Iranian Journal of Pharmaceutical Sciences Summer 2005: 1(3): 131-142www.ijps.ir

R

Original Article

The Effect of Formulation Type on the Release of BenzoylPeroxide from Microsponges

Ali Nokhodchi*, Mitra Jelveghari, Mohammad-Reza Siahi, Siavoosh Dastmalchi

Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences,Tabriz, Iran

AbstractBenzoyl peroxide (BPO) is a first-line topical treatment in acne vulgaris, and

it is superior to antibiotics, because the bacteria do not develop resistance to it. Skinirritation is a common side effect, and it has been shown that controlled release ofBPO from a delivery system to the skin could reduce the side effects while reducingpercutaneous absorption. Therefore, the purpose of the present investigation was toprepare suitable controlled release formulations for BPO. This study examinedwhether the type of topical formulation (cream, gel and lotion) can affect therelease behavior of BPO from microsponges. Benzoyl peroxide microparticleswere prepared using an emulsion solvent diffusion method by adding an organicinternal phase containing benzoyl peroxide, ethyl cellulose and dichloromethane intoa stirring aqueous phase containing polyvinyl alcohol. The loading capacity of thedrug content and the mean particle size of microparticles were determined. BPOmicroparticles were then incorporated into various formulations (creams, gels andlotions) for release studies. The micrograph of microsponges showed that theywere spherical in shape and contained pores. It was shown that the drug:polymerratio, stirring rate, volume of the dispersed phase influenced the particle size anddrug release behavior of the formed microsponges and that the presence of emulsifierwas essential for microsponge formation. The results showed that, generally, anincrease in the ratio of drug:polymer resulted in a reduction in the release rate ofBPO from microsponges which was attributed to a decrease in internal porosity ofthe microsponges. The release data showed that the highest release rate was obtainedfrom lotions containing BPO microparticles and the lowest was obtained fromcream formulations.

Keywords: Drug release; Drug:polymer ratio; Microsponge; Particle size; Porosity. Received: April 12, 2005; Accepted: May 29, 2005

1. Introduction Benzoyl peroxide (BPO) is a first-line

topical treatment in acne vulgaris. However,

its use can cause mild skin irritation anddryness. BPO is an old and establishedtreatment agent with keratolytic andantibacterial action. It was described as atherapeutic aid in the treatment of burns,ulcerations, and various cutaneous and mucousmembrane infections, and it has been found to

*Corresponding author: Ali Nokhodchi, Department ofPharmaceutics, Faculty of Pharmacy, Tabriz University of MedicalSciences, Tabriz 51664, Iran.Tel (+98) 411-3392606, Fax (+98) 411-3344798E-mail:nokhodchi@tbzmed.ac.ir

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132

be among the most effective models of acnetherapy [1, 2]. BPO is superior to antibioticsbecause the bacteria do not develop resistanceto it, and it is preferred over keratolytic agentsdue to its bactericidal effect.

Skin irritation is a common side effect,and it has been shown that controlled releaseof BPO from a delivery system to the skincould reduce the side effects while reducingits percutaneous absorption. Encapsulationof BPO can reduce the side effects to a greatextent [2, 3].

The encapsulated form has receivedincreasing attention as a means for controlledrelease purposes [4]. Previous studies showedthat controlled release formulations of BPOreduced the skin irritation due to the reductionin the release rate of the drug from formulation[5]. A popular method for the encapsulationof water-insoluble drugs within waterinsoluble polymers is the emulsificationsolvent diffusion method [6, 7]. The solventdiffusion process is easier to conduct and isless prone to agglomeration of themicrosponges, and also is more economic.Solvent diffusion is a process by whichmicroencapsulation can be readily performedin the laboratory without the need ofspecialized equipments. Selecting theappropriate method requires consideration of

the physicochemical properties of the corematerial (drug and polymer) in conjunctionwith the characteristics of the process.

