International Journal of Pharmaceutics 309 (2006) 139–145
`
`The physicodynamic properties of mucoadhesive polymeric films
`developed as female controlled drug delivery system
`∗
`
`Jin-Wook Yoo, Kiran Dharmala, Chi H. Lee
`Department of Pharmaceutical Sciences, School of Pharmacy, University of Missouri, Kansas City, MO 64110, United States
`
`Received 30 June 2005; received in revised form 15 November 2005; accepted 16 November 2005
`Available online 10 January 2006
`
`Abstract
`
`To develop an efficient female controlled drug delivery system (FcDDS) against sexually transmitted diseases (STDs), the polymeric films
`containing sodium dodecyl sulfate (SDS) were prepared with various compositions of Carbopol 934P, hydroxypropyl methylcellulose (HPMC)
`and polyethylene glycol (PEG). The physicochemical properties of mucoadhesive polymeric films, such as tensile strength, contact angle, swelling
`ratio and erosion rate in a vaginal fluid stimulant (VFS), were characterized. In addition, the drug release profile of SDS from the films and
`mucosal residence time were evaluated using a simulated dynamic vaginal system. It was demonstrated that the films made of Carbopol, HPMC
`and PEG were colorless, thin and soft and had proper physicodynamic properties for FcDDS. An increase in Carbopol content elevated tensile
`strength and swelling ratio but decreased the contact angle, erosion rate and the SDS release rate from the films. The films containing 0.25% (w/v)
`PEG as well as 0.75% (w/v) of combining Carbopol and HPMC remained on the vaginal tissue for up to 6 h. The films containing the ratio of
`Carbopol:HPMC:PEG = 1.5:1.5:1 and 1:2:1 seem to be optimal compositions for FcDDS, as they showed good peelability, relatively high swelling
`index and moderate tensile strength, and achieved the target release rate of SDS for 6 h.
`© 2005 Elsevier B.V. All rights reserved.
`
`Keywords: Mucoadhesive polymeric films; Female controlled drug delivery system; Carbopol; Hydroxypropyl methylcellulose; Physicochemical properties
`
`1. Introduction
`
`Sexually transmitted diseases (STDs) caused by human
`immunodeficiency virus (HIV), human simplex virus (HSV),
`human papillomavirus (HPV) and other pathogens continue to
`be a major health threat around the world. It is estimated that
`about 19 million STD infections occur annually in the United
`State (Weinstock et al., 2004). According to the World Health
`Organization (WHO), as of 2003, 19.2 million women were liv-
`ing with HIV/AIDS worldwide, accounting for approximately
`50% of the 40 million adults infected with HIV/AIDS. Biolog-
`ically, young women are more susceptible to STDs than men
`because of substantial mucosal exposure and sex without con-
`dom use. Consequently, complications of STDs are greater and
`more frequent among women, and serve as a significant cause
`of reproductive health morbidity (Risbud, 2005).
`For the protection of women against STDs, various types of
`preventive tools have been developed. The immunological vac-
`
`∗
`
`Corresponding author. Tel.: +1 816 235 2480; fax: +1 816 235 5190.
`E-mail address: leech@umkc.edu (C.H. Lee).
`
`0378-5173/$ – see front matter © 2005 Elsevier B.V. All rights reserved.
`doi:10.1016/j.ijpharm.2005.11.020
`
`cine for AIDS has been investigated, but it is several years away
`from clinical application. Under these situations, the mucoad-
`hesive formulations containing microbicides or prophylactic
`agents seem to be an alternative choice to control and prevent the
`rapid spread of STDs (Harrison, 2000). Sodium dodecyl sulfate
`(SDS) is an efficient microbicidal agent. SDS, which denatures
`membrane proteins of cells and pathogens, is an alkyl sulfate
`surfactant derived from an organic alcohol. SDS at very low
`concentrations completely inactivates HIV, HPV and HSV after
`a brief exposure at physiologic temperatures (Kreb et al., 1999).
