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Drug Delivery, 11:89–95, 2004Copyright c© Taylor & Francis Inc.ISSN: 1071-7544 print / 1521-0464 onlineDOI: 10.1080/10717540490280688

Development of Mucoadhesive Dosage Formsof Buprenorphine for Sublingual Drug Delivery

Nandita G. Das and Sudip K. DasIdaho State University, College of Pharmacy, Pocatello, Idaho, USA

The development of mucoadhesive formulations of buprenor-phine for intended sublingual usage in the treatment of drug ad-diction is described. The formulations include mucoadhesive poly-mer films, with or without plasticizers, and mucoadhesive polymertablets, with or without excipients that enhance drug release and/orimprove tablet compaction properties. The mucoadhesive polymersstudied include carbomers such as Carbopol 934P, Carbopol 974P,and the polycarbophil Noveon AA-1, with excipients chosen frompregelatinized starch, lactose, glycerol, propylene glycol, and var-ious molecular weights of polyethylene glycol. The developmentof plasticizer-containing mucoadhesive polymer films was feasible;however, these films failed to release their entire drug content withina reasonable period. Thus, they were not determined suitable forsublingual usage because of possible loss by ingestion during rou-tine meal intakes. The mucoadhesive strength of tablet formula-tions containing Noveon AA-1 appears to be slightly superior to theCarbopol-containing tablets. However, the Carbopol 974P formu-lations exhibited superior drug dissolution profiles while provid-ing adequate mucoadhesive strength. The tablet formulations con-taining Carbopol 974P as mucoadhesive polymer, lactose as drugrelease enhancer, and PEG 3350 as compaction enhancer exhib-ited the best results. Overall, the mucoadhesive tablet formulationsexhibited superior results compared with the mucoadhesive filmformulations.

Keywords Buprenorphine, Compressed Tablet, Drug Abuse, Film,Mucoadhesion, Sublingual

Therapies to prevent and/or treat drug abuse need carefulconsideration of the biopharmaceutical aspects of the treatmentdrugs and suitable delivery systems that can provide an idealtherapeutic profile and improve patient compliance. Ideally,drugs for the treatment of abuse must possess sufficiently long

Received 2 July 2003; accepted 12 August 2003.The authors acknowledge Peter Willeitner for his technical assis-

tance during the preliminary formulation phase of the dosage forms.Address correspondence to Sudip K. Das, Idaho State University,

College of Pharmacy, 970 South 5th Avenue, Pocatello, ID 83209-8334,USA. E-mail: [email protected]

half-lives that allow reduction in frequency of administration,slow metabolism to inactive metabolites, thus requiring less drugto be administered, and lack of addiction potential of their own.Buprenorphine has gained much interest in recent years in thetreatment of opioid-type drug addiction. It has strong analgesicand narcotic antagonist activity and is 25–50 times more po-tent than morphine (Gutstein and Akil 2001). Pharmacologi-cally, buprenorphine, a highly lipophilic semisynthetic deriva-tive of the opioid alkaloid thebaine, is a partial opiate agonist.It has agonistic effect on the mu and antagonistic effect on thekappa receptors, with the agonist properties predominating atlow doses and antagonist properties predominating at higherdoses (Cowan, Lewis, and Macfarlane 1977). A partial agonistis less likely to cause respiratory depression, which is the majortoxic effect of opiate drugs, compared with full agonists such asheroin and methadone. Buprenorphine hydrochloride, the water-soluble salt form of buprenorphine, has a mean plasma half-lifeof 3.21 hr (Kuhlman et al. 1996) and is highly metabolized inthe intestinal wall and liver to norbuprenorphine, which is aweakly active metabolite with half-life of 57 hr (Kuhlman et al.1998). Both buprenorphine and norbuprenorphine form inactiveglucuronides (Iribarne et al. 1997).

Compared with the potential of buprenorphine as a first- orsecond-line agent in the treatment of opiate addiction, studies onbuprenorphine drug delivery systems are relatively few. A sub-cutaneously implanted system utilizing a cholesterol-glyceryltristearate matrix produced sustained analgesic effect in rats for12 weeks or more (Pontani and Misra 1983). In an early studyon noncrystalline prodrugs of buprenorphine, synthesized fortransdermal delivery, success was limited because the lipophilicform was sequestered in the lipid-rich skin layers (Stinchcombet al. 1996). A matrix-type transdermal patch of buprenorphine(Transtec