The prepared BPO microspongeformulations, can clearly increase the periodof time that the active ingredient is in contactwith the skin surface or within the epidermis,while minimizing its penetration through thedermis to the systemic circulation. This systemprovides maximum efficacy, minimumirritancy, extended product stability andimproved aesthetic properties in an efficientand novel delivery system.

The purpose of the present investigationwas to prepare BPO microsponges. We alsoinvestigated the factors affecting the particlesize of microsponges. This study examinedwhether the type of topical formulation(cream, gel and lotion) can affect the releasebehavior of BPO from microsponges.

2. Matrials and methods 2.1. Materials

Benzoyl peroxide, polyvinyl alcohol(PVA; MW=10600–11000), dichloromethane,acetone, methanol, polyethylene glycol 400,and benzophenon, liquid paraffin, tri-ethanolamine, stearic acid, all were fromMerck (Darmstadt, Germany). Ethyl cellulosewas purchased from Sigma-Aldrich, carbomer

Table 1. Effect of drug:polymer ratio, stirring rate, concentration emulsifier, solvent and non-solvent amounts on the averagediameter and drug content of BPO microsponges.Parameter Formulations Theoretical Mean drug Drug loading

drug content (%) drug loading (%) capacity (%±SD)BPO: EC ratio MDS*1 (1:1) - - -(rpm=4000) MDS3 (3:1) 69.23 49.37 71.31±3.31

MDS5 (5:1) 78.94 63.16 80.01±1.32MDS7 (7:1) 84.00 74.54 88.74±1.25MDS9 (9:1) 87.10 85.38 98.03±2.16MDS11 (11:1) 89.19 83.44 93.56±0.81MDS13 (13:1) 90.70 87.17 96.11±0.70

Dichloromethane MDS13-A (5 ml) - 86.95 95.87±4.05volume (ml) MDS13-B (10 ml) 90.70 72.21 79.61±3.89

MDS13-C (15 ml) 90.70 66.67 73.51±3.74

Stirring rate (rpm) MDS13-D (1000) 90.70 54.83 60.45±5.33MDS13-E (2000) 90.70 64.93 71.59±4.89MDS13-F (3000) 90.70 71.23 78.53±4.92

*MDS = Microsponge Delivery System

Benzoyl peroxide release from microsponges

940 (BFG, USA). Silastic membrane wasprovided by Biogene, (Mashad, Iran). Whitebeeswax was achieved from Thoton and Ross(Huddersfield, UK).

2.2. Preparation of microspongesBPO microsponges were prepared by

emulsion solvent diffusion method. To preparethe internal phase, BPO was dissolved in 20ml of dichloromethane. In this procedure,dichloromethane was an effective solvent todissolve both the drug and the polymer. Whilethe external phase, 60 ml of an aqueoussolution containing 5.6 g of 5% w/v PVA, wasplaced in the vessel and stirred with propellertype agitator at 4000 rpm, and the internalphase was poured into external phase. Thesystem was thermally controlled at 25 °C ina water bath.

An agitation up to 30 min permits theformation of microsphere and after 8 h ofstirring, the experiment was stopped as thedichloromethane was removed from thereaction. At this stage, the formedmicrosponges were filtered through the filterpaper, washed with distilled water and traydried at the room temperature and wasweighted.

The effects of the process variables suchas drug:polymer ratio, stirring rate and solventvolume on the mean particle size of themicroparticles were investigated. BPOmicrospheres were prepared using variousdrug:polymer ratios (3:1, 5:1, 7:1, 9:1, 11:1and 13:1), while keeping the other variables(stirring rate of 4000 rpm, emulsifierconcentration 5.6 g of 5% w/v, solvent 20ml and non-solvent 60 ml) constant. Similarly,to determine the effect of stirring rate on themean particle size of microparticles,microsponges were prepared at variousstirring rates (1000, 2000, 3000, 4000 rpm),while keeping the drug:polymer ratio at 13:1,emulsifier concentrations at 5.6 g,dichloromethane 20 ml and non-solvent 60 ml.

