ISSN- 0975-1491
ResearchArticle
ATRANSDERMALGLUCOSAMINEFORMULATIONIMPROVESOSTEOARTHRITICSYMPTOMS
INANOPENCLINICALSURVEY
NGGUATHUA1,MBBS;LEEYUMING2,MBBS;ANDJONATHANOBAJE3*,PHD
1
SheffieldClinic,BLK69#01361,TaoPayohLor4,Singapore310069,2ComwellMedicalClinic,BLK6#0180HougangAve,Singapore
5300063EunosTechpark,60KakiBukitPlace#0408,Singapore415979Email:ugane07@yahoo.com
Received:13Feb2011,RevisedandAccepted:12March2011
ABSTRACT
Objective:Toevaluatetheefficacyandsafetyofanewtransdermalformulationofglucosamineinthetreatmentofosteoarthritis(OA).
Method:Fortyfour(44)patientswithmildtomoderateOAattending16differentoutpatientclinicsinSingaporewererecruitedinto the4week
study.Threecriteriawereusedtoquantifytheseverityofdiseaseactivityevaluatedbeforeandaftertreatmentwithonegram(3timesdaily)of
Urahtransdermalglucosamine(UTG)creamformulationviz:Ritchiearticularindex(RAI),functionaldisabilityassessment[DoctorsEvaluationof
Healthstatus(DEH)]andarthritisselfefficacyscale[PatientsAssessmentQuestionnaire(PAQ)].
Results:Afterfourweeks,UTGtreatmentwasobservedtoimprovedRAIpainscorefromthebaseline(day0)inalldemographicgroupandfurther
enhancedfunctionalabilities.Overall,59%ofthepatientshadagoodopinionratingforthistransdermalformulationandshowedbeneficialeffects.
Efficacyappeared tobe relatedto thesite ofarthritiswith 100% of patients havingarthritis of theshoulders reporting beneficial effectsofUTG
therapyasopposedto75%ofpatientswithankle,wristandelbowOAand58%ofkneeOArespectively.Additionally,compliancetotreatmentwas
observedtobeover95%andtherewerenoreportsofadversereactionsandnoskinirritationswereobservedatanytimepoint.Conclusion:Urah
Transdermal Glucosamine Creamsignificantlyalleviatedpainin arthritic jointswhen appliedoverfourweekssuggestinganimprovementinthe
qualityoflife.Thisresultssupportfurtherclinicaltrialintotheuseoftransdermalrouteofadministrationofglucosamine.
Keywords:Osteoarthritis,Transdermal,Glucosamine,RouteEfficacy
INTRODUCTION
Despiterecentadvancesinthemedicalsciences,arthritis,achronic
degenerativedisorderofmultifactorialaetiology,continuestobethe
most common musculoskeletal disorder in clinical practice and a
leading cause of pain and handicap in many countries.
Approximately43millionAmericans(ie16.6%oftheUSpopulation)
areknown to be afflicted by one form of arthritisorthe other 1.In
Japan,Yoshimuraetalreportedprevalenceofosteoarthritis(OA)of
thekneein25millionJapaneserepresenting30%ofthepopulation
2. Zhang et al examined 1,787 Chinese residents of Beijing and
reported prevalence of radiographic knee OA as 42.8% in women
and21.5%inmen3.Thehighprevalenceofthispotentiallydisabling
diseaseoftentranslatesintosignificanteconomicandsociocultural
implicationstopatientsandthesocietyatlarge,accountingfor25%
ofvisitstoprimarycarephysiciansandhalfofallnonsteroidalanti
inflammatoryprescriptionsintheUnitedStatesofAmerica4.
Current treatment of OA is limited to palliation through the use of
analgesicssuchasnonsteroidalantiinflammatory drugs(NSAIDs),
andthecyclooxygenase2(COX2)inhibitors 4.Thefailureofthese
conventional medications to satisfactorily treat OA has resulted in
increasingsearchforsuperiortreatmentoptions.ManyOApatients
resort to the use of unconventional treatment methods such as
herbal or selfmedication 5, spa treatments 6, and painful intra
articularinjections7.
In recent years, glucosamine has been increasingly endorsed
putatively as an overthecounter remedy for OA, with estimated
annual sales exceeding $700 million in the United States alone 8.
Although several laboratory studies have shown glucosamine to be
good chondroprotective agent 9, many reported human clinical
studies on orally administered glucosamine formulations have not
shown results complementing these laboratory findings 10. A
multicenteroralglucosamineclinicaltrialpublishedin2006bythe
American National Institute of Health concludes that glucosamine
andchondroitinsulphatealoneorincombinationdidnoteffectively
reducepainintheoverallgroupofpatientswithosteoarthritisofthe
knee 11. This contrasting report between laboratory and clinical
findings has done little to assuage skepticism on the therapeutic
efficacyofglucosaminetherapyamongpatientsanddoctors.
Obajeetal.