©R , Napp Pharmaceuticals) was recently introduced inthe European market for the management of stable cancer andnoncancer pain, and early clinical efficacy reports are fairlypromising (Radbruch 2003). Eriksen et al. (1989) reported thatthe systemic bioavailability of buprenorphine administered bynasal spray is greater than 40%, which is comparable to the

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90 N. G. DAS AND S. K. DAS

30–40% bioavailability via the intramuscular and subcutaneousroutes. Addition of 30% polyethylene glycol (PEG) 300 as aco-solvent to a nasal formulation of buprenorphine does not en-hance bioavailability of the drug any further (Lindhardt et al.2001). Buprenorphine has been studied in a microcapsule sys-tem intended for parenteral use and produced a steady in vitrorelease for 45 days (Mandal 1999). Concerns over residual or-ganic solvents used in most microparticle preparations have re-stricted FDA approval of parenteral microparticulate systems, ingeneral, and further studies are needed to evaluate their efficacyand safety in vivo.

Intravenous buprenorphine has been used in pain manage-ment for many years. The oral route of administration producespoor bioavailability of approximately 15% (McQuay, Moore,and Bullingham 1986) and lacks commercial potential. Systemicbioavailability following sublingual administration, which by-passes first pass metabolism, is much superior and has been re-ported to be up to 58% (Bullingham et al. 1982). The sublingualregion offers a nonkeratinized epithelium with high permeabilityand a smooth and relatively immobile surface with easy acces-sibility. For the treatment of drug abuse, an immediate releasesublingual tablet of buprenorphine, SubutexTM (manufacturedby Reckitt Benckiser), was recently introduced in the U.S. mar-ket. This delivery system for buprenorphine has been availablein Europe for nearly a decade and is widely used as an alterna-tive to methadone in the treatment of opiate addiction (Gasquet,Lancon, and Parquet 1999). Literature on bioavailability of sub-lingual buprenorphine presents variable numbers ranging from19–58% of the administered dose. Although sublingual deliveryof buprenorphine has been proven effective, bioavailability bythis route can be erratic because of salivary washout and invol-untary swallowing.

We hypothesize that increasing the contact time with the sub-lingual mucosa with a mucoadhesive delivery system could im-prove sublingual bioavailability and result in more predictableplasma levels of the drug, leading to better therapeutic efficacyand reproducibility. No study has been published to date on mu-coadhesive sublingual delivery of buprenorphine aimed at thetreatment of drug addiction. These dosage forms would adhereto the sublingual mucosa and withstand tongue movement fora significant period, potentially decreasing the chances of in-voluntary swallowing of the dosage form. A sustained releaseeffect also may be expected from the dosage form, which wouldmake delivery of higher doses of buprenorphine for the preferred3-times/week dosing regimen feasible with minimal side effects.With easy accessibility to the sublingual area, the delivery sys-tems can be self-administered by the patient with minimal or nosupervision that in turn can reduce health care costs involved inthe treatment of drug addiction.

In this article, we discuss the development of mucoadhesivepolymer films and tablets of buprenorphine and evaluation oftheir physical properties and drug release characteristics. Theeffect of plasticizers on the film properties was studied, as wellas the effect of excipients on “tabletability” and drug release

properties from the compressed tablets. The polymeric dosageforms described are hydrogels that swell on coming in contactwith water and do not allow prompt dissolution like an imme-diate release tablet; therefore, we anticipate that potential fordiversion of these dosage forms as a street drug for intravenoususe would be limited if applied in the clinical arena in the future.

MATERIALS AND METHODSThe carbomers Carbopol 934P, 974P and Noveon AA-1 were

obtained by the courtesy of Noveon Inc. (OH, USA). Starch1500 (pregelatinized maize starch) was obtained by the courtesyof Colorcon Inc. (PA, USA). Lactose monohydrate, glycerol,propylene glycol, PEG (MW 400, 1000, 3350, and 8000), mucin,and buprenorphine were obtained from Sigma Chemical Co.(MO, USA).

