Co esponding au ho : Padwal P achi Nandkuma .
Copy igh © 2025 Au ho (s) e ain he copy igh o his a icle. This a icle is published unde he e ms o he C ea i e Commons A ibu ion License 4.0.
Fo mula ion and E alua ion o Me o min Table s
Padwal P achi Nandkuma 1, *, Padwal Payal Heman 2, Modha e Ru uja Sa ish 2, Pa han Mujeba Rajjak 2,
Kho e Akanksha Da a ay 2 and Londhe Reema Chand kan 1
1 Assis an P o esso , Depa men o Quali y Assu ance Technique, Sama h Ins i u e o Pha macy, Belhe,Pune,
Maha ash a.
2 S uden o Sama h Ins i u e o Pha macy, Belhe, Pune, Maha ash a.
Wo ld Jou nal o Biology Pha macy and Heal h Sciences, 2025, 24(02), 049-053
Publica ion his o y: Recei ed on 21 Sep embe 2025; e ised on 01 No embe 2025; accep ed on 03 No embe 2025
A icle DOI: h ps://doi.o g/10.30574/wjbphs.2025.24.2.0944
Abs ac
Me o min hyd ochlo ide is an o al hypoglycemic d ug ha enhances glucose ole ance in ype 2 diabe es pa ien s &
lowe s basal plasma glucose le els. The pu pose o he s udy was o o mula e and op imize MET ma ix able s o SR
use. The SR ma ix able o MET was p epa ed by we g anula ion echnique using Poly inyl py olidone K30 and
hyd oxyl p opyl me hylcellulose o di e en iscosi y g ades. The in luence o a ying he polyme a ios was e alua ed.
The excipien s used in his s udy did no modi y physicochemical p ope ies o he d ug. MET has ela i ely sho plasma
hal -li e, low absolu e bioa ailabili y.
The need o he adminis a ion 2 o 3 imes a day when la ge doses a e equi ed can educe pa ien sa is ac ion.SR
o mula ion which would sus ain plasma le el o 8-12 h may be adequa e o once daily dosing o MET.SR o mula ions
a e equi ed o MET o ex end i s ac ion du a ion and o enhance pa ien compliances. The o mula ion o o al
sus ained elease sys ems has been a challenge o o mula ion scien is s because o he ailu e o such sys ems o
es ain and localize he sys em in he desi ed si es o he gas oin es inal ac . Ou o all he o mula ion ial ba ches,
F3 o mula ion e eals op imum esul s. I has been no ed ha HPMC K100M is incapable o p o iding good d ug elease
p o ile bu he combina ion o HPMC K100M and Poly inyl py olidone K30 in combina ion p o ide he bes d ug
elease kine ics. So, con olled elease ma ix able s o me o min hyd ochlo ide can be an icipa ed o minimize he
adminis a ion equency and educe dose dependen side e ec s.
Keywo ds: Me o min Hyd ochlo ide; SR Ma ix Table ; HPMC K100M; We G anula ion Technique
1. In oduc ion
Sus ained- elease (SR) o al deli e y sys ems a e in ended o a ain he apeu ically e ec i e concen a ions o d ug in
sys emic ci cula ion o e an ex ended pe iod o ime1 owa ds no el d ug deli e y o pha maceu ical echnology; SR
ma ix able s ha e gi en a new de elopmen 2. Rese oi ype o dosage o ms designed o elease d ug cons an ly and
con inuously o e sa is ac o y p olonged pe iod o ime o main ain plasma d ugs concen a ion wi hin he apeu ic
le el3. D ug p oduc s ha a e o mula ed o minimize dosing by al e ing he a e o d ug abso p ion ha e been he e
o many yea s. O all he dosage o ms, ma ix able s a e commonly used in o al sus ained elease (SR) because hey
a e easy and simple o o mula e. Ma ix sys em e e s o elease sys em, which ex ends and egula es he elease o
d ug dissol ed o dispe sed. Indeed, ma ix is a good complex o one o mo e d ugs along wi h a gelling agen i.e.
hyd ophilic polyme 4-6. I is es ima ed ha by 2025 a ound 300 million people will be diagnosed wi h diabe es7, 8.
