ME Paper Revised 2555

8/10/2019 ME Paper Revised 2555

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FORMULATION AND EVALUATION OF MELOXICAM GELS FOR TOPICAL

ADMINISTRATION

Nagia, A. El-Megrab; Haa, M. El-Na!a"# a$ Ge!a, F.%ala&a.

Department of Pharmaceutics. Faculty of Pharmacy . University of Zagazig. Egypt.

A%STRACT

For topical administration of meloxicam (ME! microemulsion gels and lipogels containing

either ethyl oleate or oleic acid as an oil phase "ere prepared. #n addition! $ydrogel and

hydroalcoholic gels containing car%opol &' as a gelling agent "ere also prepared. #n)vitro

drug release through cellophane mem%rane and permeation through the excised ra%%it s*in in

+,rensen-s phosphate %uffer (p$ .' containing /0 "1v sodium lauryl sulphate "ere

performed .2he influence of initial drug concentration (.3! .43! /0 "1" "as studied. 2he

permeation properties of ME from ethyl oleate microemulsion "hich is the %est formula

achieved "as studied in comparison to the commercially availa%le piroxicam gel. Moreover!

the anti)inflammatory activity of ME after oral and topical administration in rats "as studied

and compared to that of piroxicam gel. 2he results of an in)vitro drug release and its

percutaneous permeation revealed that the ethyloleate microemulsion gel sho"ed the highest

results. Meloxicam gel (ethyl oleate microemulsion gel /0 sho"ed good protection against

inflammation as compared to Feldene5 gel in rats.

INTRODUCTION

Meloxicam! a non)steroidal anti)inflammatory drug (6+7#D! is a preferential inhi%itor of

cyclooxygenase)8 and has demonstrated potent analgesic and anti)inflammatory activity after

oral administration (/. 6+7#Ds have %een "idely used in the treatment of rheumatoid

arthritis and other related conditions. $o"ever! they carry the ris* of undesira%le systemic

side effects and gastrointestinal irritation at the usual dose of oral administration (8.

9onsidering the fact that most inflammatory diseases occur locally and near the surface of the

: 9orresponding author; $ananelnahas


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%ody! topical application of 6+7#Ds on the inflamed site can offer the advantage of delivering

a drug directly to the disease site and producing its local effect. 2his occurs %y avoiding

gastric irritation and also reduces adverse systemic effects (=! '. $o"ever! the %arrier

properties of intact s*in limit the permea%ility of "ide variety of su%stances! including

pharmaceutical active agents.

2o overcome these pro%lems! the development of an optimal vehicle system for rapid s*in

permeation of ME is re>uired. 9urrently! microemulsions have %een recognized as good

vehicles for percutaneous a%sorption of drugs (3! 4. 2hey are clear or slightly opalescent!

isotropic? thermodynamically sta%le systems of t"o immisci%le li>uids. Microemulsions are

created %y the presence of a suita%le surfactant! usually in con@unction "ith a co)surfactant.

2hey are relatively sta%le and can solu%ilize a considera%le amount of hydropho%ic drugs in

their lipophilic domain (.

Aecently! lipogels)semisolid ointment li*e preparations) have %een investigated as vehicles for

topical drug delivery. Bipogels are o%tained %y gelling an oleaginous phase "ith a lipophilic

su%stance (C)/.

2he purpose of this study "as to formulate ME in different types of gels! namely! hydrogel!

hydroalcoholic gel! microemulsion gel and lipogel using different oils. 2he second goal "as

to evaluate the properties of ME gels li*e in)vitro drug release! percutaneous a%sorption and

comparison anti)inflammatory effect of this gel "ith the mar*eted piroxicam gel.

EXPERIMENTAL

Ma&erial"

Meloxicam po"der "as donated as a gift from Delta Pharma! 2enth of Aamadan 9ity!

Egypt! Mexicam5 ta%lets "ere purchased from Delta Pharma! 2enth of Aamadan 9ity!

