Rheological and Noxious Analysis of Some Semisolid

Available online at httpjournal-of-agroalimentaryro

Journal of Agroalimentary Processes and

Technologies 2011 17(1) 85-92

Journal of

Agroalimentary Processes and Technologies

__________________________________________ Corresponding author e-mail cadeheleanumftro

Rheological and Noxious Analysis of Some Semisolid

Formulations with Different Types of Surfactants

Simona Ardelean12 Daniela Ionescu 3 Victor Năstase 1

1 University of Medicine and Pharmacy ldquoGrTPopardquo Iassy Faculty of Pharmacy Iassy Romania 2 Pharmacy Libropharma srl Arad Romania

3University of Medicine and Pharmacy ldquoVictor Babesrdquo Timisoara Faculty of Pharmacy Eftimie Murgu Square No2 RO-300041 Timisoara

Received 14 January 2011 Accepted 11 March 2011

______________________________________________________________________________________ Abstract

Our study aims to assess the rheological parameters and toxic effects for some applications of semisolid formulations that include in their composition surfactants Sodium lauryl sulphate Tween 20 Sucrose laureate In laboratory the determinations were performed using a rheometer in standard conditions provided by regulations and on the other hand the clinically toxic side effects were investigated with aid of three groups of healthy volunteers aged 20-30 years using the patch-test application Sodium lauryl sulfate represents the surfactant determining the best rheological properties (flow viscosity) compared with the other two but laureate sucrose can lead to qualitative rheological formulations

Keywords rheological analysis surfactants semisolid formulation ______________________________________________________________________________________

1 Introduction

The oilwater (ow) creams are widely used in pharmacy and cosmetics for their therapeutic properties and as vehicles to deliver drugs and cosmetic agents to the skin The formulator must design a dermatological product which has good physical and chemical stability an attractive appearance and also provides an appropriate carrier system for the active agent The system must be non-irritant to the skin easily applied and removed from the skin Thus many formulations are complex multi-component preparations containing a number of emulsifiers polymers and other additives The most important and at the same time the most contradictory group of additives are the surfactants An understanding of the surfactants the effect elicited by them and the microstructure of such systems are essential in order to optimize the formulation and manufacture of existing products and in the design of new dermatological delivery systems [1]

The ow type creams stabilized with mixed emulsifier are at least four-phase systems which phases are the following a) crystalline hydrophilic gel phase composed of bilayers of surfactant and fatty amphiphile [2] water molecules are inserted between the bilayers thus forming interlamellar water layer b) bulk water layer water molecules bound as bulk water are in equilibrium with the interlamellarly fixed water in the gel phase Both phases form the continuous (external) phase of the system It is assumed that interlamellarly fixed water molecules exhibit different physicochemical and biopharmaceutical properties than those of the bulk water phase [2] c) lipophilic gel phase The excess of the fatty amphiphile which is not part of the hydrophilic gel phase builds up a matrix with lipophilic character d) dispersed oil phase This inner phase is mainly immobilized mechanically from the lipophilic gel phase [3]

Simona Ardelean et al Journal of Agroalimentary Processes and Technologies 2011 17(1)

86

Human skin is the largest and important target organ of the body for many application of drugs [45] It represents the natural barrier that prevents systemic exposure to environmental chemical [6] biological [7] and physical attacks [8] Skin consists of three layers epidermis dermis and hypodermis The stratum corneum (SC) layer is considered as the most external layer of the dermis in the skin and it is characterized as being strong highly flexible and self repairing It is the rate limiting layer for the penetration or diffusion of topically applied substances through the skin [67 91011] Therefore this restriction should be overcome in order to reach a therapeutic concentration [5] It has a thickness of 10ndash25 microm with about 4ndash15 layer of corneocyte [9]

It has been recognized that the vehicle in which the permeant is applied to the skin has a distinctive effect on the dermal and transdermal delivery of active ingredients Despite the fact that studies have been performed to investigate the vehicle effect on skin penetration it is still not fully understood especially for more complex formulations such as emulsions In addition the task of formulating a topical formulation not only includes the optimization for delivery of the active ingredient but also the fulfillment of the requirements for chemical and physical stability non-toxicity and aesthetic acceptability [12]

