Controlled release article

Controlled release articles which regulate the concentration of a surfactant compound at a useful level in an environment external to said articles are provided. The articles are especially adapted for use in or on the bodies of animals, including humans, to provide controlled release of surfactants having biological activity, for example, non-hormonal contraceptives.

BACKGROUND OF THE INVENTION 
The present invention encompasses articles designed to provide controlled 
release of surfactant compounds. More specifically, the articles herein 
comprise a microporous membrane releasably enclosing a solution of a 
micelle-forming surfactant compound. 
The desirability of providing metered dosage forms of biologically active 
or medicinal agents has long been recognized. Metered dosages can be 
manifest either as controlled release or sustained release of a given 
material. The distinction between "controlled release" and "sustained or 
prolonged release" has been recognized; see Cowsar, in "Advances in 
Experimental Medicine and Biology", Vol. 49, "Controlled Release of 
Biologically Active Agents", Ed. Tanquary and Lacey, Plenum Press, New 
York 1974. However, the terms are frequently used interchangeably. For the 
present purposes, "sustained release" articles are defined as those which 
prolong the time period over which a material is released into an external 
environment. Sustained release can be accomplished by incorporating a 
kinetic barrier to release within the article, e.g., diffusion through a 
polymer matrix. Conversely, the term "controlled release" as used herein 
encompasses articles which release material to an external environment in 
response to "need". In the controlled release system there is no 
persistent kinetic barrier to release within the article; instead, initial 
release to achieve an effective concentration of the material is rapid, 
and an external parameter controls this release. For example, in the 
medical uses of the present articles the concentration of active compound 
in the body fluids bathing the product is the controlling parameter. The 
major distinction between the two types of systems is that articles based 
on the controlled release principle operate by a feedback mechanism 
regulating release, whereas articles employing the sustained release 
mechanism do not. One parameter of the total system is influential with 
respect to whether controlled or sustained release ensues, namely, the 
volume of the external fluid. When the ratio of this volume to the 
membrane area available for diffusion is too high, feedback control never 
develops, and sustained, rather than controlled release, ensues. 
Controlled release articles of the present type respond rapidly to changes 
such as dilution effects in the environment external to the article, e.g., 
by body fluid changes, whereas sustained release articles do not. The net 
result is that articles based on the principle of controlled release are 
capable of rapidly establishing an effective level or concentration of a 
medicament or other agent in a selected environment, and then shutting off 
release so as to maintain the concentration at that level. In contrast, 
sustained release articles simply dispense an agent at a constant rate. 
Such articles, therefore, do not display the feedback regulation of 
release that a controlled release article displays. 
It will be recognized that articles operating by the controlled release 
mechanism provide substantial advantages over sustained release articles 
for certain uses. For example, placement of a properly formulated 
controlled release medicament system in an animal's body cavity in contact 
with body fluids very quickly establishes an effective concentration of 
the medicament in the fluids. This concentration is automatically 
maintained in response to dilution or depletion as additional fluids are 
secreted, or the medicament is bound to tissue, absorbed, etc. 
Accordingly, for uses such as in contraceptives where it is desirable to 
provide an effective amount of the contraceptive agent almost immediately, 
a controlled release system rather than a sustained release system is 
preferred. 
It has now been discovered that solutions of micelle-forming surfactant 
compounds can be releasably enclosed in a container comprising a 
microporous membrane. Articles prepared in this manner are stable and do 
not suffer osmotic rupture when placed in body cavities in contact with 
body fluids. Rather, the stable articles provide controlled release of the 
surfactant into the body fluids. Proper selection of surfactant provides a 
means for achieving various biological effects, e.g., antimicrobial 
activity, spermicidal activity, and the like. While it will be recognized 
that the articles herein can be used in any situation where controlled 
release of a surfactant into an external fluid medium is desired (as long 
as the previously noted volume to area ratio is appropriate), the 
preferred articles are especially adapted for use in body cavities such as 
the vagina. 
It is an object of the present invention to provide stable articles which 
furnish controlled release of a micelle-forming surfactant. 
It is another object herein to provide articles adapted for use in contact 
with living tissue (human or lower animal) which furnish controlled 
release of biologically active surfactants. 
It is another object herein to provide articles suitable for use as 
contraceptives. 