Microspheres were also prepared using

different volumes of dichloromethane whilekeeping the drug:polymer ratio at 13:1, andstirring speed at 4000 rpm.

2.3. Scanning electron microscopyThe morphology and appearance of

microparticles were examined by scanningelectron microscopy (SEM). The preparedmicrospheres coated with gold platinum/palladium alloy under vacuum. The coatedsamples were then examined using scanningelectron microscope (LEO 440i, England)operating at 15 kV. Photomicrographs weretaken of each sample at differentmagnifications.

2.4. Particle size distributionThe micrographs of microsponges were

transferred into the software (Scion imageanalysis) for image analysis of microparticles.Each determination was carried out on aminimum of 100 particles. These data wereconverted to percent values using the initialtotal number of particles against particle size

133

Figure 1. SEM of microsponges containing BPO at differentmagnifications.

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134

Tabl

e 2.

The

eff

ect o

fdr

ug:p

olym

er r

atio

on

the

rele

ase

char

acte

rist

ics

of B

PO f

rom

dif

fere

nt m

icro

spon

ges

form

ulat

ions

.F

orm

ulat

ion

Cre

am 2

.5%

Cre

am 5

%C

ream

10%

code

Flu

xaIn

terc

ept

r2Q

8bF

luxa

Inte

rcep

tr2

Q8b

Flu

xaIn

terc

ept

r2Q

8b

(mg/

cm2 h

)(m

g/cm

2 )(m

g/cm

2 )(m

g/cm

2 h)

(mg/

cm2 )

(mg/

cm2 )

(mg/

cm2 h

)(m

g/cm

2 )(m

g/cm

2 )(m

g/cm

2 )(m

g/cm

2 h)

(mg/

cm2 )

Pure

BPO

0.03

650.

054

0.98

40.

331

0.06

890.

050.

980

0.57

10.

1038

0.10

0.93

30.

873

MD

S30.

0162

0.11

0.97

90.

251

0.03

940.

210.

960

0.50

30.

0461

0.30

0.96

30.

645

MD

S50.

0156

0.11

0.98

90.

241

0.03

970.

180.

958

0.49

00.

0463

0.26

0.94

50.

614

MD

S70.

0156

0.11

0.98

90.

230

0.03

510.

180.

871

0.49

60.

0380

0.23

0.95

40.

564

MD

S90.

0136

0.09

0.94

70.

196

0.03

460.

150.

888

0.46

60.

0413

0.19

0.95

10.

551

MD

S11

0.01

840.

040.

927

0.18

20.

0240

0.14

0.93

30.

354

0.03

620.

180.

959

0.48

0M

DS1

30.

0168

0.02

0.93

90.

159

0.02

000.

100.

947

0.27

50.

0359

0.14

0.97

30.

438

loti

on 2

.5%

loti

on 5

%lo

tion

10%

Pure

BPO

0.24

30.

543

0.97

21.

935

0.33

40.

756

0.94

52.

567

0.39

31.

145

0.97

63.

362

MD

S30.

188

0.90

00.

971

2.09

00.

261

1.31

50.

991

2.93

20.

272

2.08

40.

850

3.54

8M

DS5

0.15

80.

927

0.98

51.

916

0.25

61.

264

0.99

52.

815

0.20

82.

105

0.77

23.

148

MD

S70.

146

0.81

90.

987

1.65

10.

271

1.13

60.

985

2.71

70.

298

1.59

50.

877

3.15

6M

DS9

0.14

10.

724

0.96

01.

527

0.21

91.

026

0.97

52.

261

0.24

71.

421

0.80

72.

668

MD

S11

0.12

30.

689

0.90

21.

371

0.16

80.

828

0.95

21.

825

0.22

31.

162

0.92

12.

407

MD

S13

0.11

70.

532

0.99

31.

210

0.15

90.

752

0.96

21.

768

0.17

41.

056

0.97

12.

044

gel 2

.5%

gel 5

%ge

l 10%

Pure

BPO

0.11

760.