IntJPharmPharmSci,Vol3,Suppl3,2011,8083
glucosamine sulphate 2KCl. Patients were instructed to apply
approximately 1 g of the cream three times daily to each of the
affected joints. If both knees were affected, both were treated and
evaluated. Treatment compliance was estimated by collecting
finished tubes before issuing new tubes. Patients were not given
specific additional instructions with regard to exercise or any
restrictionofactivities.
Table1:showsamodificationofRitchiearticularindex(mRAI)usedtoevaluatethestatusofarthriticsymptominpatients
a)ModifiedRitchieArticularIndex(mRAI)
Pain
Nopain
Slightpain
Moderatepain
Severepain
b)PatientsAssessmentQuestionnaire(PAQ)
Score
0
1
2
3
Pain
Norelief
Slightrelief
Moderaterelief
Completerelief
Score
1
2
3
4
Outcomescorewasmeasuredasthedifferencebetweentherecruitment/baselineandtheendpointscoreonthemRAIscale.Theoutcomescores
areratedasExcellent(>2.5);Good(1.5to2.4);Fair(0.5to1.4);Useless(0to0.4)andWorsethanuseless(<0).
Ritchiespainscoreandfunctionaldisabilityevaluation
At baseline and on each followup (weekly) visit, the investigators
assessed the severity of disease activity using the modified Ritchie
articular index (mRAI) 17, functional disability score [Doctors
Evaluation of Health status (DEH)] and Patients Assessment
Questionnaire(PAQ)18,asgiveninTable1a&b.
RESULTSANDDISCUSSION
Table2:Showsgeneralopinionratingofthetreatmentoutcome
Goodopinion
Pooropinion
Total
number
Excellent
Good
Fair
Good
opinion
Useless
Worsethan
useless
Poor
opinion
Safety
Male
22
68.2%
31.8%
Female
22
50%
10
50%
<65yrold
28
13
57.14%
12
42.86%
>65yrold
16
62.5%
37.5%
<1yrpain
duration
25
44%
13
56%
13yrpain
duration
10
80%
20%
>3yrpain
duration
77.8%
22.2%
22
(100%)
22
(100%)
28
(100%)
16
(100%)
25
(100%)
10
(100%)
9
(100%)
TotalGoodOpinion
26
59%
Totalpoor
opinion
18
41%
Overall, 59% of the patients had a good opinion rating for the
transdermal formulation (Table 2). The most favourable opinion
(80%) was expressed by patients with arthritic pain duration
ranging from 13 years closely followed by patients with over 3
yearsarthriticsymptoms.Fewerearlystagepatients(44%)whohad
arthritis lasting less than 1 year expressed favorable opinion when
compared with later stage (13 years and greater than 3 years
duration)patients.Thisfindingwasinterestingandunexpected.
Theexactreasonunderliningthisfindingisnotimmediatelyknown.
However,itcouldberelatedtothephysicalactivitylevelsofpatients
aslongerhistoryofarthritisisexpectedtobeassociatedwithlower
activity levels, being a progressing and disabling disease. Lower
activity level or resting of the affected joints while applying
Obajeetal.
IntJPharmPharmSci,Vol3,Suppl3,2011,8083
Table3:Showspatientsdemographic,treatmentandoutcomedata
Sex
Agerange
Patient
S/N
Male
Female
65yrs
Above
65yrs
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
TOTAL
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
22
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
22
x
x
x
x
x
x
1
1
1
1
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
28
x
x
x
x
x
x
x
x
x
x
x
x
16
DurationofpainbeforeUTG
treatment
Lessthan
13yrs
More
1yr
than
3yrs
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
25
10
9
Outcome
Durationof
treatment
Outcome
score
Rating
6weeks
4weeks
8weeks
6weeks
8weeks
8weeks
8weeks
8weeks
4weeks
8weeks
8weeks
8weeks
6weeks
4weeks
4weeks
6weeks
8weeks
8weeks
8weeks
8weeks
8weeks
8weeks
8weeks
8weeks
8weeks
6weeks
4weeks
8weeks
8weeks
1week
1week
4weeks
6weeks
6weeks
6weeks
8weeks
8weeks
8weeks
8weeks
8weeks
8weeks
8weeks
8weeks
8weeks
3
2
1.5
2
2.5
2
2
2
1
1
0
1
0.5
0.5
0.5
0
0
0.5
0
0.5
0
0.5
0.5
0.5
0
0
0
0
0
0
0
0
0.5
0
0
2
0
0
1
1
1
1
1.5
1
Excellent
Good
Good
Good
Excellent
Good
Good
Good
Fair
Fair
Useless
Fair
Fair
Fair
Fair
Useless
Useless
Fair
Useless
Fair
Useless
Fair
Fair
Fair
Useless
Useless
Useless
Useless
Useless
Withdrawn
Withdrawn
Useless
Fair
Useless
Useless
Good
Useless
Useless
Worse
Fair
Fair
Fair
Good
Fair
Table4showsopinionratingofthetreatmentoutcomebasedonsiteofpain
LocationofPain
Knee
Ankle
Shoulder/Neck/back
Wrist/Elbow
Total(n)
33
8
4
4
Goodopinion(%)
58
75
100
75
Pooropinion(%)
42
25
0
25
Ofparticularinterestisthesafetyreport.Therewerenoreports of
adversereactionsandnoskinirritationswereobservedatanytime
point. This further underlines the advantages of transdermal over
oral route of administration.Similarly,the highlevel of compliance
observed in this survey could be due to the absence of
gastrointestinalsideeffectsoftenreportedforacidicformulations.