According to the complexity of the vehicle effect on skin penetration some general guidelines are recognized for enhancing the flux of active ingredients across the skin It is well known that the flux can be optimized by maximum thermodynamic activity of the permeant in the vehicle supersaturation and incorporation of penetration enhancers which can increase the solubility of the permeant in the skin or enhance the diffusivity across the skin [13]

Surfactants are used in formulations as emulsifiers wetting agents and solubilizers and have the potential to irritate the skin The application of surfactants may lead to inflammation induced by the direct interaction of the surfactants with epidermal keratinocytes which results in the release of cytokines [14] Moreover protein denaturation [15] and swelling of the stratum corneum may also result from the interaction of surfactants with keratin [16] In addition to their irritant potential surfactants may also deplete intercellular lipids from the stratum corneum

resulting in the dehydration of the stratum corneum [17] and the different effects of surfactants on the skin (inflammation direct cytotoxic effects lipid extraction) can impair the skin barrier function [18]

Emulsion systems used in dermopharmacy as drug carriers have to fulfill a number of requirements eg acceptable physical stability chemical inertness satisfactory safety profile and drug delivery efficacy [1920] reaching at the same time optimal sensory attributes (cohesiveness spreadability) [21] The European Pharmacopoeia 60 recognizes only two mixed emulsifiers both of them of anionic type cetostearyl alcohol (type A) emulsifying and cetostearyl alcohol (type B) emulsifying the first one containing minimum 7 (ww) of sodium cetostearyl sulphate (SCS) and the second one minimum 7 (ww) of sodium lauryl sulphate (SLS) The latter surfactant is well established as cytotoxic marker chemical [22] and in vivo proved skin irritant [23] While vehicles based on these mixed emulsifiers meet general requirements for pharmaceutical bases their use is definitely accompanied by adverse skin reactions [24] or associated with unpleasing appearance and unacceptable skin feeling during application [25] Consequently overcoming the above problems is an important formulation task which may be accomplished by adequate selection of an emulsifier system [24 26 19 27 28]

2 Materials and Method

Rheological readings were made with Rheometer RV-MLV at 25 deg C Saponification index was calculated as FRX followed by a statistical validation of values [29 30 31 32]

The formulations of semisolid product which of surfactants were

[33]

oily ) at

has been used for testing 2 takenand adapted from a cosmetic form The processof semisolid formulations was by heating the twophases (aqueous and oily- phase a temperature of about 70 Co and mixing them The surfactant issoluble in the aqueous phase The two phases aremixed until cooling and solidification

To determine the tensioning capacity we have used the same three formulas according to the table Tensioning capacity was determined using extensometer Pozo Ojeda and Sune Arbusa It takes into account the diameter of the circle occupied by 1 g ointment following pressing with a glass plate (diameter 11 cm) which weighs 545 g (G0)


87

At 1 minute intervals we place on the top plate of extensometer the increasing weights in order 50 g (G1) 100 g (G2) 150 g (G3) and 200 g (G4)Then it reads the diameter of the circle formed by spreading ointment We calculate the area (πr2) which is noted by S0 S1 S2 S3 and S4 Based on these types of results are plotted extensometric curves

The noxious effect of the formulations with the higher concentration of surfactant was 2 These were tested on 3 groups of 4 volunteers These were female with ages between 25-30 years The studies were developed under the ethical principles of the Declaration of Helsinki concerning testing on human subjects including confidentiality on all records and papers The rights safety and comfort of tested human subjects are above all other scientific or social interests Before getting involved in such a study each and every human subject has freely consented knowing in detail every aspect of the testing Inclusion criteria were human volunteers who have been informed of the particularities of the tests and have freely consented to it clinically healthy Caucasians Exclusion criteria were dermatological diseases which can interfere with the final evaluation pregnancy participation in other simultaneous studies or in a short period of time tattoos sunburns scars in the tested areas [32 33 34] To test the flow curves using the formula

ατ sdot= z

where τ is the tangential pressure (Pa) z is the constant cylinder and α is the value read on the dial (the force that the semisolid opposes to the rotation) For assessing the viscosity is used the formula