Wo ld Jou nal o Biology Pha macy and Heal h Sciences, 2025, 24(02), 049-053
50
Me o min hyd ochlo ide (MET) is an o al an i-hype glycemic medica ion employed in he managemen o Type 2
diabe es in pa ien s who a e no able o con ol he disease wi h die alone and exe cise9. Unlike Insulin and
Sul onylu ea, MET does no lead o weigh gain; hence i eme ges as he i s choice o he apy o ype 2 diabe es and
is e en adminis e ed in obese indi iduals wi h ype 1 diabe es o coun e ac insulinesis ance10. Chemically, MET is (N,
N-dime hyl i idoid ca bona i e diamide hyd ochlo ide) alls unde he ca ego y o biguanides, hyd ophilic, BCS class-
III d ug11, 12. I enhances glucose ole ance by educing basal and pos p andial glucose by educing in es inal
abso p ion o glucose, educing hepa ic gluconeogenesis, enhancing glycogenesis, lipogenesis and glucose up ake by
adipocy es and muscle cells9, 13. MET is a e y wa e soluble medica ion (0.5 g/ml)gi en up o2.5 g/day in h ee
di e en doses gi en wi h ood o educe po en ial gas oin es inal side e ec s like ano exia, abdominal pain, nausea
and dia hea14.
Figu e 1 O e iew o Human Me abolism
2. Ma e ials and me hods
Me o min HCl was ob ained as a gi sample om A bo Pha maceu icals L d, New Delhi (India). Hyd oxy p opyl me hyl
cellulose, poly inyl py olidone K30, magnesium s ea a e was p ocu ed om HI media Chem. Lab, Mumbai. Talc and
sodium algina e, s a ch was bough om Loba Chemicals P . L d. Mumbai. Ace oni ile, me hanol and Isop opyl alcohol
we e HPLC g ade a ailable om Me ck L d., India. All he o he eagen s used we e o analy ical g ade. T iple dis illed
wa e was p oduced in house.
2.1. Re o mula ion s udies
2.1.1. Physical cha ac e is ics
By isual examina ion, he d ug was iden i ied o physical cha ac e s like colou , ex u e, odou e c.
2.1.2. Solubili y
Solubili y o he d ug was de e mined by aking some quan i y o d ug (abou 10 mg) in he 10 ml olume ic lasks
sepa a ely and added he 10 ml o he sol en (wa e , e hanol, me hanol, 0.1N HCL, 0.1N NaOH, chlo o o m and 7.4 pH
bu e ) Shake igo ously and kep o some ime. No e he solubili y o he d ug in a ious sol en s (a oom
empe a u e).
Wo ld Jou nal o Biology Pha macy and Heal h Sciences, 2025, 24(02), 049-053
51
2.1.3. Mel ing poin
A small quan i y o powde was placed in o a usion ube. Tha ube was placed in he mel ing poin de e mining
appa a us (Hemline) con aining cas o oil. The empe a u e o he cas o oil was g adual inc eased au oma ically and
ead he empe a u e a which powde s a ed o mel and he empe a u e when all he powde ge s mel ed.
2.1.4. FTIR spec oscopy
The sample in KB should be be ween 0.2% and 1 %. The pelle is much hicke han a liquid ilm, hus a educ ion
concen a ion in he sample is needed (Bee 's Law). Fo he die se which you will be using, app oxima ely 80 mg o he
mix u e is desi ed. Too high o an a en ion c ea es issues ha usually ha e clean pelle s. FTIR spec a o he samples
we e ob ained be ween a spec al ange om 4700 o 400 cm-1 wi h 20 scans and 4 cm-1 esolu ion.
2.1.5. De e mina ion o λ max o MET
MET, 100 mg was accu a ely weigh ed in o a 100 ml olume ic lask, dissol ed in dis illed wa e and he olume was
made up wi h dis illed wa e . Pipe e 1 ml o his solu ion.
3. Mic ome i ics p ope ies
3.1. Angle o epose
The ixed unnel and ee-s anding cone me hods employ a unnel ha is secu ed wi h i s ip a a gi en heigh , h, which
was kep 2cm abo e g aph pape ha is placed on a la ho izon al su ace. Angle o epose can be de e mined by
ollowing equa ion
θ = an-1 (h/ )
Whe e, θ is he angle o epose, his heigh o pile; is adius o base o he pile.