Egypt! Feldene5gel "as purchased from (Pfizer Pharm.9o.! 9airo! Egypt! 9ar%opol &'

"as purchased from (F oodrich 9o.! $! Ethyl oleate (E "as purchased from (7ldrich

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9hemical! Mil"au*ee!G#! leic acid "as purchased from (Flu*a! uchs! 9$! lyceryl

monostearate ($en*el! DHsseldorf! ermany! Propylene glycol (P "as purchased from

(9arl Aoth! G! ermany! 2"een C (Polyoxyethylene +or%itan Monooleate ! +odium Bauryl

sulphate! Potassium dihydrogenorthophosphate! disodiumhydrogen phosphate! sodium

chloride and ethanol "ere purchased from (El)6asser Pharmaceutical 9hemicals! 9airo!

Egypt! 2riethanolamine "as purchased from (Merc*! Darmstadt! ermany! 9arrageenan and

hydroxyl propylmethylcellulose ($PM9 "ere purchased from (+igma! +t! Bouis! M!all

chemicals "ere analytical grade. +emipermea%le 9ellophane mem%rane =1=8 (Fischer

+cientific 9o.! Bondon! England. Distilled "ater.

Me&!'$"

Preparation of hydrogel and hydroalcoholic gel samples

2he gel samples "ere prepared %y dispersing /0 9ar%opol &' in a mixture of "ater and P

(C; 8 "1" in case of hydrogel or a mixture of "ater! ethanol and P ( '; '; 8 "1" in

case of hydroalcoholic gel. ME (/0 "1" "as added to the mixtures and *ept under magnetic

stirring for /8 hrs (Formulas / and 8! 2a%le /. 2he dispersions "ere then neutralized (p$ .'

and their viscosity "as improved %y adding triethanolamine ./0 (//.

Preparation of microemulsion gel samples

2he appropriate amounts of 2"een C! P and oil (E or oleic acid "ere "eighed into

scre")capped vial as surfactant! co)surfactant! and oil (3;/;'! respectively. ME "as added

in a concentration of /0 "1" into the vial. 2he mixture "as sha*en %y using a magnetic

stirrer (/ cm! then the microemulsion gel "as formed %y the addition of 83 0 "ater "ith

continuous stirring! and it "as enhanced %y using a vortex mixer for 8 min. 2he gel of ME

samples "ere stored at 83I9 for 8' hrs for e>uili%ration (Formula =! 2a%le /.

=


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Preparation of lipogel samples

2he calculated amount (/30 "1" of monoglyceryl stearate "as heated at I9 "ith oil (E

or oleic acid to complete melting! then /0 ME "as dissolved into the melted mass (formula

' ta%le /. 2he mass "as then gelled %y cooling under stirring (/ rpm to 3I9 until

clouding of the melted mass! then allo"ing to gel at rest. 2he sample "as then maintained at

83 I9 for 8' hrs %efore use (/.

Effect of initial drug concentration

Further study "as done upon ethyl oleate microemulsion gel as it gave the %est results of drug

release and s*in permeation. 2he effect of initial ME concentration "as tested on the

permeation properties of that gel %y using other t"o drug concentrations .3 and .430

%esides /0 ME.

Solubility measurements

2he solu%ility of ME in either E or oleic acid "as determined %y adding excess amount of

drug into / ml of oil in a scre")capped vial. 2he vials "ere e>uili%rated at 83I9 for 8 hrs in

a thermostatic sha*er "ater %ath. 2he suspension "as centrifuged at = rpm for /3 min! and

the supernatant "as diluted "ith ethanol and used for the determination of ME

spectrophotometrically at Jmax K =48 nm! the %lan* "as E or oleic acid in ethanol.

Viscosity measurements

2he different formulations "ere tested at room temperature using Liscostar viscometer

(Fungila% +.7.! +pain. 2he measurements "ere made using spindle num%er 3 at 8 rpm.

In-Vitro drug release

7 one gram sample of each formulation "as accurately "eighed and placed on a

semipermea%le cellophane mem%rane (previously immersed in s,rencen-s phosphate %uffer!

p$ .' for 8 hrs to occupy a circle of 8.& cm diameter. 2he loaded mem%rane "as stretched

over the lo"er open end of a glass tu%e of 8.& cm diameter and made "ater tight %y ru%%er

%and. 2he tu%e "as immersed in a %ea*er containing /3 ml of +,rencens phosphate %uffer

'


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p$ .'. +odium lauryl sulphate /0 "1" "as added to the medium to ensure sin* condition.