Dτη = where

η is dynamic viscosity (Pa s) τ is the tangential pressure (Pa) and D is the gradient of speed (1 s or s-1)

Flow curves and rheogrammes take account into these parameters

Three groups each of five healthy female volunteers aged 20-30 years participated in patch-test application

After that the chambers were filled with the preparations and put on the ventral forearm of the subjects The skin was occluded for 24 hours with this chamber

After the occlusion time the patches were removed and the hydration level and the TEWL were measured 30 minutes later Table 1 Cosmetic formulations analyzed ndash for 100 g basis Ingredient Formula 1 Formula 2 Formula 3 Sodium lauryl sulphate

- - 051152

Tween 20 - 051152 - Sucrose laurate D1216

051152 - -

Cetyl alcohol 8 8 8 Cocoa Butter 7 7 7 Vaseline 20 20 20 Preservative solution 65 65 65

3 Results and Discussion

Rheological analyses of formulas studied have revealed the following issues presented in Figures 1 2345678

0

200

400

600

800

1000

1200

1400

1600

1 2 3 4 5 6 7 8 9 10 11 12

D (1s)

η (P

a x η (Pa x s) cod 3

η (Pa x s) cod 2η (Pa x s) cod 1

0

100

200

300

400

500

600

700

0 5 10 15

D (1s)

Tau

(Pa τ ( Pa) cod 1

τ ( Pa) cod 2τ ( Pa) cod 3

Figure 1 Rheogramme and flow curves for the three

formulations at a concentration of 05 surfactant


88

0

50

100

150

200

250

300

1 2 3 4 5 6 7 8 9 10 11 12

D (1s)

η (P



0

100

200

300

400

500

600

700

1 2 3 4 5 6 7 8 9 10 11 12

D (1s)

τ (P

a τ ( Pa) cod 1τ ( Pa) cod 2τ ( Pa) cod 3



0

50

100

150

200

250

300

350

400

450

500

1 2 3 4 5 6 7 8 9 10 11 12

D (1s)

η (P



0

100

200

300

400

500

600

1 2 3 4 5 6 7 8 9 10 11 12

D (1s)

τ (P




0

100

200

300

400

500

600

1 2 3 4 5 6 7 8 9 10 11 12

D (1s)

η (P



0

100

200

300

400

500

600

700

1 2 3 4 5 6 7 8 9 10 11 12

D (1s)

τ (P


Figure 4 Rheogramme and flow curve for the three


0

510

15

2025

3035

4045

50

S (cm2)

G0 G1 G2 G3 G4G (g)

S (cm2) cod 3S (cm2) cod 2S (cm2) cod 1

Figure 5 Extensometric curves for creams with 05

surfactant

0

10

20

30

40

50

60

S (cm2)

G0 G1 G2 G3 G4G (g)



surfactant


89

0

10

20

30

40

50

60

S (cm2)

G0 G1 G2 G3 G4G(g)


Figure 7 Extensometric curves for creams with

15 surfactant

0

10

20

30

40

50

60

S (cm2)

G0 G1 G2 G3 G4G (g)



2 surfactant

The aspect of the skin to 3 groups of volunteers after patch application with the formulations for analysis and maximum surfactant concentration of 2 for 24 hours is figurate in the followings figures Formula 1 2 and 3

(A)

(B)

Formula 1 (A) Before and (B) After 24 h

(A)

(B)

Formula 2 Tween 20 (A) Before (B) After 24 H

(A)

(B)

Formula 3 (A) Before (B) After 12 H

Many pharmaceutical and cosmetic processes such as new ingredient selections formulation preparations material packaging and shelf storage are associated with a complex flow of materials The application and acceptance of pharmaceuticals and cosmetics are also dependent on the flow properties of the final product Therefore rheological measurements an important route to revealing the flow and deformation behaviors of materials cannot only improve efficiency in processing but can also help formulators and end users find pharmaceutical and


90

cosmetic products that are optimal for their needs In general rheological measurements on pharmaceutical and cosmetic materials are performed for the following reasons to understand the fundamental nature of a system for quality control of raw materials final products and manufacturing processes such as mixing pumping packaging and filling and to study the effect of different parameters such as formulation storage time and temperature on the quality and acceptance of a final product [35]