These and other objects are obtained herein as will be seen from the 
following disclosures. 
PRIOR ART 
The following United States patents relate to articles comprising drugs 
enclosed within permeable membranes: U.S. Pat. No. 3,828,777 MICROPOROUS 
OCULAR DEVICE, issued Aug. 13, 1974 to R. A. Ness; U.S. Pat. No. 3,618,604 
OCULAR INSERT, issued Nov. 9, 1971 to R. A. Ness; U.S. Pat. No. 3,416,530 
EYEBALL MEDICATION DISPENSING TABLET, issued Dec. 17, 1968 to R. A. Ness; 
U.s. Pat. No. 3,832,252 METHOD OF MAKING A DRUG-DELIVERY DEVICE, issued 
Aug. 27, 1974 to T. Higuchi and H. M Leeper (see also U.S. Pat. No. 
3,598,122, issued 10/1971, other references cited in Higuchi, et al., as 
well as U.S. Pat. No. 3,867,519.) 
In general, the foregoing references relate to sustained release articles, 
rather than controlled release articles of the present type. The Higuchi, 
et al., patent illustrates the use of internal barriers in the article to 
achieve sustained drug release in the manner noted hereinabove. 
Attwood and Florence, J. Pharm. Pharmac., 1971, 23, Suppl. 242S, briefly 
describe the dialysis of chlorpromazine across Visking membranes and 
suggest that this phenomenon may have applications in sustained release 
technology. Attwood, et al., do not suggest the use of surfactants of the 
present type in controlled release articles. 
Lichtman, et al., Contraception 8(4) 291-7 (1973) describe a vaginal 
contraceptive device comprising a soluble film containing a nonionic 
surfactant as a spermicide. 
U.S. Pat. No. 3,694,364 LAUNDERING AID, issued Sept. 26, 1972 to J. B. 
Edwards relates to surface-modified cellulose bags (e.g., terry cloth) 
containing detergents and their use in laundry baths. 
SUMMARY OF THE INVENTION 
In its broadest aspect, the present invention encompasses controlled 
release articles especially adapted to maintaining a useful concentration 
of a surfactant compound in an environment external to said articles. The 
articles herein comprise a solution consisting essentially of a 
micelle-forming surfactant compound and solvent, normally water, said 
solution having a concentration above the critical micelle concentration 
of the surfactant compound. The solution of the surfactant compound is 
releasably enclosed in an insoluble container (i.e., a container which 
maintains its physical integrity when in contact with fluids, especially 
water or biological fluids such as serum) at least part of the wall of 
said container comprising a microporous membrane. Surfactants employed in 
the preferred articles herein designed for use in the body cavities of 
animals are characterized by an "R" value (as defined more fully 
hereinafter) greater than about 1. 
More specifically, preferred articles herein are designed for use as 
between-menstrual period contraceptives. Such articles comprise an 
envelope made wholly or partly of a microporous polymeric diffusion 
membrane (preferably cellulose) enclosing a solution of spermicidal 
surfactant at a concentration greater than the critical micelle 
concentration (cmc) of the surfactant. The term "spermicidal" as employed 
herein is intended to encompass surfactants which truly "kill" animal 
sperm, as well as those which immobilize or otherwise render sperm cells 
inactive. 
The controlled release articles herein function by means of diffusion of 
surfactant monomer through the solvent medium (typically water or 
biological fluids such as serum) in the pores of the microporous portion 
of the enclosing envelope. The micellar solution of surfactant remaining 
in the envelope serves as a reservoir which automatically releases 
additional surfactant monomer when the external monomer concentration is 
decreased. 
Articles of the present type employing surfactant solutions as the active 
ingredient have several important advantages over other types of metered 
dosage systems, and these advantages are perhaps best appreciated when 
considering the use of the articles as contraceptives. 
The use of micelle-forming surfactants as the active ingredient in the 
articles also maintains the osmotic pressure therein at a relatively low 
level. Accordingly, the pressure differential across the enclosing 
container is relatively small, and the container is stable and does not 
rupture. This desirable attribute of the present articles is to be 
contrasted with the situation which occurs when a similarly concentrated 
solution of a non-micelle-forming solute of similar molecular weight is 
enclosed in a diffusion membrane, whereupon osmotic pressures of tens or 
hundreds of atmospheres can be developed, thereby leading to rupture of 
the membrane. 