2he system "as maintained for ' hrs at =8I9 in a thermostatic sha*er "ater %ath at / rpm

(Figure/. +amples = ml "ere "ithdra"n at intervals of /3! =! '3! 4! &! /8! /C! and 8'

min! the volume of each sample "as replaced %y the same volume of fresh %uffer to maintain

constant volume! samples "ere analyzed "ithout dilution or filtration for ME content

spectrophotometrically at Jmax K =48 nm. #n case of Feldene5 gel! samples "ere analyzed

for piroxicam content at Jmax K =3C nm.

In-Vitro permeation studies

#n)vitro permeation studies "ith excised ra%%it s*in (/= "ere performed as follo"s;

7%dominal full)thic*ness s*in of male ra%%it "as o%tained from "hite 6e" Zealand ra%%its

"eighing =)' *g. 2he s*in "as carefully removed from animals and the hair "as clipped

"ithout damaging the s*in. 2he fat "as removed "ith the aid of scissor and s*in "as "ashed

and soa*ed over night in .& 0 sodium chloride solution. 2he excised s*in "as used as a

permeation mem%rane "ith the epidermal surface up"ard! the stratum corneum "as facing

the donor side of the cell and the dermal side of the s*in "as allo"ed to %e in contact "ith a

%uffer solution (Figure /. 2he procedure for the release test descri%ed a%ove "as used except

that the receptor medium contained /3 ml .&0 sodium chloride of p$ .' "ith the addition

of sodium lauryl sulphate (/0 "1v. +amples of = ml "ere "ithdra"n periodically for & hrs

and replaced "ith an e>ual volume of fresh receptor solution. ME and piroxicam "ere

assayed spectrophotometrically at =48 nm and =3Cnm! respectively.

Calculation of cumulative drug release

2he amount of ME in the total receptor solution "as determined from a cali%ration curve. 2he

cumulative drug permeated (Nn corresponding to the time of the n thsample "as calculated

from the follo"ing e>uation (/';

n)/

NnK LA9nO Ls9i iK

3


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Ghere 9n and 9i are the drug concentrations of the receptor solution at the time of the n th

sample and the i ( the first sample! respectively and L A and L+are the volumes of the receptor

solution and the sample! respectively.

Calculation of permeation parameters

2he permeation profiles of ME across ra%%it s*in from different gel formulations "ere

constructed %y plotting the total cumulative amount of ME penetratedperunit surface area

(Qg1cm8 versus time (hour as sho"n in figure '. Meloxicam steady state flux (Rss "as

calculated as the slope of linear regression line at the steady state phase for each experimental

run. Permea%ility coefficient (Sp "as calculated using the relation derived from Fic*s first

la" of diffusion! "hich descri%ed in the follo"ing e>uation;

Rss K Sp 19o

"here! 9o is the initial drug concentration in the donor (/3.

Anti-inflammatory activity of Meloxicam gel

7cute inflammatory activity model! carrageenan induced rat pa" edema method (/4 "as

applied in this study .

2he rats "eighing a%out 8 gm "ere divided into 4 groups! each group containing ' rats.

2he animals of groups /! 8 and = received /ml oral suspension of meloxicam (.8 mg1*g in

.& 0 sodium chloride (/! 8 mg of E microemulsion gel topically and 8 mg of

feldene5 gel topically! respectively. 2he gels "ere applied to the surface of the right hind

pa"! then the treated area "as immediately covered %y thin vinyl sheet and gauze. 2"o hours

later! the covers "ere removed and ./ ml of /0 carrageenan solution "as in@ected

su%cutaneously into %oth treated area and the left hind pa". 2he animals of control groups '!3

and 4 "ere treated "ith sodium chloride solution orally! microemulsion place%o gel topically

and $PM9 place%o gel topically respectively. 2he carrageenan "as in@ected in the same

manner as a%ove. 2hree hours later! the thic*ness of the right and left pa"s "as measured

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using a dial micrometer and the percentage inhi%ition of edema "as calculated (/C. 2he data

"ere reported as mean T +EM (nK' and statistical analysis "as carried out using 76L7)

test at a level of significance of P .3.

RESULTS AND DISCUSSION

In-Vitro rug !elease and Permeation Studies

Effect of gel type

2he data o%tained from release and permeation studies "ere sho"n in Figures 8)3 and 2a%le

8. 2he amount of ME released from all gel formulations sho" a linear relationship "ith the

s>uare root of time (r V.&! therefore! the release rate of the test drug follo"ed $iguchi

theoretical model (/&.