Pharmaceutical and cosmetic materials range in consistency from fluid to solid Semisolid products are the most difficult materials to characterize rheologically because they combine both liquid and solid properties within the same material Few rheological publications have addressed the dominant viscoelastic nature of a semisolid material in a detailed sense [35]

Semisolid preparations include ointments pastes cream emulsions gels and rigid foams Their common property is the ability to cling to the application surface for a reasonable period of time before they are washed off or worn off They usually serve as vehicles for topically applied drugs as emollients or as protective or occlusive dressings or they may be applied to the skin and membranes [36]These preparations are widely used as a means of altering the hydration state of the substrate (ie the skin or the mucous membrane) and for delivering the drugs (topical or systemic) by means of the topical route

One of the serious problems associated with the formulation and manufacture of topicalndashmucosal preparations is the establishment of reliable techniques for their characterization mainly because of the complexity of their physical structure [37] Consumer preference for such products depends on various properties of the preparation collectively known as the textural profile which includes appearance odor extrudability (when applicable) initial sensations upon contact with the skin spreading properties tackiness and residual greasiness after application [38] Ultimate acceptability and clinical efficacy of such preparations require them to possess optimal mechanical properties (ease of removal from the container spreadability on the substrate) rheological properties (viscosity elasticity thixotropy flowability) and other desired

properties such as bioadhesion desired drug release and absorption [39]

The efficacy of topical therapy depends on the patient spreading the formulation in an even layer to deliver a standard dose The optimum consistency of such a formulation helps ensure that a suitable dose is applied or delivered to the target site This is particularly important with formulations of potent drugs and of cosmetic active substances A reduced dose would not deliver the desired effect and an excessive dose may lead to undesirable side effects The delivery of the correct dose of the drug depends highly on the spreadability of the formulation [40]

On the other hand the surfactants or surface-active agents are amphiphilic compounds that form oriented monolayers at interfaces and exhibit higher equilibrium concentrations at interfaces than do those in a bulk solution They exhibit several characteristics including detergency foaming wetting emulsifying solubilizing and dispersing These agents are an integral part of the formulation of disperse systems for drugs and cosmetics and impart the desired physical characteristics and physical stability to these systems Overall they are responsible for the rheological properties of a formulation [41 42]

The rheological characterizations for pharmaceutical and cosmetic semisolids provide important information to facilitate their production and processing for their products Today most formulators also count on rheological results to develop customer-favored products Therefore a reliable rheometer and understanding the rheology are becoming necessary for pharmaceutics and cosmetics manu-facturers

The results obtained indicate that this semi-solid formulation offers potential advantages as a vehicle for dermopharma-ceutical and cosmetic preparations development and certainly merits further investigations

4 Conclusion

Sodium lauryl sulfate represents a surfactant determining the best rheological properties and flow viscosity compared with the other two but laureate sucrose can lead to qualitative rheological formulations In exchange sodium lauryl sulfate will cause a very severe noxious reaction compared with other surfactants


91

References

1 Eccleston GM Functions of mixed emulsifiers and emulsifying waxes in dermatological lotions and creams Colloids and Surfaces A Physicochemical and Engineering Aspects 1997 (123-124) 169-182 doi101016S0927-7757(96)03846-0

2 Koacutenya M Sorrenti M Ferrari F et al Study of the microstructure of ow creams with thermal and rheological methods Journal of Thermal Analysis and Calorimetry 2003 73(2) 623-632 doi 101023A1025442516213

3 Swarbrick JBoylan JC Ecyclopedia of Pharm Techn 5 Band Marcel Dekker Inc New York 1988 pp 171

4 Lanke SS Kolli CS Strom JG et al Enhanced transdermal delivery of low molecular weight heparin by barrier perturbation Int J Pharm 2008 365(1-2) 26-33 doi101016jijpharm200808028

5 Teichmann A Heuschkel S Jacobi U et al Comparison of stratum corneum penetration and localization of a lipophilic model drug applied in an OW microemulsion and an amphiphilic cream Eur J Pharm Biopharm 2007 67(3) 699-706 doi101016jejpb200704006