Theuseofmicelleand nanotechnology in enhancingbioavailability
of poorly soluble drugs is gaining popularity in research and the
pharmaceutical industry 1921. This has provided therapeutic agents
that could be administered to patients via routes other than the
traditionaloralorparenteralroutes.Onesuchalternativeroutethat
couldbeverybeneficialfortherapeuticagentswithtraditionallylow
bioavailabilityisthetransdermalrouteofadministration.Observed
advantagesofthetransdermalrouteofadministrationovertheoral
route and hypodermic injections includes: 1) improved control of
the rate of direct delivery into the bloodstream as it bypasses the
gastrointestinalenzymesandsignificantfirstpasseffect,2) smaller
peaktovalley fluctuation in plasma concentration especially when
patchesareadoptedand3)improvedpatientcomplianceastheyare
generally painless and causes little or no discomfort 22, 23. These
factors could account for the discrepancies in the therapeutic
efficacy of glucosamine between laboratory and clinical studies
reported previously. AghazadehHabashi et al studied the
82
Obajeetal.
IntJPharmPharmSci,Vol3,Suppl3,2011,8083
pharmacokineticsandbioavailabilityofglucosamineandconcluded
that orally administered glucosamine has rapid but low absorption
andiswidelydistributedandefficientlycleared.Theyfurtherstated
thatthegutratherthanliveristheorganmainlyresponsibleforthe
lowbioavailabilityofglucosamineandthatthelimitedabsorptionof
glucosaminesuggestsatransportdependentabsorption.Theywent
further to state that food does not significantly affect the
bioavailability of glucosamine 24. This suggest a high first pass
metabolismaswillbeexpectedformanysupplements,beingnormal
part of the human metabolic chain, with well established
degradationpathways.
In the present clinical survey, we found a new transdermal
glucosamine formulation, Urah TGC, to be effective in relieving
symptoms of arthritis. If this clinical observation is further
establishedinadouble blind studies,thiscouldopenthe way fora
new era of glucosamine research and therapy. Being a clinical
survey,directcomparisonoftheseresultswithpreviousstudiesare
difficult due to differences in methodology. However, the results
presented here are consistent with earlier reports by Cohen et al
[16] which concludes that topical application of glucosamine and
ChondroitinsulphatewaseffectiveinrelievingthepainofOAofthe
kneeandimprovementwasevidentin4weeks.Takentogether,our
surveyandthatstudyleancredencetoarouteefficacyrelationship
intheuseofglucosamineforthetreatmentofOA.
Thecurrentclinicalsurveyisnotwithoutlimitations.Beingasurvey,
there is a need to conduct a double blind study on this product as
well as enlarge the cohort and protocol. However, being the first
study to evaluate patient response to this new transdermal
formulation in this community, the survey achieved its main
objectivesandthuspavesthewayformoredetailedstudies.
ACKNOWLEDGEMENT
We are indebted to Pharmaforte Singapore Pte Ltd for organizing
thissurveyasanindependentpartywithnovestedinterest.
REFERENCES
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
APPENDIX
Inadditiontotheauthors,thefollowinginvestigatorsparticipatedin
this Survey: Dr. Richard Tan Tiong Heng, Elim Family Clinic &
Surgery, East Coast Road; Dr. M. Tahir, Crescent Clinic, Eunos
Crescent; Dr. Chow Shen Jung, Chow Surgery, Tanglin Road; Dr.
Kelvin Phua Cheng Pua, Clarke Medical Pte Ltd, Geylang; Dr. Yong
Chee Fah, Yong Clinic & Surgery, Yishun; Dr. Neo Eng Kiong, Neo
Clinic & Surgery, Bankit Road; Dr. Doris Heng, The Medical House
Clinic&Surgery,HollandClose;Dr.LeeEngSeng,HealthcareFamily
Clinic & Surgery, Sin Ming Avenue; Dr. Fong Seng Yew, Fong Clinic
MLST,MeiLingStreet;Dr.WongWeeNam,WongClinic&Surgery,
ClementiAve2;DrHuKuoMing,HuClinic,ClementiAve3;Dr.Koo
XianYeang,LimClinic&Surgery,ChaiCheeRoad;Dr.Rohaili,Usrah
MedicalClinic,BedokNorthSt.3;andDr.ThamHoeMeng,Everwell
Clinic&Surgery,OwenRoad.
83