`SDS is also of low intrinsic toxicity to skin and mucous mem-
`branes (Piret et al., 2000). In vivo toxicity study assessed using
`the rabbit vaginal irritation test has demonstrated that an expo-
`sure of vaginal mucosa to SDS at concentrations of up to 5%
`(w/v) was neither toxic nor broke vagina homeostasis (Kreb et
`al., 1999).
`Conventional vaginal formulations, such as tablets and
`creams, have been limited in use because of leakage, short
`resident time and poor patient compliance, and insufficient thera-
`peutic effects. Mucoadhesive formulations can circumvent these
`limitations (Vermain and Garg, 2000). In our previous studies,
`a gel base mucoadhesive female controlled drug delivery sys-
`
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`
`tem (FcDDS) containing SDS were developed and their efficacy
`in protection against SDS was demonstrated (Wang and Lee,
`2002, 2004). Vaginal films made of Carbopol and HPMC have
`several advantages over vaginal gels, such as portability, conve-
`nient application, long retention time, easy storage and improved
`stability of drug at the extreme condition (Garg et al., 2005).
`PEG, a hydrophilic excipient, is commonly used as a plasticizer
`in the preparation of vaginal suppositories.
`The physicodynamic properties of mucoadhesive formula-
`tions are characterized in various aspects. A contact angle is
`used as an indication of initial degree of wetting. The lower
`value of contact angle means the higher degree of wetting and
`hydrophilicity. It was also reported that contact angles were
`closely correlated to the work of adhesion, which represents
`strength of mucoadhesiveness of the film containing Carbopol
`(Li et al., 1998). The swelling capability of the polymer was also
`reported to be crucial for its bioadhesive behavior (Chen and
`Cyr, 1970) and has a great impact on their stability and release
`profiles of incorporated drugs (Mortazavi and Smart, 1993). The
`extent and rate of the water uptake flux are affected by the degree
`of cross-linking and chain length of the mucoadhesive macro-
`molecules (Smart, 1999). The adhesiveness increases with the
`degree of hydration, but which is not an unlimited process. An
`excessive swelling causes a leakage in cohesiveness of formu-
`lations and leads to an abrupt drop in adhesive strength due to
`disentanglement at the polymer/tissue interface (Peh and Wong,
`1999).
`In this study, vaginal polymeric films which are composed of
`various ratios of Carbopol 934P, hydroxypropyl methylcellulose
`(HPMC) and polyethylene glycol (PEG) and containing SDS are
`developed. We herein examined physicodynamic properties and
`SDS release profiles of mucoadhesive films to find the most
`suitable formulation for female controlled drug delivery system
`against STDs.
`
`2. Materials and methods
`
`2.1. Materials
`
`Carbopol 934P was a gift from B.F. Goodrich (Cleveland,
`OH) and Dow Chemical Company (Midland, MI), respectively.
`PEG 400, mucin and 14C-labeled SDS (0.1 mCi/ml) were pur-
`
`Table 1
`Physical properties of the polymeric films made of various compositions
`
`Compositions
`(Carbopol:HPMC:PEG)
`
`Thickness
`Tensile strength
`(␮m)a
`(N/mm2)b
`220 ± 16
`9.73 ± 0.70
`2:1:1
`223 ± 41
`10.26 ± 0.42
`1.5:1.5:1
`220 ± 21
`12.67 ± 0.44
`1:2:1
`241 ± 16
`3.71 ± 0.43
`1.2:0.8:2
`236 ± 11
`4.85 ± 0.59
`1:1:2
`230 ± 6
`5.18 ± 0.87
`0.8:1.2:2
`2:2:0
`N/A
`N/A
`a Values are expressed as mean± S.D.; n = 5.
`b Values are expressed as mean± S.D.; n = 3.
`
`SDS content (mg
`in 1 cm2)a
`22.80 ± 1.70
`24.20 ± 2.42
`25.22 ± 1.84
`25.58 ± 3.43
`22.53 ± 2.59
`23.33 ± 3.87
`N/A
`
`chased from Sigma (St. Louis, MO). All other reagents and
`solvents were of analytical grade.