6 Capt A Luzy A P Esdaile D et al Comparison of the human skin grafted onto nude mouse model with in vivo and in vitro models in the prediction of percutaneous penetration of three lipophilic pesticides Regul Toxicol Pharm 2007 47(3) 274-287 doi101016jyrtph200611008

7 Saija A Tomaino A Trombetta D et al In vitro and in vivo evaluation of caffeic and ferulic acids as topical photoprotective agents Int J Pharm 2000 199(1) 39-47 doi101016S0378-5173(00)00358-6

8 Kobayashi Y Iwai L Akutsu N et al Increased carbonyl protein levels in the stratum corneum of the face during winter Int J Cosmetic Sci 2008 30(1) 35-40 doi 101111j1468-2494200800422x

9 Kogan A Garti N Microemulsions as transdermal drug delivery vehicles Adv Colloid Interfac 2006 123-126 369-385 doi101016jcis200605014

10 Lademann J Richter H Teichmann A et al Nanoparticles - An efficient carrier for drug delivery into the hair follicles Eur J Pharm Biopharm 2007 66(2) 159-164 doi101016jejpb200610019

11 Edresi S Baie S In-vitro and in-vivo evaluation of a photo-protective kojic dipalmitate loaded into nano-creams Asian Journal of Pharmaceutical Sciences 2010 5(6) 251-265

12 Smith EW Maibach HI Surber C Use of emulsions as topical drug delivery systems In Pharmaceutical Emulsions and Suspensions (Nielloud F Marti-Mestres G eds) Marcel Dekker New York 2000 pp 259ndash270

13 Otto A Plessis J Wiechers JW Formulation effects of topical emulsions on transdermal and dermal delivery International Journal of Cosmetic Science 2009 31(1) 1ndash19 doi 101111j1468-2494200800467x

14 Van Ruissen F Carroll Le M Van der Valk JM Schalkwijk J Differential effects of detergents on keratinocyte gene expression J Invest Dermatol 1998 110 358ndash363 doi101046j1523-1747199800155x

15 Scheuplein RJ Ross L Effects of surfactants and solvents on the permeability of epidermis J Soc Cosmet Chem 1970 21 853ndash873

16 Rhein LD Robbins CR Fernee K Cantore R Surfactant structure effects on swelling of isolated human stratum corneum J Soc Cosmet Chem 1986 37 125ndash139

17 Imokawa G Surfactant-induced depletion of ceramides and other intercellular lipids implication for the mechanism leading to dehydration of the stratum corneum Exog Dermatol 2004 3 81ndash98 doi 101159000086158

18 De Fine Olivarius F Agner T Menne T Skin barrier function and dermal inflammation An experimental study of transepidermal water loss after dermal tuberculin injection compared with SLS patch testing Br J Dermatol 1993 129(5) 554ndash557 doi 101111j1365-21331993tb00483x

19 Savic S Weber C Savic MM Muller-Goymann C Natural surfactant-based topical vehicles for two model drugs Influence of different lipophilic excipients on in vitroin vivo skin performance International Journal of Pharmaceutics 2009 381(2) 220ndash230 doi101016jijpharm200907007

20 Refai H Muller-Goymann CC The influence of dilution of topical semisolid preparations on hydrocortisone permeation through excised human stratum corneum Eur J Pharm Biopharm 2002 54(2) 143ndash150 doi101016S0939-6411(02)00054-1

21 Smith EW Surber C Tassopoulos T Maibach H Topical dermatological vehicles a holistic approach In Bronaugh RL Maibach HI (Eds) Topical Absorption of Dermatological Products Marcel Dekker New York 2002 pp 457ndash463

22 OECD 2008 Guideline for the Testing of Chemicals Draft Proposal for a New Guideline In vitro Skin Irritation Human Skin Model Test Available at httpwwwoecdorg searchResult 03400en-2649-201185-1-1-1-1-100html


92

23 Fluhr JW Kuss O Diepgen T Lazzerini S Pelosi A Gloor M Berardesca ETesting for irritation with a multifactorial approach comparison of eight noninvasive measuring techniques on five different irritation types Br J Dermatol 2001 145(5) 696ndash703 doi 101046j1365-2133200104431x

