Odor Absorbing Hydrocolloid Dressings for Direct Wound Contact

Disclosure: Dr. Lipman discloses that he has received monetary compensation to conduct the study, write the manuscript, and lecture for the company producing the products discussed from Avery Dennison Medical. This study was fully funded by Avery Dennison Medical.

Patients in institutional settings, such as hospitals and nursing homes, often have or acquire chronic wounds such as those resulting from venous insufficiency and pressure ulcers—these wounds can possess a very offensive odor.¹ The most direct way of avoiding or eliminating wound odor is to prevent or eradicate the infection responsible for it. Topical antibiotics, such as metronidazole gel (0.8 w/v) have proved to be quite effective, but can generate resistant organisms. Further, the action of metronidazole can be sluggish; often several days are needed for any infection to be resolved, and meanwhile the odor is still being generated. Thus, in practice, other methods such as charcoal-based dressings are often used with or without concomitant antibiotic therapy.
Odor absorbing dressings have been marketed in one form or other for many years. During the past decades a number of charcoal based dressings have been introduced into the market. Some of the more current products are Actisorb® Silver (Johnson & Johnson Medical Ltd, Gargrave, UK), CarboFlex® (ConvaTec, Princeton, NJ), Carbonet® (Smith and Nephew Medical Ltd, Hull, UK), and LyoFoam® C (SSL International PLC, Canute Court, Toft Road, Knutsford, Cheshire, UK).
One study² investigated the effectiveness of the various charcoal cloths of odor absorbing dressings in adsorbing n-butyric and valeric acids each at an initial concentration of 0.04% (v/v). These aliphatic acids are two of the most common malodorous organic acids found in wounds. The charcoal based material was placed into a vial containing a dilute mixture of the acids and the residual concentration of acids measured using combination of gas chromatography and mass spectroscopy (GC/MS). The charcoal material from Actisorb Plus and CarboFlex were found most effective, while those from Carbonet and LyoFoam C were found inferior to the other two. A further conclusion from an extension of this study³ was that the presence of wound serum greatly inhibited adsorption of fatty acids. Wound malodor obviously emanates in part from bacterial decomposition of the proteins present in serum, and the inhibition of charcoal odor absorbency by the odor precursor is a drawback to its use.
Clearly, the propensity of charcoal to lose effectiveness in the presence of wound exudates is a serious limitation. Charcoal is also of course black and nonconformable. Neither attribute is optimal for construction of wound dressings, which ideally should be self-adhesive, conformable and able to contact the wound surface. A new series of adhesives has been developed that provide an alternative technology for the adsorption of chronic wound and other odors. The new odor absorbent adhesives can be made into dressings designed to be in direct contact with the wound.
Skin barriers can also be made from these adhesives for the protection of the skin around body openings, especially around stomas, the surgically created openings known as colostomies, ileostomies, and urostomies. These novel skin barriers are able to absorb the odor molecules that are associated with feces and urine and, thus, are potentially able to assist in the control of the odor often associated with stomas.

Methods

Methods have been developed for assessment of odor absorbing dressings. A study performed by The Surgical Materials Test Laboratory, (Princess of Wales Hospital, Bridgend, UK) developed a technique using diethylamine (DEA) detector to monitor strikethrough of liquid saturated with DEA.⁴ Another study evaluated absorption of fatty acid mixture on commercial dressings using gas chromatography (GC). Presence of wound serum was shown to inhibit fatty acid absorption.² Another report evaluated the passage of smelly wound exudate through dressing using GC.³
The present study describes a new test method using electronic nose (e-nose) technology that gives rapid, reproducible determination of odor absorption. Standard solutions of odor are prepared and corresponding e-nose responses are determined to give a calibration curve. Residual odor in the vapor phase above the samples is measured; the odor concentration in the vapor phase is proportional to the odor concentration in solution. Odoriferous substances, such as n-butyric acid, valeric acid, cadaverine, and putrescine were employed used as test odors. A diagram of the experimental set up is shown in Figure 1.
The measuring equipment used was an Airsense Analytics Portable Electronic Nose Model PEN2, supplied by WMA Airsense Analysentechnik GmbH, Schwerin, Germany. The e-nose is software driven (WinMuster V. 1.5.2, January 2003) and has an array of 10 different metal oxide semiconducting sensors positioned in a small chamber. Pumps serve to draw the test odor over the sensors from the headspace and over the absorbent dressing in the test cell. The detection limit of the hot sensors can be as low as 1 ppm, dependent on the material. The selectivity of the sensors is determined with the material, the sensor geometry, and the temperature. Sensors with good selectivity for sulphur compounds, hydrocarbons, alcohols, and amines were used in the study.
The e-nose is capable of detecting complex mixtures of gases and vapors. The e-nose also possesses the capability to sense and record deviations from standard smells to which it has been calibrated. In the present study, only single compounds were used in testing. The equipment was calibrated daily with the compounds in use to provide a standard curve against which an unknown odor level could be interpolated. Corrections were always made for the “internal smell” of the dressing, ie, the response of the e-nose to any background odor detectable in the absence of test odor.
With the Airsense equipment, the calculations are software-driven and involve the use of statistical methods such as Euclidian, PCA factor analysis, DFA discriminant function analysis, or artificial neural network mapping (Kohonen mapping).
The odor absorption data presented are comparative. They are obtained usually after 24 hours absorption time, and since the method involves a dynamic sweeping of the headspace over the sensors with pumped air, represent the instantaneous condition in the headspace above the sample. In some instances psychosensory testing, using a trained panel to smell and rank order odor intensity was used to assess the headspace odor in the test vials 24 hours post testing. In this way, it was confirmed that the new adhesives provide a permanent removal of odor. Some commercial standard adhesive products may appear to absorb some odor in the authors’ e-nose testing, but this absorption is superficial, and psychosensory evaluation confirms that the odor leaches out over time. This psychosensory testing is discussed later in the manuscript.