667

0.97

271.

331

0.12

61.

094

0.97

321.

836

0.16

82.

409

0.75

53.

315

MD

S30.

1463

0.87

720.

9795

1.72

30.

2197

1.55

680.

8973

2.81

10.

3111

2.68

30.

924

4.37

0M

DS5

0.10

490.

8115

0.98

661.

468

0.19

081.

4173

0.88

022.

452

0.31

782.

254

0.90

73.

983

MD

S70.

0976

0.71

930.

9555

1.35

80.

1699

1.34

230.

7128

2.18

50.

2762

2.03

20.

839

3.48

6M

DS9

0.07

540.

7043

0.94

951.

174

0.09

590.

936

0.91

681.

453

0.20

111.

735

0.92

32.

814

MD

S11

0.09

660.

5489

0.96

161.

154

0.09

840.

6691

0.97

331.

255

0.12

181.

055

0.92

61.

737

MD

S13

0.07

620.

5311

0.95

420.

965

0.09

380.

610

0.92

041.

116

0.11

230.

955

0.89

41.

558

aFl

ux w

as o

btai

ned

from

reg

ress

ion

anal

ysis

bet

wee

n th

e am

ount

of

drug

rel

ease

per

uni

t sur

face

are

a an

d tim

e; b

Q8

is th

e am

ount

of

drug

rel

ease

per

uni

t sur

face

are

a af

ter

8 h.

Benzoyl peroxide release from microsponges

on probability scale. The probability plotdirectly gives the mean particle size values.

2.5. Determination of drug contentHigh-performance liquid chromatography

(HPLC) was used to determine the amount ofBPO in microsponges [5]. The HPLC systemwas a Shimadzu class VP series software,version 5.03 with two LC-10AT VP pumps,UV detector SPD-10A VP, RP C18 column(250 mm x 4.6 mm, particle size 5 nm, YMC,Inc., Wilmington, NC, USA). UV detection at254 nm detected the eluent and the data wereacquired, stored, and analyzed with theinstalled Shimadzu software, the mobile phaseused was a mixture of methanol/distilledwater (75:25), the filtered mobile phase waspumped at a flow rate of 1.2 ml/min. Theretention times were 11.3 min and 7.2 min forBPO and benzophenone (the internalstandard), respectively. A standard curve wasconstructed for BPO in the range of 1-200µg/ml, using benzophenone as the internalstandard. A good linear relationship wasobserved between the peak areas of BPOstandard/internal standard in differentconcentration ratios with a correlationcoefficient of 0.9943.

2.6. Determination of loading capacity An accurately weighted quantity of BPO

microsponges (equivalent to 10 mg of BPO)were digested in 10 ml of acetone by stirringfor 30 min. The solution was filtered and 1 mlof the filtrate was added to 9 ml ofdichloromethane. The solution was subjectedto HPLC analysis as described previously.Each determination was made in triplicate.Incorporation efficiency was calculated usingthe following equation:

Incorporation Efficiency= (a/b) x 100 (where, a is the theoretical drug content andb is the entrapped drug).

2.7. Porosity studiesThe pore analysis of microsponges was

carried out using mercury intrusionporosimetry (Pascal 140, Italy). During thetest, a round sampling of microsponges isplaced in the vacuum chamber and submergedunder a pool of mercury contained within avolume-calibrated cell. As pressure isgradually increased on the cell, mercury isforced into progressively smaller pores ofthe microsponges. Thus, the apparent volumeof mercury within the calibrated cell isreduced as it penetrates into the microsponges.Changes in the surface area and poresdiameter can be easily detected with the useof mercury intrusion porosimetry, providinga reproducible method to monitor these

135

Figure 2. The effect of stirring rate (a), drug:polymer ratio(b), and dichloromethane volume (c) on the mean particle sizeof microsponges.

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136

parameters consistently to correlate them withprocessing variables or rates ingredient fromthe MDS.