24 Barany E Human in vivo skin irritancy testing In Loden M Maibach HI (Eds) Dry Skin and Moisturizers CRC Press LLC Boca Raton 2000 pp 243ndash250

25 Al-Bawab A Friberg SE Some pertinent factors in skin care emulsions Adv Colloid Interf Sci 2006 123ndash126 313ndash322 doi101016jcis200606004

26 Williams AC Barry BB Penetration enhancers Adv Drug Deliv Rev 2004 56 603ndash618

27 Harnisch S Scuhmann R Harnisch JF Muller RH Differences in the coalescence kinetics of fat emulsions in dependence on the amount of fat and age Die Pharmazie 2002 57(1) 54-57

28 Horst D Solfactants for the easy preparation of transparent hair shine improving shampoons JornComEspDeterg 2004 34 85-89

29 Ciulei I Grigorescu E Stănescu U Plante medicinale- Fitochimie şi Fitoterapie Ed Medicală Bucureşti 1993 pp 35-45

30 Grecu I Popovici V Substanţe farmaceutice auxiliare care acţionează datorită tensiunii superficiale In Substanţe farmaceutice auxiliare Ed Facla Timişoara 1988 pp33-42

31 Stănescu U Miron A Hăncianu M Aprotosoaie C Bazele farmaceutice farmacologice şi clinice ale fitoterapiei Ed bdquoGrTPopardquo Iaşi 2002

32 Farmacopeea Romacircnă ed-aX-a Ed Medicală Bucureşti 1993

33 Popovici A Ciurba A Preparate cosmetice pentru icircngrijirea feţei Formular cosmetic Ed Tipomur Tg Mureş 1998 pp 67-69

34 Gafiţanu E Unguente Forme farmaceutice ndash sisteme disperse eterogene Ed Cermi Iaşi 2000 pp193-273

35 Herh P Tkachuk J Wu S Bernzen M Rudolph BThe rheology of pharmaceutical and cosmetic semisolids American Laboratory 1998 1 12-14

36 Idson B Lazarus J Semisolids in The Theory and Practice of Industrial Pharmacy L Lachman L Lieberman HA Kanigs JL Eds Lea and Febiger Philadelphia PA 2d ed 1987 pp 215ndash244

37 Tamburic S et al A Comparison of Electrical and Rheological Techniques for the Characterization of Creams Int J Pharm 1996 137(2) 243ndash248 doi1010160378-5173(96)04528-0

38 Barry BW Grace AJ Sensory Testing of Spreadability Investigation of Rheological Conditions Operative During Application of Topical Preparations J Pharm Sci 1972 61(3) 335ndash341 doi 101002jps2600610303

39 Jones DS Woolfson AD Brown AF Texture Viscoelastic and Mucoadhesive Properties of Pharmaceutical Gels Composed of Cellulose Polymers Int J Pharm 1997 151(2) 223ndash233 doi101016S0378-5173(97)04904-1

40 Duggin G Softening Skin with Emollient Ingredients Manufacturing Chemist 1996 67(6) 27ndash31

41 Rieger MM Surfactants in Pharmacetical Dosage Forms Disperse Systems Lieberman HA Reiger MM Bankers GS Eds Marcel Dekker Inc New York NY 1988 pp285ndash366

42 Garg A Aggarwal D Garg S Singla A K Spreading of Semisolid Formulations An Update Pharmaceutical Technology 2002 26(9) 84-105


86

Human skin is the largest and important target organ of the body for many application of drugs [45] It represents the natural barrier that prevents systemic exposure to environmental chemical [6] biological [7] and physical attacks [8] Skin consists of three layers epidermis dermis and hypodermis The stratum corneum (SC) layer is considered as the most external layer of the dermis in the skin and it is characterized as being strong highly flexible and self repairing It is the rate limiting layer for the penetration or diffusion of topically applied substances through the skin [67 91011] Therefore this restriction should be overcome in order to reach a therapeutic concentration [5] It has a thickness of 10ndash25 microm with about 4ndash15 layer of corneocyte [9]