New Adhesive Developments

Hydrocolloid adhesives are a unique kind of medically useful pressure sensitive adhesive. They have 2 phases, a rubbery phase that provides pressure sensitive tack, sometimes called “dry tack”, and within which is dispersed a discontinuous phase of absorbent material. Depending upon the nature of the absorbents, and especially whether the absorbent is soluble in aqueous media or merely swellable, the adhesive composition can develop “wet tack” as it becomes imbibed with fluid. Such wet tack can also influence the adhesive power of the hydrocolloid. Hydrocolloid adhesives have a duality of attributes in that they are inherently adhesive and inherently absorbent. They have been used for many years as wound dressings because they can be applied directly to open wounds and can be secured on the surrounding intact skin, and as skin barriers because they protect the peristomal skin of ostomy patients. Hydrocolloid adhesives provide what has become known as “moist wound healing” by maintaining the skin and wound in a hydrated condition. An optimally hydrated wound heals faster,^5–7 while hydrated intact skin is less subject to irritation and injury from repeated application and removal of adhesives. Macerated skin (as opposed to optimally hydrated skin, as is observed with hydrocolloids in general), which can result from the use of conventional pressure sensitive adhesive constructions, is more vulnerable to mechanical shear forces during wear and removal.
The authors have found that hydrocolloid adhesives are extremely useful vehicles for further modification by incorporation of cyclodextrins. It is well known that cyclodextrins are used in consumer products for absorption of adventitious odors around the home, such as those resulting from smoking and from pets. The patent literature on the subject on cyclodextrins also details a number of cyclodextrin-containing products for the absorption of odors associated with the use of personal hygiene products, such as feminine sanitary hygiene products. No adhesive-based, cyclodextrin-containing odor absorbing products have heretofore been reported,⁸ and the present study presents the results of the research undertaken in this particular field.
Cyclodextrin materials are cyclic oligosaccharides containing a minimum of 6 D-(+)-glucopyranose units attached by a- (1 > 4) glucosidic bonds. Three cyclodextrins called a, b‚ and g are naturally occurring and have, respectively, 6, 7, and 8 glucose units. Cyclodextrins are known that contain up to 12 glucose units. Cyclodextrin materials can also be manufactured from starch by enzymatic degradation. In addition, many synthetic modifications of the natural material are known, for example methyl-b-cyclodextrin and hydroxypropyl-b-cyclodextrin. The conformations of the cyclic structures of these molecules are such that the molecules are arranged in rigid conical molecular shapes that have hollow interiors of well defined sizes. These internal cavities are hydrophobic in nature because the interior of the toroidal shape is predominantly composed of hydrogen atoms. The interior shapes of the cyclodextrins are able to form inclusion complexes, sometimes referred to as “host-guest” complexes, or clathrate compounds, with organic molecules which fit, completely or partially, into the cavities defined by the toroidal shapes.^9,10
Cyclodextrins, and especially mixtures of cyclodextrins with cavities of different sizes, can therefore be used to control odors, and it may be thought obvious to incorporate cyclodextrins into pressure sensitive adhesives to give useful odor absorbing compositions. However, if this is done, it will be found that such compositions absorb odorous molecules very slowly at best. This is because the complexation of odorous molecules by cyclodextrin is hindered not only by a slow rate determining diffusion process through the adhesive but also because absorption of odor by the cyclodextrin is facilitated by the presence of water.
The authors have addressed this problem by formulating a dressing material containing both cyclodextrins and conventional hydrocolloids, such as sodium carboxymethyl cellulose. The authors believe that the absorption of wound fluid (or other body fluid, depending on how the product is to be used) by the conventional hydrocolloid provides the moisture in the adhesive to activate the odor absorbing properties of the cyclodextrin in situ, thus, the hydrocolloid and the cyclodextrin act synergistically to provide both fluid and odor absorbency.