#t "as o%served that the in)vitro release data as "ell as the permeation studies "ere superior

from E microemulsion gel. 2he cumulative amounts permeated at & hrs "ere 4/4./! 8&3./3!

/'/.3 and 8=3.8 Qg1cm8 for E microemulsion gel! E lipogel! carpo%ol gel and

hydroalcoholic carpo%ol gel respectively. 2hese results "ere in agreement "ith El)Baithy and

El)+ha%oury! Gho reported that maximum fluconazole permeation and /.3 fold improvement

in drug release "ere achieved from microemulsion prepared "ith @o@o%a oil in comparison to

its corresponding lipogel (8. 2hacharodi and Panduranga Aao ( explained the mechanism

%y "hich microemulsions enhance the percutaneous a%sorption of drugs on the %asis of the

com%ined effect of %oth the lipophilic and hydrophlilic domains of microemulsion. 2he

lipophilic domain of the microemulsion can interact "ith the stratum corneum in many "ays.

2he drug dissolved in the lipid domain of a microemulsion can directly partition into the lipid

of the stratum corneum or lipid vesicles themselves can intercalate %et"een the lipid chains of

stratum corneum! there%y desta%ilizing its %ilayer structure. 2hese interactions "ill lead to

increased permea%ility of the lipid path"ay to the drugs. n the other hand! the hydrophilic

domain of the microemulsion can hydrate the stratum corneum to a greater extent. Ghen the

a>ueous fluid of the microemulsion enters the polar path"ay! it "ill increase inter lamellar


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volume of stratum corneum lipid %ilayer! resulting in the disruption of its interfacial structure.

+ince! some lipid chains are covalently attached to corneocytes! hydration of these proteins

"ill also lead to the disorder of lipid %ilayers. +imilarly! s"elling of the intercellular proteins

may also distur% the lipid %ilayers? a lipophilic penetrant li*e ME can then permeate more

easily through the lipid path"ay of stratum corneum.

#t "as o%served that the type of oil affect the release and permeation properties of ME

from microemulsion gels and lipogels. 2he cumulative amounts of ME permeated From E

microemulsion gel and lipogel "ere 4/4./ and 8&3./ Qg1cm8 respectively! compared "ith

84.3 and 8'C.C Qg1cm8from oleic acid microemulsion gel and lipogel! respectively. 2his may

%e due to increased solu%ility of ME in oleic acid "here it "as .=3 mg1ml and 8.'8 mg1ml in

E and oleic acid respectively (2a%le =! "hich lead to decreased partitioning of ME into the

s*in and hence decreased permeation (8/.

ur investigation revealed that meloxicam gels have greater viscosity in oleic acid

formulation than E formulation (2a%le '. 9onse>uently there "as a decreased release and

permeation of ME from oleic acid gels than E gels. 2he result is in agreement "ith that

previously mentioned %y $Httenrauch et al (88 and Ugri)$unyavari and Er,s (8=. 2hey

stated that! gel having a compact and close structure may have a slo"er release rate than one

of lo"er consistency.

2he enhanced drug release and permeation properties from the hydroalcoholic car%opol gel

compared to the hydrogel! could %e ascri%ed to t"o factors? first! ethanol is a vehicle *no"n

to increase the permeation of drugs through the s*in either %y attac*ing the dense %arrier

structure of the s*in (8' or %y augment the solu%ility and partitioning of the drug in stratum

cornium (83 . +econd! ethanol decreases the viscosity of carpo%ol gel (2a%le ' "hich lead to

improved drug release and permeation from the gel (Figures = and 3. 2he results are in

agreement "ith the previous investigation performed %y 9hi and Run (84! "ho demonstrated

C


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that the enhancement effect of ethanol in *etoprofen gel formulations is due to decrease of

viscosity and increased solu%ility of drug in the gel.

9omparison of the results (Figures 8 and = indicated that although there is a %etter in)vitro

release of piroxicam than meloxicam from their formulations! figure ' and 3 reflect inferior

s*in permeation of the former. 2hese results can %e attri%uted to the physicochemical

properties of drugs such as partition coefficient! vehicle solu%ility and molecular "eight

"hich determine there permeation through the complicated structure of the s*in (8!8C.