3.2. Bulk densi y (BD)
An accu a ely weighed powde blend om each o mula was ligh ly shaken o b eak any agglome a es o med and i
was in oduced in o a measu ing cylinde . The olume occupied by he powde was measu ed which ga e bulk olume.
The BD o powde blends was de e mined using he ollowing o mula.
3.3. Bulk densi y = To al weigh o powde /To al olume o powde
3.3.1. Tapped bulk densi y (TBD)
An exac ly weighed powde mix u e om each o mula was gen ly shaken o des oy any agglome a es de eloped and
i was placed in a measu ing cylinde . The measu ing cylinde was apped un il no u he change in olume was
obse ed
• which p o ided he apped olume. The TBD o powde blends was
• calcula ed by he ollowing o mula.
• TBD = To al weigh o powde /To al olume o apped Powde .
Table 1 Fo mula ion Ing edien s
Ing edien
Quan i y in mg
Quan i y equi ed
Me o min HCL
500
100
PVP K30
50
10
Lac ose monohyd a e
12.5
2.5
MCC
72.5
14.5
Magnesium S e a e
7.5
1.5
Talc
7.5
1 .5
To al
650
130
Wo ld Jou nal o Biology Pha macy and Heal h Sciences, 2025, 24(02), 049-053
52
4. Resul s
Mel ing poin o MET (pu e d ug) was de e mined o be 223-226°C. MET was soluble eely in wa e , spa ingly soluble
in me hanol and e hanol and insoluble in Ace one. Iden i ica ion o MET was ca ied ou by FTIR spec oscopy in
e e ence o ma ke compound. I was ound om he ou come o IR spec um acco ding o speci ica ion
Figu e 1. MET was ound o ha e a linea calib a ion cu e in a concen a ion ange o 2-12 µg/ml a 234nm Figu e. 2.
Angle o epose was ound by unnel me hod.
Tapped densi y and bulk densi y we e measu ed by cylinde me hod, and ca 's index (CI) was calcula ed using he
ollowing equa ion. Ca 's index = (TBD-LBD) ×100/TBD. Hausne 's a io was indica i e o in e pa icle ic ion and
could be applied o p edic powde low p ope ies. Hausne 's alue o he p epa ed g anules anged om 1.15 o 1.16
was hough o indica e good low p ope ies Table 2. The physical appea ance, able ha dness, iabili y, weigh
a ia ion andd ug con en uni o mi y o all able o mula ions was ound o be sa is ac o y and ep oducible as
obse ed om he da a in Table. 3. Table ha dness was good (6 o 8 kg/cm2) a ying wi h o he comp ession o ce
applied, and iabili y was less han 0.5% (w /w ).
The manu ac u ed able s showed low weigh a ia ion and a high deg ee o d ug con en uni o mi y, indica ing ha
we g anula ion is an accep able me hod o p epa ing good- quali y ma ix able s o me o min HCl. Fi s , he able s
we e made wi h HPMC K4M (F1) which eleased 40.61% and 81.23% o me o min HCl in 1 and 4 h espec i ely. And
he able s p epa ed wi h HPMC K15M (F2) exhibi s 81.01% d ug eleased in 4 h. Table s o mula ed wi h K100M (F3),
d ug- o-polyme a ios 5: 2 and isop opyl alcohol as g anula ing agen slow he elease o me o min HCl 36.11%,
73.65% and 93.44 a 1h, 4 h and 8 h espec i ely. F3 o mula ion has demons a ed an ideal o mula ion because o i s
closes p o ile o he a ge in elease e ms.
Table 2 Resul o p e-comp ession p ope ies o MET SR able s
Fo mula ion
LED
TBD
Angel o Repose
Ca 's Index
Hausne 's Ra io
F1
0.307
0.357
25.94+0.56
13.84
1.15
F2
0.266
0.312
26.32+0.87
14.66
1.16
F3
0.384
0.441
25.98+0.40
13.46
1.15
Table 3 Resul s o pos comp ession p ope ies o MET SR able s
F. Code
Ha dness
Thickness
Weigh Va ia ion
F iabili y %
Assay%
F1
6-7
6.48
760
0.1
96.74
F2
7-8
6.52
760
0.1
99.4
F3
6-7
6.51
780
0.1
99.5
5. Conclusion
In ou s udy, o each an in ended a ge elease p o ile, SR o mula ion o me o min HCl able s we e de eloped wi h
polyme subs ance such as HPMC K100M. I has been epo ed ha excipien like HPMC K100M wi h poly inyl
py olidone can be employed wi h we g anula ion p ocess. The use has p oduced compa able indings wi h o he
wo ks in he li e a u e in SR o mula ion p epa a ion. Bu in de eloping SR o mula ions wi h me o min HCl, i was
ound ha HPMC K100M gi es an imp o ed esul in p epa a ion o SR o mula ion p epa ed by we g anula ion
me hod.