Preparation of Mucoadhesive Polymer FilmsConsidering the comfort issue involved with a drug delivery

system designed to adhere to a sensitive and mobile area, weadjudged that a thin, flexible polymer film would be ideal forsublingual use. A general protocol used in several literature ref-erences describing polymer films was adopted. Double-filtereddeionized water was degassed under vacuum before adding thepolymers to minimize the formation of air bubbles within thegel. Each of the following polymers in 200–500 mg quanti-ties, Carbopol 934P, Carbopol 974P, and Noveon AA-1, weresolubilized in water or 95% ethanol using a paddle stirrer at1000 rpm for 10 min to result in 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0,4.5, and 5.0% w/w gels. Homogeneous gel formation for thehigher concentrations (4.5 and 5% w/w) proved difficult by stir-ring and was achieved by placing the mixtures in plastic bagsand kneading by hand to prevent formation of poorly wettedpolymer agglomerates. Amounts higher than 5.0% w/w couldnot be homogeneously solubilized. All gels were kept overnightat 4◦C to allow complete hydration, following which they werecentrifuged at 5000 rpm for 30 min to remove air bubbles be-fore film casting. Two techniques were used to cast the polymerfilms: (a) gels poured on Teflon

©R plates and placed in the ovenat 40◦C for 24 hr or until dry to the touch; and (b) gels placedbetween two Teflon

©R plates separated with 1 mm thick spacersat the edges and dried in a desiccator under vacuum for 48–72 hr.

Preparation of Plasticizer Containing MucoadhesivePolymer Films

Plasticizers were added to the aqueous gel systems describedabove to reduce brittleness, improve flexibility, and improve sur-face texture and smoothness of the films. PEG has been describedin the literature to also improve mucoadhesion properties of cer-tain polymers. Glycerol, propylene glycol, or PEG 400, 1000,3350, or 8000 were each added to the aqueous gel systems toresult in final concentrations of 0.5, 1.0, 5.0, or 10.0% w/w plas-ticizer in the system and stored overnight under refrigeration.

BUPRENORPHINE SUBLINGUAL MUCOADHESIVE DOSAGES 91

Gels were centrifuged and films were cast on Teflon©R plates

using the method (a) described previously.

Preparation of Mucoadhesive TabletsFlat-faced core tablets were prepared by direct compression

of various combinations of the polymers Carbopol 934P, 941,971P, or 974P or Noveon AA-1, with or without starch, lactose,PEG 3350 and 8000, using a hydraulic laboratory pellet press(Carver Inc., IN, USA). After testing for physical characteristicsand performing thermal analysis to study polymer-excipient in-teractions, select formulations were chosen and 8 mg buprenor-phine incorporated into each unit dose. The total weight of com-ponents per compact was kept constant at 200 mg, and a constantforce of 1 ton was applied for 60 sec. The diameter of the dieused was 13 mm, providing a potential surface contact area of1.33 cm2 for the tablets. Formulations were designed so that thetablet thickness would not exceed 2 mm and preferably be closeto 1.5 mm.

Physical Characterization and In Vitro Disintegrationand Dissolution Tests

The physical characteristics of the compacts such as thicknessand hardness were evaluated using a micrometer (Central ToolCo., RI, USA) and a manual hardness tester (Pfizer, NY, USA),respectively. Visual observations were noted for surface smooth-ness. Thermal analysis was done using a differential scanningcalorimeter (MDSC 2920, TA Instruments, DE, USA) by plac-ing 2–4 mg samples in sealed aluminum pans and ramp heatingfrom room temperature to 300◦C at a scan rate of 10◦C/min.All components were scanned in their pure state and comparedwith thermograms of the compressed tablets to observe changesin peak position or any characteristics that would indicate inter-actions between the drug and excipients. In vitro disintegrationtests were done using a single-station USP disintegration appa-ratus (Erweka, NJ, USA) and double-distilled deionized water(ddH2O) as the medium. In vitro dissolution tests were doneusing a USP dissolution apparatus (Vankel, NJ, USA) with thebasket rotating at 50 rpm in 500 mL ddH2O at 37◦C. Then 5-mLsamples were withdrawn at selected time intervals until the gelmatrix completely dissolved.

The amount of buprenorphine in the dissolution sampleswas estimated by UV spectroscopy (Lambda-Bio, Perkin-Elmer,MA, USA). The reference medium for UV spectroscopy wasobtained by dissolving a drug-free tablet in 500 ml ddH2O. Mu-coadhesive strength was estimated by using a manually oper-ated surface tension apparatus (DuNuoy Tensiometer, Cenco,IL, USA) modified for this purpose and similar to a design re-ported by Robert, Buri, and Peppas (1988). A schematic sketchof the instrument is presented in Figure 1. We replaced the sus-pension ring (meant for measuring surface/interfacial tension)with an A-shaped wire affixed to an aluminum plate (weight456 mg, thickness 0.5 mm, and diameter 2 cm) at the open ends.One face of the mucoadhesive tablet was immobilized on the

FIG. 1. Schematic of modified tensiometer used for mucoadhesion studies.

aluminum plate using glue and the system was suspended. Next30% (w/w) mucin gel was placed on the metal station at the baseof the tensiometer. The tablet was brought into contact with themucin gel, manually, and held in place for 10 sec. The dial onthe tensiometer was then gently twisted until separation occurredand the reading at the point of separation was noted.