`
`2.2. Preparation of polymeric films
`
`Polymeric films composed of various ratios of Carbopol,
`HPMC and PEG were prepared (Table 1). A 3% (w/v) SDS
`in citrate buffer solution (pH 4.0) was loaded in each polymer.
`14C-labeled SDS (0.5 ␮Ci/ml) was added for evaluation of drug
`distribution uniformity and SDS release profile.
`Carbopol–HPMC solutions were first prepared and PEG was
`subsequently added to the solution. A 1% (w/v) polymeric solu-
`tion was allowed to stir for 10 h and kept until all the air bubbles
`entrapped were removed. Then, 40 ml of each polymer solution
`◦
`was poured into a Petri dish and dried in the oven at 60
`C for
`24 h. The films were carefully peeled off and stored in a stability
`◦
`chamber at 25
`C under 60% RH until next use.
`
`2.3. Vaginal fluid stimulant (VFS)
`
`Vaginal fluid stimulant was prepared using the method previ-
`ously reported (Lee et al., 2002). Mucin was dissolved separately
`in distilled water and added to the solution containing the rest
`of the components (NaCl, KCl, sodium acetate (CH3COONa),
`urea, albumin, lactic acid, amino acids and glycerol). The final
`pH of VFS was adjusted to pH 4.0 using 5% acetic acid or 1 M
`sodium hydroxide.
`
`2.4. Film thickness
`
`The thickness of each film was measured at five different
`locations (center and four corners) using a micrometer screw
`gauge (Fowler co., Japan) and a mean value of five locations
`was used as a film thickness.
`
`2.5. Determination of drug content in the films
`
`To ensure the uniformity of distribution of SDS in a film,
`a content uniformity test was performed. One square centime-
`ter of samples representing five different regions (center and
`four corners) within the film were cut, weighed and dissolved in
`VFS. Content of 14C-SDS was analyzed by Liquid Scintillation
`Counter (a model LS-6500, Beckman Coulter, Fullerton, CA).
`
`Weight (mg in 1 cm2)a
`
`Physical characteristics of film
`
`286.44 ± 12.05
`305.25 ± 22.62
`310.23 ± 14.70
`318.38 ± 16.22
`294.16 ± 18.21
`288.04 ± 12.17
`N/A
`
`Colorless, homogeneous surface, soft, easy to peel
`Colorless, homogeneous surface, soft, easy to peel
`Colorless, homogeneous surface, soft, easy to peel
`Colorless, homogeneous surface, soft, hard to peel
`Colorless, homogeneous surface, soft, hard to peel
`Colorless, homogeneous surface, soft, hard to peel
`Too brittle
`
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`
`141
`
`2.6. Measurement of tensile strength
`
`The polymer film was cut into a narrow strip with a width of
`10 mm and 30 mm in length. The film was placed between the
`higher and the lower grip of a Chatillon Digital Force Gauge
`(a model DFM-10, John Chatillon and Sons, Greensboro, NC)
`mounted on a test stand (a model LTC, John Chatillon and Sons,
`Greensboro, NC), aligning the long axis of the specimen and the
`grip with an imaginary line by joining the points of attachment
`of the grips to the machine. The two grips were kept at a distance
`of 10 mm in a same plane, and the hand wheel attached to the
`lower grip was rotated gradually until the film ruptured. The load
`at the moment of rupture was recorded and tensile strength was
`calculated using the following equation:
`tensile strength (σ) = force or load (F )
`MA
`where F is the maximum load in Newton and MA is the minimum
`cross-sectional area of the film specimen in square millimeter.
`
`2.7. Measurement of the contact angle
`
`An NRL contact angle goniometer (a model 100, Ram´e-Hart
`Instrument Co., NJ) is used to measure the contact angle of
`the polymeric films. The light source was switched on and the
`goniometer was adjusted to the path of the light. The specimen
`film was cut into around 50 mm× 30 mm in size. The adjustable
`scale on the goniometer was set horizontal. The specimen film
`was placed on the mechanical stage and height adjusted such that
`the specimen was exactly at the same height as the horizontal
`scale in the goniometer. VFS drop of 50 or 100 ␮l was settled
`on the test surface by using a microburette for 10 s. The shadow
`of each drop was considered as the arc of a circle. The contact
`angle was measured directly by adjusting the movable scale to
`the tangent at the point of contact.
