Investigation of water and

FABAD J. Pharm. Sci., 19, 1-4,1994

RESEARCH ARTICLES / BILIMSEL ARAŞTIRMALAR

Investigation of water and

Antimicrobial Agent Permeation of Polyurethane Membranes in

Relation· to their Surface Properties

Ufuk ABBASOGLU*, Mehlika PULAT**

Summary: Three types of polyurethane ^(PU) mem- branes were prepared ^by solvent-casting procedure. of Pellethane solutions containing different solvents; i.e.

THF (tetrahydrofurane), DMF(dimethylformamide), di- oxane compositions. Surface properties, water and anti- bacterial agent permeabilities of PU membranes were investigated. Water permeability values were deter- mined in the region of 1500 g/m^2• 24h. The membranes were found ta. have sufficient permeability towards anti- bacterial agent's of 1 % silver sulfadiazine and Bacitracin 10000 UI-Neomycin sulphate 100 mg ointment.

Key words : Palyurethane, membrane permeability, bacitracin, neomysin ^sulphate

Geliş tarihi 4.6.1993 Kabul tarihi ^30.9.1993

ı:nıroduc!ion

in recent ^yearsı important advances were made in the field of wound dressing membranes and various kinds were developed. General requirements for a wound dressing are as follows: a) Protection of the wound from the mierobial environment; b) Posses- sion of optimal water permeability to drain wound fluid; e) Sufficient amount of release of the anti- baeterial agent embedded in !he membrane to the wound; d) Easy adhesion to the wound surfaee and subsequent easy removal without any adverse ef- fect to !he wound; e) Be flexible and eompa!ible with wound surfaceı-s.

(*) Gazi University, Faculty of Pharmacy, Microbiology Unit, T eknikokullar 06330, Ankara.

(**) Gazi University, Faculty of Arts and Sciences, Dept. of

Oıemistry, Teknik.okullar, 06330, Ankara.

Poliüretan Membranların Yüzey Özelliklerine

Bağlı Olarak Su ve Antimikrobiyal Ajanlara

Geçirgenliğinin Araştırılması

Özet : THF (tetrahidrofuraıı), DMF (dimetilformamid) ve ^diokscın çözücülerinin farklı karışımları kullanılarak hazırlanan Pellethane çözeltilerinden, ço·zilcü dôkiim yöntemi ile üç ayrı tip poliUretan (PU) membran üretildi.

Bu membranların yüzey ôZellikleri, su ve antibakteriyel ajan geçirgenlikleri araştırıldı. Su geçirgenlik değerlerinin 1500 g/m2. Us. civarında olduğu bulundu.

PU membranların % 1 gümüş sülfadiazin ve Basitrasin 1000 UI-Neomisiıı sülfat 100 mg antibakteriyel ajan-

larını, besi ortamına geçirgenlik değerlerinin kontrolle kıyaslanabilir değerler verdiği belirlendi.

Anahtar sözcükler : Poliüretan, membran

geçirgenliği, basitrasin, neomi- sin sülfat

The surfaee properties, water and antibaeterial

agenı permeability of three different types of pol- yurethane (PU) membranes, prepared with solvent casting method, were investigated in this study.

Materials and Methods Preparation of the membranes:

The investigated membranes (Pellethane 2363- SOA, Upjohn, The Netherlands), were prepared from polyether urethane by the solvent easting method, as given in the literature6. In order to ob- tain different struetural properties, 8 ^% Pellethane solutions with various combinations of dioxane (BDH, England), THF (Merek, Germany) and DMF (Merek, Germany) were prepared. These solutions

Abbasoğlu ve Pulat

were cast over glass surfaces and mernbranes were obtained by precipitation in 20 % glycerin-water rnedium. The rnembranes produced were washed thoroughly with water; dried in vacuurn at 40°C and sterilised with ethylene oxide. The thickness of the mernbranes were 25 ± 2 µm.

SEM Inves!igations:

The surface roughness and porosity of the the PU mernbranes were determined by photographing gold coated specimens with scanning electron microscope (Model: JEOL-lSM-T-330).

Water Permeability:

The water perrneability of the membranes were measured as given in the literature7. For this, the mernbranes were streched over water filled glass jars, so that they were in contact with water, and weighed. They were weighed again after standing at 37"C and 60 % relative hurnidity for 24 hours.

The water perrneability was calculated from the difference of the two weighings and expressed as g / m²• 24 hours.