Moreover, the surfactants employed as the active ingredients of the 
contraceptive articles of the present invention appear to function by an 
entirely localized effect on motile sperm. Accordingly, undesirable 
side-effects which can accompany the use of systemic contraceptive drugs 
such as hormones are avoided. 
In addition, the use of safe, effective surfactants as the spermicide 
permits the formulator of the articles to employ a large excess of the 
spermicide therein. Controlled release allows formulation of articles 
containing more spermicide than the usual expected need but (1) reduces 
the probability of side-effects by regulating the concentration to a 
maximum level, and (2) allows for unusual variations in the amount of 
compound required or in the time period over which it might be needed. 
Accordingly, a "safety factor" of the order of 1000-fold vis-a-vis 
contraceptive efficacy can be provided by the articles. 
Finally, the contraceptive articles herein are designed for use in the 
vagina. Accordingly, the articles can be inserted by the user and do not 
require fitting by a physician as, for example, in the case of 
intrauterine devices. The articles can be retained in the vagina during 
the time between menstrual periods to provide the desired prolonged 
contraceptive protection. 
DETAILED DESCRIPTION OF THE INVENTION 
The present articles are comprised of multiple components, each of which 
are described in detail hereinafter. 
SURFACTANT 
The surfactants employed in the instant articles and processes are 
characterized by several parameters which can vary somewhat, depending on 
the ultimate use of the articles. In general, the surfactants are selected 
from those which, in combination with a microporous membrane (as described 
more fully hereinafter), provide an appropriate relationship between 
release and the desired end use of the article, e.g., spermicidal 
activity. 
The surfactants herein are characterized by their ability to dissolve in a 
solvent (normally water) and to form an association colloid therein. The 
grossly anomalous (low) osmotic pressures displayed by concentrated 
solutions of the surfactants herein are attributable to the association of 
surfactant monomers into micellar structures. This phenomenon is of 
considerable practical significance in that it allows fabrication of 
articles containing surfactants at extraordinarily high concentrations, as 
compared with concentrations permitted with other, non-associative types 
of solutes, without osmotic rupture of the enclosing membrane. In order to 
realize fully the unique advantages of surfactants in this regard, it is 
preferred to use those surfactants having a cmc of at most about 
1.times.10.sup.-3 molar (M). 
When intended for use as between-period contraceptives or to provide other 
desirable effects such as the controlled release of antimicrobial 
surfactants, it is, of course, necessary to select surfactants which 
produce the desired biological response. Moreover, to secure the benefits 
of controlled release it is necessary also to select surfactants whose 
monomers are rapidly transported through the diffusion membrane to 
establish an effective concentration of surfactant in the medium external 
to the article. 
From the foregoing consideration it will be appreciated that the desired 
biological response of a surfactant can be tested in vitro in a medium 
(such as physiological saline, which closely approximates various boly 
fluids) to determine the concentration at which the surfactant must be 
present in such medium to provide the desired response. Surfactants whose 
monomers are transported through the enclosing membrane of the article to 
provide at least the aforesaid effective concentration in the saline are 
useful herein. Over a given time period, the controlled release articles 
herein produce a stable maximum (or "plateau") concentration of surfactant 
in the external fluids. The magnitude of this plateau concentration is 
related to the cmc of the surfactant compound, and is approximately equal 
to the cmc. It follows that, for the desired effect to be realized, the 
ratio, R, of the cmc of the surfactant to its biologically effective 
concentration, C.sub.biol., in saline, i.e., 
EQU R = cmc/C.sub.biol. 
must be greater than about 1. Similar considerations hold for external 
media other than saline, i.e., fluid media such as body fluids, water, 
etc., in which the present surfactant monomers are soluble. Accordingly, 
the preferred compounds for use in the articles described herein have 
values of R which are &gt; ca. 1, i.e., 
EQU R &gt; ca. 1. 
It will be recognized that a variety of surfactants exhibit a cmc less than 
the requisite about 10.sup.-3 M and meet this criteria for use in the 
present controlled release articles. Moreover, several surfactant types 
having the requisite cmc provide desirable biological responses, e.g., 
microbiocidal or static activity and/or spermicidal activity. Moreover, 
several surfactants exhibit the requisite relationship, R &gt; ca. 1, between 
cmc and biological activity. 