Results and Discussion

The effect of water concentration on the odor absorption by the pure cyclodextrins as well as by hydrocolloid adhesives containing these cyclodextrins was studied. This was done by placing the odor absorbent material in a vial, adding 5 µL of the test odor and a variable amount of water with micropipettes. The vial was then held at 31˚C overnight and the residual odor concentration determined after 24 hours. Table 1 shows the effect of water in facilitating n-butyric acid complexation by the cyclodextrin, sodium carboxymethylcellulose (a polysaccharide usually present in most hydrocolloid compositions), and by the adhesive containing the cyclodextrin. Also shown in the same table is the effect of cyclodextrin cavity size on n-butyric acid absorption. The smaller cavity of the a-cyclodextrin is a more effective absorber than the b-cyclodextrin, while the g-cyclodextrin cavity is too large to effectively immobilize the butyric acid.
By combining cyclodextrins with aqueous absorbing agents within the adhesive matrix, a synergistic combination that absorbs odor molecules at rates and amounts comparable to the performance of charcoal based absorbents has been created. The hydrocolloid composition created also possesses other advantages over charcoal based materials. The water necessary for the cyclodextrin to function will normally be present in the wound fluid, or in contaminating urine or feces, or even be released by the skin through normal transpiration. It is through absorption of this water by the adhesive that it is made available to activate the cyclodextrin for odor absorption. The choice of cyclodextrin employed in a given formulation may be decided on the basis of the properties desired in the finished product, and the specific role that the cyclodextrin is expected to fulfill. Unmodified b-cyclodextrin is not very water-soluble and is generally not preferred if high odor absorbency is needed. Alpha-cyclodextrins, g-cyclodextrins, and certain modified b-cyclodextrins are more water soluble and more appropriate for clinical use. Mixtures of cyclodextrins are often preferred, because these will absorb a wider range of malodorous molecules than will a single cyclodextrin. The cyclodextrins to be used for a specific odor will, of course, be determined by the size, shape, and polarity of the active molecules to be absorbed.
Table 2 shows a general comparison of the performance of prototype cyclodextrin adhesives (D1-76A and D1-120C) with commercially available charcoal based dressings. The superior fluid absorption of the cyclodextrin-containing adhesive is evident.
The new hydrocolloid adhesive is much thinner and, thus, more conformable for the patient than commercially available charcoal dressings while the fluid absorption can be up to 3 times higher.
However, as has been reported previously,⁴ the odor absorbing ability of charcoal-based dressings is inhibited by wound serum. The ability of charcoal to absorb butyric acids drops when the charcoal is first treated with new-born calf serum,⁴ due to nonspecific adsorption of protein and peptides that block the active adsorption sites on the charcoal surface. Because of this, charcoal dressings are best designed with a number of layers to keep the wound exudate from contacting the odor-absorbing layer. This study compared the ability of several commercial charcoal based dressings—Actisorb® (Johnson & Johnson Medical Limited, Gargrave UK), CarboFlex® (ConvaTec, Deeside UK), Carbonet® (Smith and Nephew, Hull, UK)—to absorb odor from a calf serum medium. This study also measured the odor absorbing ability of a cyclodextrin-based adhesive using the same calf serum medium.
A graduated series of media, with increasing levels of serum, were used in these experiments. The media used consisted of 100% saline, 50%/50% saline/serum, and 100% serum. As the amount of serum was increased, the odor absorption performance of the cyclodextrin-based material was enhanced, while the performance of all 3 commercial charcoal based products was negatively affected. In 100% newborn calf serum, a good surrogate of real wound fluid; the novel cyclodextrin based hydrocolloid adhesive (D1-76A) outperformed the 3 commercial charcoal products. These data are shown in Table 3.
The authors believe that serum protein may enable the odor absorption capacity of the cyclodextrins by binding to the more hydrophilic external surface of the cyclodextrin cavity, and thereby, may modify its ability to absorb polar odor molecules. It is well known that covalent attachment of similar polar moieties to cyclodextrin structures modifies dramatically the ability of cyclodextrins to deliver certain drug actives. This is discussed in detail in the review by Loftsson et al.⁹