2.8. Viscosity measurementA Brookfield rotational digital viscometer

DVLV-II was used to measure the viscosity(cPs) of the internal and external phases at 25ºC. The spindle number was rotated at 100rpm.

2.9. Preparation of benzoyl peroxidemicrosponge creams, gels and lotions

Creams were prepared using a standardreverse emulsification method. Aqueous phasecontaining 5 g triethanolamine was addeddropwise onto the oil phase containing stearicacid (20 g), liquid paraffin (5 g), white beeswax 3 g under a stirring rate of 400 rpm.Creams were prepared by melting the oilphase components at about 70 °C and thenadding the aqueous phase at a similartemperature. Once the creams were prepared,the active component (pure BPO powder ormicrosponges containing BPO) wasthoroughly mixed at the room temperature.

Gels were prepared by dispersing 1 gcarbomer 940 in distilled water, adding BPOand neutralizing to a pH of 7 with tri-ethanolamine [8].

Lotions were prepared by dispersing theBPO powder or BPO microsponges into thePEG 400. PEG 400 was a good vehicle forthis formulation because it dissolves the drug,but is unable to dissolve ethyl cellulose.

2.10. Drug release studies Silastic membranes were mounted in static

diffusion cells and the membrane surfacedosed with 2.5, 5 and 10% BPO creams, gelsand lotions containing BPO either freelydispersed or entrapped in ESD system.Receptor fluid composed of distilledwater/acetone (1:1) was added to the cell andmaintained at 25°C because of theexceedingly low solubility of BPO in either

water or normal saline, a water/acetonemixture was selected as receptor fluid toprovide adequate “sink” conditions afterpreliminary experiments showed nointeractions of this mixture with either themembrane or the mixtures placed on the“donor” side. Drug flux through themembrane was determined by periodicallywithdrawing the receptor phase and analyzingfor percent content by HPLC. HPLC conditionwas similar to HPLC analysis as describedpreviously.

3. Results and discussion Scanning electron microscopy of

microsponges was shown in Figure 1. It isclear from the figure that microsponges havespherical shape and containing orifices. Theseorifices caused by the diffusion of the solvent(dichloromethane) from the surface of themicroparticles. The type and concentration ofemulsifier has a key role to play in thepreparation of microspheres. Without theaddition of emulsifier it is impossible to formmicrospheres.

The effect of drug:polymer ratio, thevolume of dichloromethane and stirring rateon the mean particle size of BPOmicrosponges is shown in Figure 2. In orderto investigate the effect of stirring rate on thephysical characteristics of BPO microsponges,formulation MDS13 (the highest ratio ofdrug:polymer) was chosen and the stirringrate was altered in the ranging of 1000-4000rpm. The dispersion of the internal phase ofdrug and polymer into the droplets in theaqueous phase depended on the agitationspeed of the systems. As agitation speedincreased, the size of microparticles wasreduced. For example when the rate of stirringwas increased from 1000 to 4000 rpm, themean particle size was decreased from603.9±58.4 to 310.3±34.3 µm. An increase inthe mean particle size can be attributed tothe tendency of globules to coalescence andaggregation at lower stirring rates. On the

Benzoyl peroxide release from microsponges

other hand, at higher stirring rates, a vigorous,uniform, increased mechanical shear, isimposed and this results in a rapid division ofthe formed droplets which may have lesschance of coalescing into bigger droplets [9].

Figure 2b shows that the ratio of drug topolymer played an important role in theparticle size of microsponges. It is clear fromthe figure, generally, as the ratio ofdrug:polymer increased, particle size wasdecreased. This can be attributed to theincrease in the viscosity of solutions (internalphase) with high drug content. In highdrug:polymer ratios; the amount of polymerper microsponges is less than otherformulations. When dichloromethane diffusesout, nearly all of the dispersed phase isconverted to the form of solid microspongesand separated particles appear. Therefore, inhigh drug:polymer ratios less polymeramounts surrounded the drug and decreasedthe particle sizes of microsponges. When thedispersed phase with higher viscosity waspoured into the dispersion medium biggerdroplets were formed and mean particle sizesincreased.