It has been recognized that the vehicle in which the permeant is applied to the skin has a distinctive effect on the dermal and transdermal delivery of active ingredients Despite the fact that studies have been performed to investigate the vehicle effect on skin penetration it is still not fully understood especially for more complex formulations such as emulsions In addition the task of formulating a topical formulation not only includes the optimization for delivery of the active ingredient but also the fulfillment of the requirements for chemical and physical stability non-toxicity and aesthetic acceptability [12]

According to the complexity of the vehicle effect on skin penetration some general guidelines are recognized for enhancing the flux of active ingredients across the skin It is well known that the flux can be optimized by maximum thermodynamic activity of the permeant in the vehicle supersaturation and incorporation of penetration enhancers which can increase the solubility of the permeant in the skin or enhance the diffusivity across the skin [13]

Surfactants are used in formulations as emulsifiers wetting agents and solubilizers and have the potential to irritate the skin The application of surfactants may lead to inflammation induced by the direct interaction of the surfactants with epidermal keratinocytes which results in the release of cytokines [14] Moreover protein denaturation [15] and swelling of the stratum corneum may also result from the interaction of surfactants with keratin [16] In addition to their irritant potential surfactants may also deplete intercellular lipids from the stratum corneum

resulting in the dehydration of the stratum corneum [17] and the different effects of surfactants on the skin (inflammation direct cytotoxic effects lipid extraction) can impair the skin barrier function [18]

Emulsion systems used in dermopharmacy as drug carriers have to fulfill a number of requirements eg acceptable physical stability chemical inertness satisfactory safety profile and drug delivery efficacy [1920] reaching at the same time optimal sensory attributes (cohesiveness spreadability) [21] The European Pharmacopoeia 60 recognizes only two mixed emulsifiers both of them of anionic type cetostearyl alcohol (type A) emulsifying and cetostearyl alcohol (type B) emulsifying the first one containing minimum 7 (ww) of sodium cetostearyl sulphate (SCS) and the second one minimum 7 (ww) of sodium lauryl sulphate (SLS) The latter surfactant is well established as cytotoxic marker chemical [22] and in vivo proved skin irritant [23] While vehicles based on these mixed emulsifiers meet general requirements for pharmaceutical bases their use is definitely accompanied by adverse skin reactions [24] or associated with unpleasing appearance and unacceptable skin feeling during application [25] Consequently overcoming the above problems is an important formulation task which may be accomplished by adequate selection of an emulsifier system [24 26 19 27 28]

2 Materials and Method

Rheological readings were made with Rheometer RV-MLV at 25 deg C Saponification index was calculated as FRX followed by a statistical validation of values [29 30 31 32]

The formulations of semisolid product which of surfactants were

[33]

oily ) at

has been used for testing 2 takenand adapted from a cosmetic form The processof semisolid formulations was by heating the twophases (aqueous and oily- phase a temperature of about 70 Co and mixing them The surfactant issoluble in the aqueous phase The two phases aremixed until cooling and solidification

To determine the tensioning capacity we have used the same three formulas according to the table Tensioning capacity was determined using extensometer Pozo Ojeda and Sune Arbusa It takes into account the diameter of the circle occupied by 1 g ointment following pressing with a glass plate (diameter 11 cm) which weighs 545 g (G0)


87



ατ sdot= z


Dτη = where






- - 051152


051152 - -




0

200

400

600

800

1000

1200

1400

1600

1 2 3 4 5 6 7 8 9 10 11 12

D (1s)

η (P



0

100

200

300

400

500

600

700

0 5 10 15

D (1s)

Tau

(Pa τ ( Pa) cod 1





88

0

50

100

150

200

250

300

1 2 3 4 5 6 7 8 9 10 11 12

D (1s)

η (P



0

100

200

300

400

500

600

700

1 2 3 4 5 6 7 8 9 10 11 12

D (1s)

τ (P




0

50

100

150

200

250

300

350

400

450

500

1 2 3 4 5 6 7 8 9 10 11 12

D (1s)

η (P



0

100

200

300

400

500

600

1 2 3 4 5 6 7 8 9 10 11 12

D (1s)

τ (P




0

100

200

300

400

500

600

1 2 3 4 5 6 7 8 9 10 11 12

D (1s)

η (P



0

100

200

300

400

500

600

700

1 2 3 4 5 6 7 8 9 10 11 12

D (1s)