RESULTS AND DISCUSSIONProlonging drug delivery is well recognized as an advantage

as it increases the therapeutic value of many drugs. Nevertheless,for mucoadhesive sublingual delivery, even if the system werecapable of staying in place for prolonged periods, it would still beimpractical to design a delivery system that would be retained inplace beyond 2–3 hr. If not disturbed by drinking fluids, it is diffi-cult to imagine that a sublingual drug delivery system would notbe lost while eating regular meals, which would invariably leadto loss of drug from first-pass metabolism. Therefore, our goalwas to develop a formulation that would localize buprenorphinein the sublingual area and prolong the release better than the cur-rently marketed immediate release dosage form, while releasingthe entire drug content within approximately 120 min. Addition-ally, the formulation must lack any burst release effects, mustnot exhibit drug-excipient interactions, must possess sufficientmucoadhesive strength, and possess suitable physical propertiessuch as tablet hardness, thickness, and surface smoothness forproper adhesion.

Mucoadhesive Polymer Film FormulationsFilms with No Plasticizers

The films prepared by method (a) were brittle, with variablethicknesses and uneven surfaces. The films prepared by method(b), which was hoped to improve on method (a) by controllingfilm thickness, were comparably brittle and difficult to removefrom the sandwiched Teflon

©R casting surfaces without distort-ing the structure of the film. The nature of solvent (water orethanol) used to solubilize the polymers did not appear to causea significant difference in the gel formation process or in the endproducts, except that ethanol dried faster and produced a moreuneven surface in method (a). We concluded that these formu-lations, produced using either of these methods, would not besuitable for industrial scale-up.


Films with PlasticizersIn general, the plasticizer containing polymer films were eas-

ier to fabricate and handle. The films containing either glycerolor propylene glycol as plasticizers took 48 hr or longer to setand tended to stretch irreversibly during removal from the cast-ing surface. We determined that these plasticizers are capable ofyielding films with excellent flexibility, but for ease of handlingthey must be cast on an impervious flexible backing, with thelatter incorporated as part of the formulation design as manip-ulations to the film must be done in conjunction to the backingmaterial to prevent distortion. Hence, these plasticizers may bemore suitable for designing transdermal films compared withdosage forms that need to be placed in the oral cavity, whichpreferably must be devoid of nonedible material.

In formulations containing PEG as plasticizer, the films with5.0 and 10.0% w/w plasticizer content did not set properly andwere too stretchy to be removed intact from the casting surface.The 0.5 and 1.0% w/w PEG 400-containing films exhibited thebest physical characteristics, as the surface was smooth and thefilms were flexible. Once the formulations were optimized, weadded buprenorphine to the gel during the preparation process,filled the prepared gels in a hypodermic glass syringe, and placed0.2–2 ml quantities on wax paper such that each unit dose con-tained 8 mg of buprenorphine. The drug-containing gels wereallowed to spread and set into circular discs that were formed nat-urally. As expected, an inverse relationship was noted betweenfilm diameter and thickness. Figures 2 and 3 illustrate the effectof drying conditions on film thickness and diameter produced byvarious quantities of 0.5% w/w PEG 400-containing gels. Thevacuum dried films showed greater thickness and smaller diam-eters compared with oven dried films. The 40◦C temperaturein the oven likely allows for the spread of the films more thanoccurs at room temperature in the desiccator. This phenomenonis more evident when the volume of gel to be dried is larger.

FIG. 2. Dependence of the polymer film thickness on volume of gel castand drying conditions. The drug-free formulation represented here contained2.5% w/w Carbopol 974P and 0.5% w/w PEG 400.

FIG. 3. Dependence of the film diameter on volume of gel cast and dryingconditions. The drug-free formulation represented here contained 2.5% w/wCarbopol 974P and 0.5% w/w PEG 400.

Mucoadhesive Tablet FormulationsAll tablets were observed to possess a smooth, shiny surface,

regardless of the composition; therefore, the entire surface areawould potentially be available for adhesion. Table 1 shows thedependence of tablet thickness and hardness on the compositionof some representative formulations.

