement of water insoluble drug for ophthalmic formulation’.  		 			Sunisha Kulkarni 		.  	 	 		\textit{Int. J. of Drug Delivery}  		2011.  (3)  p. .  	 
\bibitem[Masteikova and Chalupova ()]{b59}\label{b59} 	 		‘Stimuli-sensitive hydrogels in controlled and sustained drug delivery’.  		 			R Masteikova 		,  		 			Z Chalupova 		.  	 	 		\textit{Medicina}  		2003. 39 p. .  	 
\bibitem[Barretta and Nazzi ()]{b35}\label{b35} 	 		‘Synergistic interaction between TS-polysaccharide and hyaluronic acid: implications in the formulations of eye drops’.  		 			G U Barretta 		,  		 			S Nazzi 		.  	 	 		\textit{International Journal of Pharmaceutics}  		2011. 395 p. .  	 
\bibitem[Soumendra ()]{b30}\label{b30} 	 		‘Tamarind seed polysaccharide: a versatile biopolymer for mucoadhesive applications’.  		 			Sahoo Soumendra 		.  	 	 		\textit{Journal of Pharmaceutical and Biomedical Sciences}  		2010. 8  (20) .  	 
\bibitem[The Handbook of Ocular Disease Management]{b22}\label{b22} 	 		\textit{The Handbook of Ocular Disease Management},  		 	 
\bibitem[Annickludwig ()]{b26}\label{b26} 	 		‘The use of mucoadhesive polymers in ocular drug delivery’.  		 			Annickludwig 		.  	 	 		\textit{Advanced Drug Delivery Reviews}  		2005. 7 p. .  	 
\bibitem[Parkinson and Mundasad ()]{b19}\label{b19} 	 		‘Tolerance of ocular iontophoresis in healthy volunteers’.  		 			T M Parkinson 		,  		 			M Mundasad 		.  	 	 		\textit{J. Ocul. Pharmacol. Therapy}  		2003. 19 p. .  	 
\bibitem[Hh and Stefansson ()]{b15}\label{b15} 	 		‘Topical and systemic absorption in delivery of dexamethasone to the anterior and posterior segments of the eye’.  		 			Sigurdsson Hh 		,  		 			E Stefansson 		.  	 	 		\textit{Acta. Ophthalmol. Scand}  		2007. 85 p. .  	 
\bibitem[Zignani and Tabatabay ()]{b56}\label{b56} 	 		‘Topical semi-solid drug delivery: kinetics and tolerance of ophthalmic hydrogels’.  		 			M Zignani 		,  		 			C Tabatabay 		.  	 	 		\textit{Adv Drug Deliv Rev}  		1995. 16 p. .  	 
\bibitem[Felt ()]{b40}\label{b40} 	 		‘Topical use of chitosan in ophthalmology: tolerance assessment and evaluation of precorneal retention’.  		 			O Felt 		.  	 	 		\textit{International Journal of Pharmaceutics}  		1999. 180 p. .  	 
\bibitem[United State Pharmacopeia and National Formulary (USP 30)]{b24}\label{b24} 	 		\textit{United State Pharmacopeia and National Formulary (USP 30)},  		p. 2707.  	 	 (Naphazoline Hydrochloride Monograph) 
\bibitem[United State Pharmacopeia and National Formulary (USP 30)]{b25}\label{b25} 	 		\textit{United State Pharmacopeia and National Formulary (USP 30)},  		 	 	 (Pheniramine Maleate Monograph) 
\bibitem[Ip ()]{b11}\label{b11} 	 		‘Vesicular systems in ocular drug delivery’.  		 			Kaur Ip 		.  	 	 		\textit{Int. J. Pharm}  		2010. 2 p. .  	 
\end{bibitemlist}
 			 		 	 
\end{document}