`
`2.8. Swelling study
`
`VFS (pH 4.0) was used as a medium for film swelling studies.
`Plastic weighing boats with pores in the bottom was used as a
`container. Each film sample with 10 mm× 10 mm of surface
`area was weighed and placed in a preweighed container. The
`weight boat containing the film sample was then submerged
`into 25 ml VFS in a Petri dish. At predetermined time intervals,
`the weight of the swelled film was measured. The swelling index
`was calculated using parameter (Wt − W0)/W0, where Wt is the
`weight of film at time t and W0 is the weight of film at time zero.
`
`2.9. Film erosion study
`The polymeric films were cut into a size of 10 mm× 10 mm.
`The erosion degree of the polymeric film was determined by
`placing the polymeric film in 25 ml of VFS (pH 4.0) on 20 rpm
`of Orbital Shaker (a model OR-100, Daigger, IL). At pre-
`determined time intervals, a sample was removed and com-
`◦
`pletely dried in the oven at 60
`C for 24 h to determine its
`weight. Percentage remaining was calculated by using parameter
`
`Fig. 1. Simulated dynamic vaginal system used for drug release and mucoad-
`hesive tests.
`
`100− (Wp − Ws)× 100/Wp, where Wp and Ws are the original
`weight of the film and the weight of the dry film after erosion,
`respectively.
`
`2.10. In vitro release profiles of SDS
`
`A simulated dynamic vaginal system (Fig. 1) was prepared by
`assembling a slide glass and a flow rate pump. Isolated porcine
`vaginal tissue, obtained from a slaughterhouse, was cleaned,
`deprived of the connective tissue with surgical scissors with spe-
`cial care to maintain integrity of mucosa, and stored at −20
`◦
`C
`until further use. Before the experiments, porcine vaginal tis-
`sue was thawed in normal saline containing 0.1% (w/v) sodium
`azide as preservative. The porcine vagina was cut into pieces
`with 5 cm× 5 cm in size. The vaginal membrane was mounted
`◦
`with the mucosa side up on a glass slide (30
`angle slope). The
`polymeric film with 1 cm× 1 cm in size was mounted on the
`mucosal membrane. VFS (pH 4.0) was applied on the films with
`a flow rate of 5 ml/h. At predetermined time intervals, the per-
`fused VFS was collected into a receptor beaker placed under the
`slide glass for 6 h. Residence time of the films on the mucosa was
`also measured using the same system. The amount of released
`14C-SDS was analyzed by Liquid Scintillation Counter.
`
`3. Results
`
`3.1. Preparation and physical characteristics of the films
`
`Polymeric film formulations containing various ratios of Car-
`bopol:HPMC:PEG, loaded with 3% (w/v) SDS, were prepared
`and their physical properties, such as thickness, uniformity of
`drug content and weight variation, were examined (Table 1).
`Homogeneous films are translucent, colorless, thin and soft, and
`no spot or stain was found on the films. The average thickness
`of the films ranged from 220 to 241 ␮m. The differences in the
`thickness and weight between batches were within an accep-
`tance range. In peelability, the films containing 0.25% (w/v)
`PEG (C:H:P = 2:1:1, 1.5:1.5:1 and 1:2:1) were easily taken off
`
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`
`Fig. 2. Comparison of tensile strength of polymeric films. Each data point rep-
`resents the mean± S.D. of three replicates.
`
`Fig. 3. Measurement of contact angel of polymeric films. Each data point rep-
`resents the mean± S.D. of three replicates.