Tablets Prepared with Mucoadhesive Polymer OnlyIn vitro disintegration tests indicated that all pure polymer

compacts, containing no other excipients, required over 8 hr toswell and erode. We incorporated buprenorphine in the polymerCarbopol 974P (8 mg buprenorphine +192 mg polymer) andstudied the tablet for in vitro dissolution using a USP apparatus;the amount of buprenorphine released over 12 hr was very smallwhen the absorbance was recorded in the UV spectrophotome-ter. This observation corroborates the observations of McQuinnet al. (1995) who found that mucoadhesive polymer discs con-taining Carbopol 934P and 2.9 mg buprenorphine free base,when placed on the gum of human volunteers, released 0.42 ±0.18 mg of the drug over 12 hr, which translates to approxi-mately 14% drug release. This led us to conclude that the purepolymer compacts would not be capable of releasing therapeu-tically effective quantities of buprenorphine in the sublingualenvironment in vivo within a reasonable usage period.

Tablets Prepared with Mucoadhesive Polymer and PEGAddition of up to 10% w/w PEG 3350 improved the disso-

lution profile compared with the pure polymer compacts, butfurther increase in PEG content did not make additional im-provements in the dissolution rate or extent. As shown in Table 1,the addition of PEG 3350 slightly increased the hardness of thetablets; however, it did not make any difference to the tabletthickness.


TABLE 1Physical characteristics of mucoadhesive tablet formulations

Composition (% w/w)

Carbopol Carbopol Noveon934P 974P AA-1 PEG 3350 Lactose

Thickness(mm);n = 3

Hardness(kg);n = 3

Disintegrationtime (hr);

n = 3

Tensile strength(Newtons)

n = 1

100 1.78 ± 0.06 9.8 ± 0.6 9.0 ± 1.0 13.795 5 1.79 ± 0.04 10.0 ± 0.8 9.0 ± 0.75 13.085 10 5 1.81 ± 0.05 9.8 ± 0.6 8.5 ± 0.75 13.180 5 15 1.84 ± 0.10 8.8 ± 0.6 7.0 ± 0.75 1160 10 30 1.86 ± 0.10 7.4 ± 0.6 5.0 ± 0.5 8.340 10 50 1.94 ± 0.12 6.2 ± 0.8 3.0 ± 0.5 5.230 10 60 1.98 ± 0.14 5.6 ± 1.0 2.0 ± 0.2 3.9

100 1.68 ± 0.04 9.6 ± 0.6 8.5 ± 0.75 16.295 5 1.68 ± 0.04 10.0 ± 0.8 8.0 ± 0.75 16.885 10 5 1.71 ± 0.05 9.2 ± 0.6 7.5 ± 0.5 16.180 5 15 1.72 ± 0.08 7.8 ± 0.4 6.0 ± 0.5 14.060 10 30 1.76 ± 0.10 6.8 ± 0.4 4.0 ± 0.4 11.240 10 50 1.76 ± 0.10 5.4 ± 0.8 2.5 ± 0.3 8.830 10 60 1.78 ± 0.12 5.2 ± 1.0 2.0 ± 0.3 7.3

100 1.89 ± 0.02 10.6 ± 0.6 10.0 ± 1.0 15.095 5 1.82 ± 0.04 10.8 ± 0.8 10.0 ± 0.75 15.585 10 5 1.82 ± 0.02 10.4 ± 0.8 9.5 ± 1.0 14.880 5 15 1.80 ± 0.04 9.6 ± 0.6 8.0 ± 0.75 12.860 10 30 1.86 ± 0.04 8.2 ± 0.8 6.0 ± 0.5 10.140 10 50 1.88 ± 0.12 7.8 ± 1.0 4.0 ± 0.5 8.130 10 60 1.90 ± 0.14 7.6 ± 1.2 3.0 ± 0.5 6.8

Tablets Prepared with Mucoadhesive Polymer and StarchWe hypothesized that the addition of pregelatinized starch

would improve the disintegration and dissolution profiles of thecompacts and increase the porosity of the compressed poly-mer matrix. Amounts of pregelatinized starch between 5 and70% w/w were added to the formulation. But contrary to ourexpectations, all concentrations of starch increased the tablethardness beyond 12 kg and increased disintegration time beyond12 hr. There was no improvement in the dissolution profiles ofthe starch-polymer compacts compared with the pure polymercompacts; hence, the results for this group of formulations arenot discussed further.