In Vitro Microbiological Experiments:

The two antibacterial agents were filled separate- ly into sterile glass cylinders with a diameter of 15 mm and height 20 mm., whose bottoms were closed with PU mernbranes. Antibacterial agents used were silver sulfadiazine (SS) 1 % and bacitracin - neomycin sulfate (10.000 l.U. and 100 mg respective- ly) (BN) in ointment vehlcles. On the other hand, Escherichia cali ATCC 25922 and Staphylococcus aureus ATCC 25923 microorganisms were inoculated with Bi'rry rnethod to different Petri dishes con- taining Müller-Hinton Agar (Oxoid) nutrition rne- diurn with a concentration of MacFarland 0.58. The cylinders were placed, with sufficient spaces inbet- ween, onto Petri dishes with rnembrane side touch- ing the nutrition rnedium. Three membrane closed cylinders were used for each microorganisrn and ointrnent. As a control, cylinders without mem- branes, but with ointrnents were tested similarly.

The system was incubated for 16 hours at 37"C and inhibition zones were rneasured at the end of this peri od.

2

Results

The PU membranes studied were prepared with 10

% DMF - 90 % dioxane; 10 % DMF - 90 % THF and 100 % THF as solvents and are designated as (PU)A, (PU)B and (PU)C respectively (Table 1).

Surface proper!ies of the rnernbranes are studied with the SEM photographs in Fig 1 A, B, and C.

The water permeability values of the PU rnem- branes, measured as given in the literature, are giv- en in Table l.

The in vitre microbiological experirnents were carried out in accordance with the literature and the inhibition zone diarneters obtained are given in Table 2.

Discussion

Surface Properties

The PU mernbranes used in this study were pre- pared with !he classical solvent casting rnethod.

Our previous studies ha ve showed that, mernbranes prepared with different solvents have different porous structures6. This can be explained by the Hildebrand solubility parameters of the solvent, polymer and precipitant9.

As it can be seen in Fig 1, a hlghly porous structure was obtained where dioxane was employed (high average pore density and diameter) and a rough surface, but low porous structure where THF was employed. DMF was ernployed to give mechanical strenght to the structure. Average pore diameters and densities obtained from SEM photographs are summarized in Table l.

Table 1. Surface characteristics of PU membranes

Membıane Solvent Average Average Water No. s,-m Pore Pore Permeability

Demity Diameter (glm'-24 hrs.) (pore no./cm^{1) (µm)}

(PU)A 10%DMF 4.22x106 3.9 1641

90 % diox

(PU)B 10%DMF 6.70x105 2.5 1562

90%THF

(PU)c 100 % TIIF 2.20xl05 1.0 1205

FABAD J. Pharm. Sci., 19, 1 - 4, 1994

(A)

< aı

'"

Fig. 1. SEM photographs of PU membranes A) ^(PU)A, b) (PU)_8, C) (PU)c

Water Permeabililies:

The daily water loss from from the skin of a normal individual is reported to be 240 g/m'/24 hours. Wa- ter loss from a wound however, is more and can be between 3400-5200 g/m'/24 hours, depending upon the type of wound!O. Considering these values, the water permeability of wound dressing should be much higher than normal skin, in order to drain the wound properlyll-12.

The water permeability of the membranes we pro- duced were around 1500 g/m²/24 hours (Table 1). Un-

der the same conditions, the water permeabililies of the commercial wound dressing Biobrane and Op Site (Smith and Nephew ltd.) are reported to be 1400 and 500 g/m'.24 hours respecliveJy13. As can be seen in Table 1, the PU membranes prepared have higher water permeabilities than Biobrane and Op site. The most permeable one is seen to be (PU) ^A- In Vitro Microbiological Experiments:

The antibacterial agent permeabilities of the PU membranes used in this study are given in mms of

!he inhibition zone diameters, summarized in Tab- le 2. The results are assessed by the Student t test for the comparison of the means14. The difference of the membrane permeabilities as regarding microor- ganisms and anlibiotics was not found to be signifi- cant (p>0.05). When ^S. aureus is taken into consid- eration only, significant S. ^aureus is taken into consideration only, significant differences were found between (PU)A and (PU)c (p<0.05). This dif- ference does not depend on the membrane, but on the inhibilion of the microorganisms by the membrane, but on the inhibilion of the microorganisms by the antibiotic. Ali the other comparisons of permeabil- ity were not found to be significant (p>0.05). On the other hand, the anlibacterial agent permeability values of the three membranes were found to be close to the control values. A similar study was done with Omiderm. in the test using S. aureus, 17.8 mms was obtained for SS and 24.7 mms for Bn. With E. cali, 19.1 mm was reported for BN and no perme- ability for 5513.

it was concluded that, upon assessing the surface properties, water and antibacterial agent permea- bility values, the three PU membranes prepared in this study can be used as wound dressing, the besi one being (PU) A.