Development of Final Product for the Clinic

Conclusions from the above data were used to formulate MED9150H, a commercial cyclodextrin-containing hydrocolloid formulation. MED9150H is an island dressing, which is composed of a 0.3 mm standard hydrocolloid top layer and is covered by a polyurethane carrier. The MED9150H island consists of a 0.3 mm cyclodextrin-containing hydrocolloid. Evaluations were based on the odor absorbing performance of this new construction and charcoal containing dressings in calf serum. The MED9150H odor absorbency was measured after sterilization to 25 and 50 KGy, and after aging at 13 weeks at 50˚C. These severe conditions did not affect the odor absorbency of MED9150H, which performs generally better than the 3 commercial dressings. The performance data on the MED9150H formulation appear in Table 4. To obtain the data of Table 4 the e-nose was calibrated with 0 ppm, 1250 ppm, and 2500 ppm n-butyric and valeric acids. Two grams of hydrocolloid were used and a 25-cm² sample size was taken for the commercial charcoal dressings.
The MED9150H was compared in odor absorbency and fluid absorbency to Tegasorb (3M Health Care, St. Paul, Minn) and DuoDerm Extra Thin (ConvaTec, Deeside, UK). The data in Table 5 show MED9150H to have significantly greater fluid absorption in vitro and dramatically superior odor absorbency.
The data of Table 5 bring out an important limitation of the test method the authors have used to date. The test method is a dynamic technique. Air sweeps the contents of the headspace over the sensors, and thus, determines only the instantaneous concentration of odor in the headspace. The method as used says nothing about the way in which the odor is bound to the adhesive, nothing about the propensity of the odor absorbed on or in the adhesive to leach out over time.
This factor has been investigated for the 3 adhesives shown in Table 5 using an adjunct psychosensory determination. Using a trained panel of observers to assess headspace odor in the vials 24 hours after the test data in Table 5 were obtained, no perception of odor in the vials containing MED9150H was found, while the odor is readily perceivable in the headspace above the Tegasorb and DuoDerm samples.
Psychosensory evaluation confirms that the test odors are bound to the MED9150H adhesive in an irreversible manner. A separate study is being organized to evaluate in more depth this time effect.

Clinical Use Profile

The cyclodextrin-containing hydrocolloid dressings were used in a pilot trial on 2 patients with pressure ulcers. The results are shown in Figure 2. Patient 1 is an 81-year-old woman with a foot wound. Patient 2 is a 74-year-old woman with diabetes, bilateral amputation, and sacral wounds.
The clinical nurse made the following anecdotal comments, “The second lady has very bad skin and has cream applied but it is evident how much better the skin is underneath where the dressing has been. There is absolutely no odor at all with either patient despite the softening of the necrotic tissue. Normally it would be expected that odors characteristic of both dressing and wounds would be discernible” (personal communication, June 2005).

Conclusion

This report describes initial results on new odor absorbing adhesive compositions. The results suggest that these cyclodextrin materials provide a new method of controlling some of the problem odors associated with wound care and ostomy care. The new formulation MED9150H possesses the key features of fluid handling along with odor absorbency, while the traditional odor absorbing charcoal containing products seem to be noticeably short on fluid handling properties. The data also suggest that in the presence of wound serum, these new materials may outperform conventional charcoal based products in odor control. Comparison against conventional hydrocolloid dressings showed similar or better fluid handling capability, and notably better ability to absorb odors. The mechanism through which the odor is absorbed by the cyclodextrin molecule is the familiar host-guest physicochemical interaction process seen with cyclic molecules, such as cyclodextrin. The presence of serum may be accentuating these odor-absorbing interactions in the formulations tested. Early in-vivo performance with hydrocolloid dressings based on these materials appears to confirm the laboratory performance. Further studies that are randomized and controlled are in progress on this novel MED9150H formulation.
Wound care dressings using this technology are being introduced into the market by Medline Industries Inc (Mundelein, Ill) under the brand name Exuderm Odorshield®.

Acknowledgement

The authors are grateful to Avery Dennison Medical for their support and for permission to publish this manuscript.