`
`from the Petri dish, while the films containing 0.5% (w/v) PEG
`(C:H:P = 1.2:0.8:2, 1:1:2 and 0.8:1.2:2) attached more strongly
`to the bottom of Petri dish after dry. The films without PEG were
`easily peeled off, but too brittle to perform further tests. Without
`HPMC, the films were not homogenous and showed a cloudy
`surface. An assessment of drug content at five different places in
`each film revealed that SDS was distributed evenly throughout
`the films regardless of the polymer ratios.
`
`3.2. Tensile strength
`
`In producing polymeric films that are intended as a dosage
`form for intravaginal drug delivery, the films should possess
`sufficient strength to withstand mechanical damage during pro-
`duction, handling and application. The tensile strength is defined
`as the maximum stress (σ) sustained by the material. As shown
`in Table 1 and Fig. 2, tensile strength varied according to the
`compositions of the formulation. Among tested variables, the
`PEG concentration seems to be the most prominent factor in
`determining tensile strength. The films containing 0.25% PEG
`showed higher tensile strength than those containing 0.5% (w/v)
`PEG. Tensile strength was also affected by the ratio of Car-
`bopol to HPMC, even though the degree of change is less than
`that caused by PEG concentration. As the ratio of Carbopol to
`HPMC concentration decreased, tensile strength increased. The
`highest tensile strength was observed with the film which has a
`composition of Carbopol:HPMC:PEG (C:H:P)=1:2:l.
`
`3.3. Contact angle measurement
`
`A contact angle is used as an indication of degree of wet-
`ting. The higher value of contact angle means the less degree of
`wetting. It was also reported that contact angles are correlated
`to the work of adhesion, which represents strength of mucoad-
`hesiveness (Li et al., 1998). As shown in Fig. 3, the degree of
`contact angle decreased as Carbopol concentration in the films
`increased. The film with the highest concentration of Carbopol
`(i.e., the composition of C:H:P = 2:1:1) showed the lowest con-
`tact angle, which means having high wetting capability and work
`of adhesion.
`
`3.4. Swelling capability study
`
`The effects of various compositions on the swelling index
`of the film are shown in Fig. 4. The films were not dissolved
`nor eroded, indicating that the cohesiveness of the polymers
`is sufficient to guarantee the stability of the system. The films
`were rapidly swelled within 30–45 min and thereafter gradually
`reached a plateau. Films containing 0.25% (w/v) PGE showed
`higher swelling index than those containing 0.5% (w/v) PEG. As
`the concentration of Carbopol in the film increased, the swelling
`index increased. At 1.5 h, a films with 0.5% (w/v) Carbopol
`(C:H:P = 2:1:1) swelled about eight times, whereas 0.2% (w/v)
`Carbopol film (C:H:P = 0.8:0.2:2) swelled about three times.
`Since Carbopol is used as a cross-linking agent, it is expected
`that it can retain more water and higher swelling degree as its
`concentration increases.
`
`3.5. The erosion profile of the films
`
`The erosion test of the mucoadhesive films was conducted
`to evaluate the resistance force of the films in VFS. The fast
`erosion of the films in VFS may pose the problems, such as
`unexpected burst release of drug and short residence time on the
`
`Fig. 4. Swelling index of polymeric films. A film of 1 cm× 1 cm in size was cut
`and immersed in VFS (pH 4.0). Each data point represents the mean± S.D. of
`three replicates.
`
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`
`143
`
`As the ratio of Carbopol to HPMC concentration in the formu-
`lation increased, the SDS release rate from the film decreased,
`indicating the SDS release rate from the polymeric film can be
`controllable by the ratio of Carbopol to HPMC concentration.
`
`3.7. The residence time
`
`The time required for the complete removal of the polymer
`film from the vaginal tissue varied with the compositions in the
`films. The films (0.25%, w/v, PEG) containing more Carbopol
`and HPMC than PEG remained on the porcine vaginal mucosa
`for up to 6 h, but the films (0.5%, w/v, PEG) containing less
`Carbopol and HPMC than PEG were removed from the tissue
`within less than 4 h. The results of this study indicated that the
`concentration of Carbopol and HPMC is an integral factor in
`residence time of the mucoadhesive formulations.