Effect of initial drug concentration

Figure 4 and 2a%le 8 sho" the effect of initial drug concentration (.3! .43! /0 "1" on the

release and permeation of ME from E microemulsion gel. 2he results revealed that

increasing the drug concentration! results in increasing the cumulative amount permeated. 2he

cumulative amounts permeated at & hrs "ere /==.4! 8C.3 and 4/4./ Qg1cm8for gel prepared

"ith .3! .43! and /0 ME! respectively. 7 close parallel results "ere reported %y Fergany

(8&.

Anti-inflammatory activity of meloxicam gel

2a%le 3 sho"s the inhi%itory effects of ME gel on the carrageenan) induced pa" edema

compared "ith oral Mexicam5 and Feldene5 gel (.30 piroxicam. 2he data "ere reported

as mean T +EM (nK' and statistical analysis "as carried out using 76L7)test at a level of

significance of P .3. ME gel (E microemulsion produced significant inhi%itory effects!

"ith a '8.=0 inhi%ition after ' hrs and the activity "as approximately e>uivalent to that of

Mexicam5 oral ta%let! "hile more effective than that of Feldene5 gel. #n this experiment! the

normal saline and the place%o gel had no effect on carrageenan edema. ME gel significantly

inhi%ited inflammation in the treated pa" and had also some influence on edema of non)

applied pa". Ghile! Feldene had no influence on edema of non)applied pa" indicating

a%sence of any systemic effects. 2hese results "ere in agreement "ith that previously

mentioned %y upta et al (/. 2hey reported that! meloxicam gel (/0"1" sho"ed increased

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protection against inflammation as compared to piroxicam (.3 0 "1" and diclofenac (/0

"1" gels.

CONCLUSION

2he results indicated that topical preparation of miloxicam (E microemulsion gel could %e

an effective topical dosage form %eside its oral dosage form (Mexicam5 ta%let in

inflammatory condition "ith the possi%ility of less systemic side effects.

REFERENCES

/) upta! +.S? ansal! P? hard"a@! A.S? Rais"al! R and Lelpandian! 2. 9omparison of

analgesic and anti)inflammatory activity of meloxicam gel "ith diclofenac and piroxicam

gels in animal models; pharmaco*intic parameters after topical application. R. Pharmacol.

ioph. Aes. 88?/3 (8;/3)///.

8)Aafiee)2ehrani! M. and Mehramizi! 7. #n)vitro release studies of piroxicam from oil Win)

"ater creams and hydroalcoholic gel topical formulation. Drug Dev. #nd. Pharm.! 8?84

('; '& )'/'.

=) 7rellano! 7? +antoyo! +? Martin! 9 and Xgartua! P. #nfluence of propylene glycol and

isopropyl myristate on the in)vitro percutaneous pentration of declofinace sodium from

capo%ol gels. Eur. R. Pharm. +ci. /&&&? (8;/8&)/=3.

') 7rellano 7! +antoyo +? Martn 9? Xgartua P. +urfactant effect on the in)vitro percutaneous

a%sorption of declofinac sodium. Eur. R. Drug Meta%. Pharmaco*inet. /&&C? 8=(8;=)

=/8.

3) Dreher! F? Galde! P?Galther! P and Gehrli! E. #nteraction of a lecithin microemulsion gel

"ith human stratum corneum and its effect on transdermal transport. R. 9ontrol. Ael.!

/&&?'3; /=/)/'.

/


11/19

4) 6asseri! 7. 7? 7%oofazeli! A? Zia! $ and 6eedham! 2.E. Becithin)sta%ilized microemulsion;

an organogel for topical application of *etorolac tromethamine. #; phase %ehavior studies.

#ranian R. Pharm. Aes. 8=?/; 43)44.

) 2hacharodi! D. and Panduranga! S. A. 2ransdermal a%sorption of nifedipine from

microemulsions of lipophilic s*in penetration enhancers. #nt. R. Pharm. /&&'? ///; 8=3)

8'.

C) 6icola! A? Marisa! D.Z? Eugenio! A. and Dalla Fini! . Drug release from lipogel according

to gelling conditions and mechanical treatment. Drug Dev. #nd. Pharm. /&&4?88 (8; /83)

/='.

&) 6icola! A? Eugenio! A? Marisa! D.Z. and Enrico! A. Sinetics of release and simulated

a%sorption of methyl nicotinate from different ointment formulation; in)vitro)in)vivo

correlation. Pharmazie. /&&4?/3 (8;//=)//4.