Tablets Prepared with Mucoadhesive Polymer and Lactose,with or Without PEG

Lactose was the second excipient that we expected wouldincrease porosity of the swelling polymer gel matrix. Variousamounts of lactose, between 5–80% w/w, were added to theformulations. As shown in Table 1, an increase in lactose con-tent was inversely related to tablet hardness and disintegrationtime for all polymers, and the tablet thickness was directly re-lated to lactose content. At lactose content 70% w/w and above,the tablets become increasingly friable and chip easily during

removal from the die. However, tablets with relatively highlactose content and low mucoadhesive polymer concentrationsprovided the most desirable disintegration and dissolution pro-files, while providing adequate mucoadhesive force. We addedvarious amounts of PEG 3350 to the high lactose–containingformulations to investigate whether it improves “tabletability.”The addition of PEG 3350 indeed increased the hardness, re-duced friability, and improved the surface smoothness of thetablets, while maintaining the desirable disintegration and dis-solution profiles provided by the large amount of lactose inthe formulations. All formulations were tested for their mu-coadhesive (tensile) strength and the results are presented inTable 1. From our experiments and similar reports in literature,we concluded that formulations containing Carbopol 974P andNoveon AA-1 were comparable in their mucoadhesive capabil-ity and were superior to the other polymers we tested in ourformulations.

Differential scanning calorimetry (DSC) revealed no inter-actions between buprenorphine and the formulation excipients.Figure 4 shows the DSC thermograms for pure Carbopol 974P,lactose, PEG 3350, and buprenorphine, and compares them withthe scan of a compressed tablet containing all these materials.There was no shift in peak position, or appearance of new ordisappearance of existing peaks, indicating the ingredients are


FIG. 4. Differential scanning calorimetry scans for Carbopol 974P, lactose PEG 3350, and buprenorphine, compared with a tablet compact made from theseingredients.

stable and do not interact with each other physically or chemi-cally as a result of compacting stress.

There was good correlation between disintegration times anddrug dissolution profiles for these formulations. As the lactosecontent increased, disintegration time decreased and the drugdissolution was faster. Figure 5 compares the dissolution profileof buprenorphine from tablets containing 8 mg buprenorphine,60% w/w lactose, 10% w/w PEG 3350, and 30% w/w Carbopol974P, and tablets containing 8 mg buprenorphine, 60% w/w

FIG. 5. Release profiles of buprenorphine from various formulations, eachcontaining 8 mg buprenorphine; � = tablet formulation containing 60% lactose,10% PEG 3350, and 30% Carbopol 974P; • = tablet formulation containing60% lactose, 10% PEG 3350, and 30% Noveon AA-1; � = Carbopol 974Ppolymer film containing 0.5% PEG 400 as plasticizer.

lactose, 10% w/w PEG 3350, and 30% w/w Noveon AA-1.All features were identical for the two formulations except forthe mucoadhesive polymer, which was either Carbopol 974Por Noveon AA-1. As evidenced from the graph, the NoveonAA-1–based formulation showed a gradual but slow rate of re-lease, which extended the dissolution time well beyond 2 hr.Similarly, drug release from the Carbopol 974P–based formula-tion was gradual; however, this tablet was capable of releasingthe total drug content completely within the first 2 hr. Basedon previously published literature evidence, the mucoadhesiveforce generated by either formulation in vitro was adjudged tobe adequate for prolonged adhesion.

For the sake of comparison, we also included in Figure 5 thedissolution profile of a polymer film containing 8 mg buprenor-phine and 0.5% w/w PEG 400, with the balance made up ofCarbopol 974P. As shown in the graph, the film released onlyabout 30% of its drug content over the period of 220 min withthe release rate tapering off gradually with time.

CONCLUSIONSThe mucoadhesive tablet formulations produced overall su-

perior results compared with the mucoadhesive film formula-tions. The high lactose, low mucoadhesive polymer Carbopol974P and PEG 3350–containing tablet formulations exhibitedthe best overall results. These formulations provide a sustainedrelease profile of the drug without any burst release effects andexhibited no drug-excipient interactions. They were capable ofreleasing their entire drug content within 2 hr, which provides areasonable period for sublingual usage in vivo. Based on existing


literature reports, the mucoadhesive strength of these formula-tions was judged adequate for localization on the sublingualmucosal surface during the anticipated 2 hr usage period.

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McQuinn, R. L., Kvam, D. C., Maser, M. J., Mller, A. L., and Oliver, S. 1995.Sustained oral mucosal delivery in human volunteers of buprenorphine froma thin non-eroding mucoadhesive polymeric disk. J. Control Rel. 34:243–250.

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