`
`4. Discussion
`
`Polymeric films, which were made of Carbopol, HPMC and
`PEG and containing SDS as the major microbicidal agent, were
`fabricated and examined for their physicodynamic properties to
`find the most suitable composition for FcDDS. Carbopol and
`HPMC were selected as the main ingredients because they were
`proven to have good properties as gel based FcDDS (Wang and
`Lee, 2002, 2004). Carbopol, which is consisted of acrylic acid
`backbone and small amounts of polyalkenyl polyether cross-
`linking agents, is commonly used for the preparation of vaginal
`gel formulations because of its polarity and bioadhesive proper-
`ties. HPMC is proven to have good mucoadhesiveness and can
`relieve the dryness and irritation even in the case of reduced
`mucus secretions. Carbopol and HPMC have good water sol-
`ubility and the co-polymer film made of these polymers fastly
`dissolves in water and is biocompatible for vaginal delivery. A
`plasticizer, PEG, which makes a film soft, elastic and flexible,
`was added as a film-forming agent.
`Peelability is one of the important considerations in the man-
`ufacture processes and the film without PEG was excluded from
`the experiments because it was too brittle to conduct further
`analysis. Hydrophilicity and swelling index increased as Car-
`bopol content in the film increased. It was previously observed
`that Carbopol uptakes more water than HPMC (Nafee et al.,
`2004) and an addition of Carbopol enhances the swelling rate of
`the tablet formulation (Mohammed and Khedr, 2003). This may
`explain our observations that Carbopol increased the swelling
`index and decreased contact angle of the polymeric films.
`Since drugs from the films are released by both diffusion
`and erosion, the rate of erosion of the system was examined.
`Even though higher concentrations of Carbopol showed greater
`swelling capability, the erosion rate of the films decreased as
`Carbopol content increased, implying that Carbopol is able to not
`only increase the degree of the hydration and mucoadhesiveness,
`but also maintain the morphology of the films in the vaginal
`cavity. Since the cross-linked network in Carbopol enables the
`entrapment of drugs in the hydrogel domain, the films made of
`Carbopol hydrogels are neither water-soluble nor eroded. Since
`HPMC is a linear hydrophilic polymer which does not have a
`
`Fig. 5. Erosion degree of polymeric films. A film of 1 cm× 1 cm in size was cut
`and immersed in VFS (pH 4.0) on 20 rpm of a shaker. Each data point represents
`the mean± S.D. of three replicates.
`
`vaginal mucosa. The reaming percentage of the films expressed
`as a function of time is shown in Fig. 5. The films were eroded
`quickly within 1 h and then gradually increased before reaching
`a plateau. At 4 h, the film made of C:H:P = 0.8:1.2:2 was eroded
`up to 86%, whereas the film made of C:H:P = 2:1:1 was eroded
`only up to 53%. Even though higher concentrations of Carbopol
`showed greater swelling capability, the erosion rate of the films
`decreased as Carbopol content in the film increased.
`
`3.6. SDS release profile
`
`The release rate of SDS from the films was described as a
`function of time as shown in Fig. 6. The simulated dynamic
`vaginal system used in this study mimics the physicodynamic
`conditions of the vagina. The percentage amount of the total
`SDS released from the films gradually increased as a function
`of wearing time. In all formulations, the burst release of SDS
`from the films was observed within first 2 h, and then gradually
`increased up to 6 h. About 46, 54 and 74% of the total SDS
`loaded in the film were released within 6 h from mucoadhesive
`films made of C:H:P = 2:1:1, 1.5:1.5:1 and 1:2:1, respectively.
`
`Fig. 6. The release profile of SDS from the polymeric films. The polymeric film
`with 1 cm× 1 cm in size was mounted on the mucosal membrane. VFS (pH 4.0)
`was applied on the films with a flow rate of 5 ml/h. Each data point represents
`the mean± S.D. of three replicates.
`
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`
`covalently cross-linked structure, HPMC easily forms a gel layer
`upon hydration and is highly erodible, leading to a burst release
`of a loaded drug (Katzhendler et al., 1997; Baluom et al., 2000;
`Giunchedi et al., 2000).