/) 6icola! A? Eugenio!A and Enrico! A. Effect of gelling conditions and mechanical

treatment on drug availa%ility from a lipogel. Drug Dev. #nd. Pharm. 8/? 8(8; /43

)/.

//) Barrucea! E? 7rellano! 7? +antoyo! +. and Xgartua P. #nteraction of tenoxicam "ith

cyclodextrins and its influence on the in)vitro percutaneous penetration of drug. i%di.!

8/? 8(=; 83/)84.

/8) 7%u)Zaid! +.+? El)hamry! $.7? $ammad! M? Mo*htar! M. Phase study and

characterization of certain developed multicomponent colloidal systems and their potential

application as carrier for an antimicro%ial agent. 7lex. R. Pharm. +ci. 83? /& (8;/=/)

/'.

/=) 7l)+u"ayeh! +.7. 2ransdermal delivery of isoradipine through excised ra%%it s*in effect

of vehicle and drug concentration. +audi Pharm. R. 8=?//(/)8; '4)38.

/') onsho! 7? #manidis! ? Logt! P? Sern! E.A? 2suge! $? +u! M.$? 9hoi +.$ and $iguchi!

G. 9ontrolled (trans dermal delivery of an antiviral agent (7cyclovir. #; an in)vivo

//


12/19

animal model for efficacy evaluation in cutaneous $+L)#nfection. #nt. R. Pharm. /&&? 43

(=; /C=)/&'.

/3) Ahee! .R? Goo! R.+? $"ang! +.R? Bee! X.G. and Bee! 9.$. 2opical oleo)hydrogel

preparation of *etoprofen "ith enhanced s*in permea%ility. Drug Dev. #nd. Pharm.

/&&&?83 (4;/)84.

/4) Gada! X? Etoh! X? hira!7? Siamata! $? Soide!2? #shihama! $. and MizushimaX.

Percutaneous a%sorption and anti)inflammatory activity of indomethcin in ointment. R.

Pharm. Pharmacol. /&C8?='; '4)'4C.

/) ad! +.9. 7nimal Models in 2oxicology. ad! +.9 and 9henglis! P.9; Marcel De**er!

#nc.! 6e" Xor*! /&&8! C83.

/C) alata!.F. Master 2hesis. Formulation and evaluation of certain anti)inflammatory

Drugs in emulgels. /&&&! /=/.

/&) $iguchi! G.#. 7nalysis of data on the medical release from topical ointments. R. Pharm.

+ci./&48? 3/; C8)C'.

8) El)Baithy! $.M. and El)+ha%oury!S.M.F. 2he Development of 9utina Bipogels and

Microemulsion el for 2opical 7dministration of Fluconazole. 77P+ Pharm. +ci. 2ech.

88? =('? article =3;/)&.

8/)9eschel .9.! Maffei 9. and Bom%ardi .+. 9orrelation %et"een the transdermal

permeation of *etoprofen and its solu%ility in mixtures of a p$ 4.3 phosphate %uffer and

various solvent. Drug Deliv. 88;&(/? =&)'3.

88) $Httenrauch! Fric*e!+. and aumann!L. +tate of order! properties and pynamics of

structure in shear)crystallized ointments. Pharmazie. /&C8?= (/; 83)8C.

8=) Ugri)$unyadvYri E. and Er,s #. +tudium der elstru*tur Lon Sunstvaslinen. Pharm. #nd.

/&C4? 'C;&4&)&8.

8') %ata X.! 2a*ayama S.! Maitani X.! Machida X.! and 6agai 2. Effect of ethanol on the

permeation of ionized and non ionized declofenac. #nt. R. Pharm. /&&=? C&;/&/)/&C.

/8


13/19

83) Megra% 7.6.! Gilliam 7.9. and arry .G. estradiol permeation across human s*in!

silastic and sna* s*in mem%ranes; the effect of ethanol; "ater co)solvent systems. #nt. R.

Pharm. /&&3? //4;//)//8.

84) 9hi! +.9 and Run! $.G. Aelease rate of *etoprofen from poloxamer gel in a mem%raneless

diffusion cell. R. Pharm. +ci. /&&/?C (=; 8C)8C=.