Based solely on the foregoing considerations, representative examples of 
surfactants useful herein include nonionic surfactants such as C.sub.10 
H.sub.21 (OCH.sub.2 CH.sub.2).sub.5 OH (abb. C.sub.10 EO.sub.5) and 
C.sub.10 H.sub.21 (OCH.sub.2 CH.sub.2).sub.6 OH (C.sub.10 EO.sub.6); 
semipolar surfactants such as C.sub.12 H.sub.25 S(NH).sub.2 CH.sub.3 and 
C.sub.12 H.sub.25 (CH.sub.3).sub.2 AsO; and cationic surfactants such as 
C.sub.16 H.sub.33 N.sup.+ (CH.sub.3).sub.3,Cl.sup.- and C.sub.16 H.sub.33 
N.sup.+ C.sub.5 H.sub.5,Cl.sup.-. These surfactants are characterized by R 
.gtoreq. 2 and cmc &lt; 10.sup.-3 M. 
It is to be understood that other surfactants having the requisite cmc of 
10.sup.-3 M, or less, but which exhibit lower biological activity 
(especially as spermicidal agents), i.e., surfactants wherein ca. 1 &lt; R &lt; 
2, can be employed in the instant articles. However, the biological 
response to these latter surfactants is somewhat less than that of the 
preferred group, and the efficacy margin, i.e., R-1, is not as great. 
Included among this group of surfactants are C.sub.12 EO.sub.9 ; C.sub.16 
EO.sub.1 SO.sub.4.sup.-,Na.sup.+ ; C.sub.12 (CH.sub.3).sub.2 PO; C.sub.10 
EO.sub.4 ; C.sub.12 (C.sub.2 H.sub.5)PO; C.sub.16 ammoniopropanesulfonate; 
.beta.-OHC.sub.12 (CH.sub.3).sub.2 PO; and nonylphenol nonaethoxylate. 
As can be seen from the foregoing, various surfactant types are useful in 
the controlled release articles herein. However, when articles designed 
for use as between-period contraceptives are being prepared, additional 
physio-chemical properties of the surfactants must be considered. For 
example, the surfactants should be toxicologically acceptable for use in 
the body over extended time periods. The surfactants should also be 
non-irritating to the delicate tissues of the vagina and uterus. The 
surfactants should not substantially bind serum proteins found in the 
vaginal area between periods of menstrual flow, inasmuch as the bound 
surfactant-protein moiety does not function as a spermicide and 
accelerates the depletion of surfactant from the reservoir within the 
article. Finally, the surfactant should be selected from those which do 
not bind to ionically charged sites in the enclosing diffusion membrane, 
since binding leads to unregulated transport through the membrane. 
Based on the foregoing factors, and considering the high spermicidal 
activity of the compounds, the C.sub.10 EO.sub.5 and C.sub.10 EO.sub.6 
surfactants are most preferred for use in the present contraceptive 
articles. As between these latter compounds, C.sub.10 EO.sub.5 has the 
advantage of the lower molecular weight, and therefore provides more 
monomer per given weight of compound. Accordingly, C.sub.10 EO.sub.5 is 
most preferred for use in the between-period, controlled release 
contraceptive articles of this invention. 
It will be recognized that the surfactants disclosed hereinabove are all 
well-known from the detergency arts and can be made by various 
art-disclosed processes. 
It is to be understood that mixtures of surfactants result in the formation 
of mixed micelles and preferential migration of the more soluble monomer. 
Monomer release from mixed surfactants is, therefore, not rigorously 
controlled and, while such mixtures are operable, they are not preferred 
for use herein. 
CONTAINER 
Broadly, the present articles comprise the surfactant solution and a 
container therefor. At least one portion of the container comprises a 
microporous membrane which permits the controlled release of surfactant 
monomers into the environment external to the container, but which 
prevents the transport of the larger surfactant micelles. In short, the 
membrane acts as a selective "sieve" at the colloidal/molecular level. 
Containers used in the present articles can be partly made of any stable 
material such as glass, plastic, etc., which is not permeable, even to 
surfactant monomers. At least some portion of such containers must 
comprise the microporous membrane to allow controlled monomer release. 
Preferred articles are those wherein the container comprises an envelope 
of the membrane. 