Table. 2. Inhibition zone diameters(mm) of different antibacte- rial agents in solid nutrition medium

E. coli S. aureus

SS BN SS BN

(PU)A 17.3±0.6 19.3±0.6 19.0±1.0 22.0±1.0 (PU)B 17.7±0.6 19.5±0.5 18.7±1.0 20.7±1.0 (PU)c 17.7±0.5 20.7±0.7 18.7±0.9 18.0±1.0 Control 23.0±0.5 23.2±0.6 24.0±0.09 23.3±0.6

3

Abbasoğlu ve Pulat

Kaynaklar 8. Barry, A. L., Garcia, F. and Thrupp, L. D., "An lm- proved Method for Testing the Antibiotic Suscep- tibility of Rapidly Growing Pathogens", Am. J. Clin.

Pathol., 53, 149-157, 1970.

4

1. Park, G. B., "Burn Wound Covering - A Review", Biomed Med. pev. Art. Org. 6, 1-8, 1978.

2 Nathan, P., Law, E. j., Macmillan, B. G., Murphy, D. F., Ronel S. H., Andrea, M.

J.

A., "A New Biomaterial for the Control of Infection of the Burn Wound", Trans. Am. Sac. Artif. Intern.

Organs, 22, 30-37, 1976.

3. Robb, E. C., Fitz, D. G. and Nathan, P., "Delivery of Topical Antimicrobial Agents Silver Sulfadiazine, Gentamicin and Nystatin to Infected Burn Wounds in Rats from Preloaded Synthetic Dress- ing", Trans. Am. Sac. Artif. Jntern. Organs, 26, 533- 546, 1980.

4 Nathan, P., Robb, E. C., Law, E. J. and Macmillan, B. C., "A Clinical Study of Antimicrobial Agents Delivered to Bum Wounds from Drug Loaded Synthetic Dressing", J. Trauma, 22, 1015-1032, 1982.

5. Zachary, L., "Heggers, j. P., Robson, M. C., Leach, A., Ko, F. and Berta, M. "The Use of Topical Anti- microbials Combined with Biobrane in Burn Wound Infections", J. Trauma, 22, 833-848, 1982.

6. Kiremitçi, M.; Pulat, M., Şenvar, C., Şerbetç~ A. 1.,

Pişkin, E., ''Structural and Collular Characteriza- tion of Solvent-Casted Polyurethane Membranes"

Clinical Materials, 6, 227-237, 1990.

7. "Annual Book of ASTM Standards", American So- ciety for Testing Materials, Philadelphia, p. 815, 1972.

9. Solvent Formulating Maps for Elvacite Acrilic Resins, E. 1. Du Pont de Nemours and Co., PA 12- 770, 1971.

10. Lamke, L. O., Ni!sson, G. E. and Reithner, H. L.,

"The Evaporative Water Loss from Burns and Water Vapor Permeability of Grafts and Artificial Membranes Used in the Treatment of Burns", Burns, 3, 159-165, 1977.

11. Gardezi, S. A.R,, Chaudhary, A. M., Sial, .G.A.K., Ahmad, !. artd Rashid, M., "Role of Polyurethane Membrane in Post Operative Wound Manage- ment", /. Pak. Med. Assoc, 33, 219-222, 1983.

12. Golan, j., Eldat, A., Rudensky, B., Tuchman, Y., Sterenberg, N., Ben-Hur, N., Behar, D. and Jus- zynski, M., "A New Temporary Synthetic Skin Sub- stitute", Burns, 11, 274-277, 1985.

13. Behar, D., Juszynski, M., Ben-Hur, N., Galan, J.,

Eldad, A. Tuchman, Y ., Sterenberg, N. and Ruden' sky B., "Omiderm, a New Synthetic Wound Cov- ering: Physical Properties and Drug Permeability Studies", J. Biomed. Mat. Res. 20, 731-738, 1986.

14. Düzgüneş, O., Kesici, T., Gürbüz, F., "istatistik Metodları I" A.Ü. Bas., Ankara, 1983.

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