8)o X.! 2erua*i $.! 2etsuya $.!` 2oshino%u +.!Sazuhi*o R.!Sen@i +.! and Xasunori M. +*in

disposition of drugs after topical application in hairless rats. 9hem. Pharm. ull. /&&&? (4;

'&)3'.

8C) ernhard P. G and ernhard 9. B. +*in penetration of nonsteroidal anti)inflammatory

drugs out of a lipophilic vehicle; influence of the via%le epiderm i". R. Pharm. +ci.8?

CC(/8;/=84)/==/.

8&) Fergany? 7.M. 2opical permeation characteristics of diclofenac sodium from 6a 9M9

gels #n comparison "ith conventional gel formulation. Drug Dev. #nd. Pharm. 8/?

8(/;/C=)/&.

/=


14/19

2a%le /

9omponents of different gel formulations

F'r()la *)a&i&ie" b+ gra(" re)ire$ &' reare / gra(" '0 gel

Formula /

9ar%opol hydro)gel

./ g cor%opal! &.&g (C ; 80"1" "ater ; P

Formula 8

9ar%opol hydroalcoholic gel

./ g car%opol ! &.&g (';';80"1" "ater ; P ; E$

Formula =

Microemulsion gel

3g 2"eenC! /g P! 'g ethyl oleate or oleic acid! 8.3g "ater

Formula '

Bipogel

/.3g monoglyceryl stearate! C.3g ethyl oleate or oleic acid

2a%le8

Percutaneous permeation parameters of ME through a%dominal ra%%it s*in from various

formulations (Mean T +E! n K =

F'r()la&i'

C)()la&i1e

a(')& a& 2!r"

3*2!, 4g56(78

Fl)9

3:"",

4g56(75!r8

Per(eabili&+

C'e00i6ie&

3, C(5!r

/ -


15/19

2a%le '

Liscosity measurements of different gel %ases (Mean T +E! nK=

el %ase Liscosity (cp

Mi6r'e()l"i' gel=

E

leic acid

=8=/= T 8C&&

'C'=T 3C=C

Li'gel=

E

leic 7cid

=&'= T /&'4

/''3&4 T /&&C

9ar%opol gel

$ydroalcoholic car%opol gel

884/8 T //34

/=/= T 33'Feldene5 gel /'CC T 3/

2a%le 3

Evaluation of the anti)inflammatory activity of meloxicam microemulsion gel (Mean T +E! nK'

0inhi%ition0+"elling (mean +EM+ample

)

'/.48

3.'3 T =.&3

==.3'T :/.83

9ontrol /

Meloxicam ta%let

6on treated foot2reated foot6on treated foot2reated foot

9ontrol8

E microemulsion

9ontrol=

Feldene5 gel

)

8.=/

.)

Zero

)

'8.=

)

8'.&

4=.44 T/C.3=

3.= T /=.=

3/.C T C.38

3&.=' T C.&'

'4.8CT&.&

84.4T3.3':

33.C T 3.3=

'/.&3 T &.3/:

9ontrol/K animals administered normal saline.

9ontrol8K animals treated "ith place%o microemulsion gel.

9ontrol=K animals treated "ith place%o $PM9 gel.

P: .3 compared "ith the control.

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Aa%%it s*in loaded "ith

sample (donor

9over "ith a small open

83 ml %ea*er

+ha*ing "ater

%ath [

Figure (/; 9ross)sectional diagram of the drug permeation apparatus (2hermostatic sha*er

"ater %ath.

Figure 8; Aelease profiles of meloxicam from different microemulsion gels and lipogels

across standard cellophane mem%rane in comparison "ith feldene5 gel. (nK=! mean O +E

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Figure =; Aelease profiles of meloxicam from t"o car%opol gels across standard cellophane

mem%rane in comparison "ith Feldene gel.

Figure '; Permeation profiles of meloxicam across a%dominal ra%%it s*in from different

microemulsion gels and lipogels in comparison "ith feldene5 gel. (nK=! mean O +E.

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Figure 3; Permeation profiles of meloxicam from t"o car%opol gels across a%dominal ra%%it

s*in in comparison "ith Feldene5 gel.

Figure 4; Effect of initial drug concentration on the amount of meloxicam permeated from E

microemulsion gel through a%dominal ra%%it s*in.

/C


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ME Paper Revised 2555

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Transcript of ME Paper Revised 2555