Membranes useful herein are characterized by parameters which reflect the 
membrane's strength, integrity and ability to act as a selective "sieve" 
for surfactant monomers, as follows. 
The membranes should be substantially water-insoluble so that they maintain 
their strength and integrity when in contact with body fluids. (Of course, 
if the articles are to be used in contact with other types of fluids, 
appropriate solubility relationships must be considered.) 
The membranes should be of a thickness (wet) less than about 150 microns 
(.mu.) and are most preferably about 25-50.mu. thick (wet). Membranes 
thicker than about 150.mu. (wet) tend to impede release of surfactant 
monomer, whereas thicknesses below ca. 5-10.mu. (wet) cause the articles 
to be subject to osmotic rupture even by the relatively low osmotic 
pressures of the concentrated surfactant solutions used in the articles. 
When the articles are to be used in contact with body fluids and tissues, 
as in the contraceptive articles herein, the membranes should be 
toxicologically acceptable. Moreover, the membrane material will most 
preferably be immunoligically acceptable and will not be rejected by the 
body's natural defense mechanisms nor have any untoward effect on the rate 
of antibody formation, and the like. 
Finally, the membrane must have the ability to act as a sieve for the 
surfactant monomers in order to provide the controlled release benefit of 
the article. An important consideration in this regard is that the 
surfactant must not be soluble to any substantial extent in the membrane 
material. If the surfactant were to be soluble in the membrane material, 
uncontrolled release would ensue. 
The membranes employed herein comprise a solid wall material having 
multiple miniscule pores therethrough, i.e., are microporous. The pores of 
the membrane are filled, or substantially filled, with solvent (e.g., 
water) for the surfactant monomer. In use in the containers of the instant 
articles, surfactant monomers migrate from the inner reservoir of 
surfactant solution to the external environment by means of diffusion 
through the solvent in these solvent-filled pores, which pores extend from 
inner to outer surfaces of the articles. 
It will be appreciated by those skilled in the art that pore diameters of 
the membranes herein cannot be specified in absolute terms. Indeed, when 
dealing with pore sizes at the molecular level (i.e., at the dimensions of 
surfactant monomers), measurement techniques are only indirect and 
generally constitute a determination of which molecules (or association 
colloids) will pass through a given membrane and which will be retained, 
coupled with approximations of the molecular dimensions of the molecules 
that do pass. 
Based on the foregoing, the pores in the membranes used in the present 
articles are characterized by diameters on the order of the size of the 
surfactant monomers herein, but are smaller than the surfactant micelles 
(i.e., association colloids comprising ca. 100-1000 monomer units). An 
experimental Surfactant Transport Procedure for selecting microporous 
membranes having the appropriate pore size for use in the articles is set 
forth below. 
Membranes suitable for use as the container can be made from any material 
which possesses the above-described characteristics and properties. For 
example, suitably perforated polyethylene, polypropylene, 
polyvinylchloride, etc., sheeting can be used in the present articles. 
Highly preferred membranes herein are prepared from water-swellable 
polymers such as polyvinyl alcohol (suitably modified so as to be 
water-insoluble) and cellulose. Cellulose is a highly preferred membrane 
material, inasmuch as it has a long history of safety when used in 
prolonged contact with animal tissue. Such swellable polymers (or polymer 
precursors) can be cast into membranes which swell to about 1.8 to 2.0 
times their dry thickness on contact with water. This swelling action 
automatically opens pores in the polymer membrane, and these pores are of 
the proper size to permit passage of surfactant monomers, and to prevent 
passage of surfactant micelles, through the membrane. 
Methods for casting swellable cellulose membranes are well-known and form 
no part of this invention. In general terms, a cellulose derivative (e.g., 
cellulose acetate) is dissolved in a suitable solvent (e.g., acetone) and 
the solution is spread onto a smooth surface, whereupon the solvent 
evaporates leaving a continuous film of the cellulose derivative. The film 
of cellulose derivative is thereafter converted back to cellulose (e.g., 
with aqueous ammonia in the case of cellulose acetate) and swollen with 
water to provide a membrane suitable for use as the container of the 
present articles. 
As will be appreciated from the foregoing, a variety of materials can be 
used as the membranous container portion of the controlled release 
articles, with solvent-swellable polymers being the most preferred due to 
their inherent sub-microscopic porosity in the swollen state. An 
experimental procedure which can be used to select membranes for use 
herein is as follows. 