τ (P




0

510

15

2025

3035

4045

50

S (cm2)

G0 G1 G2 G3 G4G (g)



surfactant

0

10

20

30

40

50

60

S (cm2)

G0 G1 G2 G3 G4G (g)



surfactant


89

0

10

20

30

40

50

60

S (cm2)

G0 G1 G2 G3 G4G(g)



15 surfactant

0

10

20

30

40

50

60

S (cm2)

G0 G1 G2 G3 G4G (g)



2 surfactant


(A)

(B)


(A)

(B)


(A)

(B)




90










4 Conclusion



91

References
























92






















87



ατ sdot= z


Dτη = where






- - 051152


051152 - -




0

200

400

600

800

1000

1200

1400

1600

1 2 3 4 5 6 7 8 9 10 11 12

D (1s)

η (P



0

100

200

300

400

500

600

700

0 5 10 15

D (1s)

Tau

(Pa τ ( Pa) cod 1





88

0

50

100

150

200

250

300

1 2 3 4 5 6 7 8 9 10 11 12

D (1s)

η (P



0

100

200

300

400

500

600

700

1 2 3 4 5 6 7 8 9 10 11 12

D (1s)

τ (P




0

50

100

150

200

250

300

350

400

450

500

1 2 3 4 5 6 7 8 9 10 11 12

D (1s)

η (P



0

100

200

300

400

500

600

1 2 3 4 5 6 7 8 9 10 11 12

D (1s)

τ (P




0

100

200

300

400

500

600

1 2 3 4 5 6 7 8 9 10 11 12

D (1s)

η (P



0

100

200

300

400

500

600

700

1 2 3 4 5 6 7 8 9 10 11 12

D (1s)

τ (P




0

510

15

2025

3035

4045

50

S (cm2)

G0 G1 G2 G3 G4G (g)



surfactant

0

10

20

30

40

50

60

S (cm2)

G0 G1 G2 G3 G4G (g)



surfactant


89

0

10

20

30

40

50

60

S (cm2)

G0 G1 G2 G3 G4G(g)



15 surfactant

0

10

20

30

40

50

60

S (cm2)

G0 G1 G2 G3 G4G (g)



2 surfactant


(A)

(B)


(A)

(B)


(A)

(B)




90










4 Conclusion



91

References
























92






















88

0

50

100

150

200

250

300

1 2 3 4 5 6 7 8 9 10 11 12

D (1s)

η (P



0

100

200

300

400

500

600

700

1 2 3 4 5 6 7 8 9 10 11 12

D (1s)

τ (P




0

50

100

150

200

250

300

350

400

450

500

1 2 3 4 5 6 7 8 9 10 11 12

D (1s)

η (P



0

100

200

300

400

500

600

1 2 3 4 5 6 7 8 9 10 11 12

D (1s)

τ (P




0

100

200

300

400

500

600

1 2 3 4 5 6 7 8 9 10 11 12

D (1s)

η (P



0

100

200

300

400

500

600

700

1 2 3 4 5 6 7 8 9 10 11 12

D (1s)

τ (P




0

510

15

2025

3035

4045

50

S (cm2)

G0 G1 G2 G3 G4G (g)



surfactant

0

10

20

30

40

50

60

S (cm2)

G0 G1 G2 G3 G4G (g)



surfactant


89

0

10

20

30

40

50

60

S (cm2)

G0 G1 G2 G3 G4G(g)



15 surfactant

0

10

20

30

40

50

60

S (cm2)

G0 G1 G2 G3 G4G (g)



2 surfactant


(A)

(B)


(A)

(B)


(A)

(B)




90










4 Conclusion



91

References
























92






















89

0

10

20

30

40

50

60

S (cm2)

G0 G1 G2 G3 G4G(g)



15 surfactant

0

10

20

30

40

50

60

S (cm2)

G0 G1 G2 G3 G4G (g)



2 surfactant


(A)

(B)


(A)

(B)


(A)

(B)




90










4 Conclusion



91

References
























92






















90










4 Conclusion



91

References
























92






















91

References
























92






















92





















Documents

Rheological and Noxious Analysis of Some Semisolid