The effect of the amount ofdichloromethane on the mean particle sizeof BPO microsponges was shown in Figure2c. The results showed that increasing thesolvent volume (dichloromethane) decreasesthe particle size of microsponges (compareformulations MDS13-A, MDS13-B andMDA13-C). When the viscosity of the internalphase of these formulations was investigated,it was found that the particle sizes ofmicrosponges were proportional with theviscosity of the dispersed phase. The resultsshowed that the viscosity of the polymersolutions containing 5, 10 and 15 ml ofdichloromethane is 139, 52 and 33.3mN/m2.S, respectively. The viscosity of theexternal phase was 20.4 mN/m2.S. When thedispersed phase with higher viscosity(MDS13-A containing 5 ml dichloromethane)was poured into the continuous phase

(external phase), due to the higher viscosityof the internal phase, the globules of theformed emulsion probably need more energyto divided into smaller particles and biggerdroplets were formed and the mean particlesizes were increased. In other studies, Barkaiet al. [10] and Pongpaibul et al. [11] showedthat the particle size depends on the solventvolume and the drug:polymer ratio, whensolvent diffusion method is utilized forpreparing microspheres.

The incorporation efficiencies of BPO inthe microspheres were between 60–96%.Incorporation efficiency data were compared.They were found to be significantly differentdepending on the variation of drug:polymerratio (Table 1). The results of the loadingefficiency (incorporation efficiency) showedthat the higher drug loading efficiencies wereobtained at the higher drug:polymer ratios. Forexample, for MDS9, MDS11 and MDS13the drug loading efficiencies were above 90%.The use of higher amounts of BPO whenpreparing microsponges at higherdrug:polymer ratios caused slightly anincrease in the viscosity of the dispersedphase. When dichloromethane diffuses out,nearly all of the dispersed phase is convertedto the form of solid microsponges andseparated particles appear. The highest drugloading capacity of these formulations can beexplained through the fact that the amount ofdrug per unit polymer is greater than that inother formulations. Table 1 also showed thatwhen the amount of dichloromethaneincreased from 5 to 15 ml, the efficiency ofdrug loading decreased. This is due to thelow amount of the drug in higher volume ofdichloromethane.

In order to investigate the effect of vehicleon the release of BPO from topicalformulations, various formulations such asgel, creams and lotion containing puredispersed BPO or BPO microsponges wereprepared. The release profiles of BPO fromgel, cream and lotion are shown in Figures 3,

137

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4 and 5, respectively. Different percentages ofBPO microsponges (2.5, 5 and 10% w/w)were incorporated in the cream, lotion and gelformulations and the drug release from theseformulations was studied. These figures alsoshow the effect of drug:polymer ratio on therelease of the drug from cream, lotion and gelformulations. In order to better comparisonbetween the release profiles of differentformulations, a linear relationship between Q(the cumulative amount of drug penetratedthrough the unit surface area of themembrane) and the time was obtained after 1h (see r2 values in Table 2). The cumulativeamount released increased with an increase inthe concentration of active ingredient in theformulation. These figures also show that theamount of drug released at first hour is highercompared to the amount of drug release for thenext hour. This could be due to the presenceof non-encapsulated BPO in theseformulations. When the free BPO wasreleased, the flux remained constant for thenext 7 hours. This flux represents the releaseof entrapped drug from microsponges.

Slopes of the linear portion of the releaseprofiles were calculated. These slopesrepresented the rate of release or flux of BPOfrom different formulations (Table 2). Theflux results showed that, generally, the flux ofdrug from different formulations is as follows:lotions > gels > creams. In other words, therelease of drug from lotions is the fastest.Comparing Q8 (the amount of BPO releasedafter 8 h) for different ratios of drug:polymeralso showed that the Q8 was lower for themicrosponges with lower porosity ofmicrosponges (see Tables 2 and 3).