`The erosion rate of films made of Carbopol and HPMC are
`easily controllable by modulating their ratio. For the initial stage,
`the films were quickly eroded as HPMC was swelled and eroded
`first. After the initial stage, however, the erosion slowed down
`because remaining Carbopol did not dissolve well. The same
`pattern can be applied to the SDS release profile. As Carbopol
`concentration increased, the SDS release rate decreased, sug-
`gesting the release profile of SDS from the polymeric film can
`be controlled by Carbopol concentration. Although the swelling
`degree in polymer formulations is well correlated with drug
`release rate, high swelling degree did not increase the SDS
`release rate from the films. This can be explained by the combin-
`ing property of Carbopol and HPMC, which have the different
`swelling and erosion characteristics.
`The residence time of polymeric films on the vaginal tis-
`sue was greatly affected by the ratio between Carbopol and
`HPMC. The films containing 0.75% (w/v) of Carbopol and
`HPMC and 0.25% (w/v) PEG remained on the tissue for at least
`6 h, whereas those (total 0.5%, w/v, of Carbopol and HPMC) of
`0.5% (w/v) PEG were detached from the tissue within 4 h, indi-
`cating two mucoadhesive polymers (i.e., Carbopol and HPMC)
`significantly affects the retention time on the vaginal cavity. PEG
`does not have mucoadhesive property, thus not affecting the res-
`idence time of the formulation on the vaginal mucosa. However,
`in our formulations, an increase in PEG concentration decreased
`the residence time by reducing the concentration of Carbopol
`and HPMC. Due to the short resident time, the films containing
`0.5% (w/v) PEG were excluded from the SDS release study.
`According to the reported physiological data, about
`0.5–0.75 g mucus is present in the vagina at any time in healthy
`women of reproductive age. Based on the maximum vaginal
`secretion rate (5 ml/h) and the maximum volume of mucus in
`the vagina (0.75 ml) (Hunter and Nicholas, 1959), the concen-
`tration of SDS in the mucus upon being releases from the films
`could be calculated. The SDS concentration in the vaginal mucus
`within 10 min after loading of the films were about 0.014, 0.036
`and 0.073% (w/v) for the films made of C:H:P = 2:1:1, 1.5:1.5:1
`and 1:2:1, respectively. The required SDS concentrations to
`achieve total inactivation of HIV-1 and HIV-2 are 0.025 and
`0.0125% (w/v), respectively (Howett et al., 1999). Therefore,
`the polymeric films made of C:H:P = 1.5:1.5:1 and 1:2:1 met
`the minimum concentration required for the pharmacological
`activity within 10 min after their application in vagina. These
`film formulations maintain a controlled release rate of SDS for
`up to 6 h under the normal physiological conditions and can be
`used as a fast-responsive device against STD.
`The film made of 0.5% (w/v) PEG does not seem to be
`a proper formulation for the FcDDS because of poor peela-
`bility, low tensile strength and short residence time. All films
`containing 0.25% (w/v) PEG showed good peelability, high ten-
`sile strength and prolonged retention time. The films made of
`C:H:P = 1.5:1.5:1 and 1:2:1 (w/v) were found to be suitable for
`FcDDS against STD.
`
`5. Conclusion
`
`The mucoadhesive vaginal films composed of various ratios
`of Carbopol, HPMC and PEG and containing SDS were for-
`mulated by a casting method. It was demonstrated that the films
`have proper physicodynamic properties and compliable physical
`appearance for FcDDS. An increase in Carbopol content in the
`film elevated tensile strength and swelling ratio but decreased
`the contact angle, erosion rate and SDS release rate from the
`films. HPMC influenced the erosion rate and SDS release rate
`from the films, whereas PEG affected peelability as well as res-
`idence time of the films by changing concentration of Carbopol
`and HPMC. A proper combination of the polymers is integral to
`maintain mucoadhesiveness and optimal release profiles of SDS.
`
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