Surfactant Transport Procedure 
A cell for testing transport of surfactant monomers through membranes is as 
follows. A 40 mm (diameter) .times. 50 mm (length) poly-methylmethacrylate 
rod is halved and each half is suitably machined to provide cavities 16 mm 
(diam.) .times. 10 mm (depth), such that the cavities abut when the rod 
halves are reassembled. Each cavity is provided with two inlet holes for 
filling and sampling. A brass clamp is used to hold the two cell halves 
firmly together. 
The surfactant transport is carried out in the following manner. A 4 cm. 
.times. 4 cm. square of the membrane material to be tested is sandwiched 
between the cell halves, enclosing a 3 mm. glass head on each side of the 
membrane to provide stirring. The cell cavities are filled with saline and 
the inlet holes plugged with waterproof tape. After equilibrating 
overnight at 37.degree. C, the saline in one half of the cell is replaced 
with a solution of known concentration of radiotagged surfactant. The 
inlet hole is again taped, and the cell is placed in a 37.degree. C bath 
in a device which allows the cell to be rotated axially at 50 rpm. 
Periodically, the cell is raised from the bath and the solution in the 
desired compartment sampled. 
A typical procedure using a membrane cut from viscose cellulose dialysis 
tubing (Matheson Scientific, 18970-20) is as follows. After equilibrating 
the cell and charging one side with surfactant as above, the cell is 
maintained in the 37.degree. C bath for varying time periods, after each 
of which the tape is removed from the inlet holes and 10 microliter 
(.mu.1) samples are removed by syringe. The samples are expressed below 
the surface of 100 .mu.1 of distilled water in a counting vial. In the 
subsequent scintillation counting, each sample vial is charged with 10 
.mu.1 of a solution of 0.8% 2-diphenyloxazole and 0.01% of 
1,4-bis-[2-(4-methyl-5-phenyloxazolyl)]-benzene in a 1:1 ethanol/toluene 
mixture. The vials (one for each time period) are then placed in the 
refrigerator compartment of a counting instrument and cooled to 4.degree. 
C before being counted for 5 minutes each. The counts per minute are 
converted to ppm by applying a factor found by counting one or more 
standard samples. By taking samples at regular intervals, a curve plotting 
the surfactant concentration in the initially surfactant-free side of the 
cell versus the time of sampling can be drawn which describes the 
transport of the surfactant across the membrane. 
Following the Surfactant Transport Procedure set forth hereinabove, the 
cell cavity designated (A) is charged with surfactant solution and the 
cavity designated (B) is charged with saline. The cell, whose cavities are 
separated by the test membrane, e.g., swollen, microporous cellulose 
dialysis tubing (dry thickness 25.mu.; swollen thickness 50.mu.) is then 
equilibrated in the indicated manner. The concentration of surfactant 
transported to cavity (B) is determined in the foregoing manner, and the 
graph of the concentration of surfactant in (B) v. time is plotted. 
A plot of the concentration (B) as the ordinate and time (t) as the 
abscissa describes a monomer transport curve which rises sharply at the 
outset, and which gradually flattens. The slope of the sharply rising 
portion of the curve (i.e., over the first two hours of surfactant monomer 
transport) is the primary slope, S.sub.1, and that of the flattened 
portion of the curve (i.e., 20 hours, and longer, of monomer transport) is 
the secondary slope, S.sub.2. 
For controlled release articles of the present type, the combination of 
surfactant and membrane should yield a monomer transport curve wherein 
S.sub.1, i.e., 
EQU (d[B]/dt); t = 0 - 5 hrs. 
is reasonably steep, and S.sub.2, i.e., 
EQU (d[B]/dt); t &gt; 20 hrs. 
is reasonably flat, ideally zero. The intercept at zero time of the 
secondary transport data, having slope S.sub.2, should be about equal to 
the cmc of the surfactant being tested. The ratio of S.sub.2 /S.sub.1 is 
from 0 to about 0.1. S.sub.1 should be no less than about 
50.times.10.sup.-6 moles l.sup.-1 hr..sup.31 1, and preferably should be 
in the range of about 200.times.10.sup.-6 moles l.sup.-1 hr..sup.-1 to 
about 750.times.10.sup.-6 moles l.sup.-1 hr..sup.-1. 
Based on the foregoing, surfactant/membrane combinations can be selected 
which will provide controlled release articles of the present type. A 
highly preferred article herein which is particularly useful as a vaginal 
contraceptive comprises from about a 5% to about a 50% (wt.) aqueous 
solution of C.sub.10 EO.sub.5 enclosed within a microporous, swollen 
cellulose membrane (dry thickness ca. 25.mu.; swollen thickness ca. 
50.mu.).

The following non-limiting examples illustrate controlled release articles 
of the present type suitable for use as vaginal contraceptives, and the 
like. 
EXAMPLE I 
A flat sheet of commercial cellulose acetate about 75.mu. thick and 
measuring about 7 in. .times. 10 in. is subjected to thermoforming methods 
known in the art to produce six hemispherical indentations 1 in. in 
diameter in the sheet. These indentations are filled to ca. 25% of their 
total volume with pure C.sub.10 EO.sub.5 surfactant (using ca. 1 ml. of 
surfactant). A second flat sheet of cellulose acetate film is 
solvent-sealed over the original sheet covering the indentations using 
techniques known in the art. 
The individual, filled and sealed indentations are then cut from the 
composite sheet to provide six articles which are then immersed in a 7.4 M 
ammonia solution containing 10% by weight sodium chloride for the 96 hours 
at 50.degree. C. This ammonia treatment regenerates cellulose by 
deacetylating the cellulose acetate. Water passes through the membrane 
under the influence of osmotic forces during the deacetylation, partially 
filling the sealed articles. 
Following the ammonia treatment, the articles are immersed in distilled 
water, whereupon they fill completely under the influence of osmosis, the 
entrapped air diffusing out leaving an article consisting of a closed 
container of regenerated cellulose enclosing a ca. 25% solution of 
C.sub.10 EO.sub.5 surfactant. 
An article of the foregoing type exhibits a monomer transport curve with 
S.sub.2 /S.sub.1 of ca. 0. 
An article of the foregoing type is placed in the vagina posterior to the 
introitus. The article is worn during the time between menses and safely 
delivers a spermidically effect amount of C.sub.10 EO.sub.5 to the vaginal 
area. 
In the article of Example 1 the C.sub.10 EO.sub.5 is replaced by an 
equivalent amount of C.sub.10 EO.sub.6 and equivalent results are secured. 
In the article of Example I the pure C.sub.10 EO.sub.5 is replaced by an 
equivalent amount of a 90:10 (wt.) mixture of C.sub.10 EO.sub.5 and 
C.sub.10 EO.sub.6 and good spermicidal activity over about a 21-day period 
is secured. 
EXAMPLE II 
An article especially adapted for providing controlled release of a 
surfactant compound into an external environment of relatively small 
volume and moisture content is as follows. 
Polyethylene tubing ca. 2 mm. diameter .times. 5 cm. long is dipped in a 
solution of cellulose acetate/acetone and withdrawn, thereby depositing a 
film of cellulose acetate on the tubing. The acetone solvent is allowed to 
evaporate, thereby solidifying the cellulose acetate on the tubing. The 
cylindrical cellulose acetate film (thickness of about 25.mu.) is 
thereafter removed from the polyethylene form and one end is sealed by 
dipping in a droplet of cellulose acetate/acetone. 
The foregoing cylinder, sealed at one end, is filled to about 75% of its 
volume with a 50% (wt.) aqueous solution of decyldimethylphosphine oxide 
surfactant. The open end of the cellulose acetate cylinder is sealed in 
the above-described manner. 
The cylinder containing the phosphine oxide solution is deacetylated using 
3.7 M aqueous ammonia containing 10% sodium chloride at room temperature 
for 48 hours. Thereafter, the filled cylinder is immersed in water for 
several hours, allowing most of the residual ammonia and sodium chloride 
to diffuse into the water bath. 
An article prepared in the foregoing manner is especially useful as a glass 
de-fogging agent under conditions of high humidity. For example, an 
article of the above type is taped on the internal side of the face plate 
of a diving mask out of the field of view. When placed over the diver's 
face, the usual fogging of the face plate caused by the formation of small 
water droplets thereon is avoided by the release of the surfactant from 
the article.