In contrast to the other studies [12-14], thepresent study showed that generally anincrease in the ratio of drug:polymer resultedin a reduction in the release of BPO frommicrosponges. They described that as thepolymer amount increases, the matrix wall ofmicrosponges becomes thicker. The formationof a thicker matrix wall leads to slower releaserate of drug caused by longer diffusion path.Similar observations to our results were madefor ketoprofen microsponges [13], but theauthors did not provide an explanation fortheir observations.

In order to find the reason for theobservation made in our studies, pore analysisof microsponges was carried out and theresults are shown in Table 3. It has beenreported that the pore diameter can have asignificant effect on the release rate of theingredient, and also affects the migration ofthe active ingredient from the microspongeparticle into the vehicle in which the materialis dispersed. As an example, it has beenreported that menthol in various MDS, whenthe release rate constant was plotted versus logpore diameter, a straight line was obtained;indicating that the rate of release isproportional to the cross-sectional area of thepore diameter [6]. We could not establish anyrelationship between pore diameters and therelease rate of BPO from microsponges. Ourresults showed that apart from pore diameter,the number of pores is also important factorin controlling the release rate of BPO frommicrosponges. In order to show the impacteffect of the number of pores on the releaserate of BPO from microsponges, the totalporosity of microsponges, total surface area

Table 3. Results obtained from porosimetry experiments carried out on different microsponge formulations.Ratio of Total cumulative Total specific Pore radius Porosity (%)drug:polymer volume (cm3/g) surface (m2/g) (µm)MDS3 (3:1) 3.968 0.651 23.973 22.43MDS5 (5:1) 2.448 0.518 17.080 15.39MDS7 (7:1) 1.920 0.385 17.184 14.17MDS9 (9:1) 1.764 0.420 17.599 12.13MDS11 (11:1) 1.623 0.292 20.030 11.02MDS13 (13:1) 1.447 0.265 24.488 9.87

Benzoyl peroxide release from microsponges

and total volume of pores of microspongeswere calculated (Table 3). The results showthat, generally, the lower release rate wasobtained for microsponges with low porosity,low surface area and low volume. Therefore,a reduction in the release rate could be due tothe low porosity of microsponges in MDS13(Table 3). The results also show that the Q8values (i.e. the amount of BPO released after

8 h) were lower for the microsponges withlower porosity of microsponges (see Tables 2and 3).

4. ConclusionThe main site of pharmacological action

is the pilosebaceous canal [1]. BPO penetratesthrough the follicular opening, probably bydissolving into sebaceous lipids, and in this

139

Figure 3. The release profiles of BPO from gel formulations containing different concentrations of BPO.

A Nokhodchi et al. / IJPS Summer 2005; 1(3): 131-142

140

environment exerts its antimicrobial activity.Skin irritation is a common side effect, and acorrelation exists between efficacy andirritation [1, 2]. The controlled release ofBPO from a delivery system to the skin couldalter this correlation by maintainingintrafolicular penetration while reducingpercutaneous absorption. The microparticlesare too large to pass through the stratum

corneum, hence they would be expected toremain on the skin surface, gradually releasingtheir contents over time. This release patternprevents excessive accumulation of activeagent in the epidermis and, as a result, mayenhance the safety of any topically applieddrugs. For example, it has been shown thatencapsulated BPO has a lower irritation effecton the skin in comparison to the formulations

Figure 4. The release profiles of BPO from cream formulations containing different concentrations of BPO.

Benzoyl peroxide release from microsponges

containing uncapsulated BPO powders [5].Because the pharmacological activity of BPOis as a consequence of its ability to penetrateinto the skin preferentially through thefollicular openings, a controlled-releasetopical delivery system might reduce thepercutaneous absorption of BPO withoutaffecting its intrafollicular penetration, therebyreducing the irritancy of the drug withoutsacrificing efficacy.

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Figure 5. The release profiles of BPO from lotion formulations containing different concentrations of BPO.

A Nokhodchi et al. / IJPS Summer 2005; 1(3): 131-142

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