Wo ld Jou nal o Biology Pha macy and Heal h Sciences, 2025, 24(02), 049-053
53
Compliance wi h e hical s anda ds
Acknowledgmen s
We since ely acknowledge he con inuous guidance, mo i a ion, and cons uc i e eedback p o ided by ou men o ,
[D ./P o . P achi Padwal]. Thei expe ise and pa ience ha e been ins umen al in shaping his e iew pape . We also
ex end ou g a i ude o [Sama h ins i u e o pha macy] o p o iding he necessa y academic en i onmen and
esou ces ha suppo ed his wo k
Disclosu e o con lic o in e es
No con lic o in e es o be disclosed.
Re e ences
[1] Colombo R, Be ini P, San i P, Peppas NA. Swellable ma ices o con olled d ug deli e y, Gel-laye beha io ,
mechanisms and op imal pe o mance. Pha m Sci Tech Today. 2000; 3:198-204.
h ps://doi.o g/10.1016/S1461-5347(00)00269-8
[2] Chowda y P, S a ani T, Bashee uddin MD. Fo mula ion and e alua ion o sus ained elease able s o na eglinide
by using na u al polyme s. In J Ad Pha m Sci. 2017; 9(1):8-13. h ps://doi.o g/10.5138/09761055.2065 3.
Khan J, Yuen KH, Bee Hong N, Chi neni M, Elhassan GO, Al-Dhali S, Kaleemullah M. P epa a ion and in- i o
e alua ion o di e en con olled elease polyme ic ma ices con aining ke op o en. Heal h MED. 2010; 4
(2):386-392
[3] B ahmanka DM, Jaywalk SB. Biopha maceu ics and Pha macokine ics Pha macokine ics, 2nd Ed. Vallabh
P akashan, Delhi, 2009:399-401.
[4] Lee VHL. Con olled D ug Deli e y Fundamen als and Applica ions: in luence o D ugP ope ies on Design, 2nd
Ed, Ma cel Dekke , Inc, New Yo k. 1987:16-25.
[5] Vish ak ama P, Sha ma S. Liposomes: an o e iew. J D ug Deli The . 2014; 4(3):47-55.
h ps://doi.o g/10.22270/jdd . 0i0.843
[6] Ri u B, Dixi RR, Gup a HV, Pa el PS. Fo mula ion and cha ac e iza ion o sus ained elease ma ix able o
me o min hyd ochlo ide. In J Pha m Recen Res. 2009; 1:49-53.
[7] Jain SK, Gup a A. De elopmen o geluci e 43/01 beads o me o min hyd ochlo ide o loa ing deli e y. AAPS
Pha m Sci Tech. 2009; 10:1128-1136. h ps://doi.o g/10.1208/s12249-009-9302-6
[8] Chouldhu y PK, Ka M, Chauhan CS. Cellulose ace a e mic osphe es as loa ing depo sys ems o inc ease gas ic
e en ion o an idiabe ic d ug: o mula ion, cha ac e iza ion and in i o - in i o e alua ion. D ug De Ind Pha m.
2008; 34:349-354. h ps://doi.o g/10.1080/03639040701542531
[9] Ba ie e G, Ta a y M, Rigaud M. Me o min: A ising s a o igh he epi helial mesenchymal ansi ion in
oncology. An icance Agen s Med Chem. 2013; 13(2):333-340.
h ps://doi.o g/10.2174/1871520611313020018
[10] Rojas L, Gomes MB. Me o min: an old bu s ill he bes ea men o ype 2 diabe es. Diabe ol Me ab Synd . 2013;
5 (1):6. h ps://doi.o g/10.1186/1758-5996-5-6
[11] Nayak AK, Pal D, San a K. Tama ind seed polysaccha ide egellan mucoadhesi e beads o con olled elease o